Increased muscle mass protects against hypertension and renal injury in obesity

Joshua T. Butcher, James D. Mintz, Sebastian Larion, Shuiqing Qiu, Ling Ruan, David J. Fulton, David W. Stepp

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


Background-Obesity compromises cardiometabolic function and is associated with hypertension and chronic kidney disease. Exercise ameliorates these conditions, even without weight loss. Although the mechanisms of exercise’s benefits remain unclear, augmented lean body mass is a suspected mechanism. Myostatin is a potent negative regulator of skeletal muscle mass that is upregulated in obesity and downregulated with exercise. The current study tested the hypothesis that deletion of myostatin would increase muscle mass and reduce blood pressure and kidney injury in obesity. Methods and Results-Myostatin knockout mice were crossed to db/db mice, and metabolic and cardiovascular functions were examined. Deletion of myostatin increased skeletal muscle mass by _50% to 60% without concomitant weight loss or reduction in fat mass. Increased blood pressure in obesity was prevented by the deletion of myostatin, but did not confer additional benefit against salt loading. Kidney injury was evident because of increased albuminuria, which was abolished in obese mice lacking myostatin. Glycosuria, total urine volume, and whole kidney NOX-4 levels were increased in obesity and prevented by myostatin deletion, arguing that increased muscle mass provides a multipronged defense against renal dysfunction in obese mice. Conclusions-These experimental observations suggest that loss of muscle mass is a novel risk factor in obesity-derived cardiovascular dysfunction. Interventions that increase muscle mass, either through exercise or pharmacologically, may help limit cardiovascular disease in obese individuals.

Original languageEnglish (US)
Article numbere009358
JournalJournal of the American Heart Association
Issue number16
StatePublished - Aug 1 2018


  • Hyperglycemia
  • Hypertension
  • Myostatin
  • Nicotinamide-adenine dinucleotide phosphate
  • Oxidase 4
  • Reduced form
  • Skeletal muscle

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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