Transcription
Yep, yep. So it seems, uh, right. I'm a guy with a hammer, and the fat cell is the nail. So I see, I see the relevance of the fat cell when it comes to metabolic health everywhere. You can see its fingerprints, in a way, throughout the body. And I say that, I make that bold statement because I believe the evidence most strongly suggests that the fat cell is the origin of insulin resistance. And that's something, of course, we've touched on to, to varying degrees. And I figured we have just really put the hammer to it this time.
So, uh, the evidence for this, I'll touch on as I discuss it. But briefly, to kind of explain my provocative little title to this tidbit or this, this discussion, the metabolic classroom is that, that it's something I've mentioned before. Fat tissue, what we can pinch and jiggle, can grow through two different mechanisms. It can be that each individual fat cell is getting very big. That is hypertrophy of the fat cell. Or and or, but mostly or, it grows through a mechanism of hyperplasia, where each individual fat cell is getting a little big, but then before it ever gets too big, new fat cells move into the tissue. We literally make new fat cells. That is what hyperplasia means, the synthesis of new cells. So we have either hyperplastic fat growth or we have hypertrophic fat growth. And again, the difference is with hypertrophic, the cell number is set, but each individual cell is getting big. With hyperplastic, there's no set number. There's almost a limitless potential for for making new cells. And because of that, no cell ever needs to get very big because it always has new cells coming in to help carry the load.
Now, to take this view a little further and to now incorporate an analogy. In the case of hypertrophic fat tissue growth, it's like we have a hotel that just reaches a point of no vacancy. There's a finite capacity for fat storage through hypertrophic growth. In contrast, with hyperplastic growth, there's always room. There's always, there's always vacancy. The moment some of the rooms get filled, well, this is a hotel that can simply create new hotel rooms. And so it can continue to hold more and more occupants, or in this case, more and more fat tissue.
Now, there's a lot to talk about, perhaps another time, what it is that's contributing to that fat within the cell. Whether it is the synthesis of new fat from glucose, which happens. Whether it is just pulling in fats from the blood and storing that fat, which also happens. But that is a topic for another time, perhaps. But maybe I'll also add, because there's a lot of uncertainty or question about this, typically in the average person, by the time we finish puberty, our fat cell number is done. Whatever, as we are going through infancy and childhood and puberty, when we finish puberty, which is typically mid to late teens for a girl, in late teens to early 20s for a boy, or I should say woman and man in that case, then fat cell number is done. Because of that, um, not only does that reflect on the importance of of, you know, getting through childhood and puberty well and making it easier or more difficult throughout the rest of that life, um, to a degree, to to have a healthy body weight, but that also means because most people get a set point when they enter adulthood, that means the number of fat cells is set. And thus, most people who are gaining weight are gaining weight through hypertrophy. And the number of people who can go that hyperplastic route is thought to be anywhere from 10 to 15% of obese people. So we have a handful of people that grow through hyperplasia, and then the majority of people who get fat through hypertrophy.
Now, that's all fine and dandy, right? Because the, everyone listening so far, just thinking, well, I don't care about those differences. It's just that I'm getting fat or I'm not. The problem with hypertrophic fat, each does have a problem, mind you. And I guess each has a, a plus. The problem of hypertrophic fat growth is that as each individual fat cell is reaching its maximum dimensions, because there is a point beyond which a cell cannot be healthy, it becomes insulin resistant. So that hypertrophic fat cell, within, in the midst of elevated insulin, insulin is always force-feeding a fat cell to take in more fat. It can't stop that. It doesn't stop that. What the hypertrophic fat cell does, and this is something I'll get to more when we talk about how to know whether your fat cells are too big, is that this fat cell is now no longer listening to insulin telling it to not break down its fat. One of insulin's main effects on a fat cell is not only to stimulate the uptake and storage of fat, but also inhibiting the breakdown of the fat. That latter aspect becomes compromised. So in the hypertrophic fat cell, insulin is trying to inhibit the breakdown of fat, a process called lipolysis. And now this hypertrophic fat cell says to insulin, forget you. You want me to continue to be big? I cannot get bigger. I have to start leaking this fat out. As you are continuing to force-feed me more, I can't stop the force-feeding, but I am going to stop listening to you telling me to keep it in. And now I'm going to start leaking this fat. And that gets to what I'm going to come back to in just a moment, namely the free fatty acids. If someone has free fatty acids circulating in their blood, that has come from fat spills. Now, that stands in contrast to triglycerides. Everyone knows about triglycerides. We've talked about them. Triglycerides are the fat that you're making or you're eating. It's not the fat that your fat cells are releasing. So when the liver is making fat, it's making triglycerides. That's how it is releasing it. When the fat that we from our diet is coming in, it's coming in as triglycerides. So that's the difference if anyone is thinking of those two terms, triglycerides versus free fatty acids, and they don't appreciate the difference, that's the difference, at least in part. Triglycerides are fat that we have made from the liver or we've eaten. And free fatty acids are the fats that we've broken down from our fat cells, or in other words, the fats that come from lipolysis.
