The Obesity Podcast Ep. 5: The Evolving Science Of Adipose Tissue | J&J MedTech

This episode explores the evolving science of adipose tissue and its role in metabolic health. Prof. Wolfrum explains how fat tissue is a dynamic, hormone-producing organ regulating appetite and energy balance, far beyond a passive energy store. The discussion spans adipose cell diversity, differences between subcutaneous and visceral fat, brown vs white adipocytes, and the therapeutic potential of converting “white” fat into “brown.” The conversation also links molecular research with clinical practice, including how bariatric surgery changes fat composition, why treatment responses vary, and how future personalised therapies may integrate GLP-1 drugs with metabolic surgery.

Transcript

SPEAKER_03 0:14

Hi everyone, I'm welcome you to the next episode of our obesity podcast. My name is Marco Bito, erotic surgery from Switzerland, and as always, it's my pleasure to also welcome Paulina Salmanen with me.

SPEAKER_00 0:27

Hi, everybody, and uh it's great to have uh you here with us in beautiful Barcelona. We were here to have the European chapter meeting for the World Federation for Obesity Surgery. So, if so, and that's why we're here. Unfortunately, we're not uh Christian is not able to join us in person here in Barcelona, but we welcome our guest.

SPEAKER_03 0:49

Which is uh Professor Christian Wolfum uh from the Nangyang Technology Technological University in Singapore, which you recently joined in the summer, right?

SPEAKER_01 1:01

Yeah, I joined just three months ago.

SPEAKER_03 1:04

Yeah. And I hope you manage to adapt uh in this uh very short period of time because originally you're from Zurich, this is where we know each other from.

SPEAKER_01 1:15

It's it's a great place to be. Obesity and diabetes is of course a big topic here in Asia as well. So I think it's also a good place to uh to do that kind of research.

SPEAKER_03 1:26

Yes. And you're already speaking about your research. The reason why we were very much looking forward to talk to you today was your role as world expert in adipocyte research. So maybe to start with the first question, what actually drew you into this field? At what point did you decide to you know invest time into studying adipose tissue?

SPEAKER_01 1:52

So so I have uh I'm coming from a rather chemistry background, and I started off in a in a biophysics field, and then I moved a lot to lipids as quite interesting molecules, and and uh then I noticed that these lipids are of course extremely relevant for all metabolic processes, and and the main organ that controls lipids, especially the lipids that are probably not so good for us, is the adipose tissue. And uh that that started when I started my own research group in 2007. And uh since then I think uh we have shown and others have shown, and I think it became evident then that adipose tissue is not just a boring place where you store excess fat, and then if it's there's too much, then there's a problem, but it's it's way more complicated. It's it's a very complicated tissue full of different cells, and it plays very important roles in the body to determine whether you are healthy or you get sick, and uh that's of course, from a scientist's perspective, wonderful because there's a lot you can study in this context.

SPEAKER_00 3:00

That's actually what our previous guest, Lena Carlsson uh from Sweden, said that uh adipose tissue is more like a metabolic organ.

SPEAKER_01 3:10

Yeah, I think that is nowadays accepted. When I started, it was probably rather considered a storage organ, and it has shifted nowadays. People would would really say it's a metabolic organ, is of course stores uh fat, right? Excess energy that you eat gets stored in adipose tissue or should get stored in adipose tissue. If you if it doesn't, then you have a problem. Um uh it but it also regulates the rest of the body, it produces hormones, so uh substances that control other aspects of the body, even including uh how much appetite you have, how much you eat, um, how much uh certain other organs react, how your energy consumption is so so the adipose tissue is really um also a regulator of whole body function, if you want.

SPEAKER_03 4:01

Right, okay, so we we already right dive into the you know what adipose tissue is doing, but maybe we can go one step back and and and look at adipose tissue itself. So you know, um I I was talking about adiposites, and you are talking about adipose tissue. Is is that you know, are these like two terms that we can use together, or you know, what's the difference is what are the differences between both?

