The Dangerous Invisible Fat You’re Not Paying Attention To | Prof. Jimmy Bell

0:00Dr Karan: Too much visceral fat is dangerous. It raises your risk of cancer and heart disease and you might not even know you've got too much of it. Even slim people can have harmful levels of visceral fat. So I'm joined by Prof. Jimmy Bell to find out exactly how to deal with it. If you're looking to be healthy, weight is not the thing that you should be worrying about. I'm Dr Karan and in this podcast I speak to the world's foremost experts in science and medicine to cut through the BS of modern health advice. Thanks as always to Loam Science for sponsoring the show, the world's first invisible fiber blend with clinical trials.

0:35Dr Karan: Professor Jimmy Bell, before we start this conversation, I just want to relay an anecdote, a nostalgic anecdote I had when I was a medical student in an anatomy lab. And when I was first slicing into a human cadaver. As one does. As one does. Yeah, it's a very peculiar job. But my understanding of fat changed irreversibly after that moment. I didn't fully understand as a first year medical student, the depths of fat. And when I sliced into the human body, and I saw this marbled yellowish structure around various organs in the human body, I was blown away by where fat managed to find itself in the human body.

1:16Dr Karan: And then I begin to understand that, okay, there's different types of fat, there's this visceral fat, and then there's brown fat, you know, early on in in our life, you're an expert in obesity and especially in visceral fat. For a lot of people listening who think of fat as this big umbrella term, what are the different types of fat and specifically narrowing in on visceral fat, why do we think about that as harmful fat? That's a great question. And I really liked the way you started this conversation because people always start on a negative, say how much fat should I have? Or how do I get rid of it?

1:48I started looking at fat as something that is essential and in your body. Let's start by how fat has moved from what people call a tissue, a dumping ground for excess energy. It graduated to be an organ. So what does it mean? It actually communicates, it sends signals across your body. And bit by bit, we discover that fat is an organ that actually interacts with every single other organ, as you would expect. And I'd like to think of fat or adipose tissue more likely, because unfortunately we interchange the two. Adipose tissue, as you imagine a country and it's a confederate country. So they all belong to the same country, like United States, and you have different states.

2:30And even though the composition is more or less very similar in different parts of your body, they all have slightly different functions. They do slightly different things, but yet they're communicating with each other. So they work in conjunction with each other, but at the same time, they have their own role. So fat is, you know, your subcutaneous fat, which is a fat outside, the one that you pinch around your body, whatever, that has several functions like mechanical functions, stop you from bumping into, no, stop you, but when you bump into things, stop you from branch as a buffer, it stops you from getting very cold or whatever, but it stores lots of the excess energy that you might need in time.

3:07So also it stores the excess energy that you don't need. You have to store it away. It's a good way of storing energy that you can actually use. But then there are other fat depots, like the visceral fat, that have a slightly different role. And that role is actually quite a benign role. It's needed for immune responses, infertility. The visceral fat also. Yeah, visceral fat. It's communicating, sending this what's called adipokines, so these are signal molecules, peptides, and so forth. They're going to different parts of your body telling, do this, don't do that. And they're getting signals, either electric signals or chemical signals to the adipose tissue to tell the adipose tissue, do this, do that, release more fat, take on more fat and so forth.

3:51And each fat depot has different signaling system and different way of reacting to the signaling and difference. And that's actually quite important. So when you were doing the surgery, you started seeing the fat as one entity, but also with lost personalities.

4:08Dr Karan: Yeah. Yeah, I mean, fat is geographically different depending on where it is. It also has different functions. And, you know, to your point, we often paint fat as a bad thing. You were saying at the start of the discussion, people want to get rid of fat, but you outlined so many mechanical, hormonal and neurochemical functions that it does. It's an endocrine organ, which churns out so many things involved in reproductive function, but also, you know, as a mechanical buffer as a thermoregulatory organ as well. I think it's funny, there was this very memeable viral study that was done a few years ago on, it was leading on the premise of thick thighs save lives.

4:50Dr Karan: And the science was obviously where they found that fat in the gluteo femoral region, a more subcutaneous fat in the hips, buttocks, and thighs was associated with an improved metabolic and cardiovascular risk profile and glucose and lipid profile compared to fat in the central abdominal area, which was likely to be more visceral, which I think was interesting to almost reprogram and recalibrate a lot of people's understanding of fat that actually this subcutaneous fat isn't on its own bad. And to your point, can it actually be some sort of siphon or storage tank to make sure that any harmful fat or fatty acids doesn't escape into the places where it shouldn't be and sequester them.

