Dietary stearic acid regulates mitochondria in vivo in humans

Deniz Senyilmaz-Tiebe,Aurelio A Teleman,Peter Nawroth,Sandro Altamura,Daniel H Pfaff,Antonio Vidal-Puig,Sam Virtue,Martina U Muckenthaler,Jürgen G Okun,Kathrin V Schwarz,Thomas Fleming

doi:10.1038/s41467-018-05614-6

Abstract

Since modern foods are unnaturally enriched in single metabolites, it is important to understand which metabolites are sensed by the human body and which are not. 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. This could explain part of the epidemiological differences between C16:0 and C18:0, whereby C16:0 increases cardiovascular and cancer risk whereas C18:0 decreases both.

Highlights

Since modern foods are unnaturally enriched in single metabolites, it is important to understand which metabolites are sensed by the human body and which are not
We aimed to study whether acute changes in C18:0 in serum triglycerides (C18):0 intake in humans affect mitochondrial morphology and function in vivo
We first asked subjects to eat for 2 days a lowfat vegan diet which is low in C18:0, to bring everyone to a lowC18:0 baseline regardless of their habitual diet (Fig. 1a)

Summary

Introduction

Since modern foods are unnaturally enriched in single metabolites, it is important to understand which metabolites are sensed by the human body and which are not. Feeding C18:0 to Drosophila animals regulated mitochondrial fusion in vivo, and led to organismal consequences: dietary supplementation with C18:0 was able to partially rescue the impaired locomotion and reduced lifespan resulting from mitochondrial dysfunction caused by mutations in the Parkinsons genes Pink[1] or parkin[16] This indicates that flies can sense and respond to levels of C18:0 in their diets. C18:0 intake led to a drop in circulating acylcarnitine levels, suggesting increased fatty acid beta-oxidation in vivo This identifies C18:0 as a lipid metabolite sensed in humans, and raises the possibility that dietary C18:0 activates part of the physiological response through which the human body handles lipids

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Conclusion