Li Zilun, Zhang Zili, Ke Liangru, Sun Yanshuang, Li Wenxue, Feng Xiang, Zhu Wei, Chen Sifan
Division of Vascular Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, P.R. China.
State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou, P.R. China.
FASEB J. 2020 Mar;34(3):4527-4539. doi: 10.1096/fj.201902222R. Epub 2020 Jan 31.
Obesity has become an epidemic concern in modern society. The chronic obesity is associated with metabolic disorders, such as hyperglycemia, hyperlipidemia, fatty liver, and cadiovascular disease, which cause high risk for mortality. The novel potential strategy to overcome obesity is to "burn out" the extra fat via "browning" of the white adipose tissues. The phytochemical resveratrol (Res) has attracted substantial attention due to its powerful amelioratory effects in metabolic diseases. However, how Res regulates the browning of adipose tissues remains largely elusive. Our data show that the NAD -dependent deacetylase silent information regulator 1 (Sirt1) mediates Res-induced browning and fat reduction of adipocytes, as well as other Res-improved metabolic phenotypes including hyperglycemina and hyperlipidemia in mice. Interestingly, we found that the major metabolites of Res in vivo (Res-3-O-glucuronide, Res-4'-O-glucuronide, and Res-3-O-sulfate) were much less potent in promoting browning gene expressions and reducing fat content in comparison to Res itself in mouse and human adipocytes in vitro, suggesting the importance and necessarity to enhance the bioavailability of Res in vivo in consideration of therapeutic application. Taken together, our findings clarify the beneficial effects of Res on excess fat utilization via promotion of browning in a Sirt1-dependent manner, suggesting the potential therapeutic application of Res in the treatment of obesity and related metabolic disorders.
肥胖已成为现代社会中一个备受关注的流行病问题。慢性肥胖与代谢紊乱有关，如高血糖、高血脂、脂肪肝和心血管疾病，这些都会导致高死亡风险。克服肥胖的新潜在策略是通过白色脂肪组织的“褐变”来“燃烧”多余的脂肪。植物化学物质白藜芦醇（Res）因其在代谢疾病中的强大改善作用而备受关注。然而，Res如何调节脂肪组织的褐变在很大程度上仍不清楚。我们的数据表明，NAD依赖性脱乙酰酶沉默信息调节因子1（Sirt1）介导了Res诱导的脂肪细胞褐变和脂肪减少，以及Res改善的其他代谢表型，包括小鼠的高血糖和高血脂。有趣的是，我们发现，与Res本身相比，Res在体内的主要代谢产物（Res-3-O-葡萄糖醛酸苷、Res-4'-O-葡萄糖醛酸苷和Res-3-O-硫酸盐）在促进褐变基因表达和降低脂肪含量方面的作用要弱得多，这表明在考虑治疗应用时提高Res在体内生物利用度的重要性和必要性。综上所述，我们的研究结果阐明了Res通过以Sirt1依赖的方式促进褐变对多余脂肪利用的有益作用，提示Res在治疗肥胖及相关代谢紊乱方面具有潜在的治疗应用价值。
