What You Need To Know: The gene known to be associated with breast cancer susceptibility, BRCA 1, plays a critical role in the normal metabolic function of skeletal muscle, according to a new study. Mutations in the BRCA1 gene may also put people at increased risk for metabolic diseases like obesity and type 2 diabetes, this research indicates.
Background: The gene known to be associated with breast cancer susceptibility, BRCA 1, plays a critical role in the normal metabolic function of skeletal muscle, according to a new study led by University of Maryland School of Public Health researchers. Dr. Espen Spangenburg, associate professor of kinesiology, and his laboratory team are the first to identify that the BRCA1 protein is expressed in the skeletal muscle of both mice and humans, and that it plays a key role in fat storage, insulin response and mitochondrial function in skeletal muscle cells.
The Evidence: Dr. Spangenburg and colleagues, including researchers from the University of Maryland School of Medicine, Brigham Young University, Karolinska Institutet in Sweden, and East Carolina University, found that the BRCA1 protein exists in both mouse and in human skeletal muscle. This is the first evidence since the discovery of BRCA1 in 1994 that the gene is expressed in human muscle cells.
- They further established that the protein produced by the BRCA 1 gene binds with a protein known to play an important role in the metabolism of fat in muscle cells known as Acetyl-CoA carboxylase or ACC. After a period of exercise, the BRCA 1 protein binds to ACC, which helps “turns it off.” This deactivation of ACC encourages the utilization of fatty acids by the muscle.
- Once they established that the two proteins complex together, they sought to answer if BRCA1 plays a critical role in regulating muscle metabolic function. To do so, they “knocked out” the gene so that it was no longer being expressed in the muscle cells cultured from healthy, active and lean female subjects. This was done using shRNA technology specific for BRCA1 in human myotubes (skeletal muscle fiber cells).
The result was that the muscle cells started to look diseased. The removal of BRCA1 from the cells, which simulated what could happen in the cells of a person with a BRCA1 mutation, resulted in increased lipid storage, decreased insulin signaling, reduced mitochondrial function and increased oxidative stress. These are all key risk factors for the development of metabolic diseases, such as obesity, type 2 diabetes and cardiovascular disease.
“Our findings make it clear that BRCA1 plays a protective role against the development of metabolic disease,” Dr. Spangenburg explains. “This gene needs to be there, and should be considered a target to consider in the treatment of type 2 diabetes and/or obesity.”
I’m Dr. Michael Hunter.
The small print: The material presented herein is informational only, and is not designed to provide specific guidance for an individual. Please check with a valued health care provider with any questions or concerns. As for me, I am a Harvard- , Yale- and UPenn-educated radiation oncologist, and I practice in the Seattle, WA (USA) area. I feel genuinely privileged to be able to share with you. If you enjoyed today’s offering, please consider clicking the follow button at the bottom of this page.
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1. K. C. Jackson, E.-K. Gidlund, J. Norrbom, A. P. Valencia, D. M. Thomson, R. A. Schuh, P. D. Neufer, E. E. Spangenburg. BRCA1 is a Novel Regulator of Metabolic Function in Skeletal Muscle.. The Journal of Lipid Research, 2014; DOI: 10.1194/jlr.M043851;
2. University of Maryland. “Breast cancer gene could play critical role in obesity, diabetes.” ScienceDaily. ScienceDaily, 12 March 2014. <www.sciencedaily.com/releases/2014/03/140312114836.htm>.