Butyrate improves insulin sensitivity and increases energy expenditure in mice.
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.


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-gamma coactivator-1alpha 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.
Antioxidant and Gene Regulation Laboratory, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA, USA.
Zhanguo
Z
Gao
Jun
J
Yin
Jin
J
Zhang
Robert E
RE
Ward
Roy J
RJ
Martin
Michael
M
Lefevre
William T
WT
Cefalu
Jianping
J
Ye
D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D002087:Butyrates / Q000494:pharmacology* / Q000627:therapeutic use; D004041:Dietary Fats / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects*; D006655:Histone Deacetylases / Q000378:metabolism; D007328:Insulin / Q000502:physiology*; D007333:Insulin Resistance / Q000502:physiology*; D024821:Metabolic Syndrome / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D008931:Mitochondria, Muscle / Q000187:drug effects / Q000378:metabolism; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D009765:Obesity / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000187:drug effects / Q000235:genetics; D014157:Transcription Factors
D002087:Butyrates; D004041:Dietary Fats; D007328:Insulin; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D006655:Histone Deacetylases