{"id":13293,"date":"2017-05-02T00:00:47","date_gmt":"2017-05-02T07:00:47","guid":{"rendered":"https:\/\/vermont.salk.edu\/?post_type=disclosure&#038;p=13293"},"modified":"2024-01-30T15:11:25","modified_gmt":"2024-01-30T23:11:25","slug":"exercise-pill-boosts-athletic-endurance-70-percent","status":"publish","type":"disclosure","link":"https:\/\/www.salk.edu\/es\/news-release\/exercise-pill-boosts-athletic-endurance-70-percent\/","title":{"rendered":"\u201cExercise-in-a-pill\u201d boosts athletic endurance by 70 percent"},"content":{"rendered":"<p>LA JOLLA\u2014Every week, there seems to be another story about the health benefits of running. That\u2019s great\u2014but what if you can\u2019t run? For the elderly, obese or otherwise mobility-limited, the rewards of aerobic exercise have long been out of reach.<\/p>\n<div class=\"row\" style=\"\"><div class=\"col-md-10 col-md-push-1\"><div class=\"video-anchor\" id=\"video-Dkb2He9lKh0\"><\/div><div class=\"embed-responsive embed-responsive-16by9\"> <iframe class=\"embed-responsive-item\" src=\"\/\/www.youtube.com\/embed\/Dkb2He9lKh0?rel=0\" webkitallowfullscreen mozallowfullscreen allowfullscreen><\/iframe><\/div><!-- .embed-responsive --><\/div><!-- .col-md-*size --><\/div><!-- .\/row -->\n<p>Salk Institute scientists, building on earlier work that identified a gene pathway triggered by running, have discovered how to fully activate that pathway in sedentary mice with a chemical compound, mimicking the beneficial effects of exercise, including increased fat burning and stamina. The study, which appears in <a href=\"http:\/\/www.cell.com\/cell-metabolism\/fulltext\/S1550-4131(17)30211-5\" target=\"_blank\" rel=\"noopener noreferrer\"><em>Metabolismo celular<\/em><\/a> on May 2, 2017, not only deepens our understanding of aerobic endurance, but also offers people with heart conditions, pulmonary disease, type 2 <a href=\"https:\/\/www.salk.edu\/es\/science\/research\/metabolism-and-diabetes\/\">diabetes<\/a> or other health limitations the hope of achieving its benefits pharmacologically.<\/p>\n<p>\u201cIt\u2019s well known that people can improve their aerobic endurance through training,\u201d says senior author <a href=\"https:\/\/www.salk.edu\/es\/scientist\/ronald-evans\/\">Ronald Evans<\/a>, Howard Hughes Medical Institute investigator and holder of Salk\u2019s March of Dimes Chair in Molecular and Developmental Biology. \u201cThe question for us was: how does endurance work? And if we really understand the science, can we replace training with a drug?\u201d<\/p>\n<figure id=\"attachment_13297\"  class=\"wp-caption alignright\"><img loading=\"lazy\" decoding=\"async\" width=\"300\" height=\"292\" class=\"img-responsive wp-image-13297 size-pr-300\" src=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2017\/05\/Layer1-300x292.jpg\" alt=\"Partial view of a mouse calf muscle stained for different types of muscle fibers: oxidative slow-twitch (blue), oxidative fast-twitch (green), glycolytic fast-twitch (red).\" srcset=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2017\/05\/Layer1-300x292.jpg 300w, https:\/\/www.salk.edu\/wp-content\/uploads\/2017\/05\/Layer1-768x746.jpg 768w, https:\/\/www.salk.edu\/wp-content\/uploads\/2017\/05\/Layer1-1024x995.jpg 1024w, https:\/\/www.salk.edu\/wp-content\/uploads\/2017\/05\/Layer1-147x143.jpg 147w, https:\/\/www.salk.edu\/wp-content\/uploads\/2017\/05\/Layer1-458x445.jpg 458w, https:\/\/www.salk.edu\/wp-content\/uploads\/2017\/05\/Layer1-585x569.jpg 585w, https:\/\/www.salk.edu\/wp-content\/uploads\/2017\/05\/Layer1-553x537.jpg 553w, https:\/\/www.salk.edu\/wp-content\/uploads\/2017\/05\/Layer1-750x729.jpg 750w, https:\/\/www.salk.edu\/wp-content\/uploads\/2017\/05\/Layer1-945x918.jpg 945w\" sizes=\"auto, (max-width: 300px) 100vw, 300px\" \/><figcaption class=\"wp-caption-text\">Partial view of a mouse calf muscle stained for different types of muscle fibers: oxidative slow-twitch (blue), oxidative fast-twitch (green), glycolytic fast-twitch (red). <\/p>\n<p> <a href=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2017\/05\/Layer1.jpg\" target=\"_blank\" rel=\"noopener noreferrer\">Haga clic aqu\u00ed<\/a> para obtener una imagen en alta resoluci\u00f3n.