Abstract 470: Increasing Muscle Mass As A Therapeutic Target For The Cardiometabolic Syndrome
Increases in muscle mass, as observed with exercise, are positive influences of cardiometabolic health. Muscle mass is limited by myostatin and deletion of myostatin results in a hypermusclar phenotype that has been shown to improve glucose tolerance in obese mice. The effects on vascular and hepatic endpoints are unknown.
Hypothesis: Increasing muscle mass by deletion of muscle growth negative regulator myostatin, improves NOX-limited vasodilation and hepatic steatosis. Myostatin deletion increased muscle mass in both lean (gastrocnemius 57.93%) and obese mice (gastrocnemius 79.64%). Fasting glucose, HbA1c and glucose tolerance are improved in obese myostatin null mice. Obese mice demonstrated increased markers of oxidant load and superoxide-mediated impairment of acetylcholine (Ach)-induced vasodilation compared to lean mice. Deletion of myostatin in obese mice improved Ach-induced vasodilation in mesenteric arteries without effects in lean mice. Response to nitroprusside were similar in all groups. Treatment with GKT(1х10-6 mol/L, NADPH oxidase inhibitor) restored impaired vasodilation in obese mice. Obese mice, with or without myostatin, displayed gross histological steatosis. Elevations in AST and ALT were evident in obesity and unaffected by myostatin deletion. In contrast, evidence of fibrosis (Gomori trichome, collagen mRNA expression) was reversed in obese, hypermuscular mice. Bilary dysfunction, as evidenced by increased in bilirubin, was improve in obese mice lacking myostatin as were plasma level of alkaline phosphatase. Taken together, these data suggest that increasing muscle mass by deletion of myostatin improves the metabolic syndrome as evidence by alleviation of glucose intolerance, endothelial dysfunction and hepatic fibrosis.
Author Disclosures: D. Stepp: None. S. Qiu: None. J.D. Mintz: None. D. Fulton: None.
This research has received full or partial funding support from the American Heart Association, Greater Southeast Affiliate (Alabama, Florida, Georgia, Louisiana, Mississippi, Puerto Rico & Tennessee).
- © 2014 by American Heart Association, Inc.