5:34Yeah, absolutely. I think let's step back a bit and let's look at the roles in plural of adipose tissue. The one that we all know is you eat too much energy, you have to put it somewhere. You know, it's a survival trait and we need that. We can't just take energy and just throw it away. It takes a lot of time to get that energy. Second, fat in the wild is very difficult to get. I would say to people that we are programmed to get three things, sugar, salt and fat. Those were extremely difficult to obtain. Okay, if you live by the sea, salt is not a problem. But if you live inland, salt is very difficult to obtain.

6:13Sugar, extremely difficult to obtain. Either fruit, which the wild fruit do not have that much sugar, contrary to what people thing. And that's why honey was actually so precious, because it was very difficult to get honey. Hence the word honeymoon. Yeah, it's because people in ancient time, when they got married, they were given a pot of honey. It wasn't also because you got married, but also you got honey because it was so precious. And then there was fat. And there's very little fat around in the world, in the wild. There are lots of green things that have very little fat, most of the fat that we will have access to in the wild will either have hooves to run away or they have claws to eat us.

6:58So fat was very precious, salt, sugar, fat, yeah, precious. Once you obtain them, you want to keep them. And the adipositio does a fantastic job in keeping those excess energy. You store it away, so it's a storage place. It communicates with the outside. How? Well, if your fat levels start dropping, your brain starts saying to you the signals coming from the adipose tissue to the brain saying, we're going down in energy, go and get some. So we get that signal, leptin, discovering a few decades ago that revolutionized the way we looked at adipose tissue. Also, adipose tissue has a memory, a biological So they had done experiment, this mainly in animals, where they transplanted visceral fat to sarcotinous fat, to the sarcotinous area.

7:49The visceral fat still maintains memory, still carry on thinking, I am a visceral fat adipocyte and I carry on doing it. If you do the reverse, it still thinks it's a sarcotinous. So there's a biological memory. Eventually takes on the role of the new location, but it takes a long time to actually do it.

8:09Dr Karan: So the visceral fat, I mean, you know, whilst we label different fats as having different functional roles and capacities, overall, an excess of visceral fat is more harmful to the body from a metabolic perspective and a hormone perspective than too much subcutaneous fat, you know, all things being relative. Why is that? Okay. So there's, why do you get visceral fat? So we all have to have this fat depots. We use MRI to scan people and measure, and this is the only way to measure accurately or CT scan, because you don't actually use CT on people if you don't need to. But with MRI you can actually scan.

8:49And we have scanned the largest people that you can find, mobile people, people with Prada-Willi syndrome. It's a terrible condition where they don't have satiety effects. So they're always hungry. Imagine you're starving, it doesn't matter how much you eat, you still feel hungry. And so these people, it's a genetic condition, they cannot stop eating. I can imagine it becomes very, very large. We have scanned those people. We have scanned Olympic athletes, rowers, who have almost no fat, they still have visual fat. What does this tell us? That these fat depots are essential. It doesn't matter how much you try to get rid of them, they're still going to be there.

9:30So there's an essential fraction which is required. Yeah. The issue is when that amount is starting increasing and the question that we haven't actually been able to answer, but people have hints of what happened. Why does it increase? And why does it increase? Because as you take more and more energy, it all goes primarily to your external fat, your sarcootenoid fat. Then the sarcootenoid fat, just to be kind of like cartoon-like, it goes like, hey guys, you know, I got too much energy, I got too much energy, what do I do with this? It's like you're filling my glass with fat, eventually gets full, and this is called the overflow hypothesis, that it starts saying I cannot cope with this, I cannot expand as much as I would like to, that excess fat has to go somewhere.

10:18And I start looking for the other fat there, but it starts saying, guys, you have to help me. It goes to the visceral fat, It goes to the liver. It goes to the pancreas. It goes around your heart. It goes in your muscle. Each of those fat depots have a different detrimental effect once it passes a certain level.

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12:28Dr Karan: Now, the argument you've made, obviously, which is very valid, is the fact that in extreme states, in obesity, for example, you exceed the storage capacity of subcutaneous fat and then you get an overflow, the spillover of some of this fat. which can lead to this harmful fatty deposits and visceral fat. Now, if we also assume that the more obese someone is or the most excess adipose tissue someone has, a higher percentage of that will be accumulated as visceral fat. But you can also have someone who appears thin on the outside, but they can have a higher than necessary amount of visceral fat on the inside.

