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Can the liver be saved by blocking AR?

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What is AR? It is the enzyme aldose reductase. An enzyme that processes excessive cytosolic glucose into sorbitol. Before we look at a study involving AR , let us first look at what is required for fat formation in the liver. Also see an older post on the same topic. In the first study, we see that activation of the enzyme SCD1 is required for fat storage in the liver. Without it, this cannot occur. This enzyme desaturates longer saturated fats, namely palmitic acid and stearic acid, into monounsaturated fatty acids. Since palmitic acid C16:0 is formed mainly by de novo lipogenesis from acetyl-CoA molecules, it is at the same time rapidly elongated to stearic acid C18:0 and further desaturated by the enzyme SCD1 to oleic acid C18:1. Perhaps it is not so much about the desaturating enzyme SCD1 itself, but rather about the presence of oleic acid C18:1. This fatty acid is absolutely essential for fat storage in triglycerides. So essential that shutting down desaturation prevents fat stor...
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Are plant seed oils a medicine or a poison?

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It is strange. Mechanistically, it is clear that dietary linoleic acid is associated with increased oxidative stress and odd auto-oxidation products such as 4-HNE, which is a molecule that binds to enzymes in a way that prevents them from functioning properly . It even prevents its own removal, so its concentration increases, and it should be easy to arrange a simple experiment: give one group of people more linoleic acid in the diet than the control group receives, and the result should be a clear difference. But that is not how it works. Thus, for example, when Tucker Goodrich, a well-known blogger and proponent of the theory about the harmfulness of linoleic acid, is asked on the X network to support with a human study that linoleic acid causes inflammation, he presents a study with this conclusion : "Our meta-analysis suggested that increasing dietary LA intake does not have a significant effect on the blood concentrations of inflammatory markers. However, the extent of chang...
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Is Alcoholic Liver Damage Really Caused by Alcohol?

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Once again, I deliberately chose a provocative question for the title. It concerns the harmfulness of alcohol—specifically, ethanol itself. Do not understand this as me defending excessive or habitual alcohol consumption. No, alcohol consumption is addictive. But research conducted some time ago suggested that alcohol in small amounts might actually be beneficial, whereas now it is claimed that any amount of alcohol is harmful, even very small amounts. And that does not seem very likely to me, if I consider that alcohol can help activate the enzyme ALDH2, which appears to be very important for the detoxification of aldehydes derived from polyunsaturated oils, such as 4-HNE. Why am I asking this question? Think about it! What if there existed some dietary component that could suppress or even repair liver damage during alcohol consumption. Wouldn’t that imply that the liver is being damaged by some other substance? It could not be alcohol itself! With this, I loosely follow up on a prev...
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Can glycine help extend lifespan or make you younger?

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A slightly provocative question, right? But why not try to look for answers even to questions like this. We will look at two studies on aging and lifespan related to glycine. The first study directly shows in mice that administering glycine (8% by weight) in the diet starting at 9 months of age extends lifespan in male mice by approximately 6%, and in females slightly less, by 4%. The study was conducted at three different sites using specially crossbred genetically heterogeneous mice. Lifespan extension was consistent and statistically significant at all sites. Alongside the glycine test, other interventions were also tested at one site (aspirin at two concentrations, inulin, TM5441), but these did not demonstrate lifespan extension. The credibility of the results therefore appears to be high. The diet used was 5LG6 with 12% fat and 22% protein. Another important finding of this study is that supplementation does not worsen health status and is safe. Causes of death in the glycine gr...
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Which amino acid suppresses chronic inflammation?

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Many readers already of course suspect which amino acid it might be, but I’ll leave that for later. It is becoming increasingly clear that the main problem of modern civilization diseases could be one relatively little-known, but in our time overly active enzyme. You already know it from previous posts: aldose reductase AR, the beginning of the polyol pathway. Yes, it is the enzyme that converts glucose into sorbitol and subsequently the enzyme SORD breaks it down by converting it into fructose. It is also the enzyme that processes 4-HNE, an aldehyde derived from the omega-6 linoleic acid, into active inflammatory signaling molecules. I have already shown here how sorbinil, an AR inhibitor, completely suppresses inflammation signaling caused by LPS, i.e., bacterial endotoxins. Switching off AR interrupts signaling to other cells; no chronic tissue inflammation then takes place. This may be good in the case of inflammation activation by dead material such as LPS. It may not be so good d...
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Does glycine function as an AR inhibitor? Does it suppress endogenous fructose production?

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It occurred to me to start looking for a relationship between glycine supplementation and the polyol pathway, specifically whether glycine might have some relationship to the activity of aldose reductase (AR). This enzyme (together with fructokinase KHK) appears to be at the center of events related to obesity, oxidative stress, chronic inflammation, etc. Turning it off interrupts inflammatory signaling and the response to endotoxins, but it also disrupts the breakdown of certain toxins. Its inhibition therefore may not always be desirable. And it seems to me that I have found a certain connection between glycine and AR. It is a rather innocent-looking cataract study in diabetic rats from 2019. The authors apparently had the same idea: what if glycine interacts with aldose reductase? And they tested it in diabetic rats. And it worked! The study was conducted in such a way that at a certain point the rats’ pancreas was chemically damaged, so insulin production stopped. This leads to an...
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Does fatty food increase longevity?

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Aging of the organism appears to depend on food intake. I have previously pointed out that prolonging life can probably be achieved by preventing any overeating, even short-term . During a discussion on the X network, the well-known blogger Peter ( @Peter_InNorfolk ) shared a study examining the lifespan of rats on three diets: a standard diet (16% of calories from fat), a moderately high-fat diet (35% of calories from fat) without quantity restriction, and the same diet but restricted to the same caloric intake as the standard diet. He mainly commented on the shortening of lifespan on the unrestricted high-fat diet, which he attributes to the relatively high content of omega-6 linoleic acid in the fat, i.e., in lard. Control – low-fat pellets, IHF – high-fat diet with isocaloric restriction, FHF – high-fat diet without restriction, experiment performed on male rats. The high-fat diet without restriction (FHF) slows metabolism and reduces heat production. However, from the previous pos...
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