Calpain 3 gene expression in skeletal muscle is associated with body fat content and measures of insulin resistance

<b>OBJECTIVE</b>: To investigate whether skeletal muscle gene expression of <i>calpain 3</i> is related to obesity and insulin resistance.<br /><br /><b>DESIGN</b>: Cross-sectional studies in 27 non-diabetic human subjects and in <i>Psammomys obesus</i>, a polygenic animal model of obesity and type 2 diabetes.<br /><br /><b>MEASUREMENTS</b>: Expression of <i>CAPN3</i> in skeletal muscle was measured using Taqman fluorogenic PCR. In the human subjects, body composition was assessed by DEXA and insulin sensitivity was measured by euglycemic-hyperinsulinemic clamp. In <i>Psammomys obesus</i>, body composition was determined by carcass analysis, and substrate oxidation rates, physical activity and energy expenditure were measured by whole-body indirect calorimetry.<br /><br /><b>RESULTS</b>: In human subjects, <i>calpain 3</i> gene expression was negatively correlated with total (<i>P</i>=0.022) and central abdominal fat mass (<i>P</i>=0.034), and with blood glucose concentration in non-obese subjects (<i>P</i>=0.017). In <i>Psammomys obesus</i>, <i>calpain 3</i> gene expression was negatively correlated with circulating glucose (<i>P</i>=0.013) and insulin (<i>P</i>=0.034), and with body fat mass (<i>P</i>=0.049). Indirect calorimetry revealed associations between calpain 3 gene expression and carbohydrate oxidation (<i>P</i>=0.009) and energy expenditure (<i>P</i>=0.013).<br /><br /><b>CONCLUSION/INTERPRETATION</b>: Lower levels of expression of <i>calpain 3</i> in skeletal muscle were associated with reduced carbohydrate oxidation and elevated circulating glucose and insulin concentrations, and also with increased body fat and in particular abdominal fat. Therefore, reduced expression of <i>calpain 3</i> in both humans and <i>Psammomys obesu</i><i>s</i> was associated with phenotypes related to obesity and insulin resistance.<br />