1. Academic Validation
  2. Triptolide enhances lipolysis of adipocytes by enhancing ATGL transcription via upregulation of p53

Triptolide enhances lipolysis of adipocytes by enhancing ATGL transcription via upregulation of p53

  • Phytother Res. 2020 Dec;34(12):3298-3310. doi: 10.1002/ptr.6779.
Xiaoyu Wang 1 Meixue Xu 1 Ying Peng 1 Qimuge Naren 1 Yanting Xu 1 Xin Wang 1 Gongshe Yang 1 Xin'E Shi 1 Xiao Li 1
Affiliations

Affiliation

  • 1 Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A & F University, Yangling, Shaanxi, China.
Abstract

Lipolysis is an essential physiological activity of adipocytes. The Patatin Like Phospholipase Domain Containing 2 (PNPLA2) gene encodes the Enzyme adipose triglyceride Lipase (ATGL) responsible for triglyceride hydrolysis, the first step in lipolysis. In this study, we investigated the potential of triptolide (TP), a natural plant extract, to induce weight loss by examining its effect on ATGL expression. We found that long- and short-term TP administration reduced body weight and fat weight and increased heat production in brown adipose tissue in wild-type C57BL/6 mice. In 3T3-L1 fibroblasts and porcine adipocytes, TP treatment reduced the number of lipid droplets as determined by Oil Red O and BODIPY staining, with concomitant increases in free fatty acid and triglyceride levels in the culture medium. Combined treatment with TP and p53 inhibitor reversed these lipolytic effects. We next amplified the ATGL promoter region and identified conserved p53 binding sites in the sequence by in silico analysis. The results of the dual-luciferase reporter assay using a construct containing the ATGL promoter harboring the p53 binding site showed that p53 induces ATGL promoter activity and consequently, ATGL transcription. These results demonstrate that TP has therapeutic value as an anti-obesity agent and acts by promoting lipolysis via upregulation of p53 and ATGL transcription.

Keywords

ATGL; adipose; lipolysis; p53; transcription; triptolide.

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