SPEAKER_01 4:29

Very, very relevant point, and it's good that you bring this up because people use it as an interchangeable term. So adipose tissue as this uh fat tissue that you see, and the adipocyte as the cell that stores the lipid. Uh, and but in reality, you you can't actually uh use this terminology in one-to-one terms, because when you look at the number of cells within adipose tissue, the adipocytes, the cells that store the fat is actually only 20 to 30 percent. 70 to 80 percent is something else immune cells, endothelial cells that make up your vessels. Uh um, yeah, these are the main cells in there. And the adipocytes, from a volume perspective, is most because they store lipids and they become very, very big, uh, and that's take up most of the volume. But from the cell number perspective, uh just 30 percent. And that makes it so interesting because that tells you the other cells have a function as well, and they contribute to what adipose tissue is doing. So you have to really differentiate these two. If we discuss uh healthy versus unhealthy obesity, this plays a major role in this context.

SPEAKER_00 5:41

Can you clarify to the listeners like the all the simplify how like the different adipose tissues that we actually have without going back to the cell level? So maybe simplify that to everybody.

SPEAKER_01 5:56

So the adipose tissues, we have adipose tissue throughout the body, right? It's it's it's probably more than just a storage organ in the case of the face and the eye, it's also a kind of a mechanical cushion, uh, most likely, and in other cases as well. I think the biggest for our purposes here, maybe the most important distinction we could talk about is the adipose tissue that is directly under the skin, which people term subcutaneous, and the uh visceral adipose tissue. It's it's a loose terminology, but we have to use one of them, right? Uh, is the one that surrounds your internal organs. And it's very clear that this plays another role. Odipus tissue under the skin is probably less problematic from a health perspective than adipose tissue that surrounds your organs and uh in your intestine and all the visceral organs.

SPEAKER_03 6:53

So, you know, from being a baratic surgeon, I know when we do these operations and we have this view into the abdominal cavity of our patients, we always have the feeling that it like macroscopically looks different, right? You got this or mental fat tissue, which is sometimes very fragile and sometimes it's not, and then it looks very, very rough while the surface of other fatty tissue is rather smooth. So, and you're telling this is due to the 70 or 80 percent of non-edipus tissue is in there. Do I understand that correctly?

SPEAKER_01 7:29

Yeah, I think this is something people haven't looked at. It is partly due to the other cells in there. It has partly to do with cell size of the adipocytes, probably in these uh patients that have a lot of adipose tissue where the adipocytes coming back to the cells have grown very large, that could affect how the tissue is behaving. So, in visceral adipose tissue, the adipocytes are often bigger than in the subcutaneous area. That's one aspect that can make a difference, and even from patient to the next, right? So one has bigger adipocytes than the other. This you cannot tell by looking at the tissue, you would have to do a microscopic analysis of this. And secondly, uh, subcutaneous and other depots often have uh linings, uh basically barriers in terms of um uh yeah, uh yeah, in like not membranes really, uh barriers that that surround the tissue and maybe keep it in place and keep it in one uh piece. Uh and the visceral deposit tissue has this as well to a certain extent, but they might be compromised if it's growing everywhere. But again, this is a very important question, and I don't think it's it's really fully understood uh why this is so different, the tissue is so different in morphology from one person to the other, and that might also play a role. But of course, for that you would have to look inside, which is not that trivial.

SPEAKER_00 8:56

But then again, looking at going back to what Marco said, like macroscopically, it looks different. And and of course, uh, it most likely when you look at the functions, the metabolic function may be different from mesenterial fat, for a mental fat. I think there is also some data showing that different layers of subcutaneous fat are, you know, maybe acting a bit different.

