48: Strategies for Fat Burning with Dr. Ben Bikman

Hello and welcome to this week's episode of the Metabolic Classroom. I am Professor Ben Bickman, biomedical scientist in all things metabolism and professor of cell biology. One of my great pleasures is to explicitly study fat tissue. I am a fat scientist. That is one of the cell types that I explore the most, whether it's cells, fat cells growing in my lab in the petri dish, or. Or whether we are taking biopsies of fat from humans to study how fat tissue works, the dynamics. Now, we have been exploring several aspects of fat tissue. Today is the happy ending. In the past, we've been talking about some of the endocrinology of adipose tissue. So what are the hormones that come from it? We've been talking about some of the drugs that influence it. And we're going to revisit this a little bit. We've been talking about sex specific effects and how fat cells grow and even how they shrink. And we're going to revisit some of how they shrink today because the topic for today is strategies for fat loss. And there is a lot to unpack here. So let's see what we can do in the time that we have. I never like for these to be too long. I'm sure you feel the same way. After all, most students do. So the first topic, or to provide a bit of an overview first, I want to cover, once again, touch on drugs, but that was explicitly a topic in a previous metabolic classroom. So please go back and watch that entire lecture for more of those details that I won't go into now. So we're just going to lightly revisit drugs with a particular mention on GLP1 agonists, just because those are so popular right now. Then we're going to go into surgical intervention, which is not something I speak about very much, but there's some really neat things to teach you about with regards to bariatric surgeries and liposuction surgery, and then lastly, lifestyle, which of course is a very big topic that is the elephant in the room. There can be no understanding of strategies or really appreciating the key strategy for fat loss if you do not discuss lifestyle interventions, particularly of course, nutrition. So let's get started for the first part, first section of this discussion and very briefly, because again, we've discussed this at much greater length earlier. Drugs for fat loss, and specifically the GLP1 agonists. These are going to encompass virtually any drug where the. The suffix of the name of the drug is lutide, like semaglutide or liraglutide indeed, semaglutide being the most common. That's the one that is in the very, very popular Wovian Oic and used in other ones as well. And they have different trade names even, that continue to kind of stack onto the complexity. So there's a lot of different ways you can call this the main mechanism of drug of action, rather, for the GLP1 agonists, is the redu, the reduction in cravings. Now, remember, remember being me saying that because you watched it before, the earliest use of the GLP1 agonists was used at a much lower dose than is commonly used now. And this was a dose that was effective at inhibiting glucagon, insulin's opposite. Whereas insulin seeks to reduce blood glucose, glucagon seeks to increase it. And it's in fact a hormone that Most diabetics, type 1 and type 2, struggle with. In other words, diabetes is just as often a disease of too much glucagon as it is a disease of too little or not functioning insulin in the case of type 1 or type 2, respectively. So at the lower doses, GLP1 agonist drugs worked by reducing glucagon and thereby improving diabetes. And then at these higher doses, the famous mechanism of action now is that food is moving much more slowly through the intestines. So whereas in the untreated individual, they eat a meal and the food sits in their stomach for, say, three to four hours or so before, you know, getting mulched around before moving down further into the small intestine for digestion and absorption. The food may sit in the stomach for up to 24 hours or something, a much, much longer time. And because of that, you just don't want to eat. So it really starts reducing cravings. Now, one interesting note that I did not discuss before is that one of the common side effects of these drugs and is sexual dysfunction or a loss of libido. So when cravings are reduced, it goes beyond just the cravings of what you're going to eat. So that's just something to consider. And again, they do work. No doubt about it, by stopping eating, you will lose weight. As I elaborated earlier, however, up to 40% of that weight loss can come from lean mass. And then if the day should ever arrive that a person decides to get off the drug, they will regain their fat mass very easily. But the ability to regain that lean mass that they've lost is really going to be dependent on a lot of variables, particularly age. And if we're talking about someone who's a little past middle age. Good luck gaining that lean mass back. It's going to be very, very difficult, if possible at all. All right, so that's what we'll discover for that's what we'll discuss with regards to drugs. Now let's move on to surgeries. Weight loss or metabolic surgeries, as it's some commonly called, is