Dr Rupy: Fat, this curious, wonderful and often misunderstood organ is the subject of today's podcast with Professor Liesbeth van Rossem and Dr Mariëtte Boon, authors of the incredible book Fat: The Secret Organ. And yes, it is an organ. Professor Liesbeth van Rossem is an internist endocrinologist at the Erasmus University Medical Centre, Rotterdam. She is also co-founder of the Obesity Centre and has an internationally leading position in the field of obesity and biological stress research. Dr Mariëtte Boon is an internal medicine specialist in training and her research performed at the Leiden University focuses on fat metabolism. And honestly, today's conversation is a whirlwind running through a fantastic variety of topics all to do with fat. You're going to learn about why fat is an organ, what mechanisms drive hunger and satiety, how you can stimulate satiety to eat less, why stress can cause fat, why liposuction unfortunately does not work, the number and size of fat cells and if they change throughout your life, as well as fat on inflammation, immune health and fertility. It is an incredible conversation and their book, Fat: The Secret Organ, is a must-read for anyone interested in this subject. We didn't get time to deep dive into some of the other topics in their book, such as the evidence-based lifestyle recommendations, but I highly recommend you get a copy and I think you're going to find today's conversation super, super useful. Remember, you can join the newsletter where I share three things to help you live a healthier, happier life every single week. Something to eat, read or listen to, and you'll get a free seven-day meal plan as well when you sign up at thedoctorskitchen.com. For now, here is my conversation with Professor Liesbeth and Dr Mariëtte Boon.
Dr Rupy: Professor, Doctor, thank you so much for joining me on the podcast today. It's a pleasure to have you both here. I notice in both of your biographies, I believe, Liesbeth, you are an athletics fanatic. Is that right?
Liesbeth: Oh, that's right. I love long jump and I love sprinting, but I'm not a long distance, not an endurance athlete, to be honest.
Dr Rupy: I've tried to be endurance myself in the past, actually. Like I've done a half marathon, but I've never completed a marathon. Yeah, I think a marathon is a bit pushing it for me.
Liesbeth: I admire that so much, people who are able to run a marathon or a half a marathon. I really, I really like to to to stand in the in the audience and and shout and help them, but well, 100 metres is for me more than enough and long jump with 30 minutes, 30 metres is already long enough. I like the the reactive and and the high speed athletics.
Dr Rupy: Yeah, yeah, definitely, definitely. Those fast muscle twitch fibres. And and Mariëtte, you were, you were a tennis fan as well.
Mariëtte: Oh, yes. Currently, I am more into watching the tennis, but also, of course, due to the corona regulations, it's more difficult to to play it yourself, but yeah, I really love to play tennis. Also, as as Liesbeth mentioned, the the very fast movements, I really like that.
Dr Rupy: Yeah, brilliant, brilliant. Well, I mean, your book is absolutely fantastic. We were talking a bit about before the show started recording about how the book is being used in in policy decisions across both medicine as well as people who don't have a medical background being able to access it. I think it's fantastically written. My question to start off with is, how you guys both came to obesity and everything to do with fat as a research area yourselves? Where where was that interest peaked for for you both?
Mariëtte: Yeah, for me, it already started, I guess, during my medical study. Myself, I am, yeah, I used to be very thin always, and I didn't really understand why. That fascinated me because I always ate, I always eat a lot. I also exercise a lot, but that that really intrigues me. And the other way around intrigues me as well. How how how can it be that some people so easily can gain weight? How does it work? And yeah, that really started my interest for this research area and it well, it it never let go of me.
Liesbeth: Yeah, I think for me it also started during med school already. I think in the 90s, I was also doing athletics then and some people were very just in a few trainings, they they started to to gain muscle mass and some still kept a layer of fat. And actually, my my mother was overweight and she was always busy with dieting and you know, she was cooking healthy for the rest of the family, but she was always in weird kind of dieting. And later on, I understood there were some underlying causes making her fat. And then in the 90s, when I was on med school, then then the leptin was just discovered. And I won an award to go to the US doing at the University of Maryland and Johns Hopkins University, doing some research there. And there the whole field appeared to me that it's so such an interesting world that that obesity is really complex and that fat is an organ secreting hormones. I mean, that was so fascinating. And then I understood when I went back to the Netherlands and finished my studies, well, I I thought we have to do more with concerning research here.
Dr Rupy: Yeah, no, it's absolutely fascinating. And and right at the start of the book, what I really appreciated was the history surrounding fat and how it's more recently transitioned from something that we thought as something as desirable to something that is sort of like public enemy number one. But also throughout the stages of our evolution, how important and necessary fat was. I wonder if we can talk briefly about that sort of the anthropological aspect of of fat.
Mariëtte: Yeah, that that's that really fascinates me as well because of course, the evolutionary purpose of our body fat is it it it is a large storage organ for for nutrients. And well, our ancestors did not always have access to food. So yeah, we we are really as humans dependent on our fat stores. So we have enough fat stores to go without food for about 40 or 50 days, depending on how much you you move, of course. But it's it's a very important store. So it was really appreciated by our ancestor. And there are already, there is some art, some some small statues of a woman. We also show that in the book of a woman who has, well, a lot of body fat. And that was really appreciated. It's sort of the white gold in your body. And as you mentioned, also during the 17th, 18th century, it was sort of, well, when you had a lot of money, you could buy a lot of food. You had a very big posture. That was really appreciated. But indeed, in the 20th century, it became clear that it is unhealthy to have too much fat. And from that on, it was seen as as more of an enemy. And also, previously, people who had a lot of fat were thought to be kind. They they were described also in literature back then. They were they were jolly, jolly fat people. They were very kind. And later on, that shifted. They were, they were dumb, they were, well, not kind at all. And well, that that's really, really fascinating, I think.
Dr Rupy: Yeah, yeah, no, it's very interesting to see that and how art and culture and literature has sort of changed the perspective that we have of people of different weight categories and aesthetic categories as well. I wonder, I mean, the the the title of the book, the subtitle was The Secret Organ. And this whole concept of fat being an organ, I think is relatively new. Liesbeth, can you describe about what we we mean by fat being an organ?
Liesbeth: Yeah, I think it's important that people indeed realize that it's an active hormone producing organ, more than than hundreds of hormones are being produced in the fat, but also all kinds of substances which are important for, for example, the immune system. And there's a great communication between the fat mass, communication between the brain, between other organs, also the intestines. And to to realize that it's an organ, you can easier also understand that when you have too much fat, that that's a disease, that the whole communication between the organ fat and the the brain, for example, is disturbed. And that's crucial. This communication is so important because, so so too much fat is is basically making you sick, like and also a heart or a liver can be sick, but also your fat can be sick. And it's also now in in Europe, it's being called a chronic relapsing disease. And that's important because once your fat is sick, the the body becomes sort of reprogrammed that if you have a high weight, that the body wants always to go up to the higher weight again. And therefore the the the combating obesity is so so hard. And at the same time, it's also called a gateway disease because 230 complications have been described from obesity. And the most known, of course, are type two diabetes, cardiovascular disease. But also 13 forms of cancer, for example, are obesity related, depression, because also these inflammatory factors can also signal to the brain and also these hormones, they give also brain disturbances, mood disorders, infertility can exist, joint complaints, but also more severe course of infections, for example, like we see nowadays with with COVID-19. So those are the most known complications, but there are so many more. So it's both a gateway disease to other diseases, but when you have too much fat itself, it becomes, it changes within the communication between fat and brain and other organs. So that's really important to to realize.
