Rethinking Obesity: Time to Stop Blaming Calories

The Midnight Cake Phenomenon. You know that "I shouldn't, I really shouldn't," but you do it anyway feeling. That feeling that you're constantly in battle with yourself. Knowing there's a smart choice, but having a deep unstoppable urge to do the other thing. But now I want to tell you something you may not have thought about. You probably just imagine you're in a fight with your mind, something you may be able to conquer via sheer will. So, There's hope, but what you may not fully realize is you're also in a battle with another part of your body that cannot be conquered by will. It will always eat the metaphorical cake if given the opportunity to do so. Your fat cells. As early as the early 1900s, scientists have proposed, now quoting, that adipose tissue, fat tissue, in individuals predisposed to obesity has an exaggerated tendency to take up and sequester fat. And then downstream of that, After the fact, your mind may follow the fat cell sequestering fat, like a puppy dog following its owner. Bear in mind— and prepare— there's gonna be a lot of analogies in this video. Your mind follows the fat cells, and then your mind drives you to eat more calories. But the inciting event, the etiology, the cause of the plump fat cell is defective fuel partitioning. Now, a new landmark paper in the journal Obesity has compiled an opus entitled Trapped Fat: Obesity Pathogenesis as an Intrinsic Disorder in Metabolic Fuel Partitioning. Let's dig in, but not to the cake. Welcome to my channel, stay curious. Now, after reading this lovely and comprehensive paper, I myself was trapped. I was trapped between a desire to bring you a deep dive into every metabolic model and sub-experiment discussed in this wonderful paper, and keeping things kind of high level so more people could follow along, but with a little bit less of a deep dive. And then my girlfriend decided for me by giving me a swift slap upside the head after I babbled to her about neuron glia cholesterol trafficking for 15 minutes and convinced me to bring you the 50,000-foot view version. So you can thank her for that. What I'm going to do now in this video is explain the 50,000-foot view. Then I'm going to discuss the value of animal models and the practical limitation of human studies. And finally do my best to give you some actionable takeaways. So, the 50,000-foot view. Now for the 50,000-foot view. Calling back to the prior quote, adipose tissue, fat tissue, in individuals predisposed to obesity has an exaggerated tendency to take up and sequester fat. The theory explains obesity as a primary intrinsic disorder that biases fuel partitioning from oxidation, burning, to storage. So reducing circulating fuel availability and oxidation, fuel burning, while increasing body mass. You're not putting logs on the fireplace, you're throwing them into the garage. And this results in a downstream drive to stimulate energy intake, hunger, and reduce energy expenditure as compensatory responses to restore homeostasis. This is the process of obesity development. Now, what is really, really, really— 3 really is enough, let's add 2 more— really, really important here is that the model is consistent with thermodynamics. It's not breaking thermodynamics. It just doesn't assume that the binge drives fat gain per se, but rather that metabolic dysfunction and maladaptive fuel partitioning drives fat into storage, and then downstream you get hungry, and that is when the binge occurs, which actually can perhaps perpetuate a vicious cycle depending on what you're binging on. That binge analogy points me to some lines from the paper that I wanna read, because believe it or not, I'm not trying to troll calories in, calories out. I'm not trying to be troublesome. At least not entirely. I'm trying to be a little bit troublesome. But anyway, I'm going to read this block quote. It's a little bit jargony, so hang in there, and I'm going to explain what I think it means after the fact. So here are the lines: Although excess adiposity may occur with food restriction, such as by pair feeding or even underfeeding relative to controls, the magnitude of fat accumulation will be reduced relative to ad libitum feeding conditions. If the mice have their calories restricted, this observation demonstrates that increased food intake in response downstream to a shift in fuel flux towards storage may facilitate the full manifestation of an obese phenotype, but not that the increased intake constitutes the initiating event. So what they're saying here is, yes, we can manipulate biology such that you have an experimental group and a control group, and the experimental group is fed the same number of calories— that's pair feeding— or even fewer calories, and they still gain more fat. However, in order to fully manifest an obese phenotype, all things being equal, given the experimental group's metabolism, physiology, that