Research ArticleMetabolism

The short-chain fatty acid propionate increases glucagon and FABP4 production, impairing insulin action in mice and humans

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Science Translational Medicine  24 Apr 2019:
Vol. 11, Issue 489, eaav0120
DOI: 10.1126/scitranslmed.aav0120

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A metabolic dysregulator in hiding

Propionate is a short-chain fatty acid that is a commonly used food preservative. Tirosh et al. now show that propionate induces postprandial hyperglycemia in mice, resulting in a counter-regulatory hormonal response. Propionate increased norepinephrine release by the sympathetic nervous system, leading to an increase in circulating glucagon and the adipokine fatty acid–binding protein 4 (Fabp4), which jointly induced liver glycogenolysis and compensatory hyperinsulinemia. Long-term exposure of mice to a daily low dose of propionate resulted in a gradual weight gain and insulin resistance. Studies in humans highlight the potential contribution of propionate in the diet to the development of insulin resistance and obesity.