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OBJECTIVE-We examined 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% wt/wt in the high-fat diet. Insulin sensitivity was examined with insulin tolerance testing and homeostasis model assessment for insulin resistance. Energy metabolism was monitored in a metabolic chamber. Mitochondrial function was investigated in brown adipocytes and skeletal muscle in the mice.
RESULTS-On the high-fat diet, supplementation of butyrate prevented development of insulin resistance and obesity in C57BL/6 mice. Fasting blood glucose, fasting insulin, and insulin tolerance were all preserved in the treated mice. Body fat content was maintained at 10% without a reduction in food intake. Adaptive thermogenesis and fatty acid oxidation were enhanced. An increase in mitochondrial function and biogenesis was observed in skeletal muscle and brown fat. The type I fiber was enriched in skeletal muscle. Peroxisome proliferator-activated receptor-7 coactivator-1α expression was elevated at mRNA and protein levels. AMP kinase and p38 activities were elevated. In the obese mice, supplementation of butyrate led to an increase in insulin sensitivity and a 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. Diabetes 58:1509-1517, 2009
Recent studies suggest that natural compounds represent a rich source for small thermogenic molecules, which hold potential in the prevention and treatment of obesity and insulin resistance. Several natural products, such as resveratrol (1,2), bile acid (3), and genipin (4), have been reported to increase thermogenic activities in animal or cellular models. In the current study, we provide evidence for the thermogenic activity and therapeutic value of a short-chain fatty acid, butyric acid, in a mouse model of metabolic syndrome. Butyric acid has four carbons in the molecule (CH^sub 3^CH^sub 2^CH^sub 2^-COOH) and becomes sodium butyrate after receiving sodium. Sodium butyrate is a dietary component found in foods such as cheese and butter. It is also produced in large amounts from dietary fiber after fermentation in the large intestine, where butyric acid is generated together with other short-chain fatty...