13:10Dr Karan: Are those just edge cases or are they more common than we think? They are far more common than you say. You're absolutely right. We don't know exactly what happens, but I think physical activity has something to do with it. So if you maintain your weight through simply calorie restriction, you don't get the right signals to where to put the fat. And you end up putting the percentage that go into your psychotinus is much lower than your physical activity. It goes to your visceral fat. Now, why visceral fat? It's important because it's a very dynamic fat depot. You put fat in your external part of your body, it's a continuous fat, it takes time to come out, especially around the hips.

13:52Hence why people think that in the hips, storing fat in the hips is actually good. Or less harmful, less harmful, not good, less harmful than in the abdominal area. area. Because the adipose tissue in the visceral area is very dynamic, it's also very reactive to its surroundings. And when you actually have obesity, you have very low chronic inflammation. And the word inflammation becomes very important because you can have obesity with no inflammation, and then the harmful effects are much more attenuated than you should actually have lots of inflammation. And visceral fat then gets infiltrated by inflammatory cells.

14:40And then this starts creating a vicious circle that the inflammation calls more inflammatory cells, more signals go out, more come in, and then your whole body become inflamed. And your visceral fat then start releasing fat into your liver, into your other areas.

14:57Dr Karan: I guess, you know, there was a really striking study done. I think there was over 15 ,000 people where they looked at people with normal BMIs with and without central obesity. And I think their central obesity was measured by the, you know, the waist height ratio. And a man with a normal BMI with central obesity, so a proxy of that visceral fat had an 87 % higher mortality risk than a normal BMI man without central obesity, which just almost independently suggests that visceral fat on its own, independent of weight or BMI, is detrimental for health in excess. In excess, absolutely. And that's the key word, in excess.

15:37Yes. But you see, you don't get visceral fat in excess on its own. No. So when we do MRI scan of subjects, if you got high levels of visceral fat, you also get high levels of liver fat fat and you also get pancreas fat. Because of the spillover. Oh, the spillover, exactly. Exceeding the storage capacity of the... Of his fat. So when you put weight on, the thing that we have seen, the fat goes first into your adipose tissue, meaning the sarcogeanous adipose tissue, and then it goes into the visceral area, then into the liver and the pancreas, and then into the muscle. And this is an important fat depot.

16:18We call it IMAD, the intramuscular adipose tissue.

16:22Dr Karan: And just on that, I mean, speaking about, you were saying that people who are, you know, toffee, thin on the outside, fat on the inside, it's far more common than most people realize. Are there any telltale signs that, you know, just by looking at someone, that someone could be like that? Or could we use some proxies like the waist to height ratio to suggest that someone has a higher degree of visceral fat with some degree of accuracy? Okay. If you want to know with certainty, you have to have an MRI scan. Yeah, of course. Or a CT scan. I mean, that's the only way to do it. The second way you could do it is, my colleague, Professor Louise Thomas, she's amazing.

17:00She can look at someone and can actually guesstimate exactly how much fat they will have or whatever. She's quite weird actually. Yeah, she's actually quite amazing. We became quite obsessed with people body shape. When you start doing scanning, you start looking people around the street and you see the pattern and you start going like this person and so forth. But lead to MRI. For most of us, yeah, if you take a piece of string, okay, and measure your height, yeah, with a piece of string and then fold it in two, put it around your waist, okay? And if the two ends touch, it's likely you're relatively healthy.

17:34If it doesn't, it's very highly likely that you got high level of your soul fat and high levels of liver fat and pancreas fat. Yeah.

17:45Dr Karan: So that's the simplest way to do it. So you're to kind of say, maybe say that another way, your waist should be less than half your height. Yep. Exactly. Basically to be in a healthy zone of visceral fat. That's very well put. Yeah. But that does no guarantee. And that's where the, that's where the toffees come into the thin outside of the fat. So maybe that's a good gross screening at home. And if you exceed that, could you maybe we warrant a scan to actually quantify that objectively? Yeah. I would then say, okay, to the people who are still say, say you are within the zone of the healthy, look at your lifestyle.

18:25How much physical activity do you do? Yeah. And we just done a study with the UK Power Bank. I don't know if the audience are familiar with the UK Power Bank. The UK Power Bank is the most amazing thing. Let me praise first of all, explain to people what the UK power bank is. So over half a million people in the UK volunteer to have everything measured from the genetics, lifestyle, everything. Even answer lots of impertinent questions about personal life, which people do, except how much tax they pay. Everybody refuses to hear that yet. But I mean, let me praise first of all, the volunteers who are absolutely amazing because the amount of time they're given of their lives for no, they get nothing.

