Sodium butyrate was chronically administrated through diet supplementation at 5% w/w in a high fat diet. Supplementation of butyrate prevented development of insulin resistance and obesity in C57BL/6J mice on a high fat diet, and in mice fed on a regular diet of tributyrin. Fasting blood glucose, insulin, and insulin tolerance were all reserved in the butyrate-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, and Type 1 muscle fiber was enriched in the skeletal muscle. In genetically obese mice, supplementation of butyrate led to an increase in insulin sensitivity and reduction in adiposity. Dietary supplementation of butyrate can prevent and treat diet-induced insulin resistance.
