Newswise – CLEVELAND – Metabolic diseases such as obesity and type 2 diabetes have reached epidemic proportions in the United States, affecting approximately 30 percent of the population. Skeletal muscles play a prominent role in controlling the body’s glucose levels, which is important for the development of metabolic diseases such as diabetes.
In a study recently published in the Journal of Clinical Investigation by the Cleveland Medical Center at University Hospitals (UH) and the School of Medicine at Case Western Reserve University, researchers found that skeletal muscle significantly affects the way the body stores and metabolizes fat influence.
In the study, Dr. Mukesh K. Jain, senior author, chief academic officer at UH, and the chairman and distinguished scientist of Ellery Sedgwick Jr. and his team investigated the role of a gene called Kruppel-like factor 15 (KLF15) in skeletal muscle. The team used a mouse model with KLF15 that was specifically deleted in muscle.
This genetic manipulation resulted in a noticeable phenotype: obesity, dyslipidemia (high levels of circulating fat), glucose intolerance, insulin resistance, and a tendency to develop non-alcoholic fatty liver disease (NAFLD).
“We knew from previous work by our team that the role of KLF15 is critical to muscle health as it increases levels in humans after exercise,” said Dr. Jain, who is also Professor of Medicine and Vice Dean of University Hospitals at Case Western Reserve and Chief Scientific Officer of the Harrington Discovery Institute at UH. “Experimentally, the loss of muscle from KLF15 in mice led to a reduction in exercise capacity. The fact that KLF15 is also important for metabolic health is really exciting as it represents a potential molecular link between exercise and general health. “
The researchers also showed that a diet high in short chain fatty acids (SCFAs) can improve aspects of metabolic disorders. High fiber foods like fruits, vegetables, beans, and whole grains are high in SCFAs. Mice given this diet showed decreased weight gain and improved glucose homeostasis (blood sugar regulation). In addition, obese mice given the same diet showed increased weight loss and improved insulin sensitivity, suggesting that SCFA-rich diets may serve as both a preventive and therapeutic pathway for metabolic disorders.
“This predisposition to develop obesity and NAFLD in the presence of excess calories underscores the importance of skeletal muscle fat metabolism and organ crosstalk in the development of these serious diseases,” said Liyan Fan, lead author of the study. “This helps us to understand the different actors that contribute to metabolic diseases and, consequently, to identify targets for effective therapies.”
Taken together, these results identified skeletal muscle as an important regulator of fat metabolism and liver health, and SCFA-rich diets may be an effective and accessible complementary therapy option for metabolic disorders resulting from impaired fat management.
The next steps in this research include examining the role of muscle KLF15 in various nutritional conditions (i.e., fasting and exercise) and examining the therapeutic potential of targeting muscle KLF15.
Fan, L. et al. “The muscle cripple-like factor 15 regulates lipid flow and systemic metabolic homeostasis.” The Journal of Clinical Investigation. DOI: 10.1172 / JCI139496
This work was supported by the NIH, the AHA Established Investigator Award from the American Heart Association, the AHA-Allen Frontiers Award, and the Transatlantic Network of Excellence from the Leducq Foundation. Part of this study was conducted at the University of Massachusetts Medical School’s National MMPC, the University of Cincinnati MMPC Center, the Case Western Reserve MMPC, and the Case Western Reserve Cryo-Electron Microscopy Core.
Via University Hospitals / Cleveland, Ohio Established in 1866, the university hospitals serve patient needs through an integrated network of 19 hospitals (including 4 joint ventures), more than 50 health centers and outpatient facilities, and 200 medical offices in 16 counties in northern Ohio. The system’s academic medical center, the Cleveland Medical Center of the University Hospitals in Cleveland University Circle, is affiliated with the Case Western Reserve University School of Medicine. The main campus also includes the Rainbow Babies & Children’s Hospital of the university clinics, which are among the best children’s hospitals in the country. University Hospitals MacDonald Women’s Hospital, the only women’s hospital in Ohio; Harrington Heart & Vascular Institute University Hospitals, a high volume national referral center for complex cardiovascular procedures; and Seidman Cancer Center of the University Hospitals, part of the NCI-designated Case Comprehensive Cancer Center. UH is home to some of the most prestigious clinical and research programs in the country, including cancer, pediatrics, women’s health, orthopedics, radiology, neuroscience, cardiology and cardiovascular surgery, digestive health, transplantation and urology. UH Cleveland Medical Center is among the top performing national surveys, including America’s Best Hospitals by US News & World Report. UH is also home to the Harrington Discovery Institute – part of the Harrington Discovery and Development Project. UH is one of the largest employers in Northeast Ohio with 28,000 doctors and employees. Promote health science and the art of compassion is UH’s vision to help its patients in the future and the organization’s unwavering mission is to heal. To teach. Discover. Follow UH on LinkedIn, Facebook @UniversityHospitals and Twitter @UHhospitals. More information is available at UHhhospitals.org.
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