19:03No benefit to themselves. Absolutely nothing. Absolutely nothing. The people who run the UK Power Bank, which are amazing people, from the radiographers to the people who actually organize the whole thing. And then the funders, of course, who actually wish it, the taxpayers and so forth. That's half a million people. We looked at people and we scanned them, 100 ,000 of them have been scanned. And then two years later, we scanned about 3 ,000. And now we're doing another 60 ,000. In the period of two years, We looked at the people who maintained their weight, the people who lost weight, different amount, and we subdivide them into small amounts, medium or large amounts.

19:44And then the people who would weight on just normal life. Now the depressing news, everybody increased the amount of fat in their body after two years, and they decreased the amount of muscle, even if you maintain your weight. Yeah. And these are people on average 60, 65, on average, they lost muscle, they gained fat, but they maintained their weight. If you then include physical activity, then that different disappears. So people maintain their muscle, maintain their weight, they do not increase their fat. So when someone is a normal weight, is in the healthy zone, and you're not doing physical activity is very likely all you're doing in maintaining your weight by maintaining the amount of fat, supplementing the weight.

20:34Dr Karan: So when people are chasing weight loss, they may be chasing the wrong thing because they're chasing an arbitrary weight goal, but that masks the underlying change in the composition where obviously they could be losing muscle and losing weight and the scale looks according to what they want, but actually that's not what they want. They actually want to lose fat, increase muscle, specifically lose visceral fat, increase muscle or maintain muscle, which they're not doing. So the actual hidden body composition metric is the key indication. Exactly. So when, and that's a problem with toffee, the people who are toffee, thin outside fat inside, that they look normal, they might even feel normal, but metabolically they are not.

21:16And in body composition, they are not. And we looked at a group of small, a few hundred people relatively young, relatively healthy, 15 % of those people, men and women were toffee and they consider themselves healthy.

21:33Dr Karan: Which also explains, I think there've been studies and meta-analysis proving that exercise independent of weight, so you can do exercise, not change your overall weight at all, but you can reduce your visceral fat percentage. Let me tell you another depressing story. and everything with this. We did exactly that study. We took a group of women, gave them everything. A gym, we paid them for a gym, personal trainer, monitor, absolutely everything. We scanned them at the beginning. We scanned them after 12 weeks, I think it was, if I remember correctly, scanned them again, measured them. We told them, look, your metabolic profile has improved incredibly.

22:13Your body composition has improved incredibly. You know, real changes here. They all went, no, I still weigh the same. And second, and this is the most important one, I still look the same. So the question is, what are we chasing? Are we chasing health or are we chasing looks? And this is an important philosophical question. It's something that I come across over and over again. And the priorities of people, unfortunately we live in a society with priority, I kind of like youth comes at the top, beauty, weight, and then health. Most people will say, no, that's not true. I was talking to my youngest son and his partner and I told them this and both of them, they said, no, no, we are worried about health.

23:02I said, yeah, but you're young and beautiful. Yeah. You're going to, young and beautiful people say, yeah. Priority shift as age shifts. But the truth is that if you're looking to be healthy, weight is not the thing that you should be worrying about. It's about your body composition, your lifestyle.

23:20Dr Karan: Well, I guess, you know, to the point we were having earlier, when you were outlining all the multitude of functions that fat has, especially when it comes to women, I mean, women and men have different fractions of total essential fat and women have a higher essential fat percentage because for reproductive function, and you know, have to have periods, they need that sort of energy reserve, right? And if we consistently seek to lower body fat percentage to such a degree that someone is chasing an eight pack or visible veins on their obliques, then you are tanking your testosterone for men. You're tanking your period cycles and you may have amenorrhea, a lack of periods for women.

23:58Dr Karan: You affect your mood and cognition. And fertility. I mean, fertility. You show that the super athletes find you very difficult to get pregnant. Well, they lost their periods. Yeah, exactly. So fat is beautiful. It's a beautiful organ. You know, this should be, which you're gonna walk around with, fat is beautiful. It just is a friend that loves you a bit too much sometimes. If we were looking at the differences between men and women, we outlined just in terms of, you know, the, an average man has a lower percentage of fat than the average woman. And that's this physiological reasons for that. Are there genetic differences in how and where geographically visceral fat specifically in subcutaneous fat percentages are distributed in men versus women?

24:43There are no known genetic markers for this. I mean, one of our colleagues looking into this, while there are hormonal differences, and it clearly that women do tend to actually deposit more external fat than visceral fat.