SPEAKER_01 9:22

This is this is all very well possible. I have to honestly say, I would argue that the data on this is still very um very preliminary. The problem is you have to first of all quantify it well, right? That's not so easy. Then you have to uh link it back to metabolic health somehow, which is also not that easy, and especially if it comes to how the tissue exactly looks. I think this is something that has really changed in the last few years, that there's more access to biopsies from these tissue where you can do cellular analysis to understand it a little bit better and link it. But I want to caution, right? Even then it remains correlation studies so far, right? So we still don't know whether tissue looking different is a driver or uh being unhealthy is making the tissue look different. This is still a possibility that it's going the other direction. But it's very clear that adipose tissue looks very different, is has different compositions based on anatomical location, but also based on health of patients in the same anatomical locations, right? So it's both. It's not just that subcutaneous is very different from visceral or mental, but also that a healthy uh person as some with who is overweight has a very different tissue composition than an unhealthy person who is overweight.

SPEAKER_03 10:45

Yeah, that that's I mean, there are so many interesting aspects. You you were referring to number of cells, and I'm not and I'm not talking about number of adipocytes within the adipose tissue. You were referring to size of different sizes of the adipocytes. Um, and we know there are different colors as well, right? There are different types of adipocytes. So it if you think that's already complex, it's even getting more complex now. So, can you tell us something about you know these colours and what that means, or at least what we know by now about you know these colors?

SPEAKER_01 11:21

Yeah, so so that I think is the most intriguing part, right? So size and number, that's two very important parameters, and now the types. So we knew already that there's at least two different types of adiposites, which are loosely termed uh brown and white, right? This name comes from the fact that uh white is clear, right? It's lots of lipids that are stored, and that makes them look a bit whitish or yellowish. And the brown one comes from a high density of mitochondria. Mitochondria, the factories within a cell in the body that uh that produce and not produce but uh generate um certain energy storage systems utilizing energy from the nutrients, and they are high in iron, and that that causes this brownish color. And these brown adipocytes are linked to quite healthy obesity. So, so probably what they are doing are not so much storing, but rather burning fat and thereby producing heat. That's at least the current hypothesis, that they are mainly there to provide uh heat production in terms of cold. That's why animals, especially rodents, have a lot more of this than humans, because we have usually not such huge issues with cold production, uh with cold protection.

SPEAKER_03 12:49

So you're telling that we got different colours of fatty tissue which exactly do the opposite from each other. One is storage, one is burning, you know, energy. So, do we all have brown Oedipus tissue to you know the same degree? And where can I find it? And what do I need to do to make it more active?

SPEAKER_00 13:12

Because then again, if it's like you know, this would be better at burning fat. So that sounds like a good idea, right?

SPEAKER_01 13:20

Yeah, so so it it is so you where is it located? It's mainly located uh underneath the uh the chin and along the vertebra, along the spine and under the in the clavicular region. I am pointing, but of course you can't see that. Um, and uh why it's exactly there, nobody really knows. A lot of people uh don't have it, or at least have no visual uh adipose tissue. And maybe I have to quickly use a bit of detail. How was this discovered? So um, people do scans where they scan for cells that take up a lot of sugar. This is indicative of a cancer cell. And there were always these artifacts uh that were very symmetrical and clearly not cancer. And this these are actually brown adipocytes that you once find sometimes in patients uh that take up a lot of sugar because they need that energy to burn, burn the energy, uh to burn the energy to produce heat, right? That's what how they were found in PET CT scans. That's where rhydiologists at one point said keep your patient warm to get to not get these artifacts. Uh, in if you use this as a measure to detect brown fat, I would say five, maybe a bit more percent of the humans can actually have normally detectable brown adipose tissue. It's more in the winter, it's uh less in the summer. You can induce it in a lot more if you cold stimulate the people, so then these cells start to appear. But the problem is it's a very non-sensitive method. So nowadays we are looking a bit more closely into adipus tissue composition, and we see that there's not just white and brown, but there's probably multiple subtypes of each, right? There's uh five different flavors of brownish and five different flavors of whitish, and we don't even yet understand what these five different flavors are doing. And there, I have to say, it seems that rather everybody has them, but they are more interspersed in the body, and not only in these anatomical locations that I just mentioned, right?

