SIRT1-dependent mechanisms and effects of resveratrol for amelioration of muscle wasting in NASH mice

Abstract

BackgroundIn non-alcoholic steatohepatitis (NASH), muscle wasting was an aggravating factor for the progression of hepatic steatosis. This study explores the potential benefits of chronic treatment with resveratrol, a strong activator of SIRT1 on the muscle wasting of NASH mice.MethodsIn vivo and in vitro study, we evaluate the SIRT1-dependent mechanisms and effects of resveratrol administration for 6 weeks with high-fat-methionine and choline deficient diet-induced NASH mice and palmitate-pretreated C2C12 myoblast cells.ResultsResveratrol treatment improved grip strength and muscle mass of limbs, increased running distance and time on exercise wheels in NASH mice. There is a negative correlation between muscular SIRT1 activity and 3-nitrotyrosine levels of NASH and NASH-resv mice. The SIRT1-dependent effect of muscle wasting was associated with the suppression of oxidative stress, upregulation of antioxidants, inhibition of protein degradation, activation of autophagy, suppression of apoptotic activity, upregulation of lipolytic genes and the reduction of fatty infiltration in limb muscles of NASH mice. In vitro, resveratrol alleviated palmitate acid-induced oxidative stress, lipid deposition, autophagy dysfunction, apoptotic signals, and subsequently reduced fusion index and myotube formation of C2C12 cells. The beneficial effects of resveratrol were abolished by EX527.ConclusionsOur study suggests that chronic resveratrol treatment is a potential strategy for amelioration of hepatic steatosis and muscle wasting in NASH mouse model.

A Molecular Insight into the Role of Antioxidants in Nonalcoholic Fatty Liver Diseases

“…In in vitro study, resveratrol treatments reversed fatty acid mixtures (oleic or palmitic acid) induced mitochondrial oxidative stress-mediated steatosis in HepG2 cells [ 96 ]. In NASH mice, resveratrol treatment decreases oxidative stress and upregulates antioxidants and lipolytic enzymes by SIRT1 activation [ 97 ]. Resveratrol treatments reduced hepatic TG levels and decreased expression of FAS, and SREBP-1c was associated with HFD-induced methylation of the Nrf2 promoter in the mouse liver.…”

The Effect of Long-Lasting Swimming on Rats Skeletal Muscles Energy Metabolism after Nine Days of Dexamethasone Treatment

“…One of the agents, which induced mitochondrial biogenesis via the AMPK–PGC-1α pathway is resveratrol. This polyphenol has been reported to be efficient in preventing muscle atrophy in several models as hypodynamia and hypokinesia [ 20 ], Dex treatment [ 21 ], non-alcoholic steatohepatitis [ 22 ], and sarcopenic obesity [ 23 ]. The previously administered physical training also prevented the muscle atrophy caused by Dex treatment.…”