24:57Dr Karan: More subcutaneous fat, and that's driven by estrogen? That is driven mainly hormonal. So then... And then the fat that they put externally, they tend to go to the hips and the thigh, which of course women have. Which is favorable. Yeah, which is favorable. Metabolically. Metabolically, physiologically. Yeah. Aesthetically not pleasing for some. For some people. And then it's very difficult to move it from there. So if you exercise and you try to burn fatware, it will go from everywhere except around your hips. Hence that saying, you know, a minute in the lips, a lifetime in the hips. Yeah. Yeah.

25:33Physiologically it is true, it's very, very hard. Yeah. While men do the opposite. They put very little fat externally on the hips, but it goes all abdominally. And that's the wrong place to put it. And it's a lot of different visceral. And the difference in a man, if you got two men and two women, and you look at the BMI, it's okay, extreme BMI, the difference in distribution is phenomenal. and men have all the wrong distribution.

26:02Dr Karan: Yes. So going back to the point, so estrogen obviously is a driver of the location of visceral fat and subcutaneous fat deposition. So in a premenopausal women with high levels of estrogen, you get a favorable metabolic profile where estrogen is protective and limits the amount of visceral fat deposition. You get a lot of subcutaneous. Now, perimenopausal, postmenopausal women, where you get a decline in estrogen and you also get in studies and you know, a unfavorable metabolic profile with lipid markers maybe going up and they may have that worsened metabolic hormonal environment because of that estrogen.

26:40Dr Karan: I assume now they get an increased risk of visceral fat deposition. Absolutely. And they start getting a distribution more male-like distribution. Higher risk of cardiovascular disease. More visual fat, more fat in the liver and the pancreas and so forth. But I do want to, you see, for a long time in health, muscle wear was at the center of health. And then came the 60s, the 70s, the 80s, and then fat took over and fat became central to health. That's the wrong way to look at it. We should look at both of them. Two friends who are talking to each other, okay? They are helping each other, yeah?

27:22But if you try to get rid of one, I mean, modern society has demonized an organ, adipose tissue. You stop 100 people on the street, and I got a pill here to get rid of all your fat, people will take it immediately. We are thinking that you need fat. You need fat to be healthy.

27:40Dr Karan: So would you rather be very skinny with no muscle or very muscular with a higher percentage of fat? I would like to be in the middle. I would like to have... And this is the key question that nobody asks, okay, is what is the correct amount, distribution, and composition of your fat? That's what we should be aiming for, to be able to tell people you should have this amount of fat distributed here and the composition, because the type of fat that you have is also important. That's an independent risk factor. You might have the right distribution, but the wrong composition. How much a role does genetics play in our baseline level of visceral fat and how that changes in our lifetime?

28:26Dr Karan: That's a very... Well, another way of asking it, is it more lifestyle that we have control over our visceral percentages or genetics? There are two schools of thought. They're still arguing. I'd say them one. So I'll tell you which one, you know, declare my position. I believe that over 60 to 80 % is lifestyle. Yes. You talk to the geneticists, they'll say exactly the reverse. But if you look at the genetic studies, and you look at this, there are lots of strong correlations and so forth. There are genetic mutation that leads to obesity, absolutely, but they're very rare. For the general population, genetic might, if you look at the size of the effect of that genetic, if you add up all the effects, is always less than 10%, 10 % to 15%.

29:14So, yeah, this is what I call the genetic dark matter, okay, which they haven't identified the genes or the group of genes. I don't know. I believe that most of it is lifestyle.

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30:32Dr Karan: So even if someone has a higher risk genetically for obesity, that is not their fate, that is simply a higher baseline risk, but it's the lifestyle that determines so many things. And, you know, there's an abundance of studies that you're no doubt aware of, smoking, saturated fat intake, exercise, resistance training, hormonal states, all of those ultimately will determine in the visceral factor. Yeah, absolutely. The amount and the composition. And what's actually interesting in the studies I come across is that we have done and other people have done. What they're showing is that, for example, there are ethnic differences in the risk of type 2 diabetes, you know, South Asian being a higher risk and Afro-Caribbean people are at lower risk.

31:20When we look at the genetics, we have not been able to find conclusive genetic differences. When we look at the body composition, we do. And what we find is that Afro-Caribbean have a higher percentage in body composition term of muscle. Yes. Yeah. Lower visceral fat, lower liver fat, lower intermuscular fat. Very important fat. But nobody pays attention. More efficient muscle because of that. Yeah. better quality. Yes, better hormonal environment. Yes, exactly. So we talk about muscle quality, okay? So you might have the same amount, but the quality. So if you look at steak and you see lots of fatty streaks or whatever, well, we do the same thing.

