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Mechanisms of Myosteatosis in Obesity and the Effects of Muscle Hypertrophy
Author(s) -
Corley Zachary L.,
Padgett Caleb A.,
Mintz James D.,
Fulton David J.,
Stepp David W.
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.03286
Subject(s) - endocrinology , medicine , myostatin , lipogenesis , skeletal muscle , muscle hypertrophy , lipid metabolism , carnitine , chemistry , lipid droplet , acetyl coa carboxylase , sarcoplasm , biology , biochemistry , pyruvate carboxylase , calcium , enzyme
Objective To determine the mechanism of ectopic lipid deposition in skeletal muscle in obesity and if any impact is conferred by increasing muscle mass. Methods Skeletal muscles from db/db mice, a well characterized model of human obesity, were isolated and myosteatosis assessed for lipid content via NMR, chemical assay and transmission electron microscopy. Genes involved in lipogenesis, lipid storage and oxidation were assessed by qPCR. To determine the effects of hypermuscularity, db/db mice were crossed with mice lacking myostatin, a myokine that inhibits muscle growth, to generate lean, obese, and hypermuscular obese mice. Results Obese mice exhibited a 3‐fold increase in muscle triglyceride content, which appeared on electron microscopy as diffuse and heterogeneous lipid droplet accumulation in individual muscle fibers. Lipogenic pathways, assessed by expression of sterol regulatory element binding protein (SREBP) and its downstream targets stearyl CoA desaturase‐1 (SCD1), acetyl‐CoA carboxylase (ACC) and fatty acid synthase (FAS), were increased in obesity as was expression of perilipins. Muscle from obese mice was characterized by accumulation of mitochondria and increased expression of carnitine palmitoyltransferase I (CPT1). Deletion of myostatin produced a 40% increase in skeletal muscle mass and reversed the observed change in lipid content and gene expression. Conclusion Obesity increases both lipogenesis and lipid oxidation in the skeletal musculature of obese mice. The balance of these processes favors lipid accumulation as evidenced by droplet formation and enhanced expression of droplet‐related proteins. Deletion of myostatin produced muscle hypertrophy and clearance of ectopic lipids. Specific links between muscle hypertrophy and excess muscle lipids remain to be defined. Support or Funding Information Title: Circadian Origins of Vascular Disease in Obesity | Investigator(s): Stepp, David W. and Fulton, David J., Augusta University, Augusta, GA | Agency: National Institute of Health (NIH) | Institute: National Heart, Lung and Blood Institute (NHLBI) | Type: Research Project (RO1) | Project #: 1RO1HL147159‐01