SPEAKER_00 15:31

This is of course jumping a bit ahead, but as you said, this may actually have a huge impact. So, do you think that uh from this basic research part that we're still at looking at and trying to understand it? Do you see a connection that in the future that we could actually use this as a means of therapy? Targeting brown fatal fat.

SPEAKER_01 15:55

People have tried for quite a while, especially looking at the classical brown fat to induce this. This it's very clear people with more brown fat are much, much healthier than the people without brown fat. So it's a good reason to do it. Whether you lose a lot of weight is a different story, but it would definitely improve the health. Um, it has been very tricky to activate it uh with different uh pharmacological means because yeah, I think the processes are decently well understood, but so far there's really nothing on the market that activates these cells. Nowadays, of course, things are changing. We can now we are better at uh the RNA technologies open new avenues, right, to target adipose tissue maybe directly. So, yes, I think there is a chance that you can actually target, for example, an RNA to adipose tissue to convert whitish into brownish adiposecytes and thereby increase your energy turnover and improve metabolic health. I want to warn whether that leads to weight loss, is a different story. Uh, because uh humans are really notoriously good at when they increase the energy expenditure by compensating very, very quickly by eating extra, and then the whole weight loss is usually gone. So healthy, yes. Weight loss, I'm a bit more careful.

SPEAKER_03 17:15

Well, at least it will reduce heating costs in some households.

SPEAKER_01 17:20

Yeah, yeah. But you have to more see it as it's also quite clear that exercising, right, is not really the main driver to lose weight. If you if you do it very actively, very rigorously and control your diet, then you you will be able to lose weight this way. But most people that exercise even regularly have don't lose a huge amount of weight, but they're much healthier, right? Much, much healthier. So so it's a and that is, I think, a very interesting concept that this could help to improve health without directly, even if the weight loss effect is a bit smaller than what one would wish.

SPEAKER_03 17:58

All right, so um thinking about that, we have a certain amount of brown adipose tissue within us and a certain amount of white adipose tissue within us.

SPEAKER_00 18:08

And five shades of each.

SPEAKER_03 18:11

Yes, exactly.

SPEAKER_01 18:12

Yeah, don't hold me to that number. That's at the moment something. How much is it? It's more than might be less than you, right?

SPEAKER_03 18:20

No, I'm just thinking of um you mentioned that there are attempts to change the fate of a adipocyte in its color by pharmacological means, right? But is it is it possible to change every white into a brown and every brown into white adipocyte? Or is that, you know, is that I I I think I know your answer, but is it more complex than this?

SPEAKER_01 18:45

No, no, no, it's a it's it's a really, really good question. And I would tell you that I think experts in the field would tend to disagree on this topic quite harshly. Uh I must say I have seen I the data I've seen also from humans suggests that you can at least turn around quite a large number of the white adipocytes, and apparently also quite fast. It's more anecdotal rather than actually real evidence, but if if you if you in animals you can change around a lot of cells. Whether these cells are changed or whether all the white ones disappear and the new brown ones come is still a matter of debate. My personal opinion is there is a high degree of flexibility in the fate of white and brown. We we would need to delve a little bit deeper. Brown are maybe their own lineage, these are then called beige, uh is a terminology that people like to use, which is basically means white brown cells within white adipus tissue. And those are probably quite a bit of them are formed from uh the white adipocytes. I I really so it yes, to answer this, I think it is possible, but uh what we can achieve long term with either pharmacological or other means is still a matter of debate.

SPEAKER_03 20:05

Well, at least make you healthy, you may not lose weight, but you know, that's that sounded pretty clear that you know, stimulating brown adipose tissue by whatever means seem to have beneficial health effects. So yeah, but taking cold shower, for example, because I I remember from these PET scans you mentioned that in those studies patients had to be stimulated by uh by cold exposure in order to you know um increase the glucose uptake of this uh brown adipose tissue. So, you know, for our patients at home taking a cold shower every morning, would that help?