32:04We put that fat in the, among the muscle fibers and so forth and inside the muscle fiber that decreases the efficiency. So we might have the same volume of muscle, but less efficient. South Asians appear to have a larger percentage of fat relative to their muscle. But if you can actually change that ratio, then the risk disappears or is reduced.

32:28Dr Karan: And that is a genetic thing. So South Asians versus white populations versus Afro-Caribbean populations for the same BMI, for the same weight, there's significant risk based on the body composition of less muscle and higher baseline level of visceral fat in South Asian populations, which means if you took someone at all of those different ethnicities at 75 kilos, the South Asian will have a higher baseline risk of metabolic issues and cardiovascular issues because of the higher visceral fat percentage. Yeah. And lower muscle. And this is what's called the skinny Indian and phenotype was actually set up an Indian group that showed this many years ago.

33:13Yeah, it turns out to be much more widely spread across different populations.

33:18Dr Karan: Our kind of world has changed rapidly in the last few years with the rise of GLP-1 medications. And I believe it was even in the step one semaglutide trial, they showed obviously a big 15 % loss in weight. But what was interesting is that out of that 15 % weight loss, 27 % of the percentage weight loss was actually visceral fat. So do you think that GLP-1 medications can be a tool not just for anti-obesity, but actually can specifically target visceral fat? And going one layer beyond that, is there a world in which we can increase the scope of indications for which someone can be prescribed GLP-1s, where they are thin on the outside, fat on the inside and GLP-1s are prescribed specifically to target visceral fat in that metabolically unhappy population.

34:06That's a very interesting question, an interesting way of looking at this. But let's step back about weight loss. So when you lose weight, okay, you lose both fat and muscle. Yes. Yeah. But more or less fixed percentage, about 75 % fat, 25%. It's very gross in numbers, but just to keep an idea. This happens regardless of what you do. If you lose weight either through any dieting process, okay? If you do a body composition analysis, the first thing that will go will be liver visceral fat. Regardless of the mode of action. That's the first place the fat gets in. Yeah. It's the last to go in, the first to come out.

34:51Circo-Tenuous fat. That's why, you know, if you exercise, okay, if you exercise, the same thing happens. You lose physical fat, liver fat, pancreas fat, muscle fat. And that's why exercising is always very difficult. People say, oh, I'm not changing weight. I still look the same. My external fat is still there. Yeah. But your internal fat is all disappearing. Metabolically you're becoming more healthy. Now let's move to GLP-1. GLP-1 does exactly the same thing. Now the controversy see about GLP-1. First of all, as a society, I feel that we are failure, okay, that we have to end up injecting people to lose weight.

35:31We should be able to educate, educate ourselves, educate people, okay, to be able to have a healthy lifestyle without the need of injection. But hey, we are here. Yeah. You know, there's a wish and there's a reality. And the reality is that the fight against obesity has been lost as a society. More and more people are becoming obese and overweight. There's no reason for that. If we control the food industry, if we control the education, okay, there are many things that we could do, but we're not doing that, okay? And the politicians are never gonna do it, okay? That's very clear. And the NHS has to struggle with this problem.

36:07It's a game changer. It's a game changer. And we have to accept that. Now, GLP-1 works very much like any weight loss system. Of course. Yeah. So you start losing fat, you lose large amount of physical fat, large amounts of fat, but you also lose muscle. And there is, and still the jury's out, is whether the ratio of fat to muscle being lost with GLP-1 is different than if you diet. We need proper studies to be done. I don't know whether the pharma companies are doing it or not. My guess is that they should be doing it. where people should be MRI before, in the middle and after they're dealing with GLP-1 and look at not only the amount of fat, but the distribution of fat, every fat type.

36:49They should be looking at every single muscle group.

36:51Dr Karan: There was an interesting study done where they did look at the MRI. They did sequential MRIs on people on GLP-1 therapy. And whilst there was a reduction in the size of muscle, to your point earlier about muscle quality, the level of intramuscular fat did decrease. So even though there was less muscle, it was a higher quality muscle on GLP-1 because it was more efficient, functionally better with less fat. So maybe there's something interesting there. Yeah. As I said, the jury is still out. The studies need to be done. And I think what's important, and to be fair to the pharma companies, which coming from me is quite difficult to do, to be fair to the pharma company, they do suggest, and this It's true also for any dietary or lifestyle intervention, they do suggest that you should include a healthy diet and exercise resistance.

37:43It is part of the program. The problem that nobody wants to do it. Yeah, nobody sticks to it. So if people are gonna take GLP-1, they should take a resistant exercise and a balanced diet.

