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:

Diabetes drug boosts survival in patients with type 2 diabetes and COVID-19 pneumonia
Sitagliptin, a drug to lower blood sugar in type 2 diabetes, also improves survival in diabetic patients hospitalized with COVID-19, suggests a multicenter observational study in Italy.
Making sense of diabetes
Throughout her 38-year nursing career, Laurel Despins has progressed from a bedside nurse to a clinical nurse specialist and has worked in medical, surgical and cardiac intensive care units.
Helping teens with type 1 diabetes improve diabetes control with MyDiaText
Adolescence is a difficult period of development, made more complex for those with Type 1 diabetes mellitus (T1DM).
Diabetes-in-a-dish model uncovers new insights into the cause of type 2 diabetes
Researchers have developed a novel 'disease-in-a-dish' model to study the basic molecular factors that lead to the development of type 2 diabetes, uncovering the potential existence of major signaling defects both inside and outside of the classical insulin signaling cascade, and providing new perspectives on the mechanisms behind insulin resistance in type 2 diabetes and possibly opportunities for the development of novel therapeutics for the disease.
Tele-diabetes to manage new-onset diabetes during COVID-19 pandemic
Two new case studies highlight the use of tele-diabetes to manage new-onset type 1 diabetes in an adult and an infant during the COVID-19 pandemic.
Genetic profile may predict type 2 diabetes risk among women with gestational diabetes
Women who go on to develop type 2 diabetes after having gestational, or pregnancy-related, diabetes are more likely to have particular genetic profiles, suggests an analysis by researchers at the National Institutes of Health and other institutions.
Maternal gestational diabetes linked to diabetes in children
Children and youth of mothers who had gestational diabetes during pregnancy are at increased risk of diabetes themselves, according to new research published in CMAJ (Canadian Medical Association Journal).
Two diabetes medications don't slow progression of type 2 diabetes in youth
In youth with impaired glucose tolerance or recent-onset type 2 diabetes, neither initial treatment with long-acting insulin followed by the drug metformin, nor metformin alone preserved the body's ability to make insulin, according to results published online June 25 in Diabetes Care.
People with diabetes visit the dentist less frequently despite link between diabetes, oral health
Adults with diabetes are less likely to visit the dentist than people with prediabetes or without diabetes, finds a new study led by researchers at NYU Rory Meyers College of Nursing and East Carolina University's Brody School of Medicine.
Diabetes, but not diabetes drug, linked to poor pregnancy outcomes
New research indicates that pregnant women with pre-gestational diabetes who take metformin are at a higher risk for adverse pregnancy outcomes -- such as major birth defects and pregnancy loss -- than the general population, but their increased risk is not due to metformin but diabetes.
More Diabetes News and Diabetes Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Sound And Silence
Sound surrounds us, from cacophony even to silence. But depending on how we hear, the world can be a different auditory experience for each of us. This hour, TED speakers explore the science of sound. Guests on the show include NPR All Things Considered host Mary Louise Kelly, neuroscientist Jim Hudspeth, writer Rebecca Knill, and sound designer Dallas Taylor.
Now Playing: Science for the People

#576 Science Communication in Creative Places
When you think of science communication, you might think of TED talks or museum talks or video talks, or... people giving lectures. It's a lot of people talking. But there's more to sci comm than that. This week host Bethany Brookshire talks to three people who have looked at science communication in places you might not expect it. We'll speak with Mauna Dasari, a graduate student at Notre Dame, about making mammals into a March Madness match. We'll talk with Sarah Garner, director of the Pathologists Assistant Program at Tulane University School of Medicine, who takes pathology instruction out of...
Now Playing: Radiolab

Kittens Kick The Giggly Blue Robot All Summer
With the recent passing of Ruth Bader Ginsburg, there's been a lot of debate about how much power the Supreme Court should really have. We think of the Supreme Court justices as all-powerful beings, issuing momentous rulings from on high. But they haven't always been so, you know, supreme. On this episode, we go all the way back to the case that, in a lot of ways, started it all.  Support Radiolab by becoming a member today at Radiolab.org/donate.