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Stressing Muscle Metabolism Prevents Obesity and Type 2 Diabetes

September 2017

Exciting new research was recently published in the EMBO Journal by the laboratory of FOEDRC Director, Dale Abel.   The study suggests that gently stressing muscle metabolism could help prevent obesity and type 2 diabetes.  The study was carried out on mice where the team found triggering a type of metabolic stress increased levels of a hormone called fibroblast growth factor-21 (FGF21).  The findings showed the animals were completely protected from obesity and diabetes. Interestingly, in the mice which had already started to develop the condition, the hormone reversed the diabetes and helped them return to a normal weight with normal blood sugar levels.

In a press release, Dr. Abel was quoted, “There is a biological phenomenon known as hormesis where a little bit of stress can be a good thing,” In other words, “there is probably a sweet spot ‘hormetically’, where creating a little bit of muscle stress could be of metabolic benefit.”

The metabolic stress process involved the team applying genetic engineering to the mice, which reduced levels of a type of protein called OPA1 in the animal's muscles.  Interestingly, the altered mice also were completely protected from the weight gain and glucose intolerance that normally develop in mice as they age or when they eat a high-fat diet. Moreover, the research team showed that reducing OPA1 levels in muscle, after mice had become obese and diabetic, reversed these problems – normalizing body weight and reversing glucose intolerance even though the high fat diet continued.

Dr.  Abel was also quoted as saying, "These experiments prove that muscle is the source of circulating FGF21 in the OPA1 deficient mice, and that muscle-derived FGF21 prevents diet-induced obesity and insulin resistance in these mice.  If there is a way that muscle could be reprogrammed to make this hormone, then that could be of therapeutic benefit."

The innovative results of this study are being recognized worldwide.

In addition to Abel, the UI research team includes several FOE DRC researchers:  Renata Oliveira Pereira, research assistant professor of internal medicine, who was the study’s first author, Satya Tadinada, Frederick Zasadny, Angela Olvera, Jennifer Jeffers, Rhonda Souvenir, Rose Mcglauflin, Alec Seei, Trevor Funari, Matthew Potthoff, Christopher Adams, and Ethan Anderson.  The team also included Karen Jesus Oliveira, Karla Maria Pereira Pires at the University of Utah School of Medicine, and Hiromi Sesaki at Johns Hopkins School of Medicine.

The research was funded in part by grants from the National Heart, Lung, and Blood Institute and the National Institute of Diabetes and Digestive and Kidney Diseases, both part of the National Institutes of Health and the American Heart Association.