Posted on Feb 13, 2019, 9 p.m.

A protein released by fat tissues in response to exercise training acts to improve glucose tolerance and has other beneficial effects on metabolic health, as published in Nature Metabolism.

Levels of transforming growth factor-beta 2 were observed to have increased in subcutaneous white adipose tissue and in the bloodstream during exercise; treatment using the adipokine was found to reduce blood lipid levels in obese mice, and reversed detrimental metabolic effects of a high fat diet in diabetic animals. Transforming growth factor-beta 2  is suggested to possibly be a potential treatment for high blood sugar and type 2 diabetes.

Gene expression was compared in the scWAT of sedentary mice and those that voluntarily trained on wheels, and they also looked for changes in gene expression in the scWAT of healthy male volunteers before and after weeks of endurance cycling training; results suggest in mice and humans prolonged exercise training led to increased levels of TGF-B2 mRNA in the scWAT.

Further testing in mice showed exercise training led to increased levels of TGF-B2 proteins in the blood and in scWAT but not in other types of fat, liver, skeletal tissue, or the heart; high intensity cycling and/or resistance training also increased blood levels of TGF-B2 in healthy middle aged men; no other interventions tested including cold exposure or caloric restrictions were found to impact TGF-B2 levels.

Transforming growth factor-beta 2 therapy was observed to improve glucose tolerance in model mice of diet induced obesity in subsequent investigations. Animals exhibited robust improvements in glucose tolerance and insulin sensitivity after being fed high fat diets for 6 weeks and then treated using TGF-B2 for 9 days. According to the Joslin Diabetes Center research team animal total body mass was observed not change while being treated, treatment was linked with reduced adipose tissue mass, lower total fat, and visceral fat as a percentage of body weight.

Inflammatory marker levels that were high in the obese mice returned to normal levels as a result of TGF-B2 therapy. Biochemical testing implicated lactic acid released during exercise in the mechanism by which TGF-B2 is increased. Serum transforming growth factor-beta 2 levels were observed to have decreased in animals given lactate lowering agents over 11 days among animals of voluntary wheel running, lactate inhibition blunted effects of exercise training on glucose tolerance.

A role for lactate has been revealed in glucose homeostasis by stimulating TGF-B2 expression and release from scWAT, according to the team; TGF-B2 is indicated to be an adipokine that increases with exercise and promotes glucose and fatty acid metabolism. Additional in vivo investigations of transforming growth factor-beta 2 treatments stimulated a variety of similar beneficial metabolic effects including reversing detrimental effects of HFF on glucose tolerance, glucose and fatty acid uptake in skeletal muscle, and modulation of macrophages.

With further investigation TGF-B2 may represent therapeutic opportunities for treating obesity induced insulin resistance, although it was noted that further safety studies would be required. The team suggest they uncovered a mechanism that underlies the effects of endurance exercise in glucose and lipid metabolism that provides perspective on exploring lactate TGF-B2 signaling axis to counteract obesity, diabetes, and other metabolic diseases, which revolutionizes the way exercise is thought about regarding its many metabolic effects, and that fat plays an role on how exercise works.

Material provided by: