Sarcopenia in the aging high-fat fed rat: a pilot study for modeling sarcopenic obesity in rodents

Abstract

Obesity has been suggested as a risk factor for sarcopenia. However, the underlying pathogenic concept of sarcopenic obesity is mainly based on phenotypical data from clinical observation. The present pilot study describes a rodent animal model which opens up prospects to carry out translational research of sarcopenic obesity in an experimental setting. Starting with 2 months, male Wistar rats were fed with a diet containing either 25 en % (control diet, CD) versus 45 en % (high fat diet, HFD) of neutral fat. At the age of 20 and 23 months quadriceps muscles were examined in vivo by magnetic resonance techniques which revealed a positive correlation between muscular fat and body weight (r = 0.639) and a negative correlation between muscular fat content and muscle volume (r = -0.742). Expression and phosphorylation status of proteins within the PKB/Akt and AMPK-dependent signaling pathway were examined in muscles of the 24 month-old animals which significantly showed a 50 percent upregulation of Ser(473)P-PKB/Akt and a 90 % constitutive downregulation of S6K1 in the HFD rats. Notably, S6K1 is a key mediator for muscular protein biosynthesis with additional negative feedback on PKB/Akt. Furthermore, muscular expression of the mitochondrial key regulator PGC-1α in the aged HFD rats was only 25 % of that concurrent controls (p = 0.029). These explorative findings in the aging high-fat fed rat might serve as a firm starting point for controlled longitudinal observations in a larger animal cohort of both sexes studying the natural history of sarcopenic obesity.