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Hydrogen Sulfide – Regulator of Gluconeogenesis, Vascular Health, Liver, Muscles, Adipose Tissue, etc.

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We continue with the effects of hydrogen sulfide on enzyme activity. We have already seen that H₂S affects the S-sulfhydration of sirtuins, i.e., the activity of deacetylases that change the activity of many enzymes by preventing their “decoration” with an acetyl group . In the case of sirtuin modification, for example, this facilitates the “decoration” of some enzymes with ubiquinone, which leads to their removal. Or it increases their activity after the removal of acetyl “decoration,” if that decoration interferes with the enzyme’s function. Even at this level, things are already quite complicated. But that’s not all. S-sulfhydration of certain sites can occur on many proteins, not just on sirtuins! Research shows that H₂S also sulfhydrates the enzyme pyruvate carboxylase (PC) and also the key metabolic switch, the enzyme AMPK. That would explain further phenomena observed both in vitro (in the test tube) and in vivo (in whole organisms) related to changes in hydrogen sulfide levels....
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Can Hydrogen Sulfide Protect Beta Cells and Heart Cells in Diabetes and Obesity?

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This is a loose continuation of the previous post about the effects of hydrogen sulfide (H₂S) on cellular metabolism . This time, we will look at a study related to diabetes, focused on the protection of insulin-producing cells—meaning the protection of pancreatic beta cells from high blood glucose levels. We will see that hydrogen sulfide activates the deacetylase SIRT2, improves antioxidant protection via GSH, reduces the level of aldehydes formed by oxidation of polyunsaturated fats in a high-glucose environment through activation of the enzyme ALDH2, and thus acts in a way that makes beta cells more resilient and able to survive even in unfavorable conditions. In the figure, we can actually see everything we need to know. If I were to follow up on the post where I showed that amino acid deficiency activates the enzyme SIRT2 and suppresses the formation of new fats , here we can see the mechanism more precisely. ALDA1  is an activator of the enzyme ALDH2, which removes toxic ald...
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Hydrogen Sulfide as a Metabolic Repairman?

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In the previous post we saw how the restriction of sulfur-containing amino acids works in a mouse model. Restricting them to one-sixth essentially prevents fat formation and storage, and re-supplementation almost immediately starts to restore fat stores again—very interesting. A similar effect is seen with overall protein restriction in the diet, as we have already noted . I was thinking about possible mechanisms and almost forgot about the post where I commented on a study linking the (in)sufficiency of amino acids, the deacetylase SIRT2, and the effects of fructose—specifically the effect of activation of the enzyme KHK, which phosphorylates fructose . The conclusion of that reasoning was that amino acid deficiency activates SIRT2 and thereby limits fat formation. This manifests itself through deacetylation and removal of the enzyme ACSS2, which activates acetate into acetyl-CoA—thus reducing the production of substrates for new fat synthesis. But fructose, via KHK, suppresses SIRT2...
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Do We Get Fat from BCAAs or SAAs? Or from Ammonia?

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In my previous post I showed results of studies on diets restricting certain specific amino acids. Overall, that “divine” construction kit consists of twenty amino acids, twenty building blocks. Some are straight sections, some are bent, some pieces allow flexibility, some allow branching—just like a classic children’s building toy. In the last post we talked about branched-chain amino acids (BCAAs). It seems that restricting them leads to weight loss in mice, but there are still some “bugs.” For example, it doesn’t work in female mice. Females are simply more resistant, and we basically don’t know what is happening in the body. I suggested the idea that since females inherently have a higher percentage of body fat, their fat tissue is more resistant to overload, e.g., when overeating. And BCAA restriction in mice is actually connected with increased food intake. So my conclusion is that the positive results in males are caused by activation of cellular senescence and insulin resistan...
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Restricting Protein or Certain Amino Acids Helps Burn Fat

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Recently, many social media influencers have been focusing on studies that surprisingly show how limiting protein in the diet leads to increased calorie burning, usually compensated by higher carbohydrate or fat intake. This is a very interesting area of research, with many unanswered questions.   The most frequently cited study was conducted on young, lean men. The results were highly surprising, hence the attention.   FGF21 is the primary factor behind the positive effects of restricting protein to around 9% of calories To maintain the same weight, caloric intake had to be significantly increased. This is related to energy expenditure through thermogenesis.  LPHC: Low-protein, high-carb diet; LPHF: Low-protein, high-fat diet;  HPD: Diet with standard protein content Is this practically applicable? Does it carry any risks? These questions still need to be answered. We don’t know. But we have other studies. For example, a recent study linked protein or bran...
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Vinegar/Acetate Protects Your Blood Vessels Activating Antioxidant Protection.

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I’ve discussed the inner lining of blood vessels — the endothelium — several times before. Virtually all studies conclude that oxidative stress causes metabolic and functional changes in these critically important cells that protect your vasculature. We already know that turbulent blood flow in vessel branches and bends triggers oxidative stress . That stress can also cause cellular senescence and reduce adaptability to changing conditions. This impairs oxygen and nutrient delivery and blocks angiogenesis — the formation of new blood vessels. Vasodilation — the ability of vessels to expand based on tissue needs — also stops working. Maintaining functional vascular endothelium is therefore vital. Let’s look at a study that examined endothelial cells in two states: a seemingly quiescent one where cells are just working, and a proliferative one where new blood vessels form. The quiescent state is different from cellular senescence, though they may appear similar. Quiescent endothelial ce...
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Cellular Senescence Arises from Temporary SIRT1 Inactivity During Fat Cell Differentiation

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I found a very interesting study linking the activity of deacetylase SIRT1 to cellular senescence in fat cells. It beautifully connects the effect of acetic acid/acetate in suppressing fat cell senescence and promoting healthy fat storage . Increasingly, we see that phenomena we consider negative are actually highly adaptive responses to specific conditions and are, in fact, beneficial. I’ve previously demonstrated this with insulin resistance . The same applies to weight gain — efficient fat storage is advantageous and does not cause obesity . On the contrary, impaired fat storage leads to weight gain. This results in permanent insulin resistance caused by senescent cells. Surprising, isn’t it? SIRT1 deacetylase protects against cellular senescence in differentiated cells during the differentiation phase. If we accept that occasionally storing energy reserves for periods of scarcity is beneficial, then safely depositing excess available calories into adipose tissue is a vital adaptat...
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