How to reap the benefits of exercise: It's in the genes

January 10, 2017
TFEB acts as a central coordinator of skeletal muscle insulin sensitivity, glucose homeostasis, lipid oxidation, and mitochondrial function in the adaptive metabolic response to physical exercise in aPGC1a-independent manner. Credit: Mansueto et al., 2017, Cell Metabolism 25, 1-15

An international team of scientists at Baylor College of Medicine, the Telethon Institute of Genetics and Medicine in Naples, Italy and other institutions has discovered that the gene TFEB is a major regulator of muscle function during exercise. Exercise triggers TFEB entering into the nucleus of muscle cells where it regulates the processes that provide energy to the muscle. These genes include those involved in glucose use, insulin sensitivity and function of the mitochondria, the energy-producer structures inside cells. This work may lead to the design of future treatments for conditions such as diabetes, obesity and metabolic syndrome. The study appears in Cell Metabolism.

In a previous study, the researchers found that TFEB can regulate the response of cells to food deprivation.

"In this study we found that TFEB controls the response of the body to ," said co-senior author Dr. Andrea Ballabio, professor of molecular and human genetics at Baylor and director of the Telethon Institute of Genetics and Medicine. "TFEB plays a central role by regulating the expression of genes that allow to use energy." TFEB is a transcription factor - a master regulator molecule inside the cell that controls the expression and function of genes.

Uncovering the role of TFEB in exercise

The scientists studied the role of TFEB in the laboratory mouse. When the researchers knocked out the mouse TFEB gene, the mice had a hard time sustaining . A closer look inside the cells showed that the mitochondria looked abnormal and were dysfunctional. The cells in the exercising could not generate enough energy to sustain physical activity. In contrast, when the scientists overexpressed the TFEB gene in mice, the mitochondria looked healthy and increased the amount of energy they normally produced.

The researchers were surprised by these results. "TFEB had not been associated with how use energy before," Ballabio said.

"This work is the product of a very fruitful international collaboration among researchers in laboratories in Italy, the UK, China and the U.S.," said Ballabio. "Our discovery of a central pathway that regulates muscle metabolism, use of glucose and mitochondrial function may have important implications in the study of diseases such as obesity and diabetes, as well as in a number of diseases in which is compromised."

Future studies aimed at identifying drugs that modulate this pathway may lead to the identification of new strategies to treat such diseases.

Explore further: Muscles have circadian clocks that control exercise response

More information: Gelsomina Mansueto et al, Transcription Factor EB Controls Metabolic Flexibility during Exercise, Cell Metabolism (2016). DOI: 10.1016/j.cmet.2016.11.003

Related Stories

Muscles have circadian clocks that control exercise response

October 20, 2016
Northwestern Medicine scientists have discovered circadian clocks in muscle tissue that control the muscle's metabolic response and energy efficiency depending on the time of day.

Two proteins offer a 'clearer' way to treat Huntington's disease

July 11, 2012
In a paper published in the July 11 online issue of Science Translational Medicine, researchers at the University of California, San Diego School of Medicine have identified two key regulatory proteins critical to clearing ...

Losing body fat could be facilitated by light evening exercise and fasting

December 20, 2016
Making muscles burn more fat and less glucose can increase exercise endurance, but could simultaneously cause diabetes, says a team of scientists from Baylor College of Medicine and other institutions.

Target identified for rare inherited neurological disease in men

August 10, 2014
Researchers at University of California, San Diego School of Medicine have identified the mechanism by which a rare, inherited neurodegenerative disease causes often crippling muscle weakness in men, in addition to reduced ...

Master gene may shed new light on lysosomal and neurodegenerative disorders

May 26, 2011
Cells, like ordinary households, produce "garbage" – debris and dysfunctional elements – that need disposal. When the mechanism for taking out this garbage fails, rare genetic diseases called lysosomal storage disorders ...

Recommended for you

A rogue gene is causing seizures in babies—here's how scientists wants to stop it

July 26, 2017
Two rare diseases caused by a malfunctioning gene that triggers seizures or involuntary movements in children as early as a few days old have left scientists searching for answers and better treatment options.

Scientists provide insight into genetic basis of neuropsychiatric disorders

July 21, 2017
A study by scientists at the Children's Medical Center Research Institute at UT Southwestern (CRI) is providing insight into the genetic basis of neuropsychiatric disorders. In this research, the first mouse model of a mutation ...

Scientists identify new way cells turn off genes

July 19, 2017
Cells have more than one trick up their sleeve for controlling certain genes that regulate fetal growth and development.

South Asian genomes could be boon for disease research, scientists say

July 18, 2017
The Indian subcontinent's massive population is nearing 1.5 billion according to recent accounts. But that population is far from monolithic; it's made up of nearly 5,000 well-defined sub-groups, making the region one of ...

Mutant yeast reveals details of the aberrant genomic machinery of children's high-grade gliomas

July 18, 2017
St. Jude Children's Research Hospital biologists have used engineered yeast cells to discover how a mutation that is frequently found in pediatric brain tumor high-grade glioma triggers a cascade of genomic malfunctions.

Late-breaking mutations may play an important role in autism

July 17, 2017
A study of nearly 6,000 families, combining three genetic sequencing technologies, finds that mutations that occur after conception play an important role in autism. A team led by investigators at Boston Children's Hospital ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.