So that's the negative of hypertrophic fat growth, or part of it. One other aspect to this is as the fat cell is getting ever bigger, and all of the fat cells in a fat tissue is getting bigger, they're pushing each other further and further away from capillaries, which are the, the thin little blood cell, blood vessels that allow a cell to get its energy in, in exchange, oxygen and carbon dioxide. So a cell must be in very close proximity to a capillary bed. And as, once, as I said, as the, all of the cells are getting bigger, they're pushing each other further and further away. And now that introduces the second problem of a fat cell that's too fat, or in other words, hypertrophic fat cells, is that they become hypoxic. They're getting too far from oxygen. And so they start secreting pro-inflammatory proteins. Part of which will be to increase the blood flow to the area, a process called angiogenesis. So we have here, we have this hypertrophic fat cell that is releasing free fatty acids because it's become insulin resistant. And it's releasing pro-inflammatory proteins because it's become hypoxic. In both instances, the hypertrophic fat cell is just trying to survive. But in so doing, releasing those two molecules, those two, two things, free fatty acids and pro-inflammatory proteins, we've now created a perfect storm for promoting insulin resistance throughout the rest of the body. That's all the negative. Indeed. And something I'll come back to in just a moment.
But the positive of hypertrophic fat growth, when you have a set number of cells, when it comes to fat tissue, is you can only get so fat. Now, that might be a very thin patina. And I'm trying to paint it to be a, maybe a better picture than it is. It's not particularly good news because the person's still fatter than they should be. But it does mean that the average person could never get to five or six hundred pounds, like you see in some ridiculous instances of super morbid obesity. The average person could never get that big because they simply couldn't store that much fat in their fat cells. It's because the fat cells have become insulin resistant and they only grow through hypertrophy, not hyperplasia.
Now, on the other side, with hyperplasia, because each individual fat cell is always small, they stay very insulin sensitive. They never become hypoxic. So that's the positive of hyperplastic fat growth is that they have a higher degree of metabolic health than you would expect. Not to say that they're healthy, but they're healthier than you'd think with regards to insulin resistance. That's the good side. The downside is their potential to get fat is almost limitless. These are the individuals who can become just fantastically overweight and and and continue to just get fatter and fatter.
Now, all that having been said, um, because I've said a lot, let's go back to the fat cell that's too fat. And what, how might someone find that out? Or maybe even, I'll say, um, how it's relevant. Now, I'd already mentioned the fact that insulin inhibits, um, the breakdown of fat. And as a fat cell is getting too big, it stops that process. Well, one of the papers that we'll have a link to is a manuscript called Quantification of Adipose Tissue Insulin Sensitivity. And anyone who has this and wants to follow along, what figure one is showing, for anyone who is able to look, is this really neat curve of basically looking at how much insulin an individual needs to to stop the release of of fats from a fat cell. And basically, if a person is lean and insulin sensitive, it doesn't take a lot of insulin. A little bit of insulin will inhibit the breakdown of fats. But as the person is becoming obese and diabetic and insulin resistant, you need more and more and more insulin in order to shut that lipolysis off. And that, of course, is a reflection or reflected, uh, reflective of the fact that the fat, those fat cells are becoming insulin resistant.
