title: Butyrate alleviates high fat diet-induced obesity through activation of adiponectin-mediated pathway and stimulation of mitochondrial function in the skeletal muscle of mice.
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.
authors.affiliation: Key Laboratory of Animal Physiology & Biochemistry, Nanjing Agricultural University, Nanjing, P. R. China.|College of Life Science and Technology, Yancheng Teachers University, Yancheng, P. R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Hong
authors.affiliation: Key Laboratory of Animal Physiology & Biochemistry, Nanjing Agricultural University, Nanjing, P. R. China.
authors.forename: Yimin
authors.initials: Y
authors.lastname: Jia
authors.affiliation: Key Laboratory of Animal Physiology & Biochemistry, Nanjing Agricultural University, Nanjing, P. R. China.
authors.forename: Shifeng
authors.initials: S
authors.lastname: Pan
authors.affiliation: Key Laboratory of Animal Physiology & Biochemistry, Nanjing Agricultural University, Nanjing, P. R. China.
authors.forename: Longfei
authors.initials: L
authors.lastname: Jia
authors.affiliation: Key Laboratory of Animal Physiology & Biochemistry, Nanjing Agricultural University, Nanjing, P. R. China.
authors.forename: Huifang
authors.initials: H
authors.lastname: Li
authors.affiliation: Key Laboratory of Animal Physiology & Biochemistry, Nanjing Agricultural University, Nanjing, P. R. China.
authors.forename: Zhenqiang
authors.initials: Z
authors.lastname: Han
authors.affiliation: Key Laboratory of Animal Physiology & Biochemistry, Nanjing Agricultural University, Nanjing, P. R. China.
authors.forename: Demin
authors.initials: D
authors.lastname: Cai
authors.affiliation: Key Laboratory of Animal Physiology & Biochemistry, Nanjing Agricultural University, Nanjing, P. R. China.|Jiangsu Collaborative Innovation Center of Meat Production and Processing, Quality and Safety Control, Nanjing, P. R. China.
authors.forename: Ruqian
authors.initials: R
authors.lastname: Zhao
mesh_terms: D052242:Adiponectin / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D002087:Butyrates / Q000494:pharmacology / Q000627:therapeutic use*; D059305:Diet, High-Fat / Q000009:adverse effects; D056284:Histone Deacetylase 1 / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D020738:Leptin / Q000097:blood; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D009765:Obesity / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D010085:Oxidative Phosphorylation / Q000187:drug effects; D011401:Promoter Regions, Genetic; D054419:Receptors, Adiponectin / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013047:Specific Pathogen-Free Organisms; D000071246:Uncoupling Protein 2 / Q000235:genetics / Q000378:metabolism; D000071247:Uncoupling Protein 3 / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D052242:Adiponectin; C499919:Adipoq protein, mouse; D001786:Blood Glucose; D002087:Butyrates; D007328:Insulin; D020738:Leptin; D054419:Receptors, Adiponectin; C000604390:Ucp2 protein, mouse; C000604393:Ucp3 protein, mouse; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3; C484389:Hdac1 protein, mouse; D056284:Histone Deacetylase 1
keywords: Pathology Section; adipoR1; adipoR2; mitochondria function; obesity; sodium butyrate