title: Butyrate stimulates adipose lipolysis and mitochondrial oxidative phosphorylation through histone hyperacetylation-associated β3-adrenergic receptor activation in high-fat diet-induced obese mice.
abstract: What is the central question of this study? Butyrate can prevent diet-induced obesity through increasing energy expenditure. However, it is unclear whether β3-adrenergic receptors (ARβ3) mediate butyrate-induced adipose lipolysis. What is the main finding and its importance? Short-term oral administration of sodium butyrate is effective in alleviating diet-induced obesity through activation of ARβ3-mediated lipolysis in white adipose tissue. Butyrate can prevent diet-induced obesity through increasing energy expenditure. However, it is unclear whether ARβ3 mediates butyrate-induced adipose lipolysis. In this study, weaned mice were were fed control (Con) or high-fat (HF) diet for 8 weeks to establish obesity. High-fat diet-induced obese mice maintained on the HF diet were divided into two subgroups; the HFB group was gavaged with 80 mg sodium butyrate (SB) per mouse every other day for 10 days, whereas the HF group received vehicle. Chromatin immunoprecipitation assay was performed to determine the status of histone H3 lysine 9 acetylation (H3K9Ac) on the promoter of the β3-adrenergic receptor (ARβ3) gene in epididymal white adipose tissue. It was shown that five gavage doses of SB significantly alleviated HF diet-induced obesity and restored plasma leptin concentration to the control level. Protein contents of ARβ3 and PKA, as well as ATGL and p-HSL (Ser563), were significantly upregulated in the HFB group compared with the HF group. Mitochondrial oxidative phosphorylation was enhanced by SB treatment. Sodium butyrate significantly increased the expression of four out of 13 mitochondrial DNA-encoded genes and significantly upregulated the protein contents of peroxisome proliferator-activated receptor-γ coactivator 1α and COX4. Moreover, SB administration enhanced the expression of ARβ3 and its downstream signalling. The G protein-coupled receptor 43 and p-CREB (Ser133) were significantly stimulated by SB. In addition, an active transcription marker, H3K9Ac, was significantly enriched on the promoter of the ARβ3 gene. Our results indicate that short-term oral administration of SB is effective in alleviating diet-induced obesity through activation of the ARβ3-mediated lipolysis in the epididymal white adipose tissue.
authors.affiliation: Key Laboratory of Animal Physiology & Biochemistry, Nanjing Agricultural University, Nanjing, 210095, PR, China.
authors.forename: Yimin
authors.initials: Y
authors.lastname: Jia
authors.affiliation: Key Laboratory of Animal Physiology & Biochemistry, Nanjing Agricultural University, Nanjing, 210095, PR, China.|College of Life Science and Technology, Yancheng Teachers University, Jiangsu, Yancheng 224051, PR, China.
authors.forename: Jian
authors.identifier: 0000-0002-3733-3904
authors.initials: J
authors.lastname: Hong
authors.affiliation: Key Laboratory of Animal Physiology & Biochemistry, Nanjing Agricultural University, Nanjing, 210095, PR, China.
authors.forename: Huifang
authors.initials: H
authors.lastname: Li
authors.affiliation: Key Laboratory of Animal Physiology & Biochemistry, Nanjing Agricultural University, Nanjing, 210095, PR, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Key Laboratory of Animal Physiology & Biochemistry, Nanjing Agricultural University, Nanjing, 210095, PR, China.
authors.forename: Longfei
authors.initials: L
authors.lastname: Jia
authors.affiliation: Key Laboratory of Animal Physiology & Biochemistry, Nanjing Agricultural University, Nanjing, 210095, PR, China.
authors.forename: Demin
authors.initials: D
authors.lastname: Cai
authors.affiliation: Key Laboratory of Animal Physiology & Biochemistry, Nanjing Agricultural University, Nanjing, 210095, PR, China.|Jiangsu Collaborative Innovation Center of Meat Production and Processing, Quality and Safety Control, Nanjing, 210095, PR, China.
authors.forename: Ruqian
authors.identifier: 0000-0002-7337-8173
authors.initials: R
authors.lastname: Zhao
mesh_terms: D000107:Acetylation / Q000187:drug effects; D052436:Adipose Tissue, White / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D002087:Butyrates / Q000494:pharmacology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000378:metabolism; D059305:Diet, High-Fat / Q000379:methods; D006657:Histones / Q000378:metabolism*; D008049:Lipase / Q000378:metabolism; D008066:Lipolysis / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009765:Obesity / Q000378:metabolism; D010085:Oxidative Phosphorylation / Q000187:drug effects*; D047492:Peroxisome Proliferator-Activated Receptors / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000187:drug effects; D022702:Receptors, Adrenergic, beta-3 / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D002087:Butyrates; D017362:Cyclic AMP Response Element-Binding Protein; D004272:DNA, Mitochondrial; D006657:Histones; D047492:Peroxisome Proliferator-Activated Receptors; D022702:Receptors, Adrenergic, beta-3; D043562:Receptors, G-Protein-Coupled; D017868:Cyclic AMP-Dependent Protein Kinases; D008049:Lipase