45: Why and Where We Store Fat with Dr. Ben Bikman

Hello and welcome to this week's episode of the Metabolic Classroom. I am your professor for the classroom today, Professor Ben Bickman. Thanks again for joining. This is going to be a topic that you will appreciate, and my hope is that at the end of it, as usual, that you will not only just be thinking of yourself as the student, but also as the teacher, paying sufficient attention to these principles that you're able to then go share them and even implement some practical steps. The back end of it all. For today and the next few episodes, we are going to be talking about fat tissue. And today's objective is to explore the crucial role that fat plays beyond how we commonly perceive it, which is simply just an energy depot. There is a lot of nuance and even complexity to this tissue that we so often only curse and at best overlook. But today we're going to be discussing how and why we store fat. And then the next Metabolic Classroom will be with some focus on aging and where we store fat. That changes with age. It also changes with, of course, between the sexes, male and female. And we will then the following talk about how fat talks, and by that I mean all of the hormones that come from fat, not only how hormones are affecting fat, that's something we're going to be talking about in these sooner episodes or classrooms, but how the fat itself is then talking to the rest of the body with some particular focus on sex differences again. And then lastly, it is what to do if you want to get rid of some fat. What are the interventions? Whether they are surgical, which have their own problems, of course, or whether it is nutrition based. All right, now with all of that as introduction and me again thanking you, let me just remind you that if you are joining me live through the Insulin IQ site, you are able to not only get this in real time, but also ask your questions in real time. And then I can get to them at the end of the classroom during the Q and A time. Now, as we start talking about fat, let's firstly explore why we store fat. Because it is something that we don't take too very warmly. Unfortunately, we curse what we pinch and jiggle, when in reality we should be quite grateful for it. First and foremost is the most obvious benefit of having fat, which is it allows us to survive a time of nutrient deficiency or caloric deficiency. Now, in this day and age, that seems like it's something very silly. The idea of having insufficient access to food is almost laughable for for most of us now. However, it doesn't take a lot to imagine a Scenario where things could change quite quickly due to employment circumstances or economic or societal problems. Should such disasters ever happen, we would be very grateful for our fat. It allows us to fast is one way of describing it. So it allows us to survive any period of scarcity whatsoever. So that's important. Now another thing about why we store fat is, that's worth highlighting is the uniqueness of humans. Now humans are unique on this planet in a number of ways. In a number of ways, myriad things differentiate us from every other animal on the planet. Among them is our metabolic capacity that humans in particular, we are the only land based mammals that are obese and we're certainly the only ones that are born obese. Now there are some other animals that can get fat, but even animals that you typically think of as fat aren't really like a cow. A cow is very, very lean. You think of other primates, even a lean human coming in at let's say 8% body fat would be considered obese if we compared that human, say apes or orangutans. Now those animals may have really distended bellies, but it's just because they're fermenting so much of the plants they're eating that is constantly distended. But in reality, the actual amount of body fat they have is exquisitely low. So we are again very unique in that we are born obese. We are the only mammals land based, because water based, like dolphins or whales of course are a bit of an exception. They're fatter, but we're not them. We don't live on the ocean, we don't, we live on the land and we're the only ones born obese. Now why that's a matter of some speculation, some theory. When it comes to some of the understandings of how we became who we are. How did we become the thinking big brained humans that we are today? There is, there is a theory in the realm of evolution, as it's all theoretical, that is called the expensive tissue hypothesis. And the expensive tissue hypothesis posits that we. And there's another theory I'll mention in a moment that's a little more closely related, but the expensive tissue hypothesis basically posits that it's our ability to both eat and store more fat that allowed our brains to get bigger and our intestines to get shorter. And those are some of the substantial differences between humans and other primates like apes, et cetera. Now the, another theory of evolution is one