Dr Rupy: Yeah. And and I in in the book, you also talk about how some people have too little fat as well. There's a a curious throughout the whole book, you've got examples and patient stories, I think, which are really helpful to contextualize everything. So can you go through some of the descriptions of how people actually suffer from conditions where they have too little fat? Because I think most people are aware of why too much fat is a bad thing, but perhaps the other side of things is is lesser known.
Mariëtte: Well, we do describe in the book, it is very rare though, that you have a certain condition in which you don't have any subcutaneous fat. And that can also be very unhealthy because as Liesbeth mentioned in the beginning, our fat produces hundreds of hormones and one of them is leptin. And when you don't have any subcutaneous fat, your leptin levels are really low. And leptin is a crucial hormone in, well, for all kinds of processes in the body. And that makes it, can make it very dangerous. And also, when you don't have any subcutaneous fat, where do you have to store your fat? This will be stored in other organs, like the liver, like the heart. And these organs start to malfunction. So therefore, you you do need your, you do need your body fat. But what is much more known is, of course, the disease anorexia nervosa, where people have a very little body fat or people who have little body fat for other reasons. And well, that can also be unhealthy because of this hormone leptin, because leptin is produced, well, when you have a lot of body fat, a lot of leptin is produced, and when you have little body fat, only little leptin is produced. And when the amount of leptin is low, this this has several consequences because in women, a certain amount of leptin is needed for women to keep menstruating. So this happens via a connection of leptin to the fertility centre in the brain. So then women stop menstruating and it has been studied that women need about 17% of body fat to keep menstruating. And it is also very important leptin for the function of our immune cells. So too little fat can also result in various serious infections and also more fragile bones. So this, I think, well, really illustrates the importance of our body fat. You you cannot go without it.
Dr Rupy: Yeah, absolutely. Yeah. I think I don't think many people have really thought about it from the perspective of your immune system and fertility as well. And and I guess just to take it a step backwards, let's talk a bit about those hormones, leptin, ghrelin, where they're produced, how they're produced, what what they're produced in response to those those hunger hormones. How does that network work?
Liesbeth: Yeah, I think it's it's it's good to to realize that we make a lot of food choices a day, over 200 food choices we make and by far the majority is unconscious. And indeed, these these hunger hormones and satiety hormones, they they play a big role in that. And for example, if you if you get hungry and your your stomach is empty, your hunger hormone ghrelin is being produced from the stomach and it makes you you extra hungry. And then when you start eating, also your satiety hormones, basically most of them in in the intestines are being produced in response to to food intake. And they signal to the brain and they give you feelings of fullness. So so it's not only we always think we stop eating because the stomach is being stretched and then we stop eating. Well, that's part of the story though, because of the the vagal nerve, the signals to the brain, but a large part of your satiety, feeling full, is is determined by satiety hormones. And that's really important because they can be disturbed if you have too much fat, for example, this communication is being disturbed. Also from the fat, we have the hormone leptin, and leptin is is have has multiple functions, actually. It's it's a key hormone. It can inhibit food intake, stimulate metabolism, which is really important as a cute effect. But at the same time, it's also a adiposity marker. So it's basically a sort scale of how much fat do you have in the in the body as storage. And this feeling full, you you sometimes you you're really full by your satiety hormones. We call that the homeostatic system and you can be really full, but you can sometimes really eat through it though. For example, when something is really delicious, like a dessert, for example, if you have a major Christmas dinner and you had meals and but somehow this dessert still fits. And that is through a different system. We call it the hedonic system. So it's basically your reward system, which also is related to the hypothalamus, which is the major centre in the brain regulating all these hormones. It's receiving hormones, but it's also sending signals. And the hedonic system is is involving other neurotransmitters like dopamine and serotonin. And they make you feel very comfortable. If you eat a dessert, you just like it so much and then this centre is is active. So through this centre, you that that's the reason that the dessert still fits, although you your satiety hormones are are on. But you can actually influence this. And and this happens happens all day, actually. If if we are walking outside, for example, to a central station and we take a train, all around us, the food environment is with posters or smells of delicious things which are not healthy, like donuts or anything. And you can try it yourself right now. If you if you imagine maybe now a large chocolate bar being just in front of you right right now. And if you really think of it and you start to get hungry, maybe you should visualize it now. And then automatically also your your hunger hormone ghrelin will be produced, but also your insulin, for example, will be produced. And if insulin is being produced, your glucose will go lower, your sugar in your blood will the levels will go lower. And then you get sort of craving for something sweet. And when we then would go out for for to to grab something to eat, we are much more prone to take something sweet than maybe an healthy healthy piece of bread or anything, because we are so sort of programmed to take this sweet already. So that's what what influencing. So we can influence it ourselves, but our environment is also influencing it heavily. And I think a very good example of that is also the the very famous mind over milkshake experiment. And and that's that's seems almost magical that our thoughts can also influence, for example, our ghrelin levels. This experiment is is is being performed by a psychologist at Yale University. They gave 46 research participants a milkshake and that contained 380 kilocalories. And half of the participants were told that it was a high calorie milkshake with 620 calories. And the other half, they were told it was a sensible milkshake with only 140 calories. And then the researchers took blood from the participants at various time points to measure their ghrelin levels. And in between the two blood draws, the the participants had to examine and to evaluate this basically incorrect milkshake label. And then they were asked to drink the milkshake and to re-evaluate it. And then that was really striking. The analysis showed that the mindset of the people who believed they had been given a high caloric milkshake, that resulted in a sharp drop of their ghrelin levels. But in contrast, the ghrelin levels of those who believed they had drunk a much lighter version of the shake, they they remained virtually unchanged. So, so likewise, the the physical reaction with respect to the the hunger hormone ghrelin was more strongly associated with the number of calories thought they had consumed than than actually the the actual calories. So, actually these researchers concluded from the effect of our food on ghrelin that it's that's probably mediated by the mind. So I think that's so interesting that our mindset can influence our response also to food. And I think that that's also what what's going on right now in in our food environment.
Dr Rupy: That is absolutely fascinating. I I I love that description of the experiment. And and just for listeners to to think about like how much, how many different pathways are involved in satiety and appetite regulation. We have leptin and ghrelin being released from various places, whether it be your stomach or your fat cells. Then you have the mechanical receptors, which is the stretching of your digestive organs, which also has an an impact on your hormone release, your hedonic pathway, as well as the perception of what you're eating as well. I mean, all these things interplay into whether we overeat, whether we eat healthier items. You have a lovely checklist, I think, in the in the book about how you can influence your own feelings of satiety. I wonder if we could talk about that for a second.
