#157 - AMA #22: Losing fat and gaining fat: the lessons of fat flux

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Hey, everyone. Welcome to Ask me anything number 22. AMA number 22. I'm once again joined by Bob Kaplan. In today's episode, we discuss fat flux, which is really technical Speak flow for how fat enters and exits a fat cell, which is exactly what determines how big a fat cell is. And how big a fat cell is is what determines how much fat a person is carrying. So anytime you hear somebody say I want to lose weight, what they're really saying is, I want to lose fat mass. And what that really means is I want my fat cells to be smaller. So if you want to understand how that works, this is an episode that's probably for you. Again, we go into it in a staggering amount of detail. This is accompanied by some slides, so if you're watching this on video, you'll see those. If not, you'll see them in the Show Notes. I recommend checking that out. Also, this video will be available in its entirety to the subscribers in the Show Notes section. If you're not a subscriber but you still want to see part of the video, it's going to be on YouTube, on our YouTube channel. So without further delay, I hope you enjoy AMA number 22.

Are you ready for another ama?

I am. I see the agenda and I'm going to share my concern up front, which is, I think it's a little ambitious. We're going to attempt to cover two topics, frankly, each of which I think is their own ama. So if by the time we get through this, it's so big that it is two AMAs, the person listening will say, what were they talking about? They just covered one topic. So as it stands at this moment, we're going to attempt to get through both. Everything that has to do with fat oxidation and fat flux and all these things you're going to explain in a second. And we're even going to try to tackle the entire topic of nicotine. So let's see if we can do it.

Like, ambitious is the right word, but yeah, let's give it a shot. So the first topic is fat flux, and We, I think a lot of questions come in about this and there's a few variations on a theme. So I'll just, I'll summarize a few of these questions for you. The first question is, why doesn't oxidation of fat necessarily mean you're losing total body fat? If I eat a low carb diet and become a, quote, fat burning machine, end quote, why don't I always lose fat on this diet? Another way of saying this too is the question is, if I'm in ketosis, doesn't it mean I'm burning fat? And just for the record, this question came in from ketogenic man Inside joke.

We get this question in one form or another constantly. So I think that's why we decided to just dedicate an entire segment to this because it's super important and it is confusing. Right? So just to be clear, let's just get the punchline out of the way first. You can absolutely be in ketosis and gain weight. You can absolutely be fat burning machine and still accumulate fat. Let's go one step further and accept the fact that we're going to use a bit of shorthand here, which is gaining weight and gaining fat, we're going to talk about interchangeably. Is that fair? Because, I mean, when people say I want to lose weight, what they really mean is I want to lose fat. When people say I want to gain weight, they usually mean I want to gain muscle. So if we can simplify this a little bit and say that people rarely want to lose muscle and gain fat, I think it helps to think about this kind of like an engineering problem, which is always dangerous in biology because engineering is frankly, cleaner and neater than biology. But I do think that we can simplify this problem without rendering our simplification unhelpful, and in doing so, really start to understand the ins and outs of this. So if we take the example you gave Bob, which is a person who says, hey, I want to lose excess body fat, and the approach I'm taking is a ketogenic diet or some form of low carbohydrate diet, does it guarantee that I'm going to lose weight? Well, again, let's break it down. We already said the first thing is losing weight means losing fat. And now let's break that down one step further. How do you lose fat? So, broadly speaking, there would be two approaches to this. One would be to reduce the total number of fat cells. Another way would be to shrink the fat cells. Now, the former is most typically something that is done with Liposuction. So that's really the way we lose fat cells, is you cut a whole bunch of them out. By the way, there were some interesting studies that were done, oh, a little over a decade ago, one published in the New England Journal of Medicine, that demonstrated that there was a totally different metabolic effect of those two approaches. I don't remember the details of it, but basically, one group lost a significant amount of total body fat having the fat cut out. The other group lost it by a dietary intervention that took the same amount of fat off. So at the end, they both had the same body composition directionally, but one had done it through reducing the number of fat cells. One had done it shrinking the fat cells. Can you guess if there was a difference between them, Bob?

I think there might be, although I'm tipped off because I think it was a New England Journal of Medicine paper.

It was, yeah. Sam Klein was one of the authors. That's right. And, yeah, there's a profound difference. So we should never confuse the metabolic benefits that come from reducing the size of adipose tissue with reducing the amount of it. The former, in the case of liposuction, is really a cosmetic procedure, whereas the latter, of course, has cosmetic benefits, but much more importantly, is a metabolic improvement. Okay, so if you accept everything I just said, then we can simplify this problem into how do you shrink a fat cell? Is that fair?