called the shore based theory of, and that is a little more nuanced but this most succinct version of it is perhaps that we are born with large brains. And the shore based theory being that we have access to omega 3 fats in particular that help fuel brain growth. But then as a part of that theory is this idea that by being born obese, a baby has the ability to born a human baby has the ability to born to, to burn a lot of fat. And when we burn a lot of fat, we make ketones very, very readily. Now there are some funny ideas about ketones burning a baby's brain or some such nonsense. The reality of human metabolism is that when a human baby doesn't eat for just a couple hours, they will get into a deep. They're burning so much fat because they have so much fat because they're born obese that they will get into a deeper state of ketosis than an adult human, even about two hours, two days rather straight of fasting. So babies get into deep ketosis substantially and very, very quickly. And it's thought to be an adaptive mechanism to help fuel the brain because the brain thrives so well on ketones. Now I'm getting a little off topic. I didn't mean to be talking so much about brain metabolism, but it is worth appreciating that perhaps one of the reasons we are born fat is because our brain benefits so much from that fat, because of our ability to rely fat as a primary metabolic fuel and in so doing creating ketones to fuel the brain. Because the more we're learning about brain metabolism, and here I am coming back to that topic, the more we appreciate that the brain thrives on ketones. Now, in addition to the caloric reserve and the potential to protect ourselves from scarcity with fat and the energy that it stores is just the fact that fat can provide some degree of protection and insulation. Insulation, particularly as the fat is stored beneath the skin, which we'll get to in a moment, but also a protection. As fat is stored within the visceral space, that fat that is stored deeper within the abdominal cavity, it provides a structure or shape to the intestines and even some degree of, indeed a protection. It's also very much a part of the immune system. Speaking of the visceral fat, that is the fat again, that's deep within the abdominal cavity, it is richly loaded with lymph nodes. Lymph nodes, of course, being a primary component, or in fact tech, if I'm being technical, a secondary component of the immune system where we can take immune related cells and let them kind of Incubate and get primed for action and then go fight an infection. So visce fat is very much connected to the immune system. That ends up actually being a blessing and a curse, as we'll get to later. Okay, now let's transition from the evolutionary role and some of the theories of why we are uniquely fat among the mammals on, on the earth. And then let's move into understanding the different types of fat. Now, there are two different ways of classifying fat tissue. And you've heard these before, I'm sure. One way is where we store it, and then the other way is how that fat behaves. So let's just talk about the actual location, because it's the simplest idea. We primarily store fat in two depots, two distinct areas, and that is subcutaneous. That's the fat that's stored right beneath the skin that I just mentioned a moment ago. That acts as a bit of an insulation. So we have subcutaneous fat, and then we have visceral fat. Again, both of these are fats I just mentioned, visceral fat being the fat that is stored deeper within the abdominal cavity. Now, there are some sex differences and genetics that play into this that we'll get to in a moment. But one way of thinking about the differences is if you can pinch and jiggle is subcutaneous fat. And then visceral fat, of course, is fat you cannot see. However, let's imagine, if you will, two men. They are best pals. They do everything together, and they've both gained 50 pounds of pure fat since they graduated from college 30 years ago. Not an uncommon amount of fat gain. They've gained the same amount of body fat again. Then they're the same weight, same height, everything. But you look at them, and one of them has fat that is spilling over his swim trunks. It's just sort of gushing or kind of flowing down his body, hanging on him. The other man, you can pinch and jiggle, and boy, does it jiggle. The other guy has a big protruding belly and it does not jiggle it. You smack it and it is hard. Which one of those two fellas do you think has more subcutaneous fat? Or in other words, fat that is stored beneath the skin? And which one do you think has more visceral fat fat stored within the abdominal cavity? Yeah, of course, the subcutaneous fat is the former. The one whose fat is pinchable and jiggable and spilling down over the sides of his swim trunks. And the other fellow who looks like he's carrying a Baby is in fact just carrying a lot of visceral fat. And that visceral fat is accumulating beneath the muscles of his abdomen. And