Mariëtte: Yeah, well, that that's indeed very interesting because you can trick that in so many ways. As Liesbeth mentioned, there are a lot of pathways that eventually result in feeling of satiety. What is also produced after you have eaten a meal are intestinal hormones. So even more hormones. And one of the intestinal hormones is GLP-1. And this hormone can also induce a feeling of satiety. And it takes about 20 minutes before GLP-1 is produced by the intestine. And well, if you try to eat slow, if you try to chew more on your food, that makes it less likely that you will eventually eat a second plate of food because, well, you then already feel satiety already after your first plate. And what you can also do is try to eat from a smaller plate because the, again, the optical illusion helps you feel fuller. So you can also trick that with your mind. And what you can also do is choose unprocessed food products as often as possible. I think that's a very important one because these induce a better satiety signal compared to ultra-processed food, which is, well, basically in all the supermarkets lying everywhere.
Liesbeth: I think in addition to that, it's it's very interesting that that Kevin Hall's group did a fascinating experience on that. It's it's was a randomized control trial where he studied 20 persons with a body mass index of of 27 and they were given both groups exactly the same amount of food with respect to calorie number, but also the the fibre, salt, carbohydrates, fat, everything, the macronutrients were very similar in two groups. But the only difference was that one group was been giving the ultra-processed food and the other group was processed, unprocessed food. So basically the food you can still recognize as a cauliflower is a cauliflower and the other food is more processed. And within two weeks, he noticed, they noticed that the group who was eating ultra-processed food, on average, they eat faster and 508 calories a day more than the than the group who ate was eating unprocessed. And within that two weeks, also they gained 1 kg of weight in contrast to the group who eat only unprocessed food, they they they lost actually 1 kg of of weight within the two weeks. And I think it's fascinating because they perfectly controlled all the circumstances, which is quite unique. And of course, it's only the short term. But it's it's it's showing some maybe some causal relation between the only difference ultra-processed, processed, unprocessed food, because we always have discussion about calories and should it be low carb, low fat. And this is showing there are probably also other mechanisms. And also interesting in this experiment was that he was showing that unprocessed food, then you see a very nice decrease of the hunger hormone ghrelin, which should be your hunger hormone should be decreasing if you eat after eating. And at the same time, one of the most important satiety hormones, the PYY, peptide YY, was increasing. But this beautiful response of the body was not present when people were eating ultra-processed food. So maybe the mechanism of eating all too much ultra-processed food is might be mediated by disturbing our hunger and satiety hormones. So that's that's new insights which which were very important, I think.
Mariëtte: It's really fascinating because we we recognize that for ourselves as well. After you have eaten something from a fast food, one hour later, you're already, you already feel hunger again. That's that's and this this study really shows how well, that that the satiety signal is is much less.
Dr Rupy: It is that is super interesting because I think a lot of the discussion that you see dominated on social media and even in academic forums are about different types of macronutrient profiles of food, which one's better versus which one is, you know, more scientifically valid. I always like to think about Occam's razor. The simplest approach is usually going to be the most effective and probably the most truthful as well. So simply moving people along that spectrum from ultra high processed to processed to unprocessed food is likely the way we need to think about all dietary approaches. And and the mechanisms that back up that are like, you know, shown in in in that experiment right there. I mean, that that for me is is a real, real sort of bold underlining of of the simple approach.
Liesbeth: Yeah, I think you have a major point right now because we see now in our offices, if we see patients living with obesity, completely the opposite happens because a lot of people are being told, if you you should lose weight, so go on a diet. And once who are really eager to lose weight, what do they do? They do crash dieting, for example, lower than 800 or even 500 kilocalories. And shocking about that was, I think, a revolutionary research of the the famous Symetron article from Australia showing that already after a couple of weeks of crash dieting, that people, of course, they lost weight, and it doesn't matter which diet you do, if you go so low in the calories, you will lose weight on the short term. Short term, so not not long term, actually. But what happens is after already after a couple of weeks, that you that they noticed that the hunger hormones increased and the satiety hormones, so the hormones which make you feel full, they decreased. And the shocking thing about the paper which shocked the world at that time, actually, that this persons were retested more than one year later. So they were already finished with their crash dieting, they eat normally, but still these disturbances were still in the same way. And when your satiety hormones are are decreased, well, you're more basically more hungry. And we also know that that your metabolism slows down from from crash dieting. So when you're more hungry and your metabolism slows down, well, that's the perfect prescription, actually, the perfect formula to to to regain your weight. And that's usually what happens for people. And I feel really sorry for my patients who have been doing for for 10 times crash dieting and one even stricter than the other. And they are sort of destroying your own system. The only solution can be if you really want to do a crash diet, then you should directly after change your behaviour to healthy behaviour. Then it can work, but not if you do only like a short-term crash diet and then your old behaviour. That that's that's really not what what's it's working. And so that that's our insights. So just eating healthy is is important. We recently also did a study, people underwent a combined lifestyle intervention, so by one and a half year coaching on healthy living, exercise, but also cognitive behavioural therapy. And also their diet was just as much as possible unprocessed food, normal, healthy diet. And then we noticed that these acute, most of these acute hunger and satiety hormones did were not disturbed, actually. So therefore, we have more and more evidence that just healthy, it seems like very clear, of course, but still you see so many people going on a diet, but just healthy eating is one of the fragments, one of the elements you can do yourself for healthy living. Actually, it's not the solution for obesity only, dieting only, eating healthy. It's much more is necessary if you're really living with obesity already. But that that's that's another story.
Dr Rupy: It's one of those tools that we we need to entertain, but it's not at the expense of everything else because as we know, and as you talk about in your book, about the associations with mental health disorders, low mood, anxiety, as well as a number of other physical issues too that you described earlier. Those are things that we also need to take into account. And I think it's a lovely segue into the bit about inflammation and fat and adiponectin as well. I wonder if we can talk about adiponectin for a little while. It's a relatively new thing that people are coming across. Can we describe what those are and and how that relates to inflammation?