SPEAKER_01 20:43

I think this is currently uh studies go uh that try this cold shower challenges. I've seen it, I haven't seen the publications with it yet, but probably it might work. There's some data on ice swimmers and winter swimmers, which you would consider to work. Some data suggests there is more brown, some data suggest that there's not. They're definitely more healthy. Um I I just environmental stimuli changes might not be enough, to be honest, to get meaningful differences. Uh, at least that's what uh the data currently suggests. I'm not arguing against the cold showers, but I would warn to over overestimate the use of them.

SPEAKER_03 21:25

That's a very important thing.

SPEAKER_01 21:26

On the other hand, you know, if you have a long cold shower, you lose a lot of energy, right? This is is is swimming, is swimming. You lose so much energy in swimming, not because you train, but because this is you lose a lot of heat, right? And that is heat that has to come from somewhere. So you have to somehow burn something that is present, either sugar, lipids, or proteins, uh, to produce that heat, right? And that again is positive in your energy balance uh because it it's on the output side.

SPEAKER_00 21:54

Okay, now we've gone from cold showers like to adipose sites, and you know, all.

SPEAKER_01 22:00

of that but when as with you're the expert in this field so can you highlight for the listeners that what is like if you would actually have unlimited funding which is of course I understand utopia but uh what would you do and what is your main focus in your current research what are you trying to find out what is the pressing question because this is really uh I think this goes all over the place because from uh from the cell level mitochondrial level to you know clinical impact and what actually because this is a multifactorial uh disease so uh highlight what you think we should do and what are you doing because so I think the data is pretty clear that these brown adipocytes maybe a better way to turn a better terminology for these cells is not brown but catabolic adipocytes catabolism meaning burning energy the brown is associated with a special mechanism so I want to be a bit careful there but cells that adipocytes that burn energy all the data out there suggests the more of the you have of those the better they are and I think we are we can now by using RNA technology probably target even in the humans the switch of cells or the increase of these catabolic adipocytes and uh what I would really like to do is is take the knowledge that we currently have which is quite substantial and try whether first in animal models and then maybe one can translate this to humans to develop RNA-based therapeutics. The problem with small molecules is always you have to have a specific target in the adipose tissue you this target must not be expressed anywhere else in the body very very very tricky very difficult to do right uh with the RNA technologies I think we now have a chance and and maybe we could really try to use this to increase the number of catabolic adipocytes use this to burn energy and then really analyze is this mainly metabolic health that's the data that we're currently having right or is it also weight loss it's especially interesting in light of all these uh incritin mematics that we're seeing out there which reduce your appetite and your intake side if we now turn the other screw right the energy expenditure side that might actually be very very interesting concept to pursue right if you're just moving the energy expenditure side burning more energy but then you have a free compensation by just eating more you lose right um the same is true with the incredible mimetics right they make you eat less but the problem is that body the body often turns down its energy use right it's well known people who've seen the biggest loser seen this right the energy expenditure of some of these people that massively fasting goes down substantially that's why they regain weight so easily if you can work both sides I don't know the body might still find a way to evade this but I I think it's a concept that hasn't been tried so uh I I hope that we can explore this test some of these things and translate this into RNA therapeutics. That would be something I would be very very interested in.

SPEAKER_00 25:17

That sounds really interesting.

