Butyrate Improves Insulin Sensitivity and Increases Energy Expenditure in Mice

Abstract

Objective- To examine the role of butyric acid, a short chain fatty acid formed by fermentation in the large intestine, in the regulation of insulin sensitivity in mice fed a high fat diet.

Research design and methods- In dietary obese C57BL/6J mice, sodium butyrate was administrated through diet supplementation at 5% w/w in the high fat diet (HFD). Insulin sensitivity was examined with insulin tolerant test and HOMA IR. Energy metabolism was monitored in a metabolic chamber. Mitochondrial function was investigated in brown adipocytes and skeletal muscle in the mice.

Results- On the HFD diet, supplementation of butyrate prevented development of insulin resistance and obesity in C57BL/6 mice. Fasting blood glucose, insulin, insulin tolerance were all reserved in the treated mice. The body fat content was maintained at 10% without a reduction in food intake. Adaptive thermogenesis and fatty acid oxidation were enhanced. An increase in mitochondria function and biogenesis was observed in the skeletal muscle and brown fat. The type 1 fiber was enriched in the skeletal muscle. PGC-1α expression was elevated at mRNA and protein levels. AMPK and p38 activities were elevated. In the obese mice, supplementation of butyrate led to an increase in insulin sensitivity and reduction in adiposity.

Conclusions- Dietary supplementation of butyrate can prevent and treat diet-induced insulin resistance in mouse. The mechanism of butyrate action is related to promotion of energy expenditure and induction of mitochondria function.