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Obesity and Hydrogen Sulfide

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In this post, I will try to summarize information from previous posts and studies and supplement it with the latest insights on the effect of enzymatic hydrogen sulfide (H2S) production on metabolism. What do we already know? Intestinal permeability A high-fat diet with sugar promotes a composition of gut bacteria that produces a large amount of hydrogen sulfide. There is so much of it that this hydrogen sulfide deprives intestinal epithelial cells of ATP energy, blocks mitochondrial complex IV, and causes leaky gut . A high concentration of H2S damages metabolism. Liver With a high-fat diet containing sugar, the liver is burdened by endotoxins (LPS) from a leaky gut. These activate aldose reductase (AR), increasing the formation of H2O2 (ROS) in the liver. According to the already known scheme, this switches on fatty acid synthesis (DNL) as well as triglyceride (TG) production and activates their export further into the body , either to be burned for heat, to produce chemical energy (...
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Hydrogen Sulfide as a Protector of Blood Vessels?

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Hydrogen sulfide, H2S, a smelly gas known for example from rotten eggs, appears to be a very important regulatory product in the body. If you read this blog regularly, this will not be any surprise to you. It has been quite a while since, while searching for the mechanism of action of sulfur amino acid restriction, I found studies that surprisingly link the restriction of these amino acids with increased production of H2S as a product of the activity of the enzyme cystathionine-γ-lyase (CSE/CTH). The main mechanism of hydrogen sulfide is S-sulfhydration of enzymes, that is, a certain change in the “decoration” of these nano-machines, which either further activates or deactivates their function. Today we will look at the effect of hydrogen sulfide on vascular endothelial cells, that is, those that influence cardiovascular diseases generally associated with LDL-C levels, that is, cholesterol. I will not repeat here that cholesterol is a very poor marker of risk for these diseases. Take a...
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Is Hydrogen Sulfide Essential for Thermogenesis? How Is It Related to Omega-6 Fat Burning?

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Do you often feel cold? Are you unable to warm up in a cooler environment? You may have a problem with hydrogen sulfide deficiency and with omega-6 fat metabolism. This condition is usually attributed to insufficient thyroid function, inadequate hormone production. But as studies in mice show us, the problem may also lie elsewhere, possibly even in a deficiency of NADPH molecules. But I am getting ahead of myself. How is thermogenesis in brown adipose tissue regulated in the first place? In one older post I pointed to a study in mice where, when they were placed in a cold environment, there was an increase in the production of succinic acid (succinate), which subsequently activated the formation of hydrogen peroxide, and this then triggered heat production by activating UCP1 proteins in brown adipose tissue. It appears that hydrogen sulfide (H2S), produced enzymatically (that is, via the CSE/CTH enzyme), also plays a role somewhere along this pathway. I found a study showing how therm...
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On the Harmfulness of Saturated Fats

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Yes, everyone knows that, after all, saturated fats are harmful ! Don’t eat them! Just look at the following image . Here we see how liver cells respond to specific free fatty acids, for example to the saturated palmitic acid (PA). We can see that palmitic acid alone produces almost no ATP, allows a large amount of calcium into the cell, causes an excess of reactive oxygen species (ROS), and triggers insulin resistance by reducing phosphorylation of the signaling molecule AKT (pAKT). The conclusion: do not eat saturated fats! It’s completely obvious. Or is it? Well, let’s continue with the same image. We also have the monounsaturated oleic acid (OA) and the polyunsaturated EPA (for example from fish oil). Then there are the combinations PA+OA and PA+EPA. And we see that PA in combination with a certain amount of unsaturated fatty acids does nothing fundamentally harmful. Why? I will use another study to show you how fat transport into the cell is probably related to the shape of unsatu...
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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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