so when you smack it, it is hard because you're smacking his skin and muscle and then the fat is beneath that. Now there are some distinct differences in the way those fat that that fat tissue behaves. And I'm just going to touch on that lightly because that's going to be a topic for next the next classroom, which is going to be all about where we store fat and again, some of the sex differences there. And so we're just lightly touching on it. Now, you've heard me talk before and if you haven't, go back and listen to the Metabolic previous Metabolic Classroom episodes about the differences in fat cell hyperplasia versus hypertrophy. You'll recall from these earlier conversations that if we store fat through hyperplasia, which is the production or multiplication of fat cells, then the fat cells are smaller, even if they are more abundant. They are smaller and smaller fat cells are insulin sensitive and healthy. They're anti inflammatory fat cells as well. In contrast, if we are storing fat through hypertrophy, that is when fat cells are all getting bigger individually, the number of fat cells isn't changing, but the size is changing and those fat cells become insulin resistant and pro inflammatory. For reasons we've discussed previously, subcutaneous fat tends to be stored as hyperplastic fat. So they're smaller, more abundant fat cells. And then visceral fat tends to be stored more as hyper, hypertrophic fat cells. So fewer in number, but larger in size. And we're going to revisit this in the next Metabolic Classroom. All right, so that is one way of defining or identifying fat storage. It's the two distinct depots, subcutaneous versus visceral. Now as I mentioned, there's another way of classifying fat as we understand the different types of fat and that is looking at its metabolic behavior. Normally, when you think of fat tissue, you're think you would imagine a tissue or cells that have a very low metabolic rate and you would be right. In fact, as a scientist who has done these studies, I can assure you that fat cells do in fact have a metabolic rate that is so low that it is almost below the point of detection that when we're testing metabolic rate in fat tissue, it is just you have to really zoom in to see any of the actual metabolic rate of those cells. Now there's, that is what we would call white fat. And that fat does look Quite white. It looks like Crisco or coconut oil. It really is. I mean, not quite as bright white as those, but it is very, very white. And that is reflective of just the pure amount of fat that is being stored within those fat cells. You see practically nothing else. And in fact, if you look at fat cells under a microscope, all you see is this big round blob. Normally, if you look at, like, if we were to look at muscle cells, it's a very busy thing. It's very dark pigmented because you're getting the nucleus, lots of mitochondria, lots of endoplasmic reticulum, and all in lysosomes and all kinds of other parts of the cell. But within the fat cell, all of that has been. The fat cell has all of those things, but all of it's been pushed to the edges to. Because it's this big bubble of fat is filling up the fat cell. It is something called the lipid droplet. And it is one big fat lipid droplet. And everything else has been pushed up to the very edges, the nucleus, the mitochondria and all the other organelles and pieces of the cells I just mentioned. So you only see this big blob of fat that is white fat. And again, it has a very, very low metabolic rate that stands in stark contrast, functionally speaking, and in appearance, to what we commonly call brown fat. Brown fat, as you might imagine, looks quite brown. In fact, it's kind of a reddish brownish hue. And that's reflective, in fact, of a much higher density of mitochondria, in part. So there's a much higher amount of mitochondria which do tend to stain or reflect a bit of a ruddy, brownish appearance. But if you look within the brown fat cells, you don't have one big blob of fat or one massive lipid droplet, to use the technical term. You have countless small little lipid droplets. Now, that's an advantage metabolically, for a cell that wants to burn fat. If you have a lot of smaller lipid droplets, you have a much more surface area where you can come in and start pulling the fat off of it to burn. And that is what the brown fat wants to do. With all of those mitochondria, the fat, the brown fat cells want to burn energy. And burn is the appropriate verb to use here because it also evokes the sense of heat. And that's what it wants to do. It's not burning the fat or glucose in order to get work done, like, say, a Muscle cell would do. A muscle cells burning calories because it wants to work, it wants to contract and relax. Well, a fat cell has no such job. It is in fact, kind of inert. It's lazy, it's just sitting there. But brown fat is burning that energy to create heat. And one interesting difference, we're going to talk more about age next