Liesbeth: Yeah, actually, well, leptin is is one of the major fat hormones, which is basically pro-inflammatory. And adiponectin, we see it actually as a beneficial hormone. It's it's with respect to inflammation, it's anti-inflammatory. And what we see actually in people living with obesity that the leptin levels are increased because it's a marker of the amount of body fat. So more pro-inflammatory. And at the same time, we see a decrease of the adiponectin, which is anti-inflammatory. And that that disbalance is really important in as one of the factors making the fat cells, which are increased in in obesity, that they are pro-inflammatory. And that is one of the major mechanisms leading to, for example, insulin insulin resistance, but also cardiovascular disease, cancer, depression, all these gateway gateway disease complications of obesity, inflammation is a major part in that. And therefore, also you see when people are decreasing their their their weight, when it's either by lifestyle intervention, pharmacotherapy or bariatric surgery, that the degree of inflammation is is is also lowering. And one of the points what we see right now is that when inflammation is continuously present, that also affects the immune system. And you have like two layers of immune system. You have your innate immune system, that's basically always that's when you're born, it's it's it's present. And then you have your adaptive immune system. And if you, for example, catch a virus or a bacteria, then then the adaptive immune system after a couple of days will recognize it and will produce, for example, antibodies against it. And both these immune systems are being disturbed in people with obesity. Basically because they are too much active all the time already, combating all these inflammatory inflammatory factors. And then what you see is if if people with obesity have a chronically active, overactive immune system, then when a virus is coming over, then the immune system is not ready enough to to to combat the the the virus, for example. And and that's one of the aspects, really not the only one because there are very many other ways leading to more severe infections, but it's also one of the ways leading to a more severe course of, for example, COVID-19 in in patients suffering from obesity.
Dr Rupy: Yeah, that's that's a really good point. And I guess to simplistically summarize, because your threshold for inflammation is so much higher already because of the leptin levels, when you do need to mount an immune response, you don't have the armory essentially to fight against pathogens. So that could be one of the reasons. And then conversely, when you're dealing with a multi-system inflammatory disease such as the one caused by COVID, again, that adds to your inflammatory burden as well, which can lead to a whole bunch of complications. And I you mentioned this in the book. I think one person listening to this might think, okay, well, if you have these fat cells and they're all creating inflammation, why don't you just suck a few out using liposuction to reduce the number of fat cells that are producing leptin? What what is the science around the number and the type of fat cells and and and the issues around that sort of simplistic argument for liposuction?
Mariëtte: Yeah, well, unfortunately, that will not work. Your body is surprisingly good at keeping the amount of fat cells constant. We don't really know how that works, but we do know that it works because we know from from studies that when you perform liposuction and literally suck out fat cells, the fat cells grow back at a different place. So in in part of the women who have undergone liposuction, we see that, well, fat cells grow back in in the breasts, for example. It's not always a really bad thing for everybody, but it it it shows that your body really wants to keep the fat cells constant. So it it it does, well, it it will not work by removing fat cells.
Liesbeth: Yeah, and actually the fat cell itself, when you're you're getting obese, then then the fat cell grow and they when you lose weight, they they become smaller, but you the number of fat cells is constant. So that's fascinating that the body is doing that. And the good news about the immune system, actually, if if one of the ways rather than liposuction, one of the ways to to to to decrease, for example, this inflammation is, for example, a combined lifestyle intervention. We we recently showed in a study where people who were living with obesity lost weight and it was really only about 5%. So not spectacular. Afterwards, they were had still obesity, but already after a couple of weeks by exercising more, not extremely, but but normal exercising, eating healthy and psychological therapy, then already this innate and adaptive immune system, we we saw better regulation and also after one and a half years on the long time, this improvements continued. So you can do something about this pro-inflammatory state yourself. And I think in in pandemics like with viruses is also important to realize that within a couple of weeks, you can already do something about your health and protect yourself naturally for with respect to the immune system by just living healthy. And you don't have to to to reach a healthy weight, but a healthier weight is already good.
Mariëtte: Yeah, I think what Liesbeth stresses is really important, the fact that already losing 5 to 10% of your body weight is really healthy. Some people think, well, I have to lose so much kilos, it will never work, but but really it it's important that when you lose 5 to 10%, not only your immune system improves, but also your glucose metabolism already can markedly improve after losing 5 to 10% of body weight. So, well, that that I think that that changes the way you can set goals for yourself. This is already a very good first goal.
Dr Rupy: Yeah, yeah, exactly. Yeah. And just, you know, having those small, sustainable goals in mind rather than these drastic sort of calorie cutting exercises where you have these incredible transformations that you see within 60 days. Although it might seem desirable to a lot of people, it's not necessarily a the healthiest intervention, particularly when you follow those people up for 12 months and you see a weight resetting and and it leads to yo-yo dieting. And I think also the the impact of those healthier lifestyle interventions, not just on fat composition, but also on immune system and the capabilities for you to fight off infections, I think again should be another sort of hook for people to to think about with these health healthy lifestyle changes. You mentioned the the fat cell number and the size of those and how those those change and and the curious sort of observation that we see where we remove fat cells and they pop up somewhere else. What determines the distribution of fat? I think some people have come across the concept of apple shapes versus pear shapes bodies. Is there a is there a particular component, maybe something genetic that determines people's sizes and shapes?
Liesbeth: Yeah, actually the the the amount of body fat and how prone you are to to develop obesity is is most of that in your genes anyway. It's actually surprising right now. You see in in Europe, almost 60% has is is overweight right now. But when you consider the environment, it's it's surprising that not almost 100% is is is overweight because the majority of the people is not living healthy right now. So some people are protected from developing obesity and some are more prone to it. So that's in general. But then where where the fat is stored is indeed also for a part already genetically determined. For example, if if it when fat is stored around the waist, that's even more genetically determined, but also other influences like hormonal influences. We see that that for as as known that males store fat more easily around their abdominal region and women more on the hips, for example, subcutaneous fat, which is basically healthy. We know the visceral fat in the abdominal region is more the unhealthy fat producing more of these pro-inflammatory factors and hormones. But also during life, you see that with aging, that women when they are postmenopausal, they change also their estrogens and and testosterone balance. Yes, women also have testosterone, they produce it in their adrenal glands and their ovaries. But their ovaries obviously are not working anymore after the the the menopause. And you see alterations in their hormonal balances and they are also more prone to develop abdominal obesity after menopause. And another important factor can be medication use or the stress hormone cortisol, which makes you also more store fat around the abdominal region. So there are many more factors also helping to determine where the fat is being stored. And you see it also in in families that that that that that just as height is partly genetically determined, that also weight and where you store your fat is there's a high polygenetic factor around that.
Dr Rupy: I was interested to know actually that there is a cortisol sensitive gene variant which gives people a particular propensity towards stress-induced fat as well. That's something that I haven't come across before.
Liesbeth: Yeah, actually that was actually the the topic of my PhD thesis. It's interesting because we know that too much of the stress hormone cortisol, it does not only cause more abdominal fat in general, but it also causes that you are longing for more high caloric food, more hungry, but especially high caloric food. So maybe you will recognize it if you're very stressed that you rather grab a chocolate bar than maybe a healthy apple. And also sugar-rich food can also increase your stress hormone cortisol. So sometimes like a visual circle can exist, either starting by stress, making you more hungry or starting to eat unhealthy and contributing to higher cortisol levels. So that's in general. But we know that some people lose weight from being stressed and some people from chronically being stressed, they they gain weight. And actually the majority is gaining weight. And part of that is indeed being also genetically determined. We because cortisol needs a receptor, so a sort of receiver which is present on basically every cell in our body. And this receptor of cortisol can be either hypersensitive, relatively more sensitive, or you can a bit a little bit be decreased sensitive for your own cortisol. And what we found in studies is that about 40, 45% of the population of the Western population is relatively more sensitive to the to your own stress hormone cortisol. And we indeed found relations with more abdominal fat mass, higher blood pressure, higher cholesterol levels, higher cholesterol levels. And in contrast, about six to maybe 10% is relatively insensitive for cortisol. And indeed, those are people who become on average taller, in males we find more muscle mass, in women we found a smaller waist circumference and protection or a relationship with lower insulin, lower cholesterol levels, but also lower risk on dementia, for example. So some are more prone to to to suffer from stress hormone than others. Maybe they experience the same amount of stress, but but how the signal is being translated at the cellular level can be different per person.
