Sarcopenic Obesity Alters Ecm-related Gene Expression In Mouse Skeletal Muscle

Abstract

Sarcopenic obesity is a metabolic syndrome where excess adipose tissue and a decline of muscle due to age results in an increased risk of disability. This is a concern in the United States because older adults are the fastest growing obese population. The extracellular matrix (ECM) in skeletal muscle is essential because it assists in stability, force transmission, and muscle remodeling. Both sarcopenia and obesity are associated with increased fibrosis, however it is not known how these co-morbidities interact during sarcopenic obesity to affect the ECM. PURPOSE: To determine if skeletal muscle ECM-related gene expression is impaired in sarcopenic obese mice. METHODS: Twelve young (3-4 months old) male C57/BL6J mice and twelve aged (22-24 months old) male mice were randomly assigned a normal chow or a high-fat diet (HFD, 60% fat) at 4 weeks of age. The gastrocnemius was excised for further analysis. ECM-related markers were determined by qPCR. Data were analyzed by two-way ANOVA and post hoc Fisher’s LSD. RESULTS: There were significant interactions in collagen I, collagen III, fibronectin, and matrix metalloproteinase 2 (MMP-2) (p<0.05). There was a 9-fold increase in collagen I gene expression in young HFD mice compared to young lean mice (p<0.05). However, there was no differences in collagen I in aged HFD and aged lean mice. There was a 3-fold increase in collagen III in young HFD mice compared to young lean mice (p<0.05). However, there was a 73% reduction in collagen III in aged HFD mice compared to aged lean mice (p<0.05). There was a 2-fold increase in fibronectin in young HFD mice compared to young lean mice (p<0.05). However, there was no difference in fibronectin in aged HFD and aged lean mice. There was a 2-fold increase in MMP-2 in young HFD mice compared to young lean mice (p<0.05). However, there was a 45% reduction in MMP-2 in aged HFD mice compared to aged lean mice (p<0.05). There was a main effect of diet to decrease MMP-9 and myoD in obese mice (p<0.05). There was a main effect of age to increase myoD in aged mice (p<0.05). There were no differences in TGF-β, myogenin, and TIMP-1. CONCLUSIONS: Aging and obesity altered ECM-related gene expression that may be partially responsible for the reduction in muscle function observed in sarcopenic obese individuals. The study was funded by the Arkansas Bioscience Institute.