something I've been very interested in for a while and in fact, ever since my dissertation work, indeed my dissertation was based on exploring some of the changes in insulin sensitivity and inflammatory status in people post gastric bypass. So the first subtopic within the surgeries here that we're going to discuss is the bariatric surgeries. And there are a handful of options here, and I want to highlight the main four. So the four key bariatric surgeries, again, sometimes called weight, sometimes called metabolic surgeries. The first one is the most famous, the longest running one, which is the roux en Y. Roux en Y from some French terms, gastric bypass, the letter Y is a term because of how the intestines actually end up looking. So the ultimate procedure is that you take the stomach, which normally is a big, you know, bulbous thing that is capable of incredible distension, which then sort of connects down, not sort of connects down in further into the small intestine. The first part of the small intestine called the duodenum. And what happens is that they go up, the surgeon will come up and cut out almost all of the stomach. And so that what is left as the, as the food is coming down the throat, the esophagus, the food just has access to a small little pouch. So there is only a pouch of a stomach left. And then as I said, normally the stomach feeds right into the, into the duodenum. However, what's happened is that further down the duodenum, it's been cut and, and then the new cut has been brought up and inserted into the pouch. So you are bypassing the stomach and the first part of the duodenum. Now that matters because the duodenum is really where the rubber meets the road when it comes to digestion. That's where you have the input of all of these pancreatic enzymes, all of these proteins that are going to break down your food. Bile acids are coming in at the top part at the duodenum. So you end up bypassing all of those things as well. As a result, the person with the smaller stomach, they're eating much less than they were before. So it's basically leading into this chronic state of fasting. And even what they do eat, because of the bypass of the duodenum, or at least the first part of the duodenum, they don't even digest it as well. And so they're eating much less. They have compromised digestion. And if you can't digest your food very, very well, then you can't absorb it. So it's essentially creating like a forced fast. That's essentially how the Roux en y gastric bypass works. Now, of course, you can imagine there are consequences to this, indeed, a lot of them. The obvious one being the poor nutrition, require, absolutely requiring supplementation. There are some things that you simply now cannot get, like vitamin B12, for example. So there are some. This becomes a lifelong supplementation, and in some instances, indeed, direct vitamin injections that a person has to get in order to prevent serious nutritional deficiencies. But it works. The person will lose substantial weight. Now, one of the problems, however, with the intestines is that they are a very dynamic tissue. It's very possible for a person to lose all that weight, but then slowly start eating more and more and more and more, pushing that little stomach pouch and growing it into something slowly bigger. Now, you'll never regain the first part of the duodenum, so the person will always have some compromised digestion. And in fact, that itself causes problems like diarrhea. But even still, the person can begin to eat a lot more, and thus it is possible to gain that weight back because the person begins eating again as much as they were before. All right, that's the most famous one, the Roux en y. Now, the other one, the next one is increasingly common, which is laparoscopic adjustable gastric banding. In this case, there is no actual snipping and cutting of the intestines. What the surgeon does is come in where the esophagus comes down and meets the big bulbous stomach. They actually just put a little pinched band around the top part of the stomach, basically pinching off, not totally off, but narrowing off a small pouch. So kind of artificially officially creating a small pouch by again putting this band on, that will kind of narrow it up. So as you're eating food, it starts to fill this little fake stomach pouch very quickly. But then eventually the food does go through that narrowed pinched band. That's where the band comes in, narrowing, pinching the stomach. It will move down, go into the rest of the stomach, and then move through an unaltered duodenum for eventual complete digestion and absorption. But because of that pinched off stomach. The person, of course, does eat a lot less because it's going to be very, very uncomfortable. You're going to feel that food literally pushing down at the bottom of your esophagus if you eat too much. And so this forces a controlled appetite. And of course, because you aren't cutting apart the intestines, there are far fewer complications to this compared to rou en y gastric bypass, but it's also less effective. Next, we have laparoscopic sleeve gastrectomy. And in this case, the sleeve term ends up really explaining what has