Now, I've kind of alluded to that already. Part of what can make this extra relevant is another study that we'll have a link to. And this is a study, the title is Adipose Insulin Resistance in Normal Weight Women with Polycystic Ovary Syndrome. Polycystic ovary syndrome, or PCOS, is the most common form of infertility in women, affecting more and more women all the time. And we've touched on that a little bit in the, in a, in a previous metabolic classroom. So I won't elaborate on the precise mechanisms whereby insulin is disrupting ovary hormone production. That was a topic at, uh, of another time. Um, but nevertheless, what's so compelling about this study is they characterized these women who had PCOS or who didn't. And they were the same body weight, same age, same waist circumference, same hip circumference. So these were women that they really matched them well. They took gals that, on the surface, they look exactly the same. And so in this, this, a lot of women would be curious about this because they would hear us say, insulin resistance is the fundamental driver of PCOS in almost all instances of it in women. And they would look at themselves and think, well, I don't look any different from my neighbor, and I have PCOS, and she doesn't. Um, so what's the deal? Well, what's so interesting in this study is they looked at a measurement of, um, adipose insulin resistance. And what they do, in fact, the third study that we linked to here is really a study that kind of outlined some of these differences. And maybe I'll come back to that in a minute. And that was the study that the title is Usefulness of Surrogate Markers to Determine Insulin Action in Fat Cells. But back to the study of women with PCOS, because it just represents the, the finesse or the ability of this adipose tissue insulin resistance kind of score or or number, um, to reveal the truth of what's going on at the fat cell. So what's so interesting, uh, as I, as everyone knows, I'm a huge advocate of measuring insulin levels in people as a marker of insulin sensitivity. And what's so, what in this, this is actually evidence that will challenge that. Because this study found that the fasting insulin in these women that were equal in weight and waist circumference and age and everything else, their fasting insulin was not statistically significant in its difference. The, the, the control women had a fasting insulin of 4.7 micro units per mil. That's the predominant US unit. And the PCOS women had a fasting insulin of 6.1, which is right at that, what I typically consider the cap. But I would say that's a good, that's a good number. Um, now, however, so, so fasting insulin is a part of what goes into this formula called Adipo IR. So just to kind of touch on that other study that I mentioned on the surrogate markers to determine insulin action and in fat cells, the Adipo IR, if anyone wants to look that up, um, even now while I'm talking, uh, it's certainly something I'm used to with my students, right? They're always looking to screen. So go ahead, look at your screen. Adipo, Adipo IR. Um, that is this, this marker of insulin resistance at the fat cell. So one, they combine the fasting insulin, although in the Adipo IR formula, they convert it to picomoles. They go to that metric-based system, which despite my affection for the US, I do believe is, is a superior, at least scientific method of measuring. Um, it, uh, nevertheless, that's beside the point. Um, but I love, love America to death. Love it. May it keep my bones until the end of time. So the fasting insulin wasn't different between these gals. But remember, but that's part of the formula, formula that they're looking at. They look at fasting insulin, but they combine that, in this case, they multiply it with the free fatty acid number. They're combining these two aspects. Each, in and of itself, is not enough, um, to to definitively point the finger at adipose tissue or adipocyte insulin resistance. And so it's, it's kind of a clever combination. They're taking the fasting insulin, which is to some degree an indicator of insulin sensitivity in the body, but then they combine it with what insulin is supposed to be doing at the fat cell, namely the release, controlling the release of free fatty acids. And even the free fatty acids in these women, in and of themselves, now both of these numbers, fasting insulin and free fatty acids, were almost statistically significant. Um, not to get into the statistics, but if they had more subjects, it probably would have, if they powered it up, so to speak, the the differences probably would have been statistical. But nevertheless, they weren't. The control women had free fatty acid levels of 0.59 millimole, and the PCOS women had levels of 0.74. But that is where the lack of statistical difference ended. Because when they combined them and figured out the adipose IR, or the Adipo IR, which was defined as picomoles of insulin, so you have to convert the insulin into picomoles, um, in their online calculators to do this, if anyone has these blood tests at home, um, then, then you can do this right now. So take the insulin in picomoles times it by the free fatty acids in millimoles. And the women with PCOS had an adipose IR that was almost double. And that was very highly statistically significant, suggesting this was not a coincidence and reflects a very real difference between these people. So that, that I wanted to highlight that one study because in PCOS, it represents a perfect kind of case study, if you will, or context in which to explore the relevance of the adipose IR.