time. But one interesting difference, when you compare babies to adults within the human family, babies have much more brown fat. And this is probably an adaptive mechanism because a newborn baby also has very little muscle. And so if baby gets cold, baby doesn't really have a good way to warm up. An adult does. An adult can shiver, and as the muscles start twitching, they start generating heat from those biochemical reactions. But a baby can't shiver. And so the baby has much more brown fat, which enables baby to be warm without the need for shivering. And that feature of brown fat tissue happens not only because of the much higher amount of mitochondria, but also the higher expression of a very interesting protein called uncoupling protein 1. Now, this is itself a bit of a deeper conversation that I'm reluctant to go into now. So we're going to hold off on really diving into coupling versus uncoupling within the mitochondria. And that can be a future metabolic classroom. In fact, insulin IQ Team, Metabolic Classroom Team, please take a note. Talk about mitochondria dynamics and uncoupling perhaps next month where we have some open topics still. But that's a fascinating conversation that is worth revisiting. So we have these two overall types. Now, there's actually one that slips in between, between white fat and brown fat. And just as a final note, on brown fat, while white fat has a metabolic rate that is so low it's hard to detect, as a scientist, we've published those reports. Brown fat actually has a metabolic rate that is on par with what we see in skeletal muscle. Now, muscle has a pretty decent metabolic rate and brown fat does too. It is multiple times high, like an order of magnitude 10 times higher than what you see from white fat. Now, again, in between the two is something that is commonly called beige fat. And we even as scientists, create this weird verb where you can take white fat and beige it, or the white fat cells have undergone Beijing. So you can see how we're making this verb, this action of this process of taking the very low metabolic rate, low mitochondrial density white fat, and having it start to behave kind of like brown fat. Now, white fat is the fat that we're storing on our bodies, to a large degree, all subcutaneous fat, the pinchable jiggle, is all white fat. Visce fat, the deeper abdominal cavity fat is all white fat. Now, what we have found and others have found as well, we've published reports from animals and humans. You can, you have a potential in the white fat to undergo a modest degree of Beijing. So it starts to increase its mitochondrial density and some uncoupling. And we found that humans can increase their fat tissue metabolic rate from their subcutaneous fat by up to about three times, simply by, in fact, by being in ketosis, actually. And we hope to do some more studies to try to optimize the timing of all of that and find out how quickly it can happen. But suffice it to say, it is white fat at the subcutaneous depot is capable of undergoing this modest conversion to behave a little more like brown fat. There's no evidence to suggest that visceral fat can do that. Indeed, in our studies of animals, we did not do visceral adipose biopsies. In humans, that would be very difficult to do. But in animals, we saw that the visceral fat did not experience this change like the subcutaneous fat did. So this is another reason why subcutaneous fat appears to be a little more beneficial, a little more favorable than visceral, not only because of its potential for a little more hyperplasia, allowing the fat cells to stay smaller, but also this potential for the fat cells to get a little hotter, if you will, to have a little more mitochondria and uncoupling. All right, now let's spend a few minutes as we transition away from where we're storing fat and the different fat types. I wanted to spend a few minutes talking about the biochemistry surrounding fat storage. First of all, it's just worth highlighting the digestion of nutrients that when we eat fat, that fat will move through. It gets digested in a bit of a curious way, which is that unlike any of the other nutrients, it moves into the lymph first and then after moving through the lymph, it comes into the blood vessels where it can then start interacting with cells and getting stored. And it is doing so on a chylomicron and it's moving within that big chylomicron like a big bus. It's being carried in the form of triglycerides. And then different tissues are going to pull a little bit from that. But generally the chylomicron is going to go to the liver and the liver is going to take care of it. It's going to store some or it's going to repackage it and release it as a vldl, another bus that's carrying different fats and different proteins. So that's a little bit of the digestion process. But if we come to the level of the fat cell, because after all, this is a conversation about storing fat, the fat cell will store fat from both fat for circulating