Butyrate alleviates high fat diet-induced obesity through activation of adiponectin-mediated pathway and stimulation of mitochondrial function in the skeletal muscle of mice

// Jian Hong 1,3,* , Yimin Jia 1,* , Shifeng Pan 1 , Longfei Jia 1 , Huifang Li 1 , Zhenqiang Han 1 , Demin Cai 1 and Ruqian Zhao 1,2 1 Key Laboratory of Animal Physiology & Biochemistry, Nanjing Agricultural University, Nanjing, P. R. China 2 Jiangsu Collaborative Innovation Center of Meat Production and Processing, Quality and Safety Control, Nanjing, P. R. China 3 College of Life Science and Technology, Yancheng Teachers University, Yancheng, P. R. China * These authors contributed equally to this work Correspondence to: Ruqian Zhao, email: // Keywords : mitochondria function, adipoR1, adipoR2, sodium butyrate, obesity, Pathology Section Received : May 09, 2016 Accepted : July 28, 2016 Published : August 12, 2016 Abstract Dietary supplementation of butyrate can prevent diet-induced obesity through increasing mitochondrial function in mice, yet the up-stream signaling pathway remains elusive. In this study, weaned mice were divided into two groups, fed control (CON) and high-fat diet (HF, 45% energy from fat), respectively, for 8 weeks. HF-induced obese mice, maintained on HF diet, were then divided into two groups; HFB group was gavaged with 80 mg sodium butyrate (SB) per mice every other day for 10 days, while the HF group received vehicle. It was shown that five gavage doses of SB significantly alleviated HF diet-induced obesity and restored plasma glucose, insulin and leptin to control levels. Muscle contents of ADP and AMP were significantly increased, which was associated with enhanced mitochondrial oxidative phosphorylation and up-regulated expression of fatty acid oxidation enzymes and uncoupling proteins, UCP2 and UCP3 in the skeletal muscle. SB significantly enhanced the expression of adiponectin receptors (adipoR1/2) and AMP kinase (AMPK), while diminished the expression of histone deacetylase 1 (HDAC1). Higher H3K9Ac, a gene activation histone mark, was detected on the promoter of Adipor1/2 , Ucp2 and Ucp3 genes that were activated in the muscle of SB-treated obese mice. Our results indicate that short-term oral administration of SB can alleviate diet-induced obesity and insulin resistance in mice through activation of adiponectin-mediated pathway and stimulation of mitochondrial function in the skeletal muscle.