And then to sum it all up, and then to open up the discussion now, and any questions that I hope people are submitting. The adipose IR score is a way of, maybe admittedly, it's too academic, but it allows someone to get that next level of scrutiny and information in their own body with regards to whether they have insulin resistance at the origins. And so if someone fit the description of say, these gals that were included in the study, by any conventional metric, they are not insulin resistant. If you were to measure their fasting insulin, you're looking at their glucose, and you're doing a HOMA score from those, everything is normal in these women by any metric. But when you get to that next level of finesse or scrutiny and combine the fasting insulin with the free fatty acids, then you see a very different story. The truth of it starts to reveal itself. So for those that are curious, might their insulin resistance just be in its first stages? That first domino is just starting to fall? Because I, of course, I say the fat cells fall first when it comes to insulin resistance. It's the first domino that then bumps into other things. And as that insulin resistance is spreading to the liver, and the muscle, and the pancreatic alpha cells, in the brain, in the blood vessels, that's when you start to have the most obvious problems of of insulin resistance. But for those who want to know it or catch it at its very earliest stages, I think the adipose or Adipo IR score, insulin in picomoles times by free fatty acids in millimoles, that's going to be probably the best way to do that.
Now, for the average person who's not, and certainly the average fella who's not worried about this in the context of of PCOS, here are some numbers that you could go with. If you have an adipose IR or an Adipo IR score of around in the 50s or so, and I would, I would say, although I'm speculating a little bit beyond what the data explicitly show, up into the maybe 70s or 80s, then you're, you're good. Your fat cells are good. If your adipose IR score is now broken into the hundreds, then that's a warning. And that's a sign that your fat cells are, in fact, insulin resistant. And those cutoffs come from that other study that I mentioned, the Usefulness of Surrogate Markers, etc. There you go. That's the discussion. And the more you know, guys. That was awesome. That was a deep one today. Yeah, that was a bit of an intellectual vomit. But it is something, it is something I'm very passionate about. And so my, my, my speed of delivery certainly reflects my passion and maybe my knowledge of the subject where I don't have to hum and ha very much. But I would want anyone to know as they sort of forgive my, my, my rate of speaking, uh, that that my enthusiasm is, is sort of born out of this genuine conviction that the fat cell matters. That we have to look at the fat cell if we really want to understand insulin resistance. And we should care for the fat cell in that regard. We want to make sure that whatever levers we can manipulate to help the fat cells not grow through hypertrophy, then we want to control them. And that's certainly something I can elaborate on. But, but that's, I think it is worthwhile where, where insulin resistance is really, uh, at the heart of so many chronic diseases, what we call the plagues of prosperity. I do think we ought to be scrutinizing the fat cell, um, certainly more than the average person does. And certainly more than just cursing it if it's making our jeans too tight. Yeah.
So I have a question that might, might not fit exactly this topic, but I feel like it does somehow. Years ago, I saw a study where they took women who had liposuction, and they looked at their leptin hormones and their, their ghrelin. I can't remember which one it was, one of the hunger hormones. And they showed that women who had, um, even though they had taken out fat cells, their hormones that should be coming from those fat cells was still the same. So their body didn't recognize, almost, at least with those hormones, that they had lost those fat cells. Yeah.
Oh, I love that you just brought this up. This is something that's been a matter of focus for me. And unfortunately, there are not a lot of clear answers. There's, I only could find one single study that hinted at what I'm going to elaborate on and speculate might be a problem with liposuction. So with liposuction, there are two, two problems. And they are problems. One is that you're taking the best fat, which is subcutaneous fat. You are physically stealing those cells from the body. You're, you're stripping fat cells from the fat tissue. And again, a topic for another time, the difference is between subcutaneous and visceral fat. Subcutaneous is that pinchable, um, jiggable fat that is actually healthy. It's good. Um, and you, you're, that's what you're pulling out of the body. You're never touching the visceral fat that's behind the muscle wall of the abdomen. So you're, one, you're pulling away the healthy fat. And by removing fat cells from the body, you are now placing a larger burden on the remaining fat cells. Because if this is like the average person who cannot just start making new fat cells, they have now, their finite number of fat cells, which is even more finite now, even less than it was before the liposuction, has to carry this greater metabolic burden. Because unless the person is changing their diet, they're going to be just as inclined to store fat as they were before. So I actually could imagine, oh, oh, the study that I found actually, it was, it wasn't liposuction, it was this cryo, whatever. Oh, yeah, cryotherapy, right? Yeah, cryotherapy, where they freeze the fat cells to death. And this was a case report of a man who had had cryotherapy done on his, on his lower abdomen, where most men store most of their fat. And he had killed all those fat cells. But what had started happening is the fat cells right above the ex, the section where they'd killed, started to get fatter and bigger. And so we had this very bizarre method of storing fat. And again, it's because if you haven't changed your diet, just stripping out fat cells isn't going to solve the problem. You're just still going to be trying to store fat. Now, these fat cells are just going to store it in a way that I would argue is even worse. And there's a study out of University of Colorado, and I think Eckel, Eckel was the senior author on the study. They looked at the cardiometabolic outcomes in women who had had liposuction. So these are women who were obese after liposuction. They weren't, they were much less fat than they were before. And conventional thinking, um, would be that although they should be healthier, because we know that body fat is such a driver of disease, and it is, they weren't healthier at all. Blood pressure didn't change, blood lipids didn't change. No single, not a single clinical marker of cardiometabolic health got better. So people need to know if they are sucking out or freezing to death their fat cells, that will not solve any problem other than you can wear those pants you wanted to wear. But you may be doing it at the expense of your overall health. You may actually be making things even, even worse. Fascinating. Yeah, that's really fascinating. Yeah. Wow. So, um, my mother, rich, stop the cryotherapy, dude. I'm going to start it now. You just got to put it on your fat head. That's right.
