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

January 10, 2017, Baylor College of Medicine
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

Group recreates DNA of man who died in 1827 despite having no body to work with

January 16, 2018
An international team of researchers led by a group with deCODE Genetics, a biopharmaceutical company in Iceland, has partly recreated the DNA of a man who died in 1827, despite having no body to take tissue samples from. ...

The surprising role of gene architecture in cell fate decisions

January 16, 2018
Scientists read the code of life—the genome—as a sequence of letters, but now researchers have also started exploring its three-dimensional organisation. In a paper published in Nature Genetics, an interdisciplinary research ...

How incurable mitochondrial diseases strike previously unaffected families

January 15, 2018
Researchers have shown for the first time how children can inherit a severe - potentially fatal - mitochondrial disease from a healthy mother. The study, led by researchers from the MRC Mitochondrial Biology Unit at the University ...

Genes that aid spinal cord healing in lamprey also present in humans

January 15, 2018
Many of the genes involved in natural repair of the injured spinal cord of the lamprey are also active in the repair of the peripheral nervous system in mammals, according to a study by a collaborative group of scientists ...

The coming of age of gene therapy: A review of the past and path forward

January 11, 2018
After three decades of hopes tempered by setbacks, gene therapy—the process of treating a disease by modifying a person's DNA—is no longer the future of medicine, but is part of the present-day clinical treatment toolkit. ...

Large-scale study to pinpoint genes linked to obesity

January 10, 2018
It's not just diet and physical activity; your genes also determine how easily you lose or gain weight. In a study published in the January issue of Nature Genetics, researchers at the Icahn School of Medicine at Mount Sinai ...


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.