Jia Yimin, Hong Jian, Li Huifang, Hu Yun, Jia Longfei, Cai Demin, Zhao Ruqian
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.
Exp Physiol. 2017 Feb 1;102(2):273-281. doi: 10.1113/EP086114.
What is the central question of this study? Butyrate can prevent diet-induced obesity through increasing energy expenditure. However, it is unclear whether β -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 β -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.
本研究的核心问题是什么？丁酸盐可通过增加能量消耗预防饮食诱导的肥胖。然而，尚不清楚β-肾上腺素能受体（ARβ3）是否介导丁酸盐诱导的脂肪分解。主要发现及其重要性是什么？短期口服丁酸钠可通过激活白色脂肪组织中ARβ3介导的脂肪分解有效缓解饮食诱导的肥胖。丁酸盐可通过增加能量消耗预防饮食诱导的肥胖。然而，尚不清楚ARβ3是否介导丁酸盐诱导的脂肪分解。在本研究中，将断奶小鼠用对照（Con）或高脂（HF）饮食喂养8周以建立肥胖模型。维持高脂饮食的高脂饮食诱导的肥胖小鼠分为两个亚组；HFB组每隔一天每只小鼠灌胃80mg丁酸钠（SB），持续10天，而HF组给予赋形剂。进行染色质免疫沉淀试验以确定附睾白色脂肪组织中β-肾上腺素能受体（ARβ3）基因启动子上组蛋白H3赖氨酸9乙酰化（H3K9Ac）的状态。结果表明，五次灌胃剂量的SB显著减轻了高脂饮食诱导的肥胖，并使血浆瘦素浓度恢复到对照水平。与HF组相比，HFB组中ARβ3和PKA以及ATGL和p-HSL（Ser563）的蛋白含量显著上调。SB处理增强了线粒体氧化磷酸化。丁酸钠显著增加了13个线粒体DNA编码基因中的4个的表达，并显著上调了过氧化物酶体增殖物激活受体γ共激活因子1α和COX4的蛋白含量。此外，SB给药增强了ARβ3及其下游信号的表达。G蛋白偶联受体43和p-CREB（Ser133）受到SB的显著刺激。此外，一种活性转录标记物H3K9Ac在ARβ3基因的启动子上显著富集。我们的结果表明，短期口服SB可通过激活附睾白色脂肪组织中ARβ3介导的脂肪分解有效缓解饮食诱导的肥胖。
