Diet dependent impact of benzoate on diabetes and obesity in mice

The gut microbiota contributes to mammalian host biology by supplying metabolites from nutrients and pro-inflammatory molecules. We have recently shown that urinary hippurate is associated with reduced risk of obesity, increased gut microbiome diversity and gene richness, and functional modules for microbial production of its precursor benzoate. Obese mice infused with hippurate exhibit profound alterations of glucose homeostasis. Here, we tested the biological effects of chronic administration of benzoate on cardiometabolic phenotypes in lean and obese mice. Benzoate induced glucose intolerance, enhanced insulin secretion, increased adiposity and stimulated liver inflammation in lean mice fed control diet. In contrast, in condition of obesity and diabetes induced by high fat diet feeding, benzoate infusion resulted in reduction of glucose intolerance, stimulation of both glucose-induced insulin secretion and β-cell proliferation, and reduction of liver triglyceride and collagen accumulation. These results combined with those previously obtained in mice treated with hippurate underline the importance of the benzoate-hippurate pathway in cardiometabolic diseases and pave the way to diagnostic and therapeutic solutions. • Benzoate treatment in lean mice impairs glucose tolerance and increases adiposity. • Benzoate infusion in lean mice regulates insulin secretion and β-cell proliferation. • Benzoate in obese mice reduces glucose intolerance and stimulates insulin secretion.