So I have one more question, if we have time. Yes. Um, you've talked kind of about a threshold before, you know, like, you're, you're saying here where your fat cells can only get too big. Um, does that mean that once you get to a certain weight, as people have become insulin resistant and carb addicted, and we gain weight, are you kind of prone, is your body trying to stay at that weight? Once you lose weight, will you always be fighting against that higher weight?
Yeah, that is such a great question. I really like the question. Um, that is not, unfortunately, too well established. What does, what we know is that people with more fat have larger fat cells. And and and again, that number. And if you have more fat cells, then, uh, you have a greater potential, of course, to be fat, to have more fat and be obese. And so that comes back to my one of my initial points where it is so important to help children and and teens get through those years in a healthy way to help mitigate or help set that number of fat cells and just potentially limit the degree to which they can become, you know, very obese. But yeah, Carly, if someone has had a lot of fat cells, either through genetics or lifestyle, and both of those would be relevant, but I would say genetics is more relevant, um, then they, this is a person who will struggle more with body fat, um, than someone who has simply has fewer fat cells. Now, there are other issues there, including the expression of lipoprotein lipase, which is an enzyme that we spoke about in a previous classroom session. We know that the fat cells from obese people have more lipoprotein lipase. They are, they're literally at each cell, better at taking in and storing fat than the fat cells of a lean individual. Um, but, and we can manipulate that a little bit, but that's part of the genetic aspect of obesity, which is very real. But yeah, Carly, anyway, to answer the question as best I can, if someone has more fat cells and they were overweight and they lose that weight, it just makes it easier for them to gain it back because those fat cells are there. That's another topic, of course, the question of, well, do the fat cells die? Our fat cells are mortal. Fat cells are not immortal. Fat cells have a lifespan of about 10 years in the average person. Um, so as we age, some of those fat cells can be replaced in like a one to one. But as we age, part of, there's a theory that part of the insulin resistance that comes from aging is that we start to run out of fat cells. Is that as we have fat cells dying, whereas we used to replace them, one died, we replaced it with one, now every two or three fat cell deaths results in only one new fat cell taking its place. And so as we age, we actually become less capable at storing fat in our fat tissue like we could before. And then that fewer number of fat cells just means greater hypertrophy of those remaining fat cells. And now the older person has to work a little harder to maintain their insulin sensitivity. But my goodness, we are covering a lot of topics. Really, each one of these things could be its own little classroom.
Yeah, let's, let's take a couple questions from some of our listeners today. From Ayon, who's watching on YouTube, is there a difference in getting back to normal weight and health between people with fat hypertrophy versus hyperplasia?
Um, I don't know. What a great question. I, I would say that, I'll speculate because I don't know of studies that have looked at weight loss in people who are known to have more hypertrophy versus hyperplasia. So I just can't give a definitive answer. I would speculate that because the hypertrophic fat cells are already trying to lose more weight by becoming insulin resistant, they're trying to control their own growth, I would speculate that the person who's fatter because of hypertrophy is going to lose weight more readily than the individual who is fatter due to hyperplasia. Now, there's someone else, someone could hear me say that, I'm already convincing myself that maybe I was wrong. And they would say, well, the insulin resistant person has naturally higher insulin, and they have to work a little harder to bring that down. That's true. But those fat cells are already becoming less responsive or unresponsive to the insulin. So I think that's going to allow them to accelerate through that weight loss a little better than someone who has just hyperplastic fat growth, who will also have elevated insulin. To my knowledge, it is unheard of for someone to be obese, certainly, and not have insulin that is several times higher, um, than what I've been, than than the kind of mid, you know, five to six micro units, which is what I consider to be a normal level.