37:56Dr Karan: So, you know, you've outlined in this and also the studies back it up, reducing calories, being in a calorie deficit has a major impact in reducing visceral fat. and this is what GLP-1s do. It forces chemically people to reduce the amount of calories they consume. They lose lean mass, they lose visceral fat, they lose subcutaneous fat. Beyond that as well, you've outlined people need to do resistance training and their study is showing independent of weight loss, it changes the composition. Resistance training exercise changes the composition internally and decreases the visceral fat. What do you think about specifically the role of fast food and ultra processed food?

38:32Dr Karan: because I'm not here to demonize anything, but - Oh, you should, you should. Yeah, things are worthwhile demonizing. No, I agree with you. And also I wanted to flag a study and I don't know if you are aware of it, but the Cardia cohort study where they tracked people over 25 years and they found in that study, people who consumed fast food more than three times a week had over a 5 % increased risk of fatty liver deposition and increased amount of visceral adipose tissue. Now, again, this is full of confounding factors. people who consistently eat takeaway food are likely to be more sedentary, maybe smoke, maybe drink alcohol, unhealthy user effect.

39:08Dr Karan: And by the corollary, people who don't eat that much fast food, going to the gym more, not smoking, and there is confounding and healthy user bias effect. But do you think there is anything specifically with fast food that has the combination of high salt, high fat, high sugar, which specifically has a role in increasing visceral fat just on that alone? Let me declare again another thing is that I love fat food and I love sugar. I'm addicted to sugar. Yeah. Yeah. So I don't, I don't know, no, I am addicted to sugar. My wife will tell you that I am addicted to sugar. And yeah, so I don't preach, I don't practice why I preach in some cases.

39:49But there are lots of studies showing that it's not only the amount of calories, but the type of calorie and the combination of calories. And I think in the case of fast food, it's exactly you enumerated the three key factors, which we mentioned earlier, fat, sugar, and salt all combined. And that combination appears with another mechanism to exacerbate the deposition of fat and exacerbate the inflammatory effect. And when you have an inflammatory effect, that increases the negative effect of having too much visual fat. So it's not so much that they, it's the form the calories come into and how the package that they come together, fat, sugar, and salt, that appears to have that exacerbated effect.

40:35Dr Karan: You mentioned before that in states of excess visceral adiposity, you get this chronic low-grade inflammation, which can continue this vicious cycle of worsening the metabolic environment in obesity. GLP-1 medications, we've seen, there'll be non-responders who lose less than 5 % of their total body weight, who'd be classified as non-responders. But even the non-responders who are on GLPs experience metabolic improvements from baseline. Do you think that's because of the anti-inflammatory effect of the drug and how it interacts with the inflammation caused by the visceral tissue? That is a very good question.

41:11This is the question I asked some of the pharmacokers and I said, isn't your drug just an anti-inflammatory drug? Possibly, yeah. And they said, we have no proof. But the question is, shouldn't we be giving GLP-1 to people with inflammatory diseases, with chronic arthritis? There are no studies done right now. Yeah, we don't know. But what I've seen from the study I have read, I know directly, I haven't done the study myself, there appears to be an anti-inflammatory effect. Now we don't know whether the anti-inflammatory effect is because fat levels are going down and therefore reducing inflammation, or whether the inflammation is helping the reduction of fat.

41:53When you lose weight, like negative calorie intake, inflammation also is reduced. So it's a chicken and egg issue. We need more data. You see, we need data, nobody's done the experiment, taking normal weight, healthy people and give them GLP-1.

42:13Dr Karan: Maybe the best data we have is in non-responders to GLP-1s. Yeah, but the non-responders are still people who are a certain weight. Yeah, they are higher than based on. So you need to give it to young people who have normal weight, who are healthy, no metabolic issues, see what happens. See what happens. Yeah. You might find out that GLP-1 is doing a similar agonist might be doing all the things beyond the appetite effect. Yeah. I mean, having spoken to many prescribers of it and speaking to a lot of people online who are patients of it, who are actually taking it off license for other indications, such as endometriosis, PCOS, which are in part inflammatory conditions, and they don't have a lot of other metabolic dysfunction.

42:56Dr Karan: They do see a reversal in some of their chronic diseases, even inflammatory bowel disease, because of the GLP-1 medication. So yeah, I do agree with you. There's something there and I don't know what the farmers are doing or who is investigating this. Unfortunately in this country, they're cutting down money into basic research. So we, before 10 or 20 years ago, we might have been able to run some of these trials now. Nobody's interested in giving us the money to do this. Something I'm very interested in personally is gut health and the gut microbiome. Is there any obvious bi-directional relationship between the gut microbiome and the gut barrier and visceral fat?

