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What Is Lipofuscin and How To Avoid Its Production?

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As the organism and its cells age, a substance called lipofuscin accumulates in the cell cytosol. It is a yellowish-brown metabolic waste (pigment) formed by oxidized fats and proteins. It is commonly called the “pigment of aging” because it gradually accumulates in cells (especially in neurons, heart muscle, liver and retina) and its amount naturally increases with age. It is not a homogeneous compound, it is probably a mixture of intertwined and interconnected chains that exhibit fluorescence. This fluorescence when stimulated by near-UV radiation is not always the same, it varies depending on the place of origin, composition and age from green to blue. The literature tells us that it is actually unprocessed cellular waste. Normally, these substances would be removed by the formation of lysosomes, organelles where unusable substances are digested and broken down into reusable material or waste. Lipofuscin is the remnant of dysfunctional lysosomes, so it shows a state where the decomp...
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Are High Blood Glucose Levels Harmful, Even Without Aldehydes?

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The effort to lower blood glucose levels seems obvious, the reason is simple. High glucose levels cause oxidative stress and damage to body organs (eyes, blood vessels, kidneys, etc.). This leads many people to promote and apply low-carb and ketogenic diets. But is it really glucose that causes it? After all, it is the most common fuel for obtaining energy so that cells can function at all. Isn't that strange? Moreover, the cell can easily defend itself against overload by means of insulin resistance. So why doesn't it work? Is it really glucose that is harmful to the body? So let's take a closer look. If you are reading this blog, I think you already know where the core of the problem is. Yes, it is the activation of an enzyme that is supposed to serve only in emergency situations, otherwise it should be deactivated. It is the enzyme aldose reductase (AR, AKR1B1). It is present in the liver, vascular endothelium, cornea, etc. It is the first enzyme of the so-called polyol ...
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How Does Linoleic Acid Shut Down Fat Metabolism in the Liver?

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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...
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How Exactly Do Seed Oils Deactivate Cellular Energy Deficiency Signaling?

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One of the main sensors of energy sufficiency in the cell, that is, a sufficient supply of ATP molecules, is the enzyme AMPK. It is activated whenever the amount of AMP molecules increases. But does it really work "every time"? An adequate energy supply for all cellular functions is so fundamental that we should ask whether certain substances can suppress this signaling. The cell then suffers from an energy deficit and enters various energy-conserving states, for example pseudohypoxia or cellular senescence , which is characterized by fermentative metabolism to reduce the production of reactive oxygen species (ROS, such as hydrogen peroxide), but also by the shutdown of processes that repair damaged DNA ( which is a common occurrence caused, for example, by UV radiation or ionizing radiation ). So, do we know of any substances that block AMPK activity? Yes, we certainly do. One is the well-known autooxidation product of the omega-6 fatty acid linoleic acid, a molecule called...
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Can Leptin Resistance Be Suppressed By Removing Aldehydes?

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The hormone leptin is produced by fat cells and is known to normally reduce the need to eat. In obese individuals, however, this mechanism does not work properly. They have higher leptin levels yet still consume more food than necessary. This condition is called leptin resistance; the body simply does not respond to leptin's signal, the signal that sufficient fuel is stored in the body. It appears that this condition is closely linked to improper protein/enzyme folding and to endoplasmic reticulum stress (ER stress), which is where enzymes are created and folded within the cell. What substances can trigger such stress? How about aldehydes formed by the autooxidation of linoleic acid? Could it be 4-hydroxy-2-nonenal (HNE)? Would activating the enzyme that breaks down HNE, namely aldehyde dehydrogenase (ALDH2), help? Would this also work to reduce leptin resistance? Perhaps the most serious effect of the increased presence of the toxic aldehyde HNE, derived by the autooxidation of li...
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Can Mitochondria Be Healed with Cis-Vaccenic Acid (Through ELOVL5 Activation)?

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We will continue exploring cis-vaccenic acid (CVA), which appears to be a very important component of one very special material used in mitochondria, specifically in the inner membrane. Yes, that material is cardiolipin, a unique phospholipid with four connected fatty acid chains. A normal phospholipid contains only three chains, while cardiolipin contains four. If you have no idea what cis-vaccenic acid is, or if you think you obtain it from milk fat, first read my previous post. It is usually stated that cardiolipin mainly contains linoleic acid (18:2n-6). However, as I found out, mitochondrial function is strongly influenced by the presence of CVA. In one study, I read that this is related to the composition of cardiolipin. Then AI found me a rather old study examining its exact composition  (dating back to 1985), where cis-vaccenic acid is mentioned. And indeed, CVA (18:1n-7) is the second most abundant fatty acid at the 2(2") positions of cardiolipin! The content of oleic aci...
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Do You Know Vaccenic Acid? And Is Cis or Trans Better?

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While exploring the positive effects of various conjugated linoleic acids (CLA), I also found studies on the effect of CLA on the development of cancer and tumors . Results from animal experiments make therapies based on supplementing several percent of CLA appear very interesting. For example, this study of artificially induced cancer (DMBA) in rats shows the effect of adding 0% (A3), 1% (B3), and 2% CLA (C3) to the diet. The results are very interesting, approximately a 10-fold reduction in both the number and size of tumors. For such a small dietary change, this is quite a large effect. What could be causing it? The same study also reports that dietary CLA reduces the activity of certain enzymes involved in processing polyunsaturated fats (D6D, delta-6-desaturase). This reduces the conversion of linoleic acid into arachidonic acid and its concentration in membranes. But it also reduces the conversion of the plant omega-3 ALA into the long-chain omega-3s EPA and DHA.  As we will...
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Is Lard Missing Something Important?

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Today we will look at how the composition of fats in a low-fat diet affects metabolism in mice, for example how it affects fatty liver development. The low-fat diet is an important factor here; the researchers did not overload the mice’s bodies, so in my opinion we are getting fairly relevant results. So what does the study tell us ? We’ll take it slowly. There are six diets here: lard (L1, L2), soybean oil (S1, S2), and a mixture of lard and soybean oil (LS1, LS2), each with either 10% or 15% fat in the diet. For example, this is the difference in blood free fatty acid levels between diets containing 10% and 15% lard. Isn’t that interesting? Such an ordinary low-fat diet. And if it contains 10% fat in the form of lard, it still works reasonably well. But if we increase the lard content by 50%, to 15%, the level of free fatty acids in the blood rises by about 75%. Clearly, something is not right here. What happens if instead of pure lard we provide a mixture of lard and soybean oil in ...
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