Chen Dandan, Duan Yanan, Yu Shuxiang, Zhang Xinwen, Li Ni, Li Jingya
School of Life Sciences, Shanghai University, Shanghai 200444, China.
State Key Laboratory of Drug Research, The National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Pharmaceuticals (Basel). 2022 Apr 13;15(4):469. doi: 10.3390/ph15040469.
Pharmacological activation of adaptive thermogenesis to increase energy expenditure is considered to be a novel strategy for obesity. Peroxisome-proliferator-activated receptor γ co-activator-1α (PGC-1α), which serves as an inducible co-activator in energy expenditure, is highly expressed in brown adipose tissues (BAT). In this study, we found a PGC-1α transcriptional activator, natural compound rutaecarpine (Rut), which promoted brown adipocytes mitochondrial biogenesis and thermogenesis in vitro. Chronic Rut treatment reduced the body weight gain and mitigated insulin sensitivity through brown and beige adipocyte thermogenesis. Mechanistic study showed that Rut activated the energy metabolic pathway AMP-activated protein kinase (AMPK)/PGC-1α axis, and deficiency of AMPK abolished the beneficial metabolic phenotype of the Rut treatment in vitro and in vivo. In summary, a PGC-1α transcriptional activator Rut was found to activate brown and beige adipose thermogenesis to resist diet-induced obesity through AMPK pathway. Our findings serve as a further understanding of the natural compound in adipose tissue and provides a possible strategy to combat obesity and related metabolic disorders.
通过药理激活适应性产热以增加能量消耗被认为是一种治疗肥胖症的新策略。过氧化物酶体增殖物激活受体γ共激活因子1α（PGC-1α）作为能量消耗中的一种诱导性共激活因子，在棕色脂肪组织（BAT）中高度表达。在本研究中，我们发现了一种PGC-1α转录激活剂——天然化合物吴茱萸碱（Rut），它在体外促进棕色脂肪细胞的线粒体生物合成和产热。长期给予Rut治疗可通过棕色和米色脂肪细胞产热减少体重增加并改善胰岛素敏感性。机制研究表明，Rut激活了能量代谢途径——AMP激活的蛋白激酶（AMPK）/PGC-1α轴，并且AMPK缺乏消除了Rut治疗在体外和体内的有益代谢表型。总之，我们发现一种PGC-1α转录激活剂Rut可通过AMPK途径激活棕色和米色脂肪产热以抵抗饮食诱导的肥胖症。我们的研究结果有助于进一步了解脂肪组织中的天然化合物，并为对抗肥胖症及相关代谢紊乱提供了一种可能的策略。