43:36Dr Karan: Are there any metabolites from the visceral fat which worsen the state of the gut and vice versa? I think it's on the contrary. I think the right microbiome has the right signaling, short-chain fatty acids mainly, that come from the gut, that help the anti-inflammatory effect and it helps the metabolism of the adipose tissue. So yeah, the gut does have an effect. I have that problem with microbiota because it's very difficult to manipulate. Yeah. Yeah. It's like trying to imagine you are dropping the middle of the Brazilian jungle and you say, go and cut a few trees again and change the whole.

44:14It's just complex. It doesn't mean that we shouldn't study or do it, but I just, yeah, it's very, very, very complex, but very important.

44:23Dr Karan: We're in an early age where it's very difficult to pin a causal route and it's a lot of association right now, it feels like. It is important, we should study it and needs more study. Yeah. One of the issues that we have now, I was thinking this on the way here, is the contamination that there's so many people doing so many things to themselves that ethically we wouldn't be allowed to do, not even to animals, but people do it to themselves. That is very, very difficult to do studies in humans nowadays that people are taking in GLP-1, creatine supplementation, vitamin supplementation, hormonal supplementation, subliminal supplementation, we don't have a normal population anymore.

45:05We don't have a clean population.

45:07Dr Karan: Yeah. And this creates real problems. From the data aspect. Yeah. If someone were listening to this and, you know, they were thin on the outside, fat on the inside, and they're doing their waist to height ratio, and that, you know, they have some of the things that we spoke about, they're not doing enough resistance training, but they are losing weight because of calorie deficit and maybe not improving their actual body composition. The topic of this conversation has been visceral fat. What can someone do? What advice would you give as an action plan to someone listening today that they can quickly over the next 60, 90, 120 days start targeting visceral fat?

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46:32Dr Karan: For durability you can count on, just like people count on you. Firestone, always dependable since 1900. Okay, I'm not going to put athletes into this, okay? Just you and me. Yeah, me. What would I do? What would I do? First of all, physical activity. If you sit a lot, walk. If you walk, walk faster. If you walk faster, start doing running. If you can't do any because you are too large or overweight or you got problems, increase your physical activity. Yeah. Somehow. Somehow. Throughout the day. Don't go just 20 minutes like I do. Don't do it on a bicycle or whatever, try to break it into across the day.

47:21Reduce the hours you spend eating. So, you know, stop eating at nine o 'clock and then start again at eight o 'clock in the morning. So it depresses your chronic inflammatory effect. Your body starts recovering. The problem with the body that is very clever, you go a baseline. This is going to sound against It gains everything that you think of, but it's very difficult to put weight on. You try and overeat. And we've done this experiment. We try to get people to double the amount of calories. The body starts going, no, no, I don't want to do this. Yeah. But what happened? We don't do that. We sneak in every day.

48:02We increase the amount of calories and then our baseline moves up. If you try to lose the weight, the body goes, no, I'm not going to do that. I'm going to fight that. even though it's a new baseline. We increase it again, this is a new baseline. That's why the body always fights against losing weight. It doesn't matter where you are. It fights against putting too much weight on, against losing weight. Nobody goes to bed slim and wakes up the next morning overweight. We all go back, go to bed slim and we put weight on bit by bit. I calculated how many tons we wake up heavier every day, something like 35 tons in the UK, weight is half heavier every day.

48:45We all put one gram on. If you do that 365 days a year, well, that's, you know, almost half a kilo. Over 10 years, okay, you got five kilos extra. But most of us put more grams per day. So we do it slowly. You need to think that if it took you that long to put your weight on, don't try to lose it fast because the body's going to fight back. Do it slowly. Your target should not be 12 weeks. Your target should be 12 months. Change your lifestyle. My wife said it very nicely. She said, this is a life sentence and you have to win every day. You have to win every day. Yeah.

49:27Dr Karan: I think it's a very important conversation because I think a lot of people, or even learned people, educators, health professionals aren't aware of the implications of visceral fat. And I think a lot of people are still swayed by BMI and the vanity metrics of what's on the scale, what people look like in front of a mirror. And we forget the most important metabolically active, crucial organ, which is fat and the different components of it. So Jimmy, thank you so much for joining. No, no, thank you. Think visceral fat, liver fat, pancreas fat, muscle fat. That's your target. Yeah. What you look in the mirror is not that important.

50:04Dr Karan: Correct. I think that's a really important message. Thank you so much. Thank you.