SPEAKER_03 25:19

That's a classical translational approach. Good luck with this right yeah but I I think uh the work that we are doing is is on the one hand basic to understand a bit more how fat cells behave how they are what they do but on the other hand also what is the impact on health right and ultimately I I think I want to make this quite clear the health is more relevant than the obesity right uh I I think uh if you have a host of uh pathologies of diseases that are coming with obesity that's the big problem right and and uh if you're healthy then that might be already a big step forward and we have to ask then ourselves is this such a huge problem being obese if if you can retain complete health maybe not the morbid obesity but some overweight this is clear that there is a certain uh flexibility in this grading right right I'm you know this is such a fascinating topic and I and I think it's a heavily overlooked area of research in the field of for example baryatic surgery but if you think about the functions of adipose tissue in the context of obesity treatment barietic surgery might be a perfect tool to you know learn more about how weight loss interferes with all the functions of these adipose tissue I I I think you're collaborating with a few centers that are focusing on barietic surgery. Can you tell us more about those projects?

SPEAKER_01 26:54

Yeah so so we've been looking at this bariatric surgery is of course very interesting because you have a substantial weight loss I think uh I mean you are the surgeon so you should know better but I think people still argue what is the mechanism of the weight loss that is happening after bariatric surgery.

SPEAKER_03 27:12

It's not pure restriction that is quite clear right definitely it's definitely more than just restricting food intake so something must happen signaling wise and the other postiche is absolutely relevant in this context uh so that is something uh that we still study so what we have we have looked now a little bit at um at especially metabolic health again right I said in the beginning we had looked at obese people or overweight no obese people actually not overweight and uh asked what is the difference between a healthy metabolically healthy and an unhealthy person and there were striking differences in in cell types and some of these cell types we don't even know what they're doing uh that we find these are then not adipocytes these are from this other 70 percent and now the question is does this also happen in biatric surgery right if you lose weight is suddenly the adipose tissue changing to a more healthy uh composition and actually it seems to be that some of these cell types that we see in healthy are also appearing uh when people lose weight after bioretic surgery so that's actually becoming more and more suggestive that these cells are very relevant but unfortunately these are not adipocytes but mesothelial cells so sorry that I can't really explain what they're doing because it's it's uh they subform some kind of precursor connective tissue but it's it's the association is extra extremely clear and and now it's the question what are these non-adipocytes maybe doing changing uh healthy to unhealthy uh or unhealthy to healthy uh tissue is that also related to is that also related to uh decreasing the chronic inflammation yeah it could be I have to say people have looked at chronic inflammation of adipose tissue now for so many years inflammation uh treating inflammation in the adipose tissue as helping with metabolic health has I don't want to say failed but hasn't worked that well yet maybe we are missing something in that concept but uh it's it's it's been described more than 20 years ago right and it's been extensively studied and there's not a single treatment out there that uh really works uh on the same level as bariatric surgery although inflammation is reduced after biologic surgery um i i'm I'm a little less uh I think this is probably rather a bystander than an actually causal effect but it might be wrong i i i i'm I'm not an expert in that area to be honest so we we we started off by describing differences in adipose tissue and adipose tissue distribution and that you know different adipose distribution types may be related to different types of comorbidity developments like you know you're having that distribution type you have a higher risk to develop type 2 diabetes and you have that distribution type and you have a lower risk for cardiovascular effects or something or lower cardiovascular risk if that is true and baratic surgery changes you know these let's say fat distribution types and even the fat composition is there any chance to use those data to to predict you know success of treatments? So will we be able in the future based on what you investigating to triage patients to different types of treatments or you know to you know how urgent someone needs to be treated?

SPEAKER_01 30:50

So so this is definitely an important point that we haven't touched upon. Importantly maybe quickly to elaborate on this point not everybody benefits the same way from any kind of treatment it actually I can expand this question to the in critinometics to the GLP1 analogs right yeah that's true some people lose a lot of weight others lose very little weight and and the question is why exactly it's it's a bit too early to say but I I it is it is one option we see clearly a difference in adipose tissue in responders non-responders in bariatric surgery especially in weight regain uh but we don't understand this yet right and and uh it's it's uh and we have only tested this in in uh single cohort so far so one would need to expand this quite substantially people have tried this in blood that has so far not really worked so well but it's also very difficult it's like finding a needle in a haystacker marker right um I think uh collaborating with many many biological surgery centers around the world this is actually quite a good chance that we look a bit at adipose tissue composition uh and try to see if in hindsight this predicts either the initial weight loss or also the chances that you fall into a regained category. So in the end you lose weight but then you regain it at some point right two things that that's something you don't want. Whether it's predictive in the end difficult to say right this is what we want to do it's clearly one aspect if Odipose tissue is involved in this process there's a pretty high chance you can use it as a predictor but I don't want to say we have have a system there. Also one has to ask analyzing a composition of a tissue is of course a quite costly and and complicated um uh approach at the moment so even if we manage to show this getting this to the level of a usable diagnostic marker is is still a long way and and we talk about intra-abdominal fat tissue right uh we we're not talking about subcutaneous tissue so you know excess also is important of assembling those tissue biopsies this is a very important point whatever I talked about this healthy unhealthy tissue is always the visceral the or mental adamant tissue yeah it's it's the subcutaneous tissue is unfortunately at least in our hands quite boring uh it doesn't be changed very much it uh it it is not very predictive and so on and so forth uh so this is this is and that is much more difficult to get but again if we understand it better maybe then also we find a marker that is secreted by one of these cells that are appearing or disappearing. So the better you understand the mechanism of what is happening the higher chance you have to find if you just search blindly it's very difficult to find things if you know what you're looking for you might be able to even find markers in the blood. So it's even if uh we can't use uh the even if we can't use an adipose tissue biopsy from the omento we can still maybe uh try to find other markers based on our knowledge of what is happening. So just increasing the knowledge might already be quite interesting and helpful.

SPEAKER_00 34:06

Of course because when you look at uh the variability of the individual response to such an uh invasive procedure as of course metabolic bioretic surgeries and you have this wide range of uh uh different outcomes and and like you said recurrent weight gain why is it that some people it's not it's not the patient's fault it's not what they're doing it is something that we still don't understand that we're not able to phenotype the patients in a way that we would better understand that how to tailor the treatments.

SPEAKER_01 34:40

Yes but but this is important right because now we have so many options we have now the GLP analogs we have the biatic surgery there are other types of aspects that are coming in and we are moving into I I know people don't like necessarily the term personalized medicine but in obesity you you have basically it's it's even if you don't say personalized you have now several possibilities to approach this problem. And if we can tell whatever you benefit from best that that would help already quite tremendously right until very recently there was just bariatric surgery so in the end it's not that that there was a lot of options right until let's say five years ago. Now even for these morbidly obese people the new drugs that are coming is still maybe is sufficient to lose enough weight right uh but I think as more therapies are coming in we can of course use our knowledge of the adipose tissue to see if this can help us uh guide the the choice of treatment that we want to use for each individual patient. And I think that is something we can probably get some ideas quite quickly. That won't take too long now that more and more people are actually on these kind of therapies.

SPEAKER_03 35:56

I think that would be of uh great interest because we are also looking within our field that some patients probably benefit from a combination of therapies, you know GLP ones before or you know in in the context of metabolic battery surgery to and that actually has there's some data showing that that may be a synergistic effect that actually when you combine the two treatments so this is really uh it's a very interesting field like a lot of is happening which is strange right I mean we know experts like you know collaborators like Carloux when we told him that after surgery and let's say suboptimal weight loss after the operation and you just added medication on it because one of the key mechanisms of you know baratic surgery is also the increase uh um increased levels of endogenous glp1 so there were people saying like oh that's crazy you know that's not going to work if if surgery fails to increase the activity of endogenous glp1 why would exogenous glp1 help but it helped so you can you can you can you can you can combine the facts and there are still so many things that we don't know. And your research certainly helps to to identify uh new you know avenues of treatment and and ways and understand the disease.

