High-Fat Diets Inhibit Housekeeping Process Inside Cells That Protects Against Diseases Of Aging

High-fat diets can inhibit a process inside cells that degrades unneeded proteins, thereby regulating  “numerous intracellular processes including glucose and lipid metabolism, circadian rhythms and DNA repair.” When damaged proteins are allowed to accumulate it results in disease. e.g  “when the toxic buildup occurs in nerve cells, neurodegenerative diseases including Parkinson’s, Alzheimer’s, and Huntington’s disease” may result.

So, I’m reading this new bit of research …

Researchers Find New Strategy For Preventing Clogged Arteries, Science Daily, 1 April 2022

Revving up a process that slows down as we age may protect against atherosclerosis, a major cause of heart attacks and strokes. In findings published online today in Proceedings of the National Academy of Sciences (PNAS), scientists at Albert Einstein College of Medicine led by Ana Maria Cuervo, M.D., Ph.D., successfully minimized artery-narrowing plaque in mice that would otherwise develop those lesions. The researchers did so by boosting chaperone-mediated autophagy (CMA), a cellular housekeeping process that Dr. Cuervo discovered in 1993 and named in 2000.

OK. And how did they boost it?

“My colleagues and I have developed drug compounds that have shown promise for safely and effectively increasing CMA activity in most mouse tissues and in human-derived cells,” said Dr. Cuervo. Einstein has filed intellectual property on this underlying technology.

Just a second. Drugs? Is that how it’s done? Didn’t I read somewhere that a high-fat diet affects this intracellular housekeeping process? I did…

Inhibitory Effect Of Dietary Lipids On Chaperone-Mediated Autophagy, PNAS, February 2012

Cytosolic proteins can be selectively delivered to lysosomes for degradation through a type of autophagy known as chaperone- mediated autophagy (CMA). CMA contributes to intracellular quality control and to the cellular response to stress. Compromised CMA has been described in aging and in different age-related disorders. CMA substrates cross the lysosomal membrane through a translocation complex; consequently, changes in the properties of the lysosomal membrane should have a marked impact on CMA activity.

In this work, we have analyzed the impact that dietary intake of lipids has on CMA activity. We have found that chronic exposure to a high-fat diet or acute exposure to a cholesterol-enriched diet both have an inhibitory effect on CMA. Lysosomes from livers of lipid-challenged mice had a marked decrease in the levels of the CMA receptor, the lysosome-associated membrane protein type 2A, because of loss of its stability at the lysosomal membrane. This accelerated degradation of lysosome-associated membrane protein type 2A, also described as the mechanism that determines the decline in CMA activity with age, results from its increased mobilization to specific lipid regions at the lysosomal membrane. Comparative lipidomic analyses revealed qualitative and quantitative changes in the lipid composition of the lysosomal membrane of the lipid-challenged animals that resemble those observed with age.

Our findings identify a previously unknown negative impact of high dietary lipid intake on CMA and underscore the importance of diet composition on CMA malfunction in aging.

The top study failed to mention the therapeutic effect of eating less fat, even though both these studies were led by the same researcher! But drugs. Right? You can’t make money from people changing their diets.

It’s as easy as eating less fat. Safe. Cheap. Effective.

These popular, high-fat keto diets may come back to bite people.

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