Weight Gain Reveals Dramatic Increases in Skeletal Muscle Extracellular Matrix Remodeling

Context: In animal models of obesity, chronic inflammation and dysregulated extracellular matrix remodeling in adipose tissue leads to insulin resistance. Whether similar pathophysiology occurs in humans is not clear. Objective: The aim of this study was to test whether 10% weight gain induced by overfeeding triggers inflammation and extracellular matrix remodeling (gene expression, protein, histology) in skeletal muscle and sc adipose tissue in humans. We also investigated whether such remodeling was associated with an impaired metabolic response (hyperinsulinemic-euglycemic clamp). Design, Setting, Participants, and Intervention: Twenty-nine free-living males were fed 40% over their baseline energy requirements for 8 weeks. Results: Ten percent body weight gain prompted dramatic up-regulation of a repertoire of extracellular matrix remodeling genes in muscle and to a lesser degree in adipose tissue. The amount of extracellular matrix genes in the muscle were directly associated with the amount of lean tissue deposited during overfeeding. Despite weight gain and impaired insulin sensitivity, there was no change in local adipose tissue or systemic inflammation, but there was a slight increase in skeletal muscle inflammation. Conclusion: We propose that skeletal muscle extracellular matrix remodeling is another feature of the pathogenic milieu associated with energy excess and obesity, which, if disrupted, may contribute to the development of metabolic dysfunction.