in the blood from triglyceride, from triglyceride rich lipoproteins, to be very precise. That is generally VLDL and ldl, a little bit of chylomicron. But again, generally the chylomicron from the diet just goes to the liver and the liver will decide what to do with it, including dumping out some or a lot. And that's going to be VLDL and ldl. So those are all the triglyceride rich lipoproteins that if they float past a fat cell, the fat cell has on its surface and other cells do too, an enzyme called lipoprotein lipase. And this is an important little thing I'm going to tell you, which is where you have lipoprotein lipase determines where you store fat. Not necessarily how much fat you store, but where you store fat. You'll notice that you don't store fat everywhere on your body. For example, I don't store fat on the top of my head. It'd be nice to have something there, but I don't store fat there. You don either. I don't store fat on the back of my hand or anywhere on my hand. I don't have lipoprotein lipase on my hand within that part of my body. I do have lipoprotein lipase, for example, on my belly. And that's, of course, largely because I'm a man. But we'll come back to that when we talk about more of the sex differences next time. But even still, as the triglyceride rich lipoprotein is flowing through the blood like VLDL or ldl, especially where we have lipoprotein lipase is where we're generally going to store more fat. And in the very next segment, in just a moment, we're going to talk about the genetics and the environmental factors that play into it. But in addition to fat contributing to fat storage, of course we have one other one. It's not going to be proteins or amino acids. It's going to be glucose. Fat can convert glucose into fat very, very well. Anyone who tells you anything Differently than that is wrong. The fat cell is perfectly capable and even delighted to take in glucose and turn it to fat. What is essential in this process is in fact, insulin. Insulin is essential at allowing a fat cell to store more fat. The evidence for this is so obvious, not only in fat cell cultures. As I've elaborated on before. We have fat cells growing in my lab literally right now, and they're surrounded by fats and glucose, all the energy they would need to get big, and they will stay very small, skinny little fat cells until we spike insulin into the culture. When we put insulin in now, the fat cells know what to do and that is to promote overall the storage. And insulin is absolutely critical even in the case of a whole body. If you have a person with type 1 diabetes, they can eat whatever they want and they need only to skip or deliberately under dose their insulin injections and they will be as thin as they want. There will not only be no lipogenesis, which is the synthesis of new stored fat, there will also be nothing to turn off lipolysis, which is the breakdown of fat. And that's where insulin is particularly powerful at inhibiting lipolysis, so preventing the breakdown, forcing the fat cell to hold on to whatever fat it's storing. Now let's move on to the final segment within this metabolic classroom, namely genetic and environmental factors that influence fat stor. There is of course genetic predisposition. It's not that you're going to have a specific gene or the or a variant of a gene that's going to determine how much fat, but rather, even though there are some genes that are very much influential there, like MC4R or leptin, but these are mutations that are very uncommon. This is not your garden variety. I'm gaining weight or I'm even obese. There's no distinct genetic mutation in, in the average version of having too much body f yet. But there is clearly something familial about it. Even if there's not a distinct genetic pattern, if mom and dad are overweight or obese, it's very likely offspring will be too. Now you can already see the conflict with regards to environment. You know, the same environment that's making mom and dad obese is going to be the same environment that this child is being raised in. But even beyond that, there is in fact a familial inheritance to this, not only determining how much body fat gets stored, but also even where a person is storing fat. And, and again, that's something we're going to be talking very explicitly about the entire time next time. So we have a genetic predisposition, again without a clear distinct set of genes, but rather a familial. And that is just a sad reality, right? If you are someone who struggles with fat and you look at your parents or siblings and they do too, this is just going to be something that is more of a struggle. There are of course, dietary influences, and indeed, I would say these are the most relevant. But it perhaps the most succinct way of describing the relevance of diet is that there must be two conditions that are met to promote the storage of fat. You cannot have fat storage with only one of them. You have to have both. And those are elevated