SARCOPENIC OBESITY ALTERS EXTRACELLULAR MATRIX GENE EXPRESSION IN MICE SKELETAL MUSCLE

Lemuel A. Brown, Richard A. Perry Jr., David E. Lee, Jacob L. Brown, Megan E. Rosa, Nicholas P. Greene, Tyrone A. Washington, University of Arkansas, Fayetteville, Arkansas; e-mail: lxb028@email.uark.edu Sarcopenic obesity is a metabolic syndrome where excessive adipose tissue and a decline of muscle mass leads to reduced mobility and is associated with an increased risk of disability. This is alarming in the United States because older adults are a rapidly growing obese population. In addition, sarcopenic obese individuals have chronic systemic low grade inflammation and decreased insulin sensitivity which negatively impacts signaling pathways that preserve muscle tissue. The extracellular matrix (ECM) in skeletal muscle is essential because it assists in stability and force transmission. Both sarcopenia and obesity are associated with increased fibrosis, however it is not known how these co-morbidities interact during sarcopenic obesity to affect ECM gene expression. PURPOSE: To determine if skeletal muscle ECM gene expression and its regulation 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) after 4 weeks of age. The gastrocnemius was excised for further analysis. Gene expression of ECM and 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\u3c0.05). There was a 9-fold increase in collagen I gene expression in young HFD mice compared to young lean mice (p\u3c0.05). However, there was no differences in collagen I gene expression in aged HFD and aged lean mice. There was a 6-fold increase in collagen III gene expression in young HFD mice compared to young lean mice (p\u3c0.05). However, there was a 73% reduction in collagen III in aged HFD mice compared to aged lean mice (p\u3c0.05). There was a 2-fold increase in fibronectin gene expression in young HFD mice compared to young lean mice (p\u3c0.05). However, there was no difference in fibronectin in aged HFD and aged lean mice (p\u3c0.05). There was a 2-fold increase in MMP-2 gene expression in young HFD mice compared to young lean mice (p\u3c0.05). However, there was a 45% reduction in MMP-2 in aged HFD mice compared to aged lean mice (p\u3c0.05). There was a main effect of diet to decrease MMP-9 in obese mice (p\u3c0.05). There were no differences in TGF-β. CONCLUSION: Sarcopenic obesity altered gene expression of ECM proteins and proteases that are involved with ECM degradation. However, TGF-β, a potent inducer of collagen synthesis was unchanged in age or diet. It appears that MMPs may be partially responsible for the changes involved with sarcopenic obese mice that will alter ECM gene expression. Funding provided by Arkansas Bioscience Institute