Dr Rupy: That is fascinating. I I really find that interesting because someone's response to stress can be in part genetically determined as to whether this is going to have a beneficial or a negative impact on your physiology. And um I I read also that it has effect on brown fat as well and the metabolism within brown fat. And that leads me on to talk about brown fat because I think people have heard through the ether that brown fat is something that is good. But I wonder if we could talk about how brown fat was discovered, um and why it's it's beneficial. Mariëtte, maybe you can.
Mariëtte: Yeah. Well, brown fat was actually the topic of my PhD thesis.
Dr Rupy: Oh, lovely. I didn't know this before. This is working very well.
Mariëtte: Very well done. So, well, it was discovered, well, we know for ages that it's already present in certain animals and also in babies. And well, first, what brown fat basically does is it it's sort of an internal heater. So it's a type of fat, but it only stores a little fat. What it mainly does is it burns fat towards heat. So it's, well, an internal heater. And the main physiological stimulus to activate brown fat is cold. So our ancestors also needed a lot of brown fat because they were not only exposed to a lot of hunger, but also to a lot of cold. So next to our muscle, we have this brown fat organ to keep ourselves warm. Well, we know that also babies have a lot of brown fat because they have a relatively large head from which they can lose a lot of heat. So therefore, they are really dependent on their brown fat to keep themselves warm because babies don't have that that much muscle. So they cannot really really shiver. And we thought until about 15 years ago that, well, the brown fat disappears when we grow older because, well, we have our muscle, we don't need it anymore. But it appeared from certain, well, nuclear studies that we still have brown fat. So in nuclear medicine, when we are looking for cancer in people, we can give people a tracer, a radioactively labeled glucose like label. And this glucose is taken up by organs that have a very large metabolism, such as cancer cells. And in that way, when you give that tracer to people, well, when it's taken up by certain spots in the body, you can, well, you can see that that can be either cancer or it can be either inflammation. And it appeared about 15 years ago that when people received this type of, well, because you give that tracer followed by a PET scan, and that people when they got this PET scan in winter times, there were whole strokes of uptake of glucose in the neck and along the large vessels. Well, that could not be cancer, of course. So they took a biopsy of it and then it appeared that it were actually, yeah, sort of fat cells. And then it was known that we still have brown fat. So that's that's really interesting because of course, in in in the current epidemic of obesity, it should be, it is so fascinating that we apparently have, well, another type of fat that if you activate it, you can increase your metabolism. So we have done a lot of studies where we cold exposed people and we really see that when you expose people to cold that their metabolism increases and that also their brown fat gets activated. And well, we estimate that when you activate your brown fat maximally, that you can approximately burn 200 to 300 kilocalories per day extra. But well, you can imagine, of course, that when that is day after day after day, that can that can really have an have an impact. So, um, we also know from studies that when people are sitting in a room for two hours per day of about 16 degrees, which is not even that cold, um, they can lose a bit of fat mass already after six weeks. So, so one of the ways by which you can activate your brown fat yourself is to, well, to to turn down the heater at home or to exercise outside in the cold. And there are also certain foods that can activate your brown fat. For instance, in red peppers, there is the substance capsaicin. And this can also activate your brown fat. And possibly that is the cause that you feel so heat after you have eaten a hot pepper.
Dr Rupy: Right, yeah. A hot pepper. Okay. Are there any other foods?
Mariëtte: Well, there are some studies suggesting that coffee also activates your your brown fat. Yeah. And possibly many more to discover.
Dr Rupy: And and with those studies that you performed yourself, how long were you cold exposing people and and what mechanism were you using to to cold expose them?
Mariëtte: Well, what we we usually cold expose people for two hours before they undergo the PET scan I I told about. And we use cooling blankets that are also used at the intensive care to cool down people. So people are sort of sandwiched between mattresses and between these mattresses, cold water is flowing. With that method, it's really cold.
Dr Rupy: Yeah, I was going to say. It sounds, it doesn't sound very comfortable.
Mariëtte: It's a really strong stimulus to to activate brown fat.
Dr Rupy: Yeah. I've I've also heard and you may have come across this through your PhD as well that um cyclists tend to have more brown fat as well. Is there a particular reason as to why that's the case?
Mariëtte: Well, in humans, we are not really sure whether exercise increases your brown fat. In in mice, it seems so. In mice, we know that the brown fat, no, I must say, in mice, we know that when mice exercise, the muscles make certain hormones and these hormones can activate brown fat. In humans, it's more difficult. There have been studies in which humans had to do an exercise intervention for several weeks. But the difficult part is that when you do a lot of exercise, your body composition changes. You get less subcutaneous fat, you get more muscle, and that changes the whole way by which your body produces heat. So what we basically see is that people who exercise a lot tend to have a little less brown fat because they have so much muscle that they, yeah, possibly therefore they don't need their brown fat so much. So we are not sure yet.
Dr Rupy: Mm, mm. That is that's super exciting to know. And I guess, you know, a little bit of cold exposure by not wearing your coat and going out for a quick walk couldn't be a bad thing.
Mariëtte: No, and the other thing is cold exposure does a lot more beneficial, has a lot of more beneficial effects. Not only does it activate brown fat, but also when you, when the cold exposure is to such an extent that you shiver a bit, you also have a lot of muscle activity, of course. And there has been a very nice study several years ago from a Dutch group in Maastricht in which they showed that when patient with type two diabetes were sitting in a cold room for six hours per day for 10 days, their, well, their glucose metabolism improved to a very large extent. Some some patient even could half the amount of insulin after only 10 days. And that's that's likely part because the muscle really contributes of course to uptake of glucose. We have a lot of muscle. So that's also one of the beneficial effects of of cold beyond brown fat.
Dr Rupy: Wow, that's that's fascinating. And I guess, you know, all these different factors can contribute to a better regulation of our weight overall, right? So a bit of exercise, standing desks, cold exposure, fidgeting, some of the things that you mentioned in the book as well, as well as a healthy diet. You know, if you're if you're shaving off like a bit of energy every cumulatively, you can see why that would result in quite drastic changes.
Mariëtte: On the long, on the long term, that can really have an impact. So there's also, but Liesbeth can tell more about that. There was a very interesting study about why you should not sit so much. Maybe Liesbeth can tell more about that. It's so fascinating.
