The Expression Of Heme Oxygenase 1 In Skeletal Muscle Of Diet Induced Obese Mice In Response To Anti‐obesity Treatment

Abstract

Background Oxidative stress plays an important role in pathogenesis of obesity. Heme oxygenase1 (HMOX1) is a rate-limiting enzyme functioning in heme catabolism, which modulates oxidative stress. Sulforaphane (SFN), a bioactive compound, and previous studies suggest that SFN could be a potential anti-obesity drug. The current study investigates HOMX1 gene expression changes in skeletal muscles (SkM) of wild type diet-induced obesity (DIO). Methods Age and weight matched of wild-type CD1 and the knockout of nuclear factor (erythroid-derived 2)-like 2 (NrF2) mice were fed a high fat diet for 16 weeks to induce DIO. Then, each group was further divided in to two subgroups and received daily intraperitoneal (ip) injections of either vehicle (25 μl) or SFN (5 mg/kg BW) for four weeks. Body weights was monitored daily during treatment. Skeletal muscle samples were assessed for HMOX1 mRNA expression using RT-PCR. Results The body weights of SFN treated WT mice have decreased significantly by -15.1%, p 0.004, while it decreased insignificantly by -2.5% in KO NrF2-/-, p=0.512. HMOX1 expression in (SkM) of WT mice was significantly upregulated following SFN treatment by seven folds, P-value of 0.024, but insignificantly increased by 1.2 folds in (SkM) of KO NrF2-/- mice, p=0.176. Conclusion SFN induces upregulation of heme oxygenase expression in wild-type mice's skeletal muscle but not the KO Nrf2 mice. The upregulation of HOMX1 in skeletal muscle could refer to the role of the Nrf2 pathway in muscle tissue as the main target for SFN treatment in obesity.