Mito
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https://www.nature.com/articles/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 ftatty 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.
Discussion
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. Unlike C18:0, C16:0 does not have this effect. This could explain part of the difference between C16:0 and C18:0 observed epidemiologically, whereby C16:0 increases the risk for cancer and cardiovascular risk whereas C18:0 reduces both7,11,12,13,14,15: if dietary C18:0 signals the intake of lipids to the human body, to activate a physiological response for lipid handling which includes fatty acid beta-oxidation, whereas C16:0 does not, this would imply that C16:0 ingestion will lead to more fat accumulation in the body than C18:0 ingestion. Fat accumulation, in turn, is a risk factor for both cardiovascular disease and cancer. Hence the balance of C16:0 to C18:0 in our diets may be important. A diet rich in C16:0 could be particularly bad because it provides lipids to the body without activating the mitochondrial response that C18:0 does. We included both healthy subjects and type-2 diabetic patients in our study, however we did not see significant differences in the basal mitochondrial morphology (Fig. 4a) or in the response to C18:0 ingestion in these two groups (Fig. 1). If anything, C18:0 ingestion caused more robust mitochondrial fusion in diabetic patients than in controls. Further work will be necessary to test whether longer-term dietary interventions with C18:0 can affect baseline levels of C18:0 in the serum, and hence mitochondrial morphology and function.
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 ftatty 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.
Discussion
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. Unlike C18:0, C16:0 does not have this effect. This could explain part of the difference between C16:0 and C18:0 observed epidemiologically, whereby C16:0 increases the risk for cancer and cardiovascular risk whereas C18:0 reduces both7,11,12,13,14,15: if dietary C18:0 signals the intake of lipids to the human body, to activate a physiological response for lipid handling which includes fatty acid beta-oxidation, whereas C16:0 does not, this would imply that C16:0 ingestion will lead to more fat accumulation in the body than C18:0 ingestion. Fat accumulation, in turn, is a risk factor for both cardiovascular disease and cancer. Hence the balance of C16:0 to C18:0 in our diets may be important. A diet rich in C16:0 could be particularly bad because it provides lipids to the body without activating the mitochondrial response that C18:0 does. We included both healthy subjects and type-2 diabetic patients in our study, however we did not see significant differences in the basal mitochondrial morphology (Fig. 4a) or in the response to C18:0 ingestion in these two groups (Fig. 1). If anything, C18:0 ingestion caused more robust mitochondrial fusion in diabetic patients than in controls. Further work will be necessary to test whether longer-term dietary interventions with C18:0 can affect baseline levels of C18:0 in the serum, and hence mitochondrial morphology and function.