Liesbeth: Yeah, actually, we often talk about we should exercise every day, resistance training and and cardiac cardio exercise. But next to that, it's a separate risk factor for cardiovascular disease and and weight gain is of course sitting too much. And it's actually not not so known why is this sedentary lifestyle also so bad, actually. And I think a couple of years ago indeed in in mice, there was a very interesting study and it has been confirmed in in humans very recently, is that as that somehow in our body, there there are now indications that we have what they call a gravito stat, which is regulation of our body weight by a sensor in in the bone cells of the legs. And we we we until a couple of years ago, we thought only leptin is the only marker of the amount of fat we have in the body that signals to the brain. And if the there is a lot of leptin, then it signals to the brain, okay, decrease your food intake, increase metabolism. Problem in obesity is that people are resistant for that leptin and this this whole system is being disturbed. It's not working properly. But now next to the leptin system, there's another system being detected that in the bone cells, there there seems to be a sensor and and that and that like seems to be a weight scale to detecting how much we weigh. And that communicates to our brain. And if we are, for example, very heavy, it communicates to our brain, okay, increase, decrease food intake, increase metabolism. And with this hypothesis, what they detected in in in mice, researchers a couple of years ago, was in last year, it was described by Olsen and and colleagues, that they performed a research with 69 persons with obesity, body mass index between 30 and 35. And they gave them, they split the group in two, and one group has to to carry a vest which was about 11% of their body weight. So the heavy vest, and the other half of the group was carrying a sort of placebo vest with only 1% of their body weight. They carried it for three weeks long, eight hours a day. And I think what was very interesting is after this time, there was more weight loss in the group with the heavy vest. And particularly, they lost more body fat, purely body fat with and they kept their muscle mass intact. And that's important because we don't want to lose weight. If you have obesity, you don't want to lose weight, you want want to lose fat and you want to keep your muscle mass because that protects you from weight weight regain on the long term. So from this experiments, they concluded that also in humans, this probably we have such a weight scale in the in the in the bone cells of the legs. And that could also maybe explain that when when we sit all day, then this this weight scale in the in the legs is is sort of tricked with thinking we are too light, we are not heavy enough. We have to increase food intake and to decrease our metabolism as a protective mechanism. So that might be one explanation. I I think of this this is made this research is of major importance and we will hear about it more. And maybe in the future, one of the ways to lose weight would be to carry a couple of hours a day a vest. Of course, don't do it yet because we have to should be studied whether you don't have too much weight on your your your knees or your get pain in your shoulders or anything. But this is one of the healthy ways of losing weight because losing weight, what we see now in our patients in the office, it's it's really hard and because this body has been reprogrammed. So we need all these alternative mechanisms to lose weight. Maybe if if we talk about also this this how to lose weight, I think it's always important to to to in when we look at a patient, what are all the factors which have contributed also to to the weight gain because we often assume it's it's it's only unhealthy lifestyle. And and yes, it's it's a lot of the times it's it's an important cause, but basically there are six categories of contributing factors or causes of obesity. So lifestyle is one of it. But then we have also mental causes, like chronic stress or depression or psychotrauma. We have medication related obesity. We found in a study that about half of the patients we saw in our obesity centre was using at least one or more medication with a potential weight gaining side effect. Some are very common medication like antidepressants, antihypertensives, antidiabetic medication, or corticosteroids, for example, are widely used. So that's category three. Category four is hormonal causes, like hypothyroidism or polycystic ovarian syndrome or more rare things exist. And then you have category five and six and that's more rare, like hypothalamic causes. People are very hungry because their hypothalamus is being disturbed. That's a rare cause. And then the monogenic or syndromic obesity. And we thought that would be also very rare. But what we notice now, if you do proper research and and you do proper diagnostics in the office, that we found in obesity centres, four to maybe even eight, 9% of the people have a mutation in an obesity gene. So one obesity gene which can directly lead to to obesity. For example, a person who has a defect in the leptin signalling system, they are have increased hunger from early age on. So they have early onset obesity, very hungry, and most of the time they are the only one in the family. They have an a striking weight difference with family members. That's the alarm symptom. And if you look at all these causes, then you can be much more effective with your therapy because sometimes when a person has a genetic obesity, then you need medication. If it's lifestyle obesity, you need lifestyle intervention and only if it's not effective, then you need pharmacotherapy to to or or bariatric surgery to to be really effective. But when someone has a psychotrauma, for example, you need sometimes psychotherapy. And when you you use medication with a weight gaining side effect, you need we try to optimize the therapy and sometimes you can taper down together with a physician, a patient should not never do that alone, but sometimes you can replace medication or you can taper out medication. And then you all kinds of therapies for obesity will be much more effective than when when you do it when you're still having three medication inducing weight gain. So there's so many ways we can do better in treating people with obesity. Because if we really want to to to combat obesity, we should do better treatments and of course, the prevention. So now basically the water tap is open and the bath is full and we should close the water tap, so to prevent more people developing overweight or obesity. So healthy food environment, healthy supermarket, healthy schools, exercise, all that. And at the same time, the people who already have obesity, so the bath is full, to unplug the bath and to treat well with combined lifestyle intervention and if necessary, pharmacotherapy or bariatric surgery. So weight reducing medication is often also indicated, but often not reimbursed, which is not a good thing right now.
Dr Rupy: Absolutely. There's so much I want to unpack there. So so we started off with the incredible research around sensors in bone cells and how they can contribute to appetite regulation and metabolism as well, I think, which is super, super interesting. And then I guess, um, one thing to take from that is, you know, standing, trying to be less sedentary anywhere, we know has positive effects and that might explain one of the mechanisms behind why that is the case as well. So again, an additional contributing factor. Um, and then one of the things I wanted to unpack was the genomic component. And I think traditionally, certainly myself, I would have thought that would have been a minority reason as to why people are putting on weight so drastically. But I guess, you know, if it's 4 to 9% of people who have a gene variant that puts them at higher risk of weight gain, that's, you know, one in 20, one in 15 people.
Liesbeth: Yeah, we actually don't know at population level because most of the obesity centres are not studying how not looking for the genetic variants. But when we looked at people who were seeking help in obesity centres, so that might be a selection of the people with the highest BMIs though. We at least from the several centres in the Netherlands, we we we studied 1,230 patients and from that group, we found 4 to even maybe 9% having such a mutation. So that was rather impressive. So to detect it, just ask the questions, when did did the obesity occur? Was it at early childhood or was it on a later age? So when it was early, it's more suspicious for it. Is is there a normal feelings of satiety? Are you normally feeling full or are you never feeling full or are you increased hungry? That's an alarm symptom. And striking weight difference with the family members. Because when everybody in the family is is obese, then it's more often either polygenic risk that that's more normal like we all have, or it's food environment or exercise environment, environmental factors, for example. That that's most common.
Dr Rupy: Yeah, yeah, that that is a really good way of structuring it as well. And I guess it brings me to a question about how we measure and monitor weight in general because right now we use BMI as a crude measure in general practice in the UK. Well, it's falling out of favour, but really we should be looking at body composition. Um, are there ways in which you think we could use body composition measures in a more effective way that can scale across healthcare services?