happened here. As I elaborated earlier, the stomach is like this big kind of bulging sac. And what happens is they essentially cut off the stomach that is bulging out and make the stomach into a tube, or it looks like a little banana, essentially. So the esophagus is a tube that's coming down. Normally it reaches the stomach and things bulge out a lot, and then it narrows again to come back into the duodenum of the small intestine. Essentially, it turns it into just one tube, all the way down. And that means food isn't able to churn and get worked around a lot in the stomach. And so you lose out on a lot of digestion, and the food just passes through very quickly. So the likelihood of diarrhea goes way up. But also there is compromised digestion, which you eat much, much less. So once again, through this forced fasting, you are going to get some weight loss and indeed, substantial weight loss. And it. While of course, this is much less complex than the roux en y gastric bypass, there is still a lot of consequences, and there always is. Anytime you start cutting the stomach apart, it's just the likelihood of infection and leaking just really starts to skyrocket. All right, now, the last one is kind of a hybrid of the first one, the roux en y gastric bypass, because you are bypassing part of the small intestine, the duodenum. Remember, that matters because that's where most digestion occurs. If you bypass the duodenum, you are not going to break down food very well. And if you don't break down the food to its smallest molecular parts, then you can't absorb it, so you're not getting it and the food just passes through you. Now, so the last one, it's this hybrid, as I said, of the bypassing the duodenum and the sleeve. So this is called the biliopancreatic diversion with the duodenal switch. So this is like you are creating the sleeve in the stomach, making it just a tube like a banana. And then you are also cutting at the duodenum and connecting that up to that new banana shaped stomach. So it is, like I said, a bit of a hybrid of the sleeve and the bypass. Naturally, you're going to be eating less because of this, because you physically can't hold it in your stomach and the food is moving through very, very rapidly, again increasing the likelihood of diarrhea, but meaning that you're not mulching and chumming the food around, because that's what the stomach is so good for. In part, it has actually more roles than that, but it takes the food and it's churning it and churning it and helping it be ready to hit those digestive enzymes in the duodenum once the food leaves the stomach. And I'm saying food, but the actual technical term is chyme. C H Y M e chyme. That's the term for the churned, broken up food as it's been sitting in the stomach getting worked around. All right, that is all of the bariatric surgeries or the so called metabolic surgeries. All of them result in substantial weight gain, although it depends somewhat on the procedure itself. The weight gain can be regained as the person pushes and forces the stomach to grow larger and larger if they haven't learned the substantial discipline that comes with just eating less. And there are complications from the surgery itself anytime with all pretty much but the banding, the adjustable banding where you're not actually cutting into the intestines. Now let's move to liposuction. Liposuction is interesting and I enjoy talking about it because it forces us to remember the actual problem when it comes to storing too much fat. You will recall from previous metabolic classrooms and because you are such studious students that when I talked about the problem of fat before, I emphasized that the problem is not one of fat mass. In other words, it does not matter how much fat you have on your body. What matters is the size of each fat cell. That's not the same thing. Right? As we've talked before about this, people can gain weight through two different processes. And we've talked about this a lot the last two episodes. Hypertrophy versus hyperplasia. If someone genetically has the ability to continue to make more fat cells, then even though they will have more fat cells, all of the fat cells are going to be quite modest in size. And because the fat cells are small, the person ends up being metabolically sound. They don't have insulin resistance. And the complications that come with it although this is relatively uncommon, most common is that a person has fat growth through hypertrophy, which is a state where the number of fat cells stays static, but the size of the fat cell is growing, and that's what matters. Now with all of that in mind, that primer reminder, think about what happens with liposuction. And one other point, actually, when someone is undergoing liposuction, where are we sucking the fat from? There are two main storage depots of fat in the human subcutaneous fat, which is the fat stored beneath the skin, and visceral fat, which is the fat that is deeper within the abdomen behind this wall of what we call the parasite peritoneal cavity. It's literally walled off in that part of the body. And, and this fat is the fat surrounding the intestines, surrounding the kidneys, worked through