BRCA1 is a novel regulator of metabolic function in skeletal muscle

Journal of Lipid Research

P. Darrell Neufer¹  Ana P. Valencia²  Kathryn C. Jackson²  David M. Thomson³  Eva-Karin Gidlund⁴  Jessica Norrbom⁴  Espen E. Spangenburg⁵  Rosemary A. Schuh⁶ 

[1] Department of Neurology, School of Medicine, University of Maryland, Baltimore, MD;Department of Kinesiology, School of Public Health, University of Maryland, College Park, MD;Department of Physiology and Developmental Biology, Brigham Young University, Provo, UT;Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden;Departments of Physiology and Kinesiology, East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, NC;Research Service, Maryland Veteran Affairs Health Care System, Baltimore, MD;

关键词: breast cancer type 1;    muscle;    gene;    mitochondria;    lipid;    insulin;   

DOI  :  

来源: DOAJ

【 摘 要 】

Breast cancer type 1 (BRCA1) susceptibility protein is expressed across multiple tissues including skeletal muscle. The overall objective of this investigation was to define a functional role for BRCA1 in skeletal muscle using a translational approach. For the first time in both mice and humans, we identified the presence of multiple isoforms of BRCA1 in skeletal muscle. In response to an acute bout of exercise, we found increases in the interaction between the native forms of BRCA1 and the phosphorylated form of acetyl-CoA carboxylase. Decreasing BRCA1 content using a shRNA approach in cultured primary human myotubes resulted in decreased oxygen consumption by the mitochondria and increased reactive oxygen species production. The decreased BRCA1 content also resulted in increased storage of intracellular lipid and reduced insulin signaling. These results indicate that BRCA1 plays a critical role in the regulation of metabolic function in skeletal muscle. Collectively, these data reveal BRCA1 as a novel target to consider in our understanding of metabolic function and risk for development of metabolic-based diseases.

【 授权许可】

Unknown