1. Academic Validation
  2. Chrysophanol Alleviates Metabolic Syndrome by Activating the SIRT6/AMPK Signaling Pathway in Brown Adipocytes

Chrysophanol Alleviates Metabolic Syndrome by Activating the SIRT6/AMPK Signaling Pathway in Brown Adipocytes

  • Oxid Med Cell Longev. 2020 Nov 12;2020:7374086. doi: 10.1155/2020/7374086.
Xueying Liu 1 2 3 Zehong Yang 4 Huixuan Li 5 Wen Luo 1 Wentao Duan 5 Junmei Zhang 3 Zhangzhi Zhu 3 Min Liu 3 Saimei Li 1 Xiaoyi Xin 6 Haoxiang Wu 3 Shaoxiang Xian 1 7 Meijing Liu 8 Changhui Liu 9 Chuangpeng Shen 1 2 3
Affiliations

Affiliations

  • 1 The First Clinical Medical College of Guangzhou University of Chinese Medicine, 16 Airport Road, Guangzhou 510405, China.
  • 2 Department of Chinese Medicine, The First People's Hospital of Kashgar Prefecture, Kashgar, Xinjiang Uygur Autonomous Region, 844000, China.
  • 3 Department of Endocrinology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, 16 Airport Road, Guangzhou 510405, China.
  • 4 Artemisinin Research Center, Guangzhou University of Chinese Medicine, 12 Airport Road, Guangzhou 510405, China.
  • 5 Science and Technology Innovation Center, Piwei Institute, Guangzhou University of Chinese Medicine, 12 Airport Road, Guangzhou 510405, China.
  • 6 Department of Chinese Medicine, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, 830011, China.
  • 7 Department of Cardiovascularology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, 16 Airport Road, Guangzhou 510405, China.
  • 8 Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, School of Medicine and Engineering, Beihang University, Beijing 100191, China.
  • 9 School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, 12 Airport Road, Guangzhou 510405, China.
Abstract

Chrysophanol, a primary active ingredient of Cassia mimosoides Linn or Rhei radix et rhizoma, has various pharmacological properties, including Anticancer, antidiabetic, and anti-inflammatory, as well as blood lipid regulation. However, whether chrysophanol can mitigate obesity, and its underlying mechanisms remains unclear. This study investigated whether chrysophanol effects energy metabolism in high-fat diet- (HFD-) induced obese mice and fat-specific Sirtuin 6- (SIRT6-) knockout (FKO) mice, targeting the SIRT6/AMPK signaling pathway in brown and white fat tissue. Our results showed that chrysophanol can effectively inhibit lipid accumulation in vitro and reduce mice's body weight, improve Insulin sensitivity and reduced fat content of mice, and induce energy consumption in HFD-induced obese mice by activating the SIRT6/AMPK pathway. However, a treatment with OSS-128167, an SIRT6 Inhibitor, or si-SIRT6, SIRT6 target specific small interfering RNA, in vitro blocked chrysophanol inhibition of lipid accumulation. Similar results were obtained when blocking the AMPK pathway. Moreover, in the HFD-induced obese model with SIRT6 FKO mice, histological analysis and genetic test results showed that chrysophanol treatment did not reduce lipid droplets and upregulated the uncoupling protein 1 (UCP1) expression. Rather, it upregulated the expression of thermogenic genes and activated white fat breakdown by inducing phosphorylation of adenosine 5'-monophosphate- (AMP-) activated protein kinase (AMPK), both in vitro and in vivo. OSS-128167 or si-SIRT6 blocked chrysophanol's upregulation of peroxisome proliferator-activated receptor-γ coactivator-1α (Pgc-1α) and Ucp1 expression. In conclusion, this study demonstrated that chrysophanol can activate brown fat through the SIRT6/AMPK pathway and increase energy consumption, Insulin sensitivity, and heat production, thereby alleviating obesity and metabolic disorders.

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