SPEAKER_01 37:21

No I and I think it's it's it's very relevant right it's still one of the most prevalent diseases that we have and and now that I'm here in the Asian context right here the people have much lower BMI metabolic health ratio so so what we consider even normal weight is here already a risk factor. And that has again must have something to do with the adipose tissue in the end right and and I can tell you the data on the Asian adipose tissues is basically non-existing there's a few groups that have started this now and looking into this but and we could learn maybe a lot from this because why are they they they at much lower fat content so susceptible to developing diseases right could of course be on the other side but I have a very uh I I have a very strong feeling that this has to do with the adipose tissue composition so then it's very timely to look into this here as well. Maybe we can even learn what can help everybody from this right by comparing two groups where metabolic health is at a BMI of 23 is already compromised.

SPEAKER_03 38:28

As you're now in Singapore so I have a very strong feeling that we soon know more about uh this issue correct oh I'm I have already uh started discussing with the bariatric surgeons here and uh some people were very good and have already collected uh hundreds of samples so I hope we can work together and look at this so that would of course help a lot so we'll see I mean I I'm just here three months I need to get uh started and have a few other things in my job here as well and besides research but um uh that's definitely something I want to look into and and again I I like that I can combine this with the large cohorts in Europe and the US of course I I think that could be quite interesting uh and maybe can lead to additional knowledge yeah understanding the biology uh differences yeah that's that's the perfect ending of of today's episode I have to say because that will be our excuse to talk to you again in at least one or two years from now when you present your your your results you know of the differences of Asian and let's say non-Asian adipose tissue um I I I I I thank you very much for for sharing your insights uh Christian um we learned that adipose tissue is not simply adipose tissue there are different you know size numbers colors metas and there are even like geographical differences in adipose tissue thank you very much for sharing that that was very enlightening thank you thank you very much for joining thank you thank you see you soon bye bye see you soon bye bye I think that was really interesting Marco with uh talking with Christian because this just you know kind of blows your mind that how many things that actually have an effect on a on also like on a pragmatic level on the patients that we treat so what do you think that you know what what's the take that you actually thought that was most interesting? That's hard to say because there was so much content in it, right? There were so many aspects where you think I think it's all over the place. Yeah we need to ask that and that's interesting and we need to actually may have an effect yeah so if I would have to summarize it I probably would say that adipose tissue is definitely something we need to take into account in the future if we talk about obesity physiology and obesity treatment it's it's much more complex than such a storage organ or place to storage energy number of adipocytes meta, the size of adipocytes meta, the color where the adipose tissue is there are different ways to stimulate it maybe to at least support the effects of the current treatments we already have or add on you know in but I think that's what actually is happening because some of the uh drugs that are in the pipeline they're actually adding on energy expenditure in addition to you know GLP1s and uh and other dual agonists so they actually are now already kind of approaching that. Absolutely and it's amazing what's going on you know on on on the edges of our field I would I would say we always you know we're baratic surgeons and we try to focus kind of you know is that limb length better than that lip length and and shall we use that pouch size and if we you know leave that anastomosis like this and so that's you know I would say against the background of what we just learned a very shallow way to look at at what we do there's so much more behind it and and and that was fascinating to hear something but then again it's like you know we've already moved uh within the field of metabolic bioetric surgery from the idea of restriction even though we still have to remind that sometimes that you know this is not this is not what are you talking about this is not what we do so it is uh by doing metabolic biotic surgery the uh what actually are the mechanisms of action behind it we don't really know all of that yet we're like very limited information that of all the things that actually also interconnect with each other absolutely we uh seriously we we need to know more about it because it's okay it's like a black box I mean thinking of what Francesco and Ricardo told us in terms of trying to come up with a new diagnosis of obesity preclinical clinical but you know the the diagnosis of obesity is still based on excess fat you know and exactly and excess adipose tissue and yeah and that that's you know based on what Christian just told us is you know seems to be you know not what we will use in 10 years from now let's put it that way yeah it's gonna be interesting to see yeah we have to do this again in 10 years to see how that goes. Lucky you so uh yeah thank you very much that was a great uh exchange of views