How to increase the feeling of satiety and lose weight (theoretically)?

I can't help myself, I have to theorize. In the previous post, we saw how easy it is to get fat, i.e. in the rat model. We also saw how to achieve weight loss again, feel free to take a look. It all follows from the fact that if we frequently change the macrobiotic ratios of the diet, i.e. the ratio of long-chain fats in relation to carbohydrates plus proteins together, the body cannot respond to the changes and derives the feeling of satiety from how quickly it fills the liver's glycogen reserves. During the entire period of adaptation to the new food composition, the body will overeat. The speed of adaptation of the metabolism to the new composition of the diet depends on the amount of short and medium fats in the food. The more of them the consumed fat contains, the faster the adaptation will take place. The lower will be the risk of overloading fat cells (or rather their poisoning with endotoxin LPS from the digestive system) and their probability of switching to pseudohypoxia.

Over-activated de novo lipogenesis (DNL) causes fat overeating.

A step change to a high-fat diet (HF) induces a peak over-consumption lasting 8 weeks in the absence of short- and medium-chain fats (soybean oil). The milk fat containing them allows for a much shorter adaptation, within one week. But even this short period of overeating is enough to activate pseudohypoxia and inflammation in some fat cells.

Fundamental changes take place already during the first week.

Glycogen stores are replenished by the availability of carbohydrates (CHin) and proteins (PRin) via gluconeogenesis (GNG). They are emptied by hepatic glucose production (HGP), de novo lipogenesis (DNL) and total lack of food, fasting. It is interesting that the control of hepatic glucose production is apparently closely linked to de novo lipogenesis (it is controlled by AMPK phosphorylation), this study shows us a significant correlation, intuition would tell us the opposite dependence, but as DNL increases, so does HGP and glycogen stores are emptying faster. So we are hungry earlier.

Glycogen = CHin + PRin - DNL - HGP

So our goal should be to achieve as much glycogen production as possible while consuming as few calories from food as possible, right? How to optimally achieve this without feeling hungry?

Interestingly, there is no fat in that formula. Is that correct? Theoretically, burning fats with activated omega oxidation can create succinate from dicarboxylic fatty acids, malate from it, oxaloacetate from malate, and glucose from oxaloacetate. But it's quite a bumpy ride after a few days of fasting or using MCT oils. So we will consider this path as negligible. Fat simply does not contribute to glycogen storage.

This suggests to me that limiting dietary fat might have its merits, it might reduce caloric intake without reducing hunger. But if we try it and do not limit the total caloric intake, we will activate DNL by increased consumption of carbohydrates and proteins, so we will not help ourselves at all, the formation of glycogen will be greatly slowed down and we will also prevent the burning of fats in the mitochondria. This will make us overeat. We are not going to burn long saturated fatty acids from our own stores. If we supplement this with omega-6 linoleic acid, we will start the metabolic syndrome in full swing. So let's try it in a different way.

Must not activate DNL, period. So it would be ideal to eat less fat, but keep the same amount of carbohydrates as before. Keep the same DNL activity. That's the same case as with caloric restriction! It should work, and we have studies that show it does. Fats will be replenished from our own reserves in the same amount as they were burned from food until then. But it doesn't work in the long term, it's probably caused by a higher level of insulin than needed, or by a change in the composition of burned fats, as much our own fat as needed is never replenished. Restriction of fat consumption will gradually force us to increase our consumption of carbohydrates and increase the activity of the DNL pathway.

We have to involve a helper, acetate or vinegar.

I would be interested in a study combining caloric restriction performed only by reducing fat consumption combined with vinegar or acetate supplementation. Supplementing with vinegar is easy, just choose foods that contain vinegar or, for example, drink vinegar milk several times a day. I tried mixing approx. 30 g of vinegar (8% acetic acid) with 70 g of milk and adding water to 200 ml. This provides approx. 2.5 g of acetate in one drink and is easy to drink. Four such drinks during the day add about 10 g of acetate, which I think is a suitable dose for AMPK activation, ACC phosphorylation and for suppression of increased DNL activation. Not encouraging, just wondering if it would work. Reduced calorie consumption associated with less hunger. That's what the theory tells me.

What could be the risks associated with vinegar.

I don't know how safe it is. Long-term activation of AMPK may knock out some important anabolic processes, like muscle building, who knows. A study for use as a food additive allows up to 270 mg/kg of body weight. So it allows up to 20 g per day. I don't advise anyone to try it. Just a theory.

Just a theory? When I think of the rice diet of Dr. Kempner, isn't that what it is? Only with the difference that at that time the acetate was probably supplied by intestinal bacteria. That's why it probably wouldn't even work in today's poisonous age, we've almost exterminated intestinal bacteria. His diet was completely fat-free, only unsalted rice, fruit juice and sugar, about 100 g. Sugar without fat works differently, fats carry poisons (LPS, endotoxin) produced by bacteria from sugar in the digestive system into the bloodstream. A completely fat-free diet works completely differently than our normal diet, here sugar helps to activate anabolic processes, i.e. muscle building. I put it here only as an example, I don't know if it is appropriate to follow it.