Researchers Identify Muscle Factor that Controls Fat Metabolism

New discovery from team at University Hospitals and Case Western Reserve University could lead to metabolic disease therapies

Metabolic diseases, such as obesity and type 2 diabetes, have risen to epidemic proportions in the U.S. and occur in about 30% of the population. Skeletal muscle plays a prominent role in controlling the body’s glucose levels, which is important for the development of metabolic diseases like diabetes.

In a recent study, published in The Journal of Clinical Investigation,University Hospitals (UH) Cleveland Medical Center and Case Western Reserve University School of Medicine researchers have found that skeletal muscle significantly affects how the body stores and metabolizes fat.

In the study, Mukesh K. Jain, MD, senior author, Chief Academic Officer at UH, and the Ellery Sedgwick Jr. Chair & Distinguished Scientist, and his team set out to investigate the role of a gene called Kruppel-like factor 15 (KLF15) in skeletal muscle. The team utilized a mouse model with KLF15 specifically deleted in muscle.

This genetic manipulation resulted in a striking phenotype: obesity, dyslipidemia (high circulating levels of fats), glucose intolerance, insulin resistance, and a propensity to develop non-alcoholic fatty liver disease (NAFLD).

“We knew from prior work by our team that the role of KLF15 was critical for muscle health, because levels are increased in humans following exercise,” explained Dr. Jain, who is also a Professor of Medicine and Vice Dean of University Hospitals Affairs at Case Western Reserve, and Chief Scientific Officer, Harrington Discovery Institute at UH. “Experimentally, muscle loss of KLF15 led to a reduction in exercise capacity in mice. The fact that KLF15 is also important in metabolic health is really exciting as it provides a potential molecular link between exercise and overall health.”

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