Reduction of muscle fiber size, muscle IGF‐1, and increased myostatin in the leptin receptor‐deficient POUND mouse

Abstract

Functional leptin receptors are expressed in skeletal muscle, but the role of leptin signaling in muscle tissue is not well understood. We examined skeletal muscle in POUND mice, which lack all functional leptin receptor isoforms, and in db/db mice, which express the short form but not the long form of the leptin receptor. POUND mice and db/db mice both showed reductions (~30%) in muscle fiber diameter within the predominantly fast‐twitch extensor digitorum longus (EDL) muscle. ELISA assays were used to quantify levels of insulin‐like growth factor 1 (IGF‐1), which enhances myogenesis, and myostatin, which constrains muscle growth, in muscle homogenates. POUND mice exhibited greater reductions in EDL muscle IGF‐1 expression compared to db/db mice. Likewise, EDL muscles from POUND mice showed a 170% increase in myostatin levels compared to controls, whereas db/db mice showed a 70% increase in myostatin protein expression. These findings suggest that progressive deletion of various leptin receptor isoforms yields increasingly severe alterations in muscle fiber protein synthesis in predominantly fast‐twitch skeletal muscle fibers. Funding for this research was provided by the National Institute on Aging (P01AG036675‐ 01A1).