Resveratrol Ameliorates High-Fat-Diet-Induced Abnormalities in Hepatic Glucose Metabolism in Mice via the AMP-Activated Protein Kinase Pathway

Caiping Lu; Hanying Xing; Linquan Yang; Kaiting Chen; Linyi Shu; Xiaojian Zhao; Guangyao Song

doi:10.1155/2021/6616906

Resveratrol Ameliorates High-Fat-Diet-Induced Abnormalities in Hepatic Glucose Metabolism in Mice via the AMP-Activated Protein Kinase Pathway

Evid Based Complement Alternat Med. 2021 Jun 25:2021:6616906. doi: 10.1155/2021/6616906. eCollection 2021.

Authors

Caiping Lu^{1

2

3}, Hanying Xing⁴, Linquan Yang⁴, Kaiting Chen^{1

2

3}, Linyi Shu^{1

2}, Xiaojian Zhao⁵, Guangyao Song^{1

2}

Affiliations

¹ Department of Internal Medicine, Hebei Medical University, Shijiazhuang 050017, Hebei Province, China.
² Department of Endocrinology, Hebei General Hospital, Shijiazhuang 050051, Hebei Province, China.
³ Department of Endocrinology, Shijiazhuang People's Hospital, Shijiazhuang 050000, Hebei Province, China.
⁴ Hebei Key Laboratory of Metabolic Diseases, Hebei General Hospital, Shijiazhuang 050051, Hebei Province, China.
⁵ Department of Thoracic Surgery, Shijiazhuang People's Hospital, Shijiazhuang 050000, Hebei Province, China.

Abstract

Diabetes mellitus is highly prevalent worldwide. High-fat-diet (HFD) consumption can lead to liver fat accumulation, impair hepatic glycometabolism, and cause insulin resistance and the development of diabetes. Resveratrol has been shown to improve the blood glucose concentration of diabetic mice, but its effect on the abnormal hepatic glycometabolism induced by HFD-feeding and the mechanism involved are unknown. In this study, we determined the effects of resveratrol on the insulin resistance of high-fat-diet-fed mice and a hepatocyte model by measuring serum biochemical indexes, key indicators of glycometabolism, glucose uptake, and glycogen synthesis in hepatocytes. We found that resveratrol treatment significantly ameliorated the HFD-induced abnormalities in glucose metabolism in mice, increased glucose absorption and glycogen synthesis, downregulated protein phosphatase 2A (PP2A) and activated Ca²⁺/CaM-dependent protein kinase kinase β (CaMKKβ), and increased the phosphorylation of AMP-activated protein kinase (AMPK). In insulin-resistant HepG2 cells, the administration of a PP2A activator or CaMKKβ inhibitor attenuated the effects of resveratrol, but the administration of an AMPK inhibitor abolished the effects of resveratrol. Resveratrol significantly ameliorates abnormalities in glycometabolism induced by HFD-feeding and increases glucose uptake and glycogen synthesis in hepatocytes. These effects are mediated through the activation of AMPK by PP2A and CaMKKβ.