Moderators of skeletal muscle maintenance are compromised in sarcopenic obese mice

Abstract

The purpose of this study was to determine whether sarcopenic obesity accelerates impairments in muscle maintenance through the investigation of cell cycle progression and myogenic, inflammatory, catabolic and protein synthetic signaling in mouse gastrocnemius muscles. At 4 weeks old, 24 male C57BL/6 mice were fed either a high fat diet (HFD, 60 % fat) or normal chow (NC, 17 % fat) for either 8-12 weeks or 21-23 months. At 3-4 months or 22-24 months the gastrocnemius muscles were excised. In addition, plasma was taken for C2C12 differentiation experiments. Mean cross-sectional area (CSA) was reduced by 29 % in aged HFD fed mice compared to the aged NC mice. MyoD was roughly 50 % greater in the aged mice compared to young mice, whereas TNF-α and IGF-1 gene expression in aged HFD fed mice were reduced by 52 % and 65 % in comparison to aged NC fed mice, respectively. Myotubes pretreated with plasma from aged NC fed mice had 14 % smaller myotube diameter than their aged HFD counterparts. Aged obese mice had greater impairments to mediators of muscle maintenance as evident by reductions in muscle mass, CSA, along with alterations in cell cycle regulation and inflammatory and insulin signaling.

Keywords: Aged; High fat; Inflammation; Insulin signaling; Old rodents.