Muscle gene may provide new treatments for obesity and diabetes

Jul 27, 2010

(PhysOrg.com) -- Skeletal muscle enables us to walk, run or play a musical instrument, but it also plays a crucial role in controlling disease. Rockefeller University scientists have now shown how a specific molecule in skeletal muscle regulates energy expenditure, a finding that may lead to new treatments for certain muscle diseases as well as diabetes, obesity and heart disease.

The researchers, led by Wei Chen, a research associate in the Laboratory of Biochemistry and Molecular Biology, focused on a protein called MED1, which makes up part of a gene regulating machine called the Mediator coactivator complex. MED1 anchors the Mediator to an array of receptors in the that activate genes, and it performs crucial functions in a variety of cells and tissue types, including development of the mammary gland and fat tissues and the oxidation of fatty acids in the liver.

In the new study, Chen and her colleagues focused on MED1’s role in skeletal muscle. The researchers created a line of mice genetically modified to lack MED1 only in . They found that the Med1 had enhanced sensitivity to insulin and improved and also resisted becoming obese even when fed a high-fat diet. Gene microarray analysis showed that when Med1 was deleted, a number of genes that are usually suppressed were activated, says Chen.

“In muscle, MED1 normally suppresses a genetic program that holds in check certain energy expenditure pathways,” says Robert G. Roeder, Arnold and Mabel Beckman Professor and head of the Laboratory of Biochemistry and Molecular Biology. “We found that these genes are unleashed when MED1 function is abrogated.”

One of these genes is UCP-1, which produces a key protein that works in certain to generate heat when animals are exposed to cold. The researchers also found that MED1 plays a role in development of muscle fibers. Muscle is composed of two kinds of fiber, called slow and fast twitch. Slow twitch fibers contract slowly and can keep going for a long time, while fast twitch contract quickly, but get tired sooner. Removing Med1 caused the muscles to switch from fast to slow twitch fibers, which the researchers think may contribute to the animals’ enhanced tolerance to glucose and sensitivity to insulin.

Chen and her colleagues also observed that some muscle in the Med1 knockout mice had an increase in the density of mitochondria, which provide energy to cells, a finding which suggests that targeting Med1 could provide new treatments for muscle diseases caused by malfunctioning mitochondria, including some types of epilepsy.

“Taken together, these dramatic results raise the significant possibility of therapeutical approaches for metabolic syndromes and muscle diseases through modulation of MED1-nuclear receptor interactions,” says Chen.

Explore further: Treating pain by blocking the 'chili-pepper receptor'

More information: Proceedings of the National Academy of Sciences 107: 10196-10201 (June 1, 2010). A muscle-specific knockout implicates nuclear receptor coactivator MED1 in the regulation of glucose and energy metabolism, Wei Chen, Xiaoting Zhang, Kivanc Birsoy and Robert G. Roeder

Related Stories

'Marathon mice' elucidate little-known muscle type

Jan 03, 2007

Researchers report in the January issue of the journal Cell Metabolism, published by Cell Press, the discovery of a genetic "switch" that drives the formation of a poorly understood type of muscle. Moreover, they found, animal ...

Key finding in rare muscle disease

Jan 17, 2007

The finding is in the current issue of Annals of Neurology, a leading international neurology journal, in work led by Professor Nigel Laing and Dr Kristen Nowak of the Laboratory for Molecular Genetics at the Western Austra ...

Researchers develop mouse model for muscle disease

Sep 05, 2006

Researchers from the University of Minnesota have identified the importance of a gene critical to normal muscle function, resulting in a new mouse model for a poorly understood muscle disease in humans.

Team identifies stem cells that repair injured muscles

Mar 05, 2009

A University of Colorado at Boulder research team has identified a type of skeletal muscle stem cell that contributes to the repair of damaged muscles in mice, which could have important implications in the treatment of injured, ...

Recommended for you

Treating pain by blocking the 'chili-pepper receptor'

9 hours ago

Biting into a chili pepper causes a burning spiciness that is irresistible to some, but intolerable to others. Scientists exploring the chili pepper's effect are using their findings to develop a new drug ...

Moving single cells around—accurately and cheaply

Aug 19, 2014

Scientists at the Houston Methodist Research Institute have figured out how to pick up and transfer single cells using a pipette—a common laboratory tool that's been tweaked slightly. They describe this ...

The difficult question of Clostridium difficile

Aug 19, 2014

The bacterium Clostridium difficile causes antibiotic-related diarrhoea and is a growing problem in the hospital environment and elsewhere in the community. Understanding how the microbe colonises the hu ...

User comments : 0