Meeting Abstract
P2.134 Monday, Jan. 5 Role of Matrix metalloproteinases in activating myostatin in the skeletal muscle in response to high fat diet induced diabesity PAKALA, K/P*; BIGA, P/R; North Dakota State University; North Dakota State University keerti.pakala@ndsu.edu
High fat diet-induced obesity (HFDIO) is associated with type 2 diabetes and metabolic dysfunction. Skeletal muscle and adipose tissue are the main sites of energy utilization and play an important role in the regulation of energy homeostasis. Obesity is also known to be a pro-inflammatory disease with increased systemic cytokine release, potentially triggering local immune responses. The intent of this project is to evaluate the relationship between muscle growth, metabolism, and the immune system, specifically targeting how matrix metalloproteinases (MMPs) and myostatin (MSTN) might interact in skeletal muscle tissue. Myostatin is a negative regulator of skeletal muscle mass and impacts body fat accumulation, and it has recently been demonstrated that MSTN plays an important role in high-fat diet induced obesity (HFDIO). Removal of MSTN results in resistance to HFDIO. In addition, we have demonstrated that different strains of mice exhibiting differential susceptibility to a high fat diet exhibit significant differential MSTN gene expression. Also, MSTN appears to bind decorin in the ECM, which is a target of MMP activity. Matrix metalloproteinases are zinc-dependent endopeptidases and have been implicated in the pathology of dystrophin-related muscle disorders and inflammatory myopathies. Activated MMP-2 and -9 are present in muscle from obese mice, and MMP-2 gene expression is highly upregulated in obese spleen tissue. MMP-9 gene expression is elevated to a greater degree than MMP-2 in muscle tissue of obese mice, suggesting a role of MMP-9 in muscle responses to inflammation and possibly MSTN activation regulation. By comparing different inbred strains of mice, we can better understand the genetic components regulating diabesity, which may lead to a better understanding of the interaction between the immune system and metabolism.
