Zhu Wanlong, Peng Ke, Zhao Yan, Xu Changjing, Tao Xuemei, Liu Yuanzhi, Huang Yilan, Yang Xuping
Department of Pharmacy, The Affiliated Hospital of Southwest Medical University, Luzhou, China.
School of Pharmacy, Southwest Medical University, Luzhou, China.
Front Pharmacol. 2022 Oct 3;13:938760. doi: 10.3389/fphar.2022.938760. eCollection 2022.
Emerging evidence suggests that butyrate, a short-chain fatty acid, may have beneficial effects on obesity and its associated metabolic comorbidities, but the related molecular mechanism is largely unknown. This study aims to investigate the role of butyrate in diet-induced obesity and metabolic disorders and the relevant regulatory mechanisms. Here, dietary supplementation with Sodium butyrate (NaB) was carried out in mice fed with a high-fat diet (HFD) or chow diet. At week 14, mice on HFD displayed an obese phenotype and down-regulated expression of thermogenic regulators including and in adipose tissue. Excitingly, NaB add-on treatment abolished these detrimental effects. Moreover, the obesity-induced insulin resistance, inflammation, fatty liver, and intestinal dysfunction were also attenuated by NaB administration. Mechanistically, NaB can promote fat thermogenesis the increased local sympathetic innervation of adipose tissue, and blocking the β3-adrenergic signaling pathway by 6-hydroxydopamine abolished NaB-induced thermogenesis. Our study reveals a potential pharmacological target for NaB to combat obesity and metabolic disorders.
新出现的证据表明，短链脂肪酸丁酸可能对肥胖及其相关的代谢合并症具有有益作用，但其相关分子机制在很大程度上尚不清楚。本研究旨在探讨丁酸在饮食诱导的肥胖和代谢紊乱中的作用以及相关调控机制。在此，对喂食高脂饮食（HFD）或普通饮食的小鼠进行丁酸钠（NaB）膳食补充。在第14周时，喂食HFD的小鼠表现出肥胖表型，且脂肪组织中产热调节因子（包括 和 ）的表达下调。令人兴奋的是，添加NaB治疗消除了这些有害影响。此外，NaB给药还减轻了肥胖诱导的胰岛素抵抗、炎症、脂肪肝和肠道功能障碍。从机制上讲，NaB可促进脂肪产热 增加脂肪组织局部交感神经支配，而用6-羟基多巴胺阻断β3-肾上腺素能信号通路可消除NaB诱导的产热。我们的研究揭示了NaB对抗肥胖和代谢紊乱的潜在药理学靶点。
