{"id":16834,"date":"2018-03-06T09:49:53","date_gmt":"2018-03-06T17:49:53","guid":{"rendered":"https:\/\/vermont.salk.edu\/?post_type=disclosure&p=16834"},"modified":"2024-01-30T15:20:07","modified_gmt":"2024-01-30T23:20:07","slug":"salk-scientists-find-power-switch-muscles","status":"publish","type":"disclosure","link":"https:\/\/www.salk.edu\/de\/news-release\/salk-scientists-find-power-switch-muscles\/","title":{"rendered":"Salk scientists find power switch for muscles"},"content":{"rendered":"

LA JOLLA\u2014If you\u2019ve ever wondered how strenuous exercise translates into better endurance, researchers at the Salk Institute may have your answer. In a study published in the journal Cell Reports<\/em><\/a> on March 6, 2018, scientists in Ronald Evans\u2019<\/a> lab have shown that the protein ERR\u03b3 (ERR gamma) helps deliver many of the benefits associated with endurance exercise.<\/p>\n

\"Top
Top left: PGC1 deficiency leads to severe muscle damage, evidenced by numerous centralized nuclei (highlighted with arrows), which is likely due to impaired mitochondrial energy metabolism (bottom left: blue staining shows impaired mitochondrial activity). Such muscle damage and mitochondrial impairment is largely rescued by ERR\u03b3 overexpression (top and bottom right). <\/p>\n

Klicken Sie hier<\/a> f\u00fcr ein hochaufl\u00f6sendes Bild. <\/p>\n

Kredit: Salk Institut<\/figcaption><\/figure>\n

\u201cERR\u03b3 helps make endurance exercise possible,\u201d says Ronald Evans, who is professor and director of the Gene Expression Laboratory and co\u2013senior author on the paper. \u201cIt gears up the energy-creating cellular power plants known as mitochondria, creating more blood vessels to bring in oxygen, take away toxins and help repair damage associated with muscle use. This makes ERR\u03b3 a really interesting potential therapeutic target for conditions with weakened muscles.\u201d<\/p>\n

The story starts with the PGC1\u03b1 and PGC1\u03b2 proteins, which stimulate 20 other proteins associated with skeletal muscle energy and endurance exercise, including one from the Evans lab called ERR\u03b3. In turn, ERR\u03b3, a hormone receptor, acts to turn on genes. The Evans lab researchers wanted to precisely understand ERR\u03b3\u2019s role in skeletal muscle energy production and how that impacts physical endurance.<\/p>\n

To unravel this relationship, the Salk team studied mice without PGC1\u03b1\/\u03b2. In some, they increased ERR\u03b3 selectively in skeletal muscle cells. This approach allowed them to measure how ERR\u03b3 and PGC1 act independently, as well as how they function in combination.<\/p>\n

Losing PGC1 had a negative impact on muscle energy and endurance. However, boosting ERR\u03b3 restored function. The team found ERR\u03b3 is essential to energy production, activating genes that create more mitochondria. In other words, they found the power switch for skeletal muscles.<\/p>\n

The lab also showed that increased ERR\u03b3 in PGC1-deficient mice boosted their exercise performance. By measuring voluntary wheel running, they found that increasing ERR\u03b3 produced a five-fold increase in time spent exercising compared to mice with no PGC1 and normal ERR\u03b3 levels.<\/p>\n

\"From
From left (front row): Ruth Yu, Ronald Evans, Wanda Waizenegger; (middle): Annette Atkins, Nanhai He, Weiwei Fan; (back): Michael Downes, Zong Wei. <\/p>\n

Klicken Sie hier<\/a> f\u00fcr ein hochaufl\u00f6sendes Bild. <\/p>\n

Kredit: Salk Institut<\/figcaption><\/figure>\n

\u201cNow that we have detected this direct target (ERR\u03b3) for exercise-induced changes,\u201d says Weiwei Fan, a Salk research associate and the paper\u2019s first author, \u201cwe could potentially activate ERR\u03b3 and create the same changes that are being induced by exercise training.\u201d<\/p>\n

In addition to increasing the number of mitochondria in skeletal muscle cells, ERR\u03b3 also increased muscular blood flow.<\/p>\n

\u201cYou have to get more blood supply in to get more energy and take away toxic metabolites,\u201d says Michael Downes, a Salk senior scientist and co\u2013senior author on the paper. \u201cERR\u03b3 boosts vascularization as well as mitochondria.\u201d<\/p>\n

But perhaps the most important finding is that ERR\u03b3 could be a significant therapeutic target in helping to repair damaged muscles.<\/p>\n

\u201cMitochondria play such a central role in cells throughout the body, but particularly in muscle cells, which tend to require more energy,\u201d says Evans. \u201cWe now know that, by increasing mitochondria energy output, ERR\u03b3 can actually rescue damaged muscle. If we can identify small molecules that specifically target ERR\u03b3, we hope to help people with muscular dystrophy and other skeletal muscle conditions.”<\/p>\n

Other authors included Nanhai He, Chun Shi Lin, Zong Wei, Nasun Hah, Wanda Waizenegger, Ming-Xiao He, Ruth T. Yu and Annette R. Atkins at Salk and Christopher Liddle at Sydney Medical School.<\/p>\n

This study was funded by: the Office of Naval Research (ONR N00014-16-1-3159), National Institutes of Health (DK057978, HL105278, HL088093, ES010337 and CA014195), National Institute of Environmental Health Sciences (P42ES010337), Department of the Navy, Office of Naval Research (N00014-16-1-3159), the National Health and Medical Research Council of Australia (512354 and 632886), The Leona M. and Harry B. Helmsley Charitable Trust (#2017PG-MED001), the Samuel Waxman Cancer Research Foundation, Ipsen\/Biomeasure and the Glenn Foundation for Medical Research. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.<\/p>","protected":false},"featured_media":16836,"template":"","faculty":[91],"disease-research":[123],"class_list":["post-16834","disclosure","type-disclosure","status-publish","has-post-thumbnail","hentry","faculty-ronald-evans","disease-research-metabolism-and-diabetes"],"acf":[],"yoast_head":"\nSalk scientists find power switch for muscles - Salk Institute for Biological Studies<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.salk.edu\/de\/news-release\/salk-scientists-find-power-switch-muscles\/\" \/>\n<meta property=\"og:locale\" content=\"de_DE\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Salk scientists find power switch for muscles - Salk Institute for Biological Studies\" \/>\n<meta property=\"og:description\" content=\"LA JOLLA\u2014If you\u2019ve ever wondered how strenuous exercise translates into better endurance, researchers at the Salk Institute may have your answer. 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