Okay, we've had a couple of people ask different versions of the same question. Ben, I think, I think a lot of our viewers or our listeners were surprised to hear you say that the number of fat cells are set by the time you finish puberty.
Yeah. Can you just take another second or two and elaborate on that?
Yeah, yeah. So that, so the process of human development is, is really, when it comes to fat cells, it really is this accelerated curve through different periods. Where during infancy, like newborn, it's huge, huge expansion of fat cells. We have a rapid increase. And that's not bad. In fact, I would almost say none of this is inherently bad. Um, so I, it's such a delicate topic, especially the conversation one of the listeners, a parent might have with a child. Um, I don't think these are conversations you can't have with a kid. I think it just has to be that the parents are just changing the culture in the home to try to help the kid without ever actually having the explicit conversation. But I say that as my oldest, as a teen now, just barely. So what the hell do I know, right? Uh, so, um, so you, we do have this curve where a fat cell number is accelerating, accelerating, it's slowing. And then we start to get later through puberty, and it's, it's still going up, but the, the curve is starting to slow. And then, and then truly, when puberty is done, which is not at the time most people think. Most people think that, oh, puberty, you're 12 or 13, and that's it. No, no. Puberty can be a 10-year process, certainly for a boy. Most men don't actually become men and stop being boys until their early 20s. That's why you can have a kid who's 21 and he still grows another two inches. You know, that is a kid who has not done puberty. So we need to expand the window or certainly push back the time where most people think puberty ends. And again, for for girls turning to women, that typically is mid to late teens. And for boys, it's, it's later. It's late teens or early 20s. And, and of course, there's that depends on the inherent differences between individuals. But the moment they're done, that period of growth is over, literally their growth. But that growth is also reflected in the end of fat cell, um, growth by way of hyperplasia. And so the, a person may be thinking, well, then how can I best intervene in my kids to help them to help that? And also help themselves, um, keep those fat cells in check. Insulin pushes fat cells to grow and, and, and even multiply very, very well. And I hate to, um, always be coming back to insulin. Now, that's my other nail that I pound on. But when it comes to fat cells, you cannot understand fat cell physiology outside the context of insulin. Insulin plays an absolute master regulatory role when it comes to fat cell growth. Um, an independent of insulin, seed oil metabolites, linoleic acid metabolites can compromise, um, the, the, it'll alter the way fat cells are growing too. So there's that, um, genetic component. And then I know it's a topic for another time, but even different ethnicities have different variants of genes in their fat cells that will dictate whether they're growing fat through hypertrophy or hyperplasia. So that really starts to explain some of the differences that we even see globally with with trends when it comes to insulin resistance and diabetes.
Yeah, from a coaching perspective, I know we have listeners and viewers today all over the map. We have people that are really sci, other scientists that follow Ben's work, but we also have people that are just new to this space. And so in the end, the bottom line is to control insulin. I mean, isn't that kind of where all roads often lead?
Well, when it comes to the fat cell and, and the cardiometabolic problems that we typically associate with fat, or, in other words, those associated with insulin resistance, to say it another way. Yeah, I, I do think the best bang for the buck is going to be to focus on insulin. Now, I'm being deliberate in how I'm saying that, which is not to say that insulin is the only variable. It is admittedly the nail that I focus on the most, just because there's a scientist, I can't spread myself too thin. But I believe the evidence strongly, um, points a finger at insulin. So if someone, they're feeling overwhelmed, and to varying degrees, we all do, and wondering what can they do to maximize their health and, and the health of their fat cell for themselves and those they love, then I strongly believe it is to folk, control carbs, focus on controlling your insulin. And I mentioned seed oils, and I do think very much strongly that those matter, um, when it comes to even fat cell health and the health of other cells. Um, and mind you, as someone's controlling their carbs, they're typically controlling seed oil consumption as well, because it's, it's those seed oils are kind of baked into all those refined carbs that are coming from bags and boxes with barcodes.