MCT for Health

Today will be more of a summary, a more general reflection. In one of my recent posts, I commented on a study that quite clearly showed that if we remove the regulatory processes limiting the rate of fat burning, then the rate of burning is suppressed only after mitochondrial damage, loss of cardiolipin, loss of the necessary phospholipids , simply through oxidative stress . It is not a good idea to switch off regulatory mechanisms and think that things will be better without regulation—they will not. If researchers try to switch mice or rats to a high-fat diet, they almost always damage their mitochondria. We now know that they will probably deprive them of sufficient cardiolipin, a phospholipid necessary for the proper functioning of the enzymes that produce cellular energy in the form of ATP molecules. We also know that this can be prevented by a different composition of fats, for example if the diet contains fish oil , or if it contains MCT oils, or if it contains vinegar/acetate ...

In the previous post, I showed how the omega-6 linoleic acid peroxidation product 4-hydroxy-2-nonenal (HNE) suppresses signaling of cellular energy deficiency, i.e., a shortage of ATP molecules . This forces the cell to switch into an energy-conserving metabolic mode, activate glucose fermentation or cellular senescence, or ultimately undergo apoptosis—programmed cell death. Today, we will look at another older study  (from 2014) in which researchers investigated whether fatty liver disease could be alleviated by suppressing the function of the AR enzyme, i.e., by inhibiting aldose reductase. If you have not yet heard of aldose reductase (AR, also known as aldo-keto reductase AKR1B1), I have published a large number of posts on this blog presenting studies showing that AR activation is the basis of virtually all modern chronic diseases, whether it is obesity , liver damage , or vascular endothelial damage . Today, the main activators of AR are not only elevated blood glucose l...

You probably already know this. Oxidative stress of any kind triggers the activity of enzymes called phospholipases, especially iPLA2γ, which releases oxidized polyunsaturated fats from the mitochondrial membrane . This is how cells monitor their condition and oxidative stress, and the released oxidized products derived from omega-6 linoleic acid (LA/ARA, e.g., 4-HNE) serve as signals for many processes. For example, they can also trigger chronic inflammation by activating aldose reductase (AR) and the polyol pathway . Elevated glucose levels (HG), when the enzyme ALDH2 functions insufficiently and 4-HNE molecules are attached to it, become problematic and instead of correcting oxidative stress they deepen it further. The missing ALDH2 activity can be restored using H2S (NaHS was used here) or by activating the CSE enzyme (e.g., by restricting methionine and cysteine in the diet ). I have many posts about this here; most of them concern liver cells or pancreatic cells, and therefore a...

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 (...

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...

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...