Diabetes

Tweaking muscle metabolism prevents obesity and diabetes in mice

mice
Credit: Martha Sexton/public domain

Mildly stressing muscle metabolism boosts levels of a beneficial hormone that prevents obesity and diabetes in mice, according to a new study by researchers at the University of Iowa.

The new findings, published in the EMBO Journal, show that triggering a certain type of metabolic stress in mouse muscle cells causes them to produce and secrete significant amounts of the anti-diabetic hormone called fibroblast growth factor-21 (FGF21), which then has widespread beneficial effects on whole-body metabolism. The mice in the experiments were completely protected from obesity and diabetes that normally develop due to aging or eating a high-fat diet. Moreover, triggering the FGF21 production after the mice had become obese and diabetic reversed these conditions and returned the mice to normal weight and blood sugar levels.

“There is a biological phenomenon known as hormesis where a little bit of stress a can be a good thing,” says E. Dale Abel, MD, PhD, professor and DEO of internal medicine at the UI Carver College of Medicine and director of the Fraternal Order of Eagles Diabetes Research Center at the UI. “The general conclusion from our study is there is probably a sweet spot ‘hormetically,’ where creating a little bit of muscle stress could be of metabolic benefit.”

Abel and his colleagues used genetic engineering to reduce levels of a mitochondrial protein called OPA1 in the muscles of mice. Mitochondria are tiny organelles that produce a cell’s energy. This OPA1 deficiency disrupted muscle metabolism and caused a small amount of muscle loss in the mice.

Despite the mild muscle atrophy, which did decrease grip strength, the older mice with OPA1 deficiency had greater endurance on the treadmill than older control mice. In addition, activity levels and energy expenditure that normally decline in mice…