<\/p>\n<p> Credit: Salk Institute\/Waitt Center<\/figcaption><\/figure>\n<p>Developing endurance means being able to sustain an aerobic activity for longer periods of time. As people become more fit, their muscles shift from burning carbohydrates (glucose) to burning fat. So researchers assumed that endurance is a function of the body\u2019s increasing ability to burn fat, though details of the process have been murky. Previous work by the Evans lab into a gene called PPAR delta (PPARD) offered intriguing clues: mice genetically engineered to have permanently activated PPARD became long-distance runners who were resistant to weight gain and highly responsive to insulin\u2014all qualities associated with physical fitness. The team found that a chemical compound called GW1516 (GW) similarly activated PPARD, replicating the weight control and insulin responsiveness in normal mice that had been seen in the engineered ones. However, GW did not affect endurance (how long the mice could run) unless coupled with daily exercise, which defeated the purpose of using it to replace exercise.<\/p>\n<p>In the current study, the Salk team gave normal mice a higher dose of GW, for a longer period of time (8 weeks instead of 4). Both the mice that received the compound and mice that did not were typically sedentary, but all were subjected to treadmill tests to see how long they could run until exhausted.<\/p>\n<p>Mice in the control group could run about 160 minutes before exhaustion. Mice on the drug, however, could run about 270 minutes\u2014about 70 percent longer. For both groups, exhaustion set in when blood sugar (glucose) dropped to around 70 mg\/dl, suggesting that low glucose levels (hypoglycemia) are responsible for fatigue.<\/p>\n<figure id=\"attachment_13298\"  class=\"wp-caption alignleft\"><img loading=\"lazy\" decoding=\"async\" width=\"458\" height=\"305\" class=\"img-responsive wp-image-13298 size-col-md-5\" src=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2017\/05\/Wanda-Waizenegger_Weiwei-Fan_Ryan-Lin_Ron-Evans_Ruth-Yu_Mingxiao-He_0X8C9952-458x305.jpg\" alt=\"From left: Wanda Waizenegger, Weiwei, Fan. Ryan Lin, Ronald Evans , Ruth-Yu and Mingxiao He\" srcset=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2017\/05\/Wanda-Waizenegger_Weiwei-Fan_Ryan-Lin_Ron-Evans_Ruth-Yu_Mingxiao-He_0X8C9952-458x305.jpg 458w, https:\/\/www.salk.edu\/wp-content\/uploads\/2017\/05\/Wanda-Waizenegger_Weiwei-Fan_Ryan-Lin_Ron-Evans_Ruth-Yu_Mingxiao-He_0X8C9952-300x200.jpg 300w, https:\/\/www.salk.edu\/wp-content\/uploads\/2017\/05\/Wanda-Waizenegger_Weiwei-Fan_Ryan-Lin_Ron-Evans_Ruth-Yu_Mingxiao-He_0X8C9952-768x512.jpg 768w, https:\/\/www.salk.edu\/wp-content\/uploads\/2017\/05\/Wanda-Waizenegger_Weiwei-Fan_Ryan-Lin_Ron-Evans_Ruth-Yu_Mingxiao-He_0X8C9952-1024x683.jpg 1024w, https:\/\/www.salk.edu\/wp-content\/uploads\/2017\/05\/Wanda-Waizenegger_Weiwei-Fan_Ryan-Lin_Ron-Evans_Ruth-Yu_Mingxiao-He_0X8C9952-147x98.jpg 147w, https:\/\/www.salk.edu\/wp-content\/uploads\/2017\/05\/Wanda-Waizenegger_Weiwei-Fan_Ryan-Lin_Ron-Evans_Ruth-Yu_Mingxiao-He_0X8C9952-585x390.jpg 585w, https:\/\/www.salk.edu\/wp-content\/uploads\/2017\/05\/Wanda-Waizenegger_Weiwei-Fan_Ryan-Lin_Ron-Evans_Ruth-Yu_Mingxiao-He_0X8C9952-553x369.jpg 553w, https:\/\/www.salk.edu\/wp-content\/uploads\/2017\/05\/Wanda-Waizenegger_Weiwei-Fan_Ryan-Lin_Ron-Evans_Ruth-Yu_Mingxiao-He_0X8C9952-750x500.jpg 750w, https:\/\/www.salk.edu\/wp-content\/uploads\/2017\/05\/Wanda-Waizenegger_Weiwei-Fan_Ryan-Lin_Ron-Evans_Ruth-Yu_Mingxiao-He_0X8C9952-945x630.jpg 945w\" sizes=\"auto, (max-width: 458px) 100vw, 458px\" \/><figcaption class=\"wp-caption-text\">From left: Wanda Waizenegger, Weiwei Fan, Ryan Lin, Ronald Evans, Ruth Yu and Mingxiao He.\u00a0<\/p>\n<p> <a href=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2017\/05\/Wanda-Waizenegger_Weiwei-Fan_Ryan-Lin_Ron-Evans_Ruth-Yu_Mingxiao-He_0X8C9952.jpg\" target=\"_blank\" rel=\"noopener noreferrer\">Haga clic aqu\u00ed<\/a> para obtener una imagen en alta resoluci\u00f3n.<\/p>\n<p> Cr\u00e9dito: Instituto Salk<\/figcaption><\/figure>\n<p>To understand what was happening at the molecular level, the team compared gene expression in a major muscle of mice. They found 975 genes whose expression changed in response to the drug, either becoming suppressed or increased. Genes whose expression increased were ones that regulate breaking down and burning fat. Surprisingly, genes that were suppressed were related to breaking down carbohydrates for energy. This means that the PPARD pathway prevents sugar from being an energy source in muscle during exercise, possibly to preserve sugar for the brain. Activating fat-burning takes longer than burning sugar, which is why the body generally uses glucose unless it has a compelling reason not to\u2014like maintaining brain function during periods of high energy expenditure. Although muscles can burn either sugar or fat, the brain prefers sugar, which explains why runners who \u201chit the wall\u201d experience both physical and mental fatigue when they use up their supply of glucose.<\/p>\n<p>\u201cThis study suggests that burning fat is less a driver of endurance than a compensatory mechanism to conserve glucose,\u201d says Michael Downes, a Salk senior scientist and co\u2013senior author of the paper. \u201cPPARD is suppressing all the points that are involved in sugar metabolism in the muscle so glucose can be redirected to the brain, thereby preserving brain function.\u201d<\/p>\n<figure id=\"attachment_13299\"  class=\"wp-caption alignright\"><img loading=\"lazy\" decoding=\"async\" width=\"282\" height=\"436\" class=\"wp-image-13299 size-full\" src=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2017\/05\/evans-release-runner.png\" alt=\"\" srcset=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2017\/05\/evans-release-runner.png 282w, https:\/\/www.salk.edu\/wp-content\/uploads\/2017\/05\/evans-release-runner-194x300.png 194w, https:\/\/www.salk.edu\/wp-content\/uploads\/2017\/05\/evans-release-runner-147x227.png 147w\" sizes=\"auto, (max-width: 282px) 100vw, 282px\" \/><figcaption class=\"wp-caption-text\">\u201cExercise-in-a-pill\u201d boosts athletic endurance by 70 percent.\u00a0<a href=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2017\/05\/evans-release-runner-cover.png\" target=\"_blank\" rel=\"noopener noreferrer\">Haga clic aqu\u00ed<\/a> para obtener una imagen en alta resoluci\u00f3n.\u00a0<\/p>\n<p> Cr\u00e9dito: Instituto Salk<\/figcaption><\/figure>\n<p>Interestingly, the muscles of mice that took the exercise drug did not exhibit the kinds of physiological changes that typically accompany aerobic fitness: additional mitochondria, more blood vessels and a shift toward the type of muscle fibers that burn fat rather than sugar. This shows that these changes are not exclusively driving aerobic endurance; it can also be accomplished by chemically activating a genetic pathway. In addition to having increased endurance, mice who were given the drug were also resistant to weight gain and more responsive to insulin than the mice who were not on the drug.