all of these around all of these tissues. Generally that's visceral and that's the fat that is generally more problematic and generally grows more through hypertrophy and generally has more pro inflammatory macrophages surrounding it. So very much a greater contributor to cardiometabolic risk than subcutaneous fat. Now back to my question that I posed a moment ago. Where do we take the fat from? With liposuction, are we cutting in through the peritoneum to suck out the visceral fat, or are we just cutting through the skin and sucking out the subcutaneous fat? Yes, of course we are taking the subcutaneous fat. Remember, that's not a bad fat, that's generally a hyperplasia fat. So generally smaller fat cells that are releasing more favorable hormones, all of which we discussed in last episode. So liposuction is typically performed on areas under the skin, like the stomach. So the belly, thighs, buttocks and upper arm, those are the general areas or lower back. But all of it is subcutaneous. Now it's no surprise that after someone has undergone liposuction, they have less fat on their body. So you could have someone who had 30% body fat and then one hour later they now have, or a couple hours later they now have 20% body fat, or 20 some percent, 22, 23%. That is a substantial loss of body fat. But how did they lose that fat? Remember, if big fat cells are the problem, then the solution is shrinking your fat cells. The solution is not removing fat cells. But that's exactly what's happened. In fact, you've removed the fat cells from the worst possible place, namely the subcutaneous fat depot, the healthy place. And so it's no surprise the body in all of its wisdom thinks if this body, if you continue to eat the same way you did before that, put all of that fat on your body. So however you were eating that, put those 50 pounds of fat on your body, your body still wants to store that much energy. But if you have gone in and removed 40% of all of your fat cells, that's way too high. 20% of all of your fat cells, that simply now means that the remaining fat cells are forced to store more of that energy where your body wanted to be, storing a certain mass of fat or amount of energy because of how you were eating, spiking insulin and providing sufficient energy to fuel the growth of the fat that insulin is signaling. Those are the two variables. Again, listen to the previous episodes for more detail on that. Then it's no that the rebound effect is that as a person regains the weight, they regain it in the areas where they didn't strip out their fat cells. Because you're not going to just start making new fat cells, you're going to store, you're going to force those remaining fat cells to store more fat, thus promoting hypertrophy. So while the short term benefit appears obvious, namely the weight loss, it's no surprise that there is no benefit in cardiometabolic outcomes. Even though the person has lost a substantial amount of fat, they lost it the way, remember, you want to shrink your fat cells, not destroy or suck out your fat cells, because it's the size of the fat cells that matter. And so the person inadvertently ends up putting this upward pressure on the remaining fat cells, placing this, if you will, a metabolic, a greater metabolic burden on the remaining fat cells. They have to now carry more energy, in other words, undergo hypertrophy. And the result of that being that they become insulin resistant and pro inflammatory. And so if you have a woman undergoes lipo liposuction to suck out butt from fat from her buttocks or hips, no surprise that she'll start to store more on her belly and even in her visceral fat depot, especially that visceral fat, because that's not one you can touch. You cannot go in and suck that out. So liposuction is absolutely something to be done almost purely for vanity's sake, because it's not going to improve metabolic outcomes. All right, so that so far has been a discussion of drugs lightly and then more of a discussion on surgeries, the bariatric surgeries and liposuction. Let's move now into the big part which is the lifestyle changes, exercise and nutrition, and then a little bit of tidbit at the end, some extras at the end with regards to lifestyle. So, firstly, exercise. My mantra when it comes to exercise and weight loss is that you exercise to be healthy or strong, and then you eat smart to be lean. You don't exercise to be lean. If one of the reasons you are exercising is to get thin, you're doing it for the wrong reason. Now, I don't want you to stop exercising, but that's not what exercise is good for. Even the American College of Sports Medicine, one of the leading authorities on exercise, has stated, probably reluctantly, that there's really no evidence that suggests exercise alone is effective for weight loss. You just can't really move the needle much. Now, it might help a little, and there's a little evidence to show that minute for minute, visceral fat is more affected, that that is the fat that you're going to burn a little more relative to subcutaneous fat. And that could be because visceral fat is more responsive to epinephrine. Epinephrine is one of the stress hormones, and one of its many