Nav: Home

Protein released from fat after exercise improves glucose

February 11, 2019

BOSTON - (February 11, 2019) - It's well-known that exercise improves health, but understanding how it makes you healthier on a molecular level is the question researchers at Joslin Diabetes Center are answering.

After performing experiments in both humans and mice, the researchers found that exercise training causes dramatic changes to fat. Additionally, they discovered that this "trained" fat releases factors into the bloodstream that can have positive effects on health. The study was published online February 11, 2019, in Nature Metabolism.

It's known that fat cells secrete proteins called adipokines, and that many adipokines increase with obesity, having harmful effects on metabolism and health.

"In contrast to the negative effects of many adipokines, our study identified transforming growth factor beta 2 (TGF-beta 2) as an adipokine released from adipose tissue (fat) in response to exercise that actually improves glucose tolerance," says Laurie J. Goodyear, PhD, Head of Joslin's Section on Integrative Physiology and Metabolism and study co-author.

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," says Goodyear, Professor of Medicine at Harvard Medical School.

Two years ago, the international research team first demonstrated that adipose tissue offers beneficial metabolic effects in response to exercise.

"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 adipokines released from fat in exercise. To do so, they ran a series of molecular experiments in both humans and mice. They identified levels of 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," says 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.
-end-
Other study authors include Hirokazu Takahashi Christiano R. R. Alves?, Kristin I. Stanford, Roeland J. W. Middelbeek, Pasquale Nigro, Rebecca E. Ryan, Ruidan Xue, Masaji Sakaguchi, Matthew D. Lynes, Kawai So, Joram D. Mu, Min-Young Lee, Estelle Balan, Hui Pan, Jonathan M. Dreyfuss, Michael F. Hirshman, Mohamad Azhar, Jarna C. Hannukainen, Pirjo Nuutila?, Kari K. Kalliokoski?, Søren Nielsen, Bente K. Pedersen, C. Ronald Kahn and Yu-Hua Tseng.

Journal reference: Takahashi et al. TGF-B2 is an Exercise-Induced Adipokine that Regulates Glucose and Fatty Acid Metabolism. Nature Metabolism, February 11, 2019.

Joslin Diabetes Center

Related Diabetes Articles:

The role of vitamin A in diabetes
There has been no known link between diabetes and vitamin A -- until now.
Can continuous glucose monitoring improve diabetes control in patients with type 1 diabetes who inject insulin
Two studies in the Jan. 24/31 issue of JAMA find that use of a sensor implanted under the skin that continuously monitors glucose levels resulted in improved levels in patients with type 1 diabetes who inject insulin multiple times a day, compared to conventional treatment.
Complications of type 2 diabetes affect quality of life, care can lead to diabetes burnout
T2D Lifestyle, a national survey by Health Union of more than 400 individuals experiencing type 2 diabetes (T2D), reveals that patients not only struggle with commonly understood complications, but also numerous lesser known ones that people do not associate with diabetes.
Type 2 diabetes and obesity -- what do we really know?
Social and economic factors have led to a dramatic rise in type 2 diabetes and obesity around the world.
A better way to predict diabetes
An international team of researchers has discovered a simple, accurate new way to predict which women with gestational diabetes will develop type 2 diabetes after delivery.
The Lancet Diabetes & Endocrinology: Older Americans with diabetes living longer without disability, US study shows
Older Americans with diabetes born in the 1940s are living longer and with less disability performing day to day tasks than those born 10 years earlier, according to new research published in The Lancet Diabetes & Endocrinology journal.
Reverse your diabetes -- and you can stay diabetes-free long-term
A new study from Newcastle University, UK, has shown that people who reverse their diabetes and then keep their weight down remain free of diabetes.
New cause of diabetes
Although insulin-producing cells are found in the endocrine tissue of the pancreas, a new mouse study suggests that abnormalities in the exocrine tissue could cause cell non-autonomous effects that promotes diabetes-like symptoms.
The Lancet Diabetes & Endocrinology: Reducing sugar content in sugar-sweetened drinks by 40 percent over 5 years could prevent 1.5 million cases of overweight and obesity in the UK and 300,000 cases of diabetes
A new study published in The Lancet Diabetes & Endocrinology journal suggests that reducing sugar content in sugar sweetened drinks (including fruit juices) in the UK by 40 percent over five years, without replacing them with any artificial sweeteners, could prevent 500,000 cases of overweight and 1 million cases of obesity, in turn preventing around 300,000 cases of type 2 diabetes, over two decades.
Breastfeeding lowers risk of type 2 diabetes following gestational diabetes
Women with gestational diabetes who consistently and continuously breastfeed from the time of giving birth are half as likely to develop type 2 diabetes within two years after delivery, according to a study from Kaiser Permanente published today in Annals of Internal Medicine.

Related Diabetes Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Setbacks
Failure can feel lonely and final. But can we learn from failure, even reframe it, to feel more like a temporary setback? This hour, TED speakers on changing a crushing defeat into a stepping stone. Guests include entrepreneur Leticia Gasca, psychology professor Alison Ledgerwood, astronomer Phil Plait, former professional athlete Charly Haversat, and UPS training manager Jon Bowers.
Now Playing: Science for the People

#524 The Human Network
What does a network of humans look like and how does it work? How does information spread? How do decisions and opinions spread? What gets distorted as it moves through the network and why? This week we dig into the ins and outs of human networks with Matthew Jackson, Professor of Economics at Stanford University and author of the book "The Human Network: How Your Social Position Determines Your Power, Beliefs, and Behaviours".