Research Article Details
| Article ID: | A04361 |
| PMID: | 33647884 |
| Source: | Aging (Albany NY) |
| Title: | Exercise in mice ameliorates high-fat diet-induced nonalcoholic fatty liver disease by lowering HMGCS2. |
| 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. |
| DOI: | 10.18632/aging.202717 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S08 | Lifestyle measures | Lifestyle intervention; weight loss; diet adaptation; dietary interventions; lifestyle modifications; Exercise | -- | -- | Details |
| S02 | Enhance lipid metabolism | triglyceride-lowering; lipid tolerance; lipid metabolism | 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) inhibitor; Decreases intestinal cholesterol absorption; FXR agonist; ACC inhibitor; FAS inhibitor; DGAT2 inhibitor; SCD-1 inhibitor | Atorvastatin; Ezetimibe; Obeticholic Acid; GS-9674; GS-0976; TVB-2640; IONIS-DGAT2rx; Aramchol; | Details |
| S03 | Anti-fibrosis | fibrosis | Angiotensin Receptor Blocker (ARB); CCR2/CCR5 antagonist; Thyroid receptor β agonist; PEGylated human FGF21 analogue; Monoclonal antibody to lysyl oxidase-like 2 (LOXL2); Galectin-3 inhibitor; FGF19 variant | Losartan; Cenicriviroc; VK-2809; MGL-3196; Pegbelfermin; Simtuzumab; GR-MD-02; NGM282 | Details |
| S05 | Anti-inflammatory | inflammatory | Bile acid; TNF-a inhibitor; Dual PPAR-α and -δ agonists; Toll-Like Receptor; (TLR)-4 antagonist; Caspase inhibitor; ASK-1 inhibitor | Ursodeoxycholic Acid; Pentoxifylline; Elafibranor; JKB-121; Emricasan; Selonsertib; | Details |
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