Liesbeth: Yeah, that's exactly the problem you you're addressing right now. We had some discussions with it also at at Europe level last week about this. And and BMI is a easy measure, but it's really not a good adiposity marker as you you suggest. And a simple way which could be applied in in in clinical practice would be to add the weight circumference at least. Of course, there are more sophisticated methods like using a DEXA scan or other scans, but it's more that's too expensive to do on on a population level. So to use the waste would be important. And of course, also look at all the comorbidities, like is there a high blood pressure, is the cholesterol levels high, how's the insulin and and glucose regulation? Because those are also symptoms of too much fat.
Dr Rupy: You mentioned these six categories as to why people put on weight. One of them I wanted to talk about was the biological effect. Um, so the biological clock and fat and how that influences appetite and sugar regulation. Mariëtte, is that something you could talk about?
Mariëtte: Yeah, well, indeed, the biological clock. So every body cell basically has its own little biological clock. We have a central biological clock in our brain that, well, is sort of the boss on all the little biological clocks in our other cells. And there's a very clear rhythm within our body. And this is dictated by when it gets light and when it gets dark again. So via the eyes, the light can tell the biological clock in our brain whether it is day or whether it is night. So certain, well, you can imagine that when it is day, we are more active. When it is night, we are sleeping. When it is day, certain processes should be very efficient because we are moving a lot, we are seeking for food, we are processing food. And during the night, we are sleeping, we should digest our food, etc. You can imagine that when you turn around this rhythm by for instance, doing night shifts, you can disturb this very well performed rhythm in our body. And that's also what we see in practice that people who do a lot of night shifts, um, they are generally fatter, they have more type two diabetes. Um, there are also some very nice epidemiological studies, for instance, a very large study that showed that when you leave on a light in your room at night, that you are a bit fatter as well. So this this biological clock is very important and you can you can also disturb that, it seems, by eating at the wrong time points. So, of course, our body, when when you get up, you you you start eating, of course. But when you eat during the whole day and also during the night, some people do that, that can also disturb the little clocks in for example, your your pancreas who has to secrete insulin all the time. It can disturb your muscle, of course. And that seems to be also important. And what what's also, I think something that should not be underestimated is sleep quality. So, well, I know from my own experience actually how how killing it can be if you are sleep deprived, for instance, when you have little children. This is this is quite, this can be harsh, I think everybody can relate to mentally, but it can also make you more fat because we know from instance, again, from epidemiological studies that people who have fewer hours of sleep are more likely to have obesity, diabetes and also cardiovascular diseases. And this is already seen even with sleep duration shorter than six or seven hours. We we also know from studies that already one night of disturbed sleep, it makes you very hungry and it makes you also crave for more unhealthy food during the next day. So that can also result in more weight gain.
Dr Rupy: This is something that I really interests me because I'm fascinated by healthcare professionals environment and how they have a propensity to be of a higher weight than people who don't work in the healthcare profession. And I believe it's a lot to do with A, sleep patterns and shift patterns, but also the food environment in which we operate because I don't know what it's like in in in Rotterdam, but we only have vending machines available to us in the middle of the night. We don't really have healthier options in the hospital environment, which needs to change regardless. But I think these are all things that are contributing to that. And and this just adds more more evidence to it.
Liesbeth: Yeah, I I think you have absolutely right. I think that that's some of the things that then people also healthcare workers working in night shifts that they these vending machines with unhealthy food is really deleterious. Of course, you you want to to maybe to help them that there is some extra food available, but I think it's so necessary to have healthy food in there because also recently new studies came out, for example, if you eat your evening evening meal, your dinner, not at 6:00 or 7:00 o'clock, but or 10:00 or 11:00 o'clock, that there are major difference in the glucose tolerance afterwards during night and all kinds of mechanisms are starting in the body which are making you more prone to gain weight. And if you're already sleep deprived and you eat at the wrong moment, that's sort of a double hit. The sleep deprivation disregulates your hunger hormones, just as Mariëtte mentioned, increased ghrelin, decreased leptin, but also your stress system activates, so more cortisol, so you're more longing for high caloric food, more abdominal obesity can can occur. All these tiny things and of course, one time might not be the difference, but if you have continuous night shifts or or work often late or you just eat later too late at night. If people ask about fasting, should I do intermittent fasting? And well, there are many times of intermittent fasting, for example, but the the the best would be to eat in the morning well and and not at night. So if you do what like to fast, do it after taking an early dinner and fast afterwards evening and night. If you do that, we you will be fine. You don't have to deal with all kinds of weird schedules, probably. Of course, we we need more longer term studies, but to to adjust to the natural biological clock is is important.
Dr Rupy: Agreed. Yeah, yeah. Um, Professor, I know that you've got an international meeting after this. I want to be quite mindful of your time, but I did want to ask you about two things actually that I I thought were fascinating in the book. There's one you've already alluded to, the hidden weight contributors, particularly medications that we use in the category of immune modulators, prednisolone, inhalers as well, as well as the other medications that could also contribute that people wouldn't really think about. And then I have to ask you about viruses and obesity. Because that kind of blew my mind about this adenovirus potentially being one of the reasons as to why people are putting on weight as well. But why don't we start with the the hidden weight contributors in the form of medications?
Liesbeth: Yeah, I think that's that's probably something we need a lot to to to know a lot more about because what we see is that many people are using medication, especially people with obesity. And for example, the corticosteroids is is one of the group which can be really, we know if you use high dose of prednisone, most people know, well, that that's a sister actually of of your your stress hormone cortisol. So it's like if you use 20-fold or 30-fold of your stress hormone cortisol, you can imagine that your weight will will increase, especially abdominal fat will increase and all the negative side effects with respect to cardio metabolic factors, cholesterol, insulin, mood disorders can occur. But that's long-term high dose. We didn't know what will happen with just lower dosages, for example, and if you use that for a long time. And more and more relations seem to be existing between, for example, use of inhalation medication and obesity. We don't know yet whether it's causally related. It's important to stress because those are association studies, but we found in really large studies now that males and females who were using, for example, nasal sprays with corticosteroids or inhalation medication for, for example, for asthma, they had an increased BMI, a little bit higher BMI, but also a little bit higher waist circumference. And important is what what what another study showed that people with obesity that about half of them and with obesity and asthma, for example, that half of the people don't have the allergic asthma, but they have more an asthma-like symptoms which are obesity related. So you can actually question whether this corticosteroid use is necessary. And in those cases, we always discuss with your pulmonologist or your GP, whether has there been lung function test? Is it really an allergic asthma? Do you really need the corticosteroid? If yes, you should continue. And sometimes the dosage can be tapered. But also if it's not, sometimes it can be stopped and it might be beneficial for weight. We don't know yet, but there are more and more indications suggesting that. So never stop on your own, of course, always discuss with your doctor. And this applies to more, we found in people with obesity, for example, 27% is using corticosteroids in any way. And we had some examples also in our clinic, for example, I had a man who who was using corticosteroid cream, but really large dosages on his whole body for a very severe eczema. And and actually he was gaining weight 30 kg in one year time and he was living a healthy life. And and I I remember when he came in to the office and his wife really confirmed, well, I'm cooking healthy every day and we are we are walking every day. How come he's gaining 30 kg again in one year time? And then when I talked to his dermatologist and we replaced the creams by weight neutral creams, actually his weight 35 kg decreased with the same healthy lifestyle. His mood improved, that was really impressive. And and the strange thing was actually also his skin disease was improving somehow. So it's sometimes really good to to take out people from this vicious circle to see what are all the contributing factors. And not always it's of course medication and sometimes it cannot be stopped, like for example, antipsychotic medication, but we should have attention that if there's a weight gaining side effect, that we help people to to live healthy lives, to to start a lifestyle intervention and if that's not enough, to to administer, for example, anti-obesity medication because it's so important for all the other diseases which can occur due to the obesity later on. And well, medication is a serious factor in that. And to be effective, it's it's good to have a screen before referring a person to to a lifestyle intervention or other therapies, is there what which medication is is is potentially contributing to your weight gain?