group, if they're given access to more calories, it allows them to more fully manifest an obese phenotype. That makes sense, right? If you have mice that you've manipulated their biology such that they're more predisposed to have fat cells that sequester calories, then in that condition, if you give them access to more food, they can potentially gain a lot more weight, right? So it's acknowledging the fact that, yeah, calories do matter in a sense, but what we're talking about here is etiology. What is the cause? So to mix analogies, going back to like fire and logs. What we care about is the match, the match that starts the fire of obesity, rather than the logs tossed on after the fact, which is our food environment. Makes sense? Now I want to talk a bit about the value of animal models and the practical limitations of human studies. A simple heuristic you see all the time is human studies are always better than animal studies. In fact, I have people telling me in the comment section, why do you even do nutritional studies on animals? Because their biology is totally different. That's pretty superficial thinking, if I do say so myself. It's a flawed heuristic. Animal models allow for much better control of intake and behavior and biological manipulations that are just not possible in humans. By contrast, it's really, really hard to control human intake and behavior, especially over the long term. So for example, let's talk about metabolic wards. You can keep people in metabolic wards, but only for a short period of time, really. And that short-term intervention can be deceptive because you can force weight gain with acute overfeeding, but that doesn't say much about the chronic results. Acute doesn't equal chronic. The chronic results that would manifest because you don't allow time for metabolic adaptation and downstream behavioral and metabolic changes. So we turn to animal models, and something to acknowledge is there is a mountain of literature showing even when animals are pair-fed, so the experimental and control group are fed the same number of calories and caloric intake is tightly matched, you can alter physiology to promote more fat gain in a calorie-independent manner. You can induce an obesity phenotype without adding calories or even with fewer calories. Now, the models abound. There are hypothalamic lesion rats, melanocortin receptor knockout rats, leptin-deficient animals, and if you want more on leptin, check out this video, animals treated with various hormones, and so on. It's really easy to dominate calories with physiology. Now, some might push back and say, "Nick, you are cherry-picking models. In this other model, there is more caloric intake associated with obesity and fat gain." To that I say, yes, but the claim is not that increased caloric intake can't occur with obesity and fat gain or downstream of it, but rather the point is to debunk the entrenched myth that calories are driving the car rather than just being the tires taking instructions from the driver. Now I'm gonna turn to actionable takeaways. Actionable takeaways because I'm trying to keep this video pretty concise. I'm gonna present you with two. The first is that realize it's a marathon, not a sprint. I know that's cliché to say, but what I mean is that if your goal is to achieve a healthy metabolism and healthy body composition over the long term, think about factors that will generate favorable fuel partitioning rather than factors that will impact the scale tomorrow morning. And yes, this could mean largely ignoring calories as a choice variable. And instead eating foods like fatty fish, fatty meat, whole eggs, full-fat dairy, extra virgin olive oil, nuts— my favorite are macadamia, you know that— and these foods, they're high calorie, but they tend to associate with better long-term body composition and weight outcomes rather than fat gain. Why? Fuel partitioning. In part, it might have to do with reducing insulin levels that could lead to fat trapping, but really the fuel partitioning model is trying to take a large umbrella approach and go beyond just the carbohydrate insulin model, which is the topic of other videos. Second, I want you to think deeply and challenge respectfully. If you've hung out If you've stuck it out with me to this point in the video, I'm gonna assume I'm preaching to the choir or the converted. So I need your help to induce a cognitive shift in those still imagining that calories are in the driver's seat. Consider, how are you going to make people think deeper, differently about obesity? If you have thoughts, please share them in the comments for my benefit and the benefit of the community. And yes, I do consider this an actionable takeaway because our metabolic health army needs troops, and I'm asking you to be one. To take part and take action for the betterment of science and the metabolic health of the future. Thank you and stay curious.