Exercise is good. Fat is bad. Or is it? Researchers at the Joslin Diabetes Center say that exercise actually produces dramatic changes to fat. The “trained” fat releases substances into the bloodstream that can help control glucose levels in the blood, possibly pointing towards new therapies for high blood sugar and type 2 diabetes.
Laurie J. Goodyear, PhD, the study co-author, said one of the substances produced by the “trained” fat — TGF-beta 2 — actually improves glucose tolerance. Not only did exercise-stimulated TGF-beta 2 improve glucose tolerance, treating obese mice with TGF beta 2 lowered blood lipid levels and improved many other aspects of metabolism.
“The fact that a single protein has such important and dramatic effects was quite impressive,” said Goodyear, Professor of Medicine at Harvard Medical School.
Two years ago, the international research team first demonstrated that adipose tissue — fat, in other words — offers beneficial metabolic effects in response to exercise.
“Changing the fat”
“Our hypothesis was that exercise is changing the fat, and as a result of that change, the fat releases these beneficial proteins into the bloodstream,” says Goodyear. “Before this discovery, we always just focused on the positive effects of muscle.”
Building on this insight, Joslin researchers sought to identify the substances released from fat in exercise. To do so, they ran a series of molecular experiments in both humans and mice. They identified levels of the substances called adipokines in men before and after a cycle of exercise. They also studied exercising mice.
Their analysis identified TGF beta 2 as one of the proteins upregulated in exercise in humans and mice. Additional investigation confirmed that levels of this one adipokine actually increased in the fat tissue as well as in the bloodstream with exercise, in both cases.
To find out if the protein promoted beneficial metabolic effects, they treated the mice with TGF beta 2. The experiment showed a number of positive metabolic effects in the mice, including improved glucose tolerance and increased fatty acid uptake.
Next, they fed the mice a high-fat diet, causing the animals to develop diabetes. To know if TGF beta 2 was actually responsible for the metabolic effects, they treated the diabetic mice with TGF beta 2. This reversed the negative metabolic effects of the high fat diet, similar to what happens with exercise.
“Our results are important because it’s really the first demonstration of an exercise-released adipokine that can have beneficial metabolic effects on the body,” says Goodyear.
Another significant finding was that lactic acid, which is released during exercise, serves as an integral part of the process. Lactate is released by the muscles during exercise then travels to the fat where it triggers the release of TGF beta 2.
“This research really revolutionizes the way we think about exercise, and the many metabolic effects of exercise. And, importantly, that fat is actually playing an important role in the way exercise works,” said Goodyear.
These findings suggest that TGF beta 2 may be a potential therapy for treatment of high blood sugar, and eventually a potential therapy for type 2 diabetes. Long-term studies will be needed to determine the safety of TGF beta 2 treatment.
The study was published online February 11, 2019, in Nature Metabolism.