effects is to stimulate lipolysis or fat breakdown in order to be burned by the body. Well, again, visceral fat is more sensitive to epinephrine, and so a little bump in epinephrine is going to have a relatively greater effect on the visceral fat. So in that sense, exercise may help, but on average, you exercise to be strong and you eat smart to be lean. And by lean, I mean shrinking fat cells. So that then takes us to nutrition. Now, again, this is something we've talked more about in previous episodes, and what I always want to highlight with nutrition is the fact that too many people get it wrong. So remember, the journey is shrinking fat cells. And a person can start this fat cell shrinking journey with one of two steps, cutting calories or lowering insulin. Now, most often, of course, people just take the cutting calories step. And the problem with that is, if you begin immediately reducing energy intake, but you haven't addressed your elevated insulin, you are going to put your body into this state of relative energy deficiency. Now, what I mean by that is, and this has been validated by studies including those by David Ludwig at Harvard, and he's done this really well. His group explored the total energy available in the blood. And by that I mean they actually measured all of the calories and nutrients in the form of nutrients in the blood and found that when diets were increasing insulin, the total energy Availability in the blood was down because energy, because insulin wants to promote the storage of energy. So if you start eating less but your. Your insulin is still high, your result, this is leading to a general reduction amount of energy available in the blood. And the brain senses this. The brain senses this low energy because it's not like the fat cells. It can't store hundreds of thousands of calories. The brain has to, with its very high metabolic rate, needs to almost constantly be relying on the energy that's available in the blood. So the brain is very sensitive to energy changes or the energy status available in the blood. So if energy coming in goes down or, or the person's cutting calories, but they haven't really addressed their high insulin yet, then they're going to get hungry. So again, if the first step of the fat cell shrinking journey is cutting calories, hunger will win. This is why you never see a reunion tour of the Biggest Loser game show. You will never see those people on a stage again because they've gained it all back. And in many instances, they've gone even beyond where they were before. Because hunger always wins. If your strategy is based on cutting calories without addressing insulin. Now, I'm not saying calories don't matter. In fact, I'll revisit that in just a moment. But there's an order to this that is much more scientifically supported. So rather than the first step being cutting calories, keep that foot in place for now on this fat cell shrinking journey along this pathway, the first step needs to be lowering insulin. Lowering insulin creates a metabolically advantageous milieu within the body. When insulin goes down, metabolic rate will go up substantially, even up to 300 calories higher. That's a pretty meaningful amount. And you also begin creating ketones. Ketones are simply products of fat burning. And that's what happens when insulin is down. Remember, the human metabolism engine is a hybrid. It's burning glucose. If insulin is elevated, or if insulin's down, the metabolic engine is burning fat. Well, if insulin stays down for an extended period of time, you're burning so much fat that you almost are burning too much in the liver. And then the liver begins creating ketones from all of this excess. And the interesting thing about ketones is ketones have a caloric value roughly comparable to glucose. And when a person's making ketones, they begin excreting them in their breath and in their urine. These are calories that are just being eliminated from the body. So that is the metabolic advantage that comes with a low insulin state. And at the same time, because insulin is low, the body is releasing this energy into the blood. The total energy available in the blood is higher. And so the brain is sensing this feast and thus says we don't need to eat. And so it's no surprise that when someone is controlling their insulin, they don't need to worry about cutting food out, cutting calories, because they begin to control their appetite. This has been shown pretty consistently in human studies that put people into two groups. The low carb ketogenic group tends to control calories on its own, even though that group is often calorie, unrestricted. In handful of studies they've done this, they will take a low fat, low calorie diet and compare it to a low carb calorie, unrestricted diet. And these people begin just controlling calories on their own. They just have this improved satiety that matters. So hunger begins to be controlled a little better. And it could be because the brain is sensing all of this energy, all of these ketones in the blood, all of this gluc, this, you know, adequate glucose, the free fatty acids, the brain is sensing all of this and thus saying to the rest of the body, hey, we