脂肪甘油三酯脂肪酶
自噬
糖皮质激素受体
化学
染色质免疫沉淀
脂质代谢
安普克
脂肪酸结合蛋白
生物化学
受体
脂肪酶
激酶
蛋白激酶A
酶
发起人
基因表达
基因
细胞凋亡
作者
Siwen Yang,Ting Liu,Chenxing Hu,Weili Li,Yu-Han Meng,Haiyang Li,Chengcheng Song,Congcong He,Yifa Zhou,Yuying Fan
出处
期刊:Pharmaceutics
[MDPI AG]
日期:2022-06-02
卷期号:14 (6): 1192-1192
被引量:2
标识
DOI:10.3390/pharmaceutics14061192
摘要
(1) Background: The glucocorticoid receptor (GR) plays a key role in lipid metabolism, but investigations of GR activation as a potential therapeutic approach have been hampered by a lack of selective agonists. Ginsenoside compound K (CK) is natural small molecule with a steroid-like structure that offers a variety of therapeutic benefits. Our study validates CK as a novel GR agonist for the treatment of obesity. (2) Methods: By using pulldown and RNA interference, we determined that CK binds to GR. The anti-obesity potential effects of CK were investigated in obese mice, including through whole-body energy homeostasis, glucose and insulin tolerance, and biochemical and proteomic analysis. Using chromatin immunoprecipitation, we identified GR binding sites upstream of lipase ATGL. (3) Results: We demonstrated that CK reduced the weight and blood lipids of mice more significantly than the drug Orlistat. Proteomics data showed that CK up-regulated autophagy regulatory proteins, enhanced fatty acid oxidation proteins, and decreased fatty acid synthesis proteins. CK induced lipophagy with the initial formation of the phagophore via AMPK/ULK1 activation. However, a blockade of autophagy did not disturb the increase in CK on lipase expression, suggesting that autophagy and lipase are independent pathways in the function of CK. The pulldown and siRNA experiments showed that GR is the critical target. After binding to GR, CK not only activated lipophagy, but also promoted the binding of GR to the ATGL promoter. (4) Conclusions: Our findings indicate that CK is a natural food candidate for reducing fat content and weight.
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