Dr Rupy: Yeah, yeah, that's a fascinating anecdote actually. I I and I think again, it it it speaks to the complexity of of why people put on weight, why people suffer with disease as well. And I think there's definitely a lot of overlap between a healthy lifestyle and improvements across a number of different areas of of medicine and and and health. Um, and uh, like I alluded to, the the the other sort of hidden contributors to to weight. One one of them I I remember reading was um about products in our food, um so plastics, endocrine disrupting chemicals, things that I haven't really looked at in much depth, uh I'll be honest. We are getting an epidemiologist actually to talk about the impact of plastics on on general well-being. But uh with particular reference to obesity, I understand that some of them do contribute to insulin resistance. Is that something you've come across, Mariëtte?
Mariëtte: Well, yeah, indeed, it seems that that certain components from from from plastics end up in our food. We we we ingest it and um it it it could affect our our body fat. We know at least, we know most from mouse studies, to be honest. And we know that these um these plastic components, for example, um BPA, um it can also end up in our fat and somehow changes the way that fat is stored, that it makes the fat more prone to to to store the fat. And it may also influence our um our appetite, um as is shown in mouse studies. In humans, we do know that these um BPA's can enter, can can end up in our body fat. We know that from biopsies and that it is found more in um in in fat from people with obesity compared to lean people. But we are not sure whether this is a causal relationship, of course. It can also be, well, people who have who are living with obesity, they do have larger fat cells. We we don't know if it's causal yet. But to be sure, and I I think we should be glad about that, um of course, um we should be careful about that and there are certain regulations now. So we don't take any risks.
Dr Rupy: Yeah, yeah, agreed. Um, and the the the adenovirus.
Mariëtte: Yeah, that is very fascinating as well. Well, also that is mostly associated from from the studies. So, um, you are referring to the adenovirus 36. Um, we do know that in um the uh that about a third of the people with obesity have this virus, while only about 10% of lean people have this virus. So you can think, well, maybe um having this virus could have contributed to part of the obesity. Of course, we don't know the causal relationship in humans. This is at least a fascinating discovery. What we do know is that you infect um chicken, for example, or or monkeys with this virus, they gain a lot of weight. And we are not really sure how. It it also seems that the the fat tissue of these animals um are more prone to store the fat. It doesn't seem that there are effects on on metabolism or on on appetite. So this is this should be further discovered. But it's a a fascinating discovery indeed.
Liesbeth: Yeah, and actually a a vaccine now is being developed for this maybe potentially fattening adenovirus 36 to help prevent obesity. So maybe that's something we will hear more about in the future.
Dr Rupy: Wow, wow. Yeah, that that's definitely one to watch. And I think the um the potential for vaccine technology and obesity is very, very exciting. Um, I want to ask you about uh new developments, but before, I was really um really impressed that you you talked about uh fat shaming and the other psychological consequences of weight in the in healthcare industry and how there are disparities and access to healthcare. Can you speak to a bit about uh that uh in terms of what we see from people whose uh experiences of healthcare have been poor as a result of the way they look?
Mariëtte: Yeah, well, in general, so maybe it's good to mention what what fat shaming is. So it it means that that people think that people with obesity are, well, less capable of of of of performing a good job, that they are dumber, that they have less willpower, for instance. I think it is very clear from what we told during this podcast that since obesity is so complicated, this is of course far from the case. But what what is really striking to us is that this fat shaming not only um happens in in in the, well, I call it general public, but it also happens in healthcare. And I think that is because of a lack of knowledge on the complexity of obesity. Maybe it's not really that they have bad intentions, but it's just that a lack of of of knowledge. So we know that people who work in healthcare also tend to believe that obesity is someone's own fault and that they just should eat less and and should exercise more. And that is frequently the advice that is given to um to patients who seek help when they have obesity. Um, I even know a patient who was told by her doctor to lose weight before getting a large surgery. But the reason she became obese was because of the corticosteroids that the same doctor prescribed. And that really um, well, that was really harsh for her. And I think that another problem is also in healthcare that um certain diseases are not always properly identified in people with obesity. So certain complaints, it is easily said, well, it's probably because of the obesity and that they are, well, that they get less good care as a consequence of that.
Dr Rupy: Yeah, I feel like we've come full circle in our conversation about the way we treat people who look a different way, who are overweight, in terms of how it was traditionally seen as something that was respectable and something that is aspirational to now something that is demonized and can actually be at the detriment of people's healthcare access. Um, your book goes into so much more detail and you you go into patient stories and, you know, we've really just scratched the surface even though we've took off so many different subject matters today. Um, and you go into a bit more of the lifestyle elements as well. But I wonder if there are any new developments that you wanted to mention that you didn't put in the book, uh, because of time constraints.
Liesbeth: We mentioned some already during the podcast, for example, the the study on on on the weight skill in the legs was briefly in the book also mentioned in in mice, but it has been detected in humans, for example.
Mariëtte: And we will save some, of course, for possibly for a next book.
Dr Rupy: Oh, epic. Yeah, no, I'd love to see that. I wonder what the sequel would be called.
Liesbeth: I think every day there are new developments and we're following the literature literally very much for our patients, but also for the science we're performing, but also for the society roles we fulfill. So we are we are keeping up with the science and we we are intending to write a second book on it.
Dr Rupy: Amazing, amazing. Well, thank you so much for your time and thank you so much for the work that you guys are doing. It's super important and you know, you're heightening people's awareness of just how complicated this issue is. Uh, and it's not as simple as calories in, calories out, you know, exercise more, eat less. Um, and it's, you know, your research that is really driving forward a greater understanding of of this complex disease and it is certainly a disease. So thank you so much for your work and and your time today.
Mariëtte: You're very welcome. It was lovely to be here.
Liesbeth: Yeah, thank you so much for the nice questions. Thank you.