obviously are in a feasted state, we don't need to eat at the moment. So hunger is just generally better controlled. Now, with that first step, the low insulin step, the person's going to get pretty far. That's going to be a big step that takes them very far down this pathway of the fat cell shrinking path. And you do this by controlling carbohydrates, prioritizing protein, and not fearing fat, indeed not fearing the fat that comes with the protein by control carbs. I to elaborate on that a little further, it's basically this, my call is to be wary of the carbs that come in bags and boxes with barcodes. If you're eating whole fruits and vegetables, not drinking them, but eating them, I submit that you're generally going to be doing very, very well and then focus more on protein and fat, because those are going to be the macronutrients that have little to no effect on your insulin. And thus insulin stays down, metabolic rate stays up, and energy mobilization continues. So you just keep moving your energy, you're breaking down all of your stored energy, all to be burned. So again, reducing insulin is all about managing macros. Control carbohydrates, prioritize protein, don't fear fat. Now after you have done that, and that has taken you very far down this pathway, don't forget you had that other step you could take, which is the controlling calories step, the best way then if you feel like you need to, to get a little further on that journey, because energy matters. But I submit not as much as controlling insulin. But if you want to take that step to control calories, then you adopt the fourth part of this after you've managed your macros, which is frequently fasting. But just remember how you end a fast matters more than how long you fast. Okay, now I've gone a little long on that, but it's worth, it was worth elaborating. So hopefully some of that is very memorable and you're able to incorporate it. Now, as a final point, I wanted to mention some kind of alternate methods here which I believe contribute to fat loss, but there's not, not a lot of data to overtly support that claim. So I'm being a little cautious about it. And that is temperature changes or contrasting therapies, sauna or cold plunge. Each of them is obviously going to increase metabolic rate. One note. And with the cold plunge, it's obvious you are shivering and shivering is going to increase metabolic rate, all those muscle spasms. But at the same time you increase your metabolic rate, particularly from your brown fat, which is something we've spoken about in previous episodes, that is a high metabolic rate fat, which exists primarily to keep you warm, so it stokes up the furnaces in order in increasing your metabolic rate, all in an effort to help maintain body temperature. And then with sauna, one of the interesting things about sauna is just the very act of sweating requires energy. Every probably 10 drops of sweat is about a calorie of energy spent. So the very process of pushing water from your blood out to your skin to evaporate or drip off you as sweat requires energy. And additionally, while you're sitting in the sauna, your heart rate is spiking up to 120 or 130, you are getting a little bit of a workout. Now, there's abundant evidence to show the cardiovascular benefits of sauna. But again, where I am being a little more careful is the fat loss claims. So in the absence of really well done studies, I can just suspect, which I do, I suspect that sauna and cold plunge are also really going to help with weight loss, but they have to be something that are adding on for really moving the fat loss needle. This is something that's going to be kind of in the extras area, that the absolute largest, most relevant variable for fat loss is diet. And remember, remember, take the low insulin step first, then worry about the controlling. Often the controlling calories will take care of themselves. But if you find that you need to go a little further on that fat cell shrinking journey, then you take the controlling calorie step by incorporating structured fasts. By structured, I mean you have a clear plan of what you're going to eat, how much you're going to eat after the fast ends. Lest you fall into this pattern of a kind of bizarre form of binging and purging, where you're fasting and feasting and making yourself sick and then fasting again. That's not a good way to do it, but it matters. So, in conclusion, the reason I focus on this is because, and indeed a lot of this, a lot of these ideas are going to be expressed in this next book of how not to get sick. Really diving down into the science behind shrinking fat cells, because that is the priority. It seems obvious, right? You think I need to lose weight to improve my metabolic health. But. But when we say lose weight, we need to think of it the right way. We're not killing fat cells. We're not freezing them off. We're not sucking them out. We are shrinking them. And you do this by lowering insulin and then adjusting energy accordingly. All right, thank you, guys. Until next time, from the metabolic classroom, remember, more knowledge, better health. I'm your teacher, Professor Ben Bickman. I will see you next time.