Research Paper Volume 13, Issue 6 pp 8960—8974
Exercise in mice ameliorates high-fat diet-induced nonalcoholic fatty liver disease by lowering HMGCS2
- 1 Rehabilitation Medicine Center, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325027, Zhejiang, China
- 2 Integrative and Optimized Medicine Research Center, China-USA Institute for Acupuncture and Rehabilitation, Wenzhou Medical University, Wenzhou 325027, Zhejiang, China
Received: September 17, 2020 Accepted: January 14, 2021 Published: March 1, 2021
https://doi.org/10.18632/aging.202717How to Cite
Copyright: © 2021 Qian et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease worldwide. Exercise is a therapeutic strategy for preventing NAFLD. However, the underlying molecular mechanisms by which NAFLD can be ameliorated through exercise are still not clear. This study investigates the mechanisms by which exercise suppresses NAFLD development induced by a high-fat diet (HFD) in mice. Male 6-week-old C57BL/6J mice were fed a normal diet or HFD for 12 weeks and then induced to swim or remain sedentary for 8 weeks. Histomorphology, inflammatory factors, fat metabolizing enzymes, fibrosis, and steatosis were determined in HFD-fed mouse liver, and levels of hepatic enzymes and molecules in the related pathways were analyzed. NAFLD mice showed evident steatosis, fibrosis, and liver injury, and an increased expression of HMGCS2, Wnt3a/ β-catenin, and phosphorylated (p)-AMPK in the liver. Exercise significantly attenuated these symptoms and downregulated the level of Wnt3a/β-catenin in lipotoxic liver tissue. Inhibition of HMGCS2 expression decreased the activation of the Wnt3a/β-catenin pathway and lowered p-AMPK in palmitate-treated HepG2. Our results suggest that exercise prevents NAFLD-associated liver injury, steatosis, and fibrosis. Exercise-mediated hepatoprotection was achieved partly via the blocking of the upregulation of HMGCS2 and the attenuation of the Wnt3a/β-catenin pathway.
Abbreviations
ALT: serum alanine aminotransferase; AST: aspartate aminotransferase; H&E: hematoxylin and eosin; HFD: high-fat diet; HMGCS2: 3-hydroxy-3-methylglutaryl-CoA synthase 2; NAFLD: nonalcoholic fatty liver disease; ND: normal diet; PFD: paraformaldehyde.