Stearic acid signaling for mitochondrial health

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SusanJ
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Stearic acid signaling for mitochondrial health

Post by SusanJ »

We've had lots of discussion about saturated fat. Here's a small study, 10 healthy and 11 type-2 diabetics, that looks specifically at stearic acid (C18:0), which is highest in beef, pork, dairy, chocolate and egg yolks.
Within the metabolite class of fatty acids, epidemiological studies have found that various fatty acids have different biological consequences when ingested. Saturated fatty acids in general, and palmitic acid (C16:0) in particular, are harmful in part because they elevate LDL cholesterol and atherosclerosis risk7. Dietary stearic acid (C18:0), however, does not increase atherosclerosis risk, and, if anything, actually reduces LDL cholesterol7,8,9,10. Indeed, increased levels of circulating C18:0 lipids are associated with reduced blood pressure, improved heart function, and reduced cancer risk11,12,13,14,15. Hence unlike other saturated fatty acids, and contrary to the general belief that saturated fatty acids are harmful, C18:0 appears to have some beneficial effects on human health. The molecular mechanisms of this, however, are not clear.
We previously showed that the fatty acid stearic acid (C18:0) signals via a dedicated pathway to regulate mitofusin activity and thereby mitochondrial morphology and function in cell culture. Whether this pathway is poised to sense changes in dietary intake of C18:0 in humans is not known. We show here that C18:0 ingestion rapidly and robustly causes mitochondrial fusion in people within 3 h after ingestion. C18:0 intake also causes a drop in circulating long-chain acylcarnitines, suggesting increased fatty acid beta-oxidation in vivo. This work thereby identifies C18:0 as a dietary metabolite that is sensed by our bodies to control our mitochondria.
After 2 days of a low-C18:0 diet, the mitochondria in neutrophils are quite fragmented; 50% of all neutrophils had fragmented mitochondria and fewer than 10% had fused mitochondria prior to ingesting the C18:0 drink (“0 h”, Fig. 1c). This was true in all 21 subjects combined (Fig. 1c), in the healthy subjects (Fig. 1e) and in the type-2 diabetic patients (Fig. 1g).

In this study, we identify stearic acid (C18:0) as a metabolite that is sensed in our diets and regulates human physiology, in particular mitochondrial morphology and function. Intriguingly, our data imply that when we eat, the C18:0 in our food causes our mitochondria to fuse within a few hours of eating. This response is impressively robust: we obtained statistically significant results with only 10 healthy subjects.
And one final tidbit, that leads me back to Russ' mantra to eat a variety of food in season.
Since it is likely unfeasible for an organism to sense all metabolites in its diet, it appears that evolution has selected certain metabolites within a class to be sensed by the organism and to act as proxies for the intake of the entire class. This sensing mechanism works in nature because natural food sources usually do not contain only single metabolites from a class, for instance leucine, but not other amino acids. Hence sensing one metabolite from a class is sufficient to indicate the presence of the entire class in the food. Modernization has changed this, however, providing humans with food sources particularly high in single metabolites such as fructose or palmitic acid. This leads to mismatches between what the body senses and what it is actually ingesting, especially when the ingested metabolite is not the one being sensed. Hence it is critical to understand which metabolites are being sensed by the human body, and what physiological responses they elicit.
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