I think so.

All right, so now let's understand the fat cell, and again, let's go back to how an engineer would think about this. An engineer would think about this by drawing a boundary around this and looking at the boundary conditions and effectively understanding what go and what comes out. Mass cannot be created from nothing, and mass cannot disintegrate into nothing. So if a fat cell gets larger, there is a net accumulation of fat in that cell relative to how much goes out of it. And the converse is true. So, again, silly example, but if you have a room and the room has 100 people in it, and there were people traveling in and out of the room constantly, if you want to understand if that room is increasing or decreasing in the number of people in it, you need to understand at every point for which there's an entry or exit what is happening. And by doing that, you can understand what is the net increase or decrease. And I like to refer to that as flux. And I won't get into why that's. Technically, that's not a perfect definition of flux, but it's sort of the way my brain works is to sort of borrow that term from physics and basically say, look, we're going to talk about this through the lens of fat flux. What is the flux of fatty acid substrate into and out of a fat cell? And can we infer the behavior of that fat cell in response to that? So I guess before I go on, Bob, I just want to make sure. Anything you want to add to that, or does that seem like a reasonable way to go after this?

A couple of things. So you alluded to it that when we talk about weight loss or weight gain or fat loss or fat gain, a lot of times we'll hear about calories in, calories out. Right. The amount of. Basically, if more energy is entering the system than leaving it, the system is getting bigger and vice versa. If more energy is leaving the system than entering it, it's more or less getting smaller. And what you're talking about is at the level of the adipose tissue. So when we're talking about how much fat is going into the adipose tissue and how much is being released and also how much is being trapped, we'll get to. I think that's important. And the second thing, too is I'm glad that you used the word flux, because you have an amazing. I don't know if you mentioned it, but you have an amazing blog post on this topic, which is the lessons of Fatflux. And when we moved your blog posts over to PeterAttiamd.com and I was privileged to adding the header images to the blog posts, and in this case, I took the liberty of. Since you used the word flux, I have a picture of the flux capacitor in the DeLorean, which I'm sure you know that it's what makes time travel possible. We could cover that in another episode. It's also an important concept. But those are a couple things that I would add.

If we didn't understand fat flux, there would be no flux capacitor. And I mean, Marty might still actually be in the future, in the past. I don't even recall both.

Depends on which one you're watching.

Depends on which version. There you go.

Yeah.

Okay, so let's start this discussion with a more technical look at what I'm talking about. And then I'm going to simplify this. So, Bob, you have a great figure of what's actually called white adipose tissue, or wat, and I'll explain what that is in a moment. But if you don't mind, can you just pull it up and share your screen so that I can see it? And everybody viewing this can Also see it?

Yes, it is up.

Okay. A lot going on in this diagram. First, let's start by why this is called white adipose tissue. So tissue makes sense, adipose fat. But why white? Well, white is to contrast it from brown. So when you're talking about fat, you always want to differentiate between WAT and bat. At some point, we will undoubtedly do a lengthy discussion on bat. BAT is very interesting. It is a form of adipose tissue that is not as prevalent as wat, but it has really unique metabolic properties, namely a higher concentration of mitochondria and therefore a much greater metabolic activity. Bob, you and I have spent a ton of time doing our own research on BAT as it pertains to cold adaptation and a whole bunch of other things around that. So let's backburner that, but I think it's worth coming back to in another episode. So what we're focusing on is what most people think of when they think of fat, which is again, if anyone's ever watched surgery on TV or something like that and or had a lipoma yanked out of their arm, you can see it's a glistening yellow, relatively acellular structure. And if you look at it under a microscope, it looks surprisingly simple. So even though, as we now know, white adipose tissue is an endocrine organ, right. It is way more complicated than it looks under a microscope. Under a light microscope, it looks like a bunch of nothing. So what you see here if you look closely is two sides. You have an inside. And I don't mean inside, I mean an inside, like a going into it side. And you have an outside. And again, I don't mean an outside, I mean a going out side. So on the left hand side of this drawing. And by the way, if you're listening to this on audio, I would encourage you to watch it on video or at a minimum, maybe hit pause and now go and look at the show notes where you'll see this diagram. But on the left hand side of this page, you could largely think of this as having two doors. So the upper left door and the lower left door are two ways that the fat cell gets fatter. And on the right hand side of this page, you have the exit door. This is how the fat cell gets skinnier. So let's talk about each of these doors.

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