Nav: Home

Researchers identify genetic switch that controls conversion of bad to good fat

May 22, 2019

Fat cells. They are the bane of a dieter's existence, but fat is important. Previous studies showed the subcutaneous white fat cells can transform to brown and beige varieties when exposed to cold stress. These dusky forms of fat, burn energy more effectively to keep an organism warm. Researchers at University of Utah Health have figured out a way to make more of these energy-burning fat cells. They have identified TLE3, a genetic switch that stops the conversion of white fat into these thermogenic varieties. The results are available online in the May 23 issue of the journal Genes and Development.

"Our story highlights that there are different types of fat cells, and TLE3 is one way to address how fat cells are programmed," said Claudio Villanueva, Ph.D., assistant professor in biochemistry at U of U Health and senior author on the paper. "If we could find therapeutic ways to inhibit TLE3, we may be able to develop interventions for type II diabetes. Therapies that help lower blood glucose levels are gravely needed."

Fat cells come in three varieties. White fat, the most common variety, is stored fat associated with metabolic disorders, like diabetes and obesity. Brown and beige fat contain more mitochondria, the energy centers of the cell, allowing these varieties to burn fuel more efficiently. Brown fat is activated in cold conditions and burned to create heat. Beige fat is found in bundles nestled within white fat, but little is known about it.

Previous research found that white fat tissue that overexpresses early B-cell factor 2 (EFB2) recruits more beige fat cells, but this protein-coding gene is triggered by many factors. Villanueva and his team focused on transducing-like enhancer 3 (TLE3), a protein situated in the same region as EFB2. They found that TLE3 acts like a switch, stopping EFB2 from converting white to beige fat and preventing energy expenditure and glucose use.

The team deleted TLE3 in mice and placed the animals in cold conditions for several days. According to Villanueva, they tried to recreate a situation where an animal would be trying to develop beige fat cells to understand impact of the loss of TLE3. In the absence of this gene, the knock-out mice recruited more beige fat cells. The team examined the impact of the abundance of beige fat on animal metabolism.

"The knock-out mice experienced enhanced energy expenditure under normal conditions and weight loss during cold conditions," said Stephanie Pearson, PhD, a researcher working in Villanueva's lab and first author on the paper. "Even without cold stimulation, the knock-out mice did not gain as much weight."

Villanueva believes these results could be used to create interventions for metabolic disorders.

"Long-term we want to identify or develop drugs that will target TLE3 that can be used as an intervention for patients with type 2 diabetes and obesity," he said.
-end-
Villanueva and Pearson were joined on this study by Judith Simcox and Sanghoon Lee at U of U Health, Anne Loft and Susanne Mandrup from University of Southern Denmark and Peter Tontonoz and Prashant Rahbhandari from University of California, Los Angeles. Their work, titled Loss of TLE3 Promotes the Mitochondrial Program in Beige Adipocytes and Improves Glucose Metabolism, received support from the National Institute of Diabetes and Digestive and Kidney Diseases and the National Institutes of Health. The team conducted their work in conjunction with the Metabolic Phenotyping Core at U of U Health and is part of the Diabetes and Metabolism Research Center, an interdisciplinary program that supports research relating to diabetes, metabolism, and overall metabolic health.

University of Utah Health

Related Diabetes Articles:

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.
New oral diabetes drug shows promise in phase 3 trial for patients with type 1 diabetes
A University of Colorado Anschutz Medical Campus study finds sotagliflozin helps control glucose and reduces the need for insulin in patients with type 1 diabetes.
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.
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.
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

Listen Again: Reinvention
Change is hard, but it's also an opportunity to discover and reimagine what you thought you knew. From our economy, to music, to even ourselves–this hour TED speakers explore the power of reinvention. Guests include OK Go lead singer Damian Kulash Jr., former college gymnastics coach Valorie Kondos Field, Stockton Mayor Michael Tubbs, and entrepreneur Nick Hanauer.
Now Playing: Science for the People

#562 Superbug to Bedside
By now we're all good and scared about antibiotic resistance, one of the many things coming to get us all. But there's good news, sort of. News antibiotics are coming out! How do they get tested? What does that kind of a trial look like and how does it happen? Host Bethany Brookeshire talks with Matt McCarthy, author of "Superbugs: The Race to Stop an Epidemic", about the ins and outs of testing a new antibiotic in the hospital.
Now Playing: Radiolab

Dispatch 6: Strange Times
Covid has disrupted the most basic routines of our days and nights. But in the middle of a conversation about how to fight the virus, we find a place impervious to the stalled plans and frenetic demands of the outside world. It's a very different kind of front line, where urgent work means moving slow, and time is marked out in tiny pre-planned steps. Then, on a walk through the woods, we consider how the tempo of our lives affects our minds and discover how the beats of biology shape our bodies. This episode was produced with help from Molly Webster and Tracie Hunte. Support Radiolab today at Radiolab.org/donate.