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And Those Proteins Again — Limit Them or Not?

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Although all nutrition experts keep convincing us that we eat too little protein—because we supposedly need all essential amino acids to build muscle—things may be far more complicated. I’d say this view of metabolism comes from findings based on studying athletes. But I’m definitely not an athlete. I understand that top athletes need to regenerate muscle with enough branched-chain amino acids (BCAAs), for example. However, the general population doesn’t wear down their muscles very much and probably recycles amino acids to a greater extent without needing to supply new ones. Mice in studies are active, but they don’t undergo any special performance training. So they may be a good model for the general population. I’ve already written here about how protein affects mouse longevity . Now let’s discuss one study that examined the short-term effects of lower protein intake on the organism using a mouse model . The study lasted only one week. Yet the changes are very striking. I increasing...
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Is It Good to Block Endogenous Fructose Production?

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In several previous posts I showed how fructose production in the liver affects metabolism through a vicious cycle of obesity . Fructose created from glucose through the polyol pathway in the liver—acts specifically via the enzyme fructokinase (KHK), which activates fructose—affects the acetylation of dozens of other enzymes through sirtuins. This makes fructose the main regulator of hepatic calorie partitioning, determining where excess energy from food is directed: either into liver glycogen or into fat, which is then sent out as VLDL to be processed by the body. In addition to regulating the allocation of calories between immediate use and transformation into fat (for storage or burning in the body), fructose also helps regulate hunger. Blocking hepatic fructokinase makes it impossible to convert calories into fat and increases the storage of excess calories in liver glycogen. A regulatory mechanism via the brain then ensures a lower need to eat and suppresses hunger. Excesses there...
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Is Longevity Related to the Suppression of Endogenous Fructose Production?

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I didn’t even realize that The Vicious Cycle of Obesity could be quite a good explanation for commenting on the results of an interesting longevity study. On X, an innocent question appeared: Quote Someone needs to explain this. "In total, 1224 participants lived to their 100th birthday" Higher levels of total cholesterol and iron and lower levels of glucose, creatinine, uric acid, aspartate aminotransferase, gamma-glutamyl transferase, alkaline phosphatase, lactate dehydrogenase, and total iron-binding capacity were associated with reaching 100 years. End of quote What is the author of the question getting at? At the results of an interesting Swedish study , in which the authors sought to describe and compare the biomarker profiles of people between the ages of 64 and 99 who eventually became centenarians, with their peers who did not reach 100 years of age. They examined how homogeneous the biomarker profiles of centenarians were earlier in life. For this, they used data f...
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Do Omega-3s Really Act Against Omega-6s, or Is It the Effect of Acetate Against Fructose?

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I’ll loosely follow up on an earlier post, where I examined the properties of fructose and acetate and how they act against each other . That post mainly dealt with enzyme acetylation — that is, the change of their “decoration” by an acetyl group. Fructose suppresses the deacetylase SIRT2 and probably also SIRT1. Acetate, on the other hand, activates SIRT1 and possibly SIRT2. Both substances thus act as regulators of the same processes, but in opposite directions. They therefore ensure balance. That’s important, because if there is an excess of one substance, its effect can be compensated by the other; we’re not left without a means of compensation — and that’s crucial. Today I’d like to connect this model with the vicious cycle of obesity , as I described in previous posts. Few people realize that the effect of polyunsaturated oils on metabolism is, in fact, the effect of fructose produced via the polyol pathway in the liver through the presence of aldehydes such as 4-HNE. This is how...
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In Which Organ Does the Vicious Cycle of Obesity Take Place?

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I got a question on X: “In which organ does the vicious cycle of obesity actually take place?” Well, I have to admit, those thoughts came so quickly that I haven’t really reflected on it much yet. The polyol pathway is active in the liver, but I’m not aware of its activity in adipose tissue. Fat synthesis takes place both in the liver and in adipose tissue. So for now, let’s stick with the hypothesis that it’s the liver. We actually have a nice study on a mouse model where they tested the knockout of fructokinase (KHK, the enzyme that activates fructose) both globally in the organism and separately in the digestive tract or in the liver. The results are very interesting. Turning off fructose processing in the digestive tract prevents fructose from entering the body fairly well; it also seems to suppress the craving for sweets and reduces the consumption of sweetened water. But it does not prevent metabolic syndrome or weight gain in any way. The result is fatty liver and obesity. Ther...
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The Vicious Cycle Causing Obesity

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I need to slow down a bit and explain in detail the obesity model I condensed into the schematic image in the previous post. Even such a guru of linoleic acid toxicity as Tucker Goodrich apparently didn’t fully understand how it works. So, from the beginning — slowly. Here’s the diagram. Where to start — from the end? This is a model of obesity development. The base image comes from a study on mouse obesity . At the end, there’s a large “WG,” meaning weight gain. The entire lower half explains that the main activator of all three processes required for storing calories as fat is hydrogen peroxide (H₂O₂). It’s not uric acid — that was tested with negative results. The activator is specifically H₂O₂ produced by the enzyme xanthine oxidase (XO), which is part of the purine degradation pathway leading to uric acid. This brings us to the vicious cycle shown in the upper half of the diagram. Here we have three inputs: a high-fat diet (HFD), meaning dietary fats; then glucose — specifically c...
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Water, Salt, and the Polyol Pathway — AR as a Villain or Protector?

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In one earlier post, I briefly mentioned the work of Dr. Rick Johnson regarding the effects of fructose , where he also discussed the impact of high salt concentration and the problems caused by restricted water intake. Both create osmotic stress, which results in activation of the polyol pathway. Let’s explore the mechanism that might reveal some ways to improve the situation—or at least guide us on what to avoid. Let’s first see what happens when the enzyme KHK is knocked out , the enzyme responsible for phosphorylating (activating) fructose. In mice, we saw that eliminating KHK activation (KHK KO) strongly suppresses the effects of both endogenous fructose (produced in the liver from glucose) and dietary fructose . So what happens when water intake is restricted? Does it activate the polyol pathway? Can KHK knockout prevent that? Shutting down fructose metabolism (KHK-KO) has no effect on fructose levels in the hypothalamus during water restriction (WR). Is dietary fructose responsi...
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