Metabolism
Understanding Fat
Why some people gain weight easily while others don't: Understanding genetic setpoints, fat sensing, and the science behind weight control.
Metabolism
Why some people gain weight easily while others don't: Understanding genetic setpoints, fat sensing, and the science behind weight control.
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A sensitive topic today: fat. We're talking about both the fat stored in your body and the fat in your food. ;-) Both can unfortunately make you sick. We could write a 200-page treatise on this subject, but we'll spare you that. There's already plenty discussed in our books and blogs. Today, let's just outline what's important.
First, let's address why overweight develops in the first place (excess energy – often stored as fat). This topic becomes increasingly relevant, as people grow heavier without necessarily understanding why. Of course, this has consequences not just for individual health, but for society and the healthcare system. Since I, Chris, no longer want to hear about "solidarity" and conformism—communism, if you will—let's focus on the individual consequences for now.
This much is certain, even if it stings:
If you gain weight, you're consuming more energy than you burn.
This is insidiously true because you can actually measure it at the cellular level, namely through the mTOR/AMPK ratio. mTOR represents growth, AMPK its opposite. The former is anabolism—building up—the latter catabolism and breakdown. In overweight individuals, energy catabolism isn't working properly; in other words, fat utilization is compromised. This is why the ratio shifts toward mTOR—often accompanied by insulin resistance, fatty liver disease, and much more. As mentioned, this can be measured precisely. But it gets more complex.
But this doesn't explain why someone eats more than they burn. Let's zoom in on the genetic level and mostly exonerate most of us. The fact is: most of us don't intentionally eat more than we need or burn. The doctor's logic typically goes: "Well, Mr. Müller, just ride your bike around the village a bit and it'll sort itself out." But the body, as a biological system, is vastly more complex.
Conversely: many people who "can't gain weight" are genetically—naturally—positioned more toward the AMPK side and have a weight setpoint that will always resist weight gain. In other words: these people simply cannot weigh 130 kg, no matter what.
Such bodies ...
There are countless ways a body can resist weight gain. In people who gain weight quickly, these mechanisms are largely disabled. To be concrete: a body that genetically could easily weigh 130 kg has a very different "room for maneuver" to lose energy—instead, it tends to store and "build up" (mTOR). This point gets overlooked far too quickly in debates. Each of us is individually predisposed to maintain a certain body mass. One person's body fights gaining 10 or 15 kg, another's embraces it gladly. We're simply not all the same—something that actually shows up nicely in statistics, where you could roughly say it splits 50/50.
In recent years, we keep seeing people want to eat ketogenically—fat-based, low-carb—hoping to reprogram their energy metabolism into a "fat burner." Unfortunately true: those who want this are usually furthest from being a fat-burning machine by nature. So you should always be careful whose literature you read. Can that person actually speak for you? If a 60-kg triathlete writes a book about low carb, a 110-kg woman should think very carefully about whether those claims apply to her.
Be that as it may: studies show that overweight people systematically underestimate their calorie intake. Especially important for keto advocates: they eat a low-carb tomato salad and don't realize that two tablespoons of oil plus 100 g of feta cheese is already 400 calories. They rely on their nutrient sensing—their nervous system's assessment of food's calorie content—to tell them when they've eaten enough ("I'm satisfied"). True: a ketogenic diet can help fine-tune this energy- and fat-detection system. But practice shows many people stumble and end up gaining rather than losing weight.
In many people who gain weight quickly, fat calories simply pass by unnoticed. They don't sense that fat even entered their system. Their nutrient sensing doesn't recognize dietary fat properly. Which brings us back to the genetic weight setpoint. Some don't notice how much they're gaining; others cannot eat anything for days after consuming 100 g of dietary fat. What's called fat sensing simply doesn't work right. In most people, this has evolutionary roots.
But who or what dictates fat sensing? Who or what determines how much fat we eat? This can get extremely complex, so let's simplify and discuss one gene variant that's common among us. The gene in question produces the CD36 fat transporter. It's responsible, among other things, for pumping fatty acids into cells and plays a key role in recognizing fats and fatty acids.
Many of us carry a gene variant known as the A-allele under the polymorphism rs1761667. This A-allele reduces the production of this protein, which results in poorer fat sensing per unit of fat. In other words: we become blind(er) to the energy density we're taking in as fat. People carrying this variant need, to put it bluntly, 150 g instead of 100 g of feta cheese to experience a comparable "stop, I've eaten enough" signal.
Here's the good news: this variant may reciprocally coincide with better carbohydrate utilization. In animal models, at least, reducing CD36 has a positive effect on carbohydrate metabolism and protects against atherosclerosis. Such adaptations may have occurred in us Europeans during the Agricultural Revolution a few thousand years ago—alternatively, it's an ancient variant from times when there wasn't much fat to eat (wild animals are, unfortunately, often quite lean). This gene variant may be harmful in the context of a high-fat diet. To be concrete: there are many people, especially in Europe, who because of their poor fat sensing combined with our high-fat Western diet, gain weight quickly.
Without even noticing.
The circle closes when you also understand that these excess fatty acids—as an energy carrier—can directly activate mTOR, paving the way for metabolic syndrome, for example. So there really is such a thing as "eating for your own metabolism"—which is why you should study yourself very carefully. Rather than reading works by people who are genotypically nothing like me.
So what helps? Simple. If my body doesn't notice how many calories—how much energy—I'm actually getting from fat, then I need to ...
actively choose lean turkey sausage instead of regular sausage.
It's really not rocket science. But it's good to understand the mechanisms behind it, because then you intervene more consciously—and that's what this is all about.
