西亚试剂：Inhibition of SREBP by a Small Molecule, Betulin, Improves

Inhibition of SREBP by a Small Molecule, Betulin, Improves Hyperlipidemia and Insulin Resistance and Reduces Atherosclerotic Plaques

Authors

Jing-Jie Tang, Jia-Gui Li, Wei Qi, Wen-Wei Qiu, Pei-Shan Li, Bo-Liang Li, Bao-Liang Song

Highlights

The small molecule betulin inhibits SREBP pathway

Betulin decreases the biosynthesis of cholesterol and fatty acid

Betulin improves insulin sensitivity

Betulin reduces atherosclerotic plaques

Summary

Sterol regulatory element-binding proteins (SREBPs) are major transcription factors activating the expression of genes involved in biosynthesis of cholesterol, fatty acid and triglyceride. In this study, we identified a small molecule, betulin, that specifically inhibited the maturation of SREBP by inducing interaction of SREBP cleavage activating protein (SCAP) and Insig. Inhibition of SREBP by betulin decreased the biosynthesis of cholesterol and fatty acid. In vivo, betulin ameliorated diet-induced obesity, decreased the lipid contents in serum and tissues, and increased insulin sensitivity. Furthermore, betulin reduced the size and improved the stability of atherosclerotic plaques. Our study demonstrates that inhibition SREBP pathway can be employed as a therapeutic strategy to treat metabolic diseases including type II diabetes and atherosclerosis. Betulin, which is abundant in birch bark, could be a leading compound for development of drugs for hyperlipidemia.

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