insulin and sufficient energy. Now, that latter point, I understand it perhaps comes off as a little vague. So let me explain it in the context of the first point. Sufficient insulin. As I somewhat elaborated on a moment ago, there can. There can literally be no fat storage on a human or any animal unless insulin is elevated. It cannot happen. It is impossible. And unless you think, well, Ben, what about all those other. Maybe a person ate a thousand calories in excess. If insulin is low, the body will compensate for that excess by both increasing its metabolic rate substantially by several hundred calories if insulin is low, and it will start wasting energy from the body in the form of producing ketones. Remember, every ketone has a caloric value roughly comparable to glucose. And when you're in ketosis, you're breathing out those ketones or urinating out the ketones, then if the problem got so bad, then glucose levels get so high that glucose is also spilling out into the urine. So the body has ways to compensate to reconcile this. But again, if insulin is low, there's no potential for fat storage. Now, if insulin is high, there is the signal for fat storage. But insulin itself is not energy. It's not the hydrocarbons that are capable of being stored as fat within the lipid droplet of a fat cell. And that's where the second point comes in. It's one thing to tell the cell to store fat, which is what insulin is doing and why. That is a drum I beat so loudly. A fat cell, like every cell, must be told what to do with the energy that's available to it. Hormones do that, particularly insulin. So again, it's one thing to tell the cell to store fat, but it's another to actually have the hydrocarbons or the calories, to say it another way to actually fuel that storage. And that's where the sufficient energy or sufficient calories comes in. So you must have an insulin stimulus to store the fat and you must have sufficient calories to fuel that storage or provide the bulk of the storage. So those are the dietary influences. And we're going to revisit those ideas in a couple weeks when we talk about the interventions to lose fat and then physical activity. Exercise is generally irrelevant, to be frank. One of my hopefully clever quips is that you eat smart to be lean, but you exercise to be strong. And so there's not really much to say. Studies that have looked only at physical activity find that it it's generally a big failure. And that's in part because if you exercise more, not only are you actually burning a fantastically small amount of calories of energy, but then you also compensate, usually getting a little hungrier the next day or so, maybe not immediately after, within the first few hours, but give it a little time and your hunger will go up. Okay, let that is the lesson. So we went through a few distinct segments, the genetic, environmental factors, and in fact, let me mention one last environmental factor. And this can be a focus because it is a big topic and that is environmental molecules, chemicals, maybe to say it a different way, whether it is from pesticides or whether it is from, from plastics or detergents, there are molecules that do promote fat storage. Case in point, we are just about to publish a paper. This is the work of a graduate student from my lab. We've just finished all the data compilation and analysis and we're just preparing the manuscript. So this is pre published asterisk on what I'm about to say. But we found that animals that were exposed to diesel exhaust particles were a little lighter, total body weight. But when you looked at the amount of fat they had relative to their body weight, it was up. And when you looked at the size of their fat cells, the fat cells were almost twice as large as the control animals that were just breathing room air. And we're not getting daily exposure to diesel exhaust. Well, there's nothing caloric about diesel exhaust. And again, the body weight didn't really change, but the composition did. They were a little scrawnier, but a little fatter. And it was largely through hypertrophy. And that was evident with some other markers that we looked at and looking at the fat cells themselves. So that is part of the environmental influences. So again, the segments in reverse was genetics and environment. We then talked a little bit about the biochemistry and the lipogenesis versus lipolysis, the different types of body fat. And even then at the beginning, some hints of the evolutionary roles or why might the body have been designed to work the way it does? Until next time in the metabolic classroom, Remember, more knowledge, better health. And with that, I'm delighted to transition us into the Q A. Thank you all for joining this live. It is so much fun to have you guys here with me. I just love it and can't thank you enough for your your support here. Please continue to come, bring friends and make sure you've subscribed to the YouTube channel too. If you ever miss one of them live.