<\/p>\n<p>\u201cExercise activates PPARD, but we\u2019re showing that you can do the same thing without mechanical training. It means you can improve endurance to the equivalent level as someone in training, without all of the physical effort,\u201d says Weiwei Fan, a Salk research associate and the paper\u2019s first author.<\/p>\n<p>Although the lab\u2019s studies have been in mice, pharmaceutical companies are interested in using the research to develop clinical trials for humans. The team can envision a number of therapeutic applications for a prescription drug based on GW, from increasing fat-burning in people suffering from obesity or type 2 diabetes to improving patients\u2019 fitness before and after surgery.<\/p>\n<p>Other authors included Wanda Waizenegger, Chun Shi Lin, Ming-Xiao He, Christopher E. Wall, Ruth T. Yu, Annette R. Atkins of Salk; Vincenzo Sorrentino, Hao Li and Johan Auwerx of the Ecole Polytechnique Federale de Lausanne; and Christopher Liddle of the <a href=\"https:\/\/sydney.edu.au\/\" target=\"_blank\" rel=\"noopener noreferrer\">University of Sydney<\/a>.<\/p>\n<p>The work was funded by the <a href=\"https:\/\/www.nih.gov\/\" target=\"_blank\" rel=\"noopener noreferrer\">Institutos Nacionales de Salud<\/a>, la <a href=\"https:\/\/www.nhmrc.gov.au\/\" target=\"_blank\" rel=\"noopener noreferrer\">National Health and Medical Research Council of Australia<\/a>, <a href=\"http:\/\/helmsleytrust.org\/\" target=\"_blank\" rel=\"noopener noreferrer\">The Leona M. and Harry B. Helmsley Charitable Trust<\/a>, la <a href=\"http:\/\/www.waxmancancer.org\/\" target=\"_blank\" rel=\"noopener noreferrer\">Samuel Waxman Cancer Research Foundation<\/a>, <a href=\"http:\/\/www.standup2cancer.org\/\" target=\"_blank\" rel=\"noopener noreferrer\">Stand Up to Cancer<\/a> y <a href=\"https:\/\/www.ipsenus.com\/\" target=\"_blank\" rel=\"noopener noreferrer\">Ipsen Bioscience, Inc.<\/a><\/p>","protected":false},"featured_media":13294,"template":"","faculty":[91],"disease-research":[123],"class_list":["post-13293","disclosure","type-disclosure","status-publish","has-post-thumbnail","hentry","faculty-ronald-evans","disease-research-metabolism-and-diabetes"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.3 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>\u201cExercise-in-a-pill\u201d boosts athletic endurance by 70 percent - 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\/es\/news-release\/exercise-pill-boosts-athletic-endurance-70-percent\/\" \/>\n<meta property=\"og:locale\" content=\"es_MX\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"\u201cExercise-in-a-pill\u201d boosts athletic endurance by 70 percent - Salk Institute for Biological Studies\" \/>\n<meta property=\"og:description\" content=\"LA JOLLA\u2014Every week, there seems to be another story about the health benefits of running. 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Wall, Hao Li, Christopher Liddle, Ruth T. Yu, Annette R. Atkins, Johan Auwerx, Michael Downes, and Ronald M. Evans","paper_title":"PPAR\u03b4 promotes running endurance by preserving glucose","subhead":"Sedentary mice given the drug ran longer without training","home_photo":"","listing_photo":"","legacy_boilerplate":[],"hide_boilerplate":[],"disable_date":false,"listing_excerpt":"<p>LA JOLLA\u2014Every week, there seems to be another story about the health benefits of running. That\u2019s great\u2014but what if you can\u2019t run? 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