Quercetin Reduces Tumor Necrosis Factor Alpha-Induced Muscle Atrophy by Upregulation of Heme Oxygenase-1

• Published in: Journal of medicinal food Vol. 21; no. 6; p. 551
• Main Authors: Kim, Yeji, Kim, Chu-Sook, Joe, Yeonsoo, Chung, Hun Taeg, Ha, Tae Youl, Yu, Rina
• Format: Journal Article
• Language: English
• Published: United States 01.06.2018
• Subjects: Animals; Heme Oxygenase-1 - genetics; Heme Oxygenase-1 - metabolism; Humans; Male; Mice; Mice, Inbred C57BL; Muscle Fibers, Skeletal - drug effects; Muscle Fibers, Skeletal - metabolism; Muscular Atrophy - drug therapy; Muscular Atrophy - etiology; Muscular Atrophy - genetics; Muscular Atrophy - immunology; NF-E2-Related Factor 2 - genetics; NF-E2-Related Factor 2 - metabolism; Obesity - complications; Obesity - genetics; Obesity - metabolism; Quercetin - administration & dosage; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - immunology; Tumor Necrosis Factor-alpha - metabolism; Up-Regulation; quercetin; muscle atrophy; inflammation; obesity
• ISSN: 1557-7600
• DOI: 10.1089/jmf.2017.4108

The inflammatory cytokine tumor necrosis factor α (TNFα), upregulated in the obese condition, promotes protein degradation and is implicated in obesity-related skeletal muscle atrophy and age-related sarcopenia. Quercetin, a flavonoid, elicits antioxidative and anti-inflammatory activities. In this study, we investigated the effect of quercetin on TNFα-induced skeletal muscle atrophy as well as its potential mechanism of action. In this study, we observed that quercetin suppressed expression of TNFα-induced atrophic factors such as MAFbx/atrogin-1 and MuRF1 in myotubes, and it enhanced heme oxygenase-1 (HO-1) protein level accompanied by increased nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) in myotubes. The HO-1 inhibitor ZnPP suppressed the inhibitory actions of quercetin on TNFα-induced atrophic responses and degradation of IκB-α in myotubes. Moreover, quercetin supplementation to high-fat diet-fed obese mice inhibited obesity-induced atrophic responses in skeletal muscle, accompanied by upregulation of HO-1 and inactivation of nuclear factor-kappa B (NF-κB), and the quercetin actions were attenuated in Nrf2-deficient mice. These findings suggest that quercetin protects against TNFα-induced muscle atrophy under obese conditions through Nrf2-mediated HO-1 induction accompanied by inactivation of NF-κB. Quercetin may be used as a dietary supplement to protect against obesity-induced skeletal muscle atrophy.