{"id":21368,"date":"2019-01-14T00:00:18","date_gmt":"2019-01-14T08:00:18","guid":{"rendered":"https:\/\/vermont.salk.edu\/?post_type=disclosure&p=21368"},"modified":"2023-12-07T16:22:21","modified_gmt":"2023-12-08T00:22:21","slug":"salk-scientists-uncover-the-health-effects-of-metabolic-magic-bullet-protein","status":"publish","type":"disclosure","link":"https:\/\/www.salk.edu\/zh\/news-release\/salk-scientists-uncover-the-health-effects-of-metabolic-magic-bullet-protein\/","title":{"rendered":"\u7d22\u5c14\u514b\u79d1\u5b66\u5bb6\u53d1\u73b0\u65b0\u9648\u4ee3\u8c22 \u201c\u795e\u5947\u5b50\u5f39 \u201d\u86cb\u767d\u8d28\u5bf9\u5065\u5eb7\u7684\u5f71\u54cd"},"content":{"rendered":"LA JOLLA\u2014The metabolic protein AMPK has been described as a kind of magic bullet for health. Studies in animal models have shown that compounds that activate the protein have health-promoting effects to reverse diabetes, improve cardiovascular health, treat mitochondrial disease\u2014even extend life span. However, how much of the effects of these compounds can be fully attributed to AMPK versus other potential targets is unknown.\r\n\r\n
\"When
When Salk scientists used the antibiotic doxycycline to activate AMPK in the livers of obese mice, steatosis-- the accumulation of fat in the liver-- declined. Mice also had lower levels of obesity, inflammation, and healthier blood sugar levels.

Click here<\/a> for a high-resolution image.

Credit: Salk Institute<\/figcaption><\/figure>\r\n\r\nNow, Salk researchers have developed a new system that lets them study in more detail than ever exactly how, where and when AMPK carries out its molecular and therapeutic functions. In the paper, published January 2, 2019 in the journal Cell Reports<\/em><\/a>, the Salk team uses the new model to activate AMPK in the livers of adult mice with fatty liver disease.\r\n\r\n\u201cThis model will allow us to answer questions that scientists could not answer before,\u201d says Salk Professor and \u7d22\u5c14\u514b\u764c\u75c7\u4e2d\u5fc3<\/a> Director \u9c81\u672c-\u8096<\/a>, who led the new work. \u201cIt really gives us a new way to define the health benefits of this specific enzyme in a wide variety of diseases.\u201d\r\n\r\nAMP-activated protein kinase, or AMPK, is known as a master regulator of metabolism. Cells activate AMPK when they are running low on energy, and AMPK is activated in tissues throughout the body following exercise or during calorie restriction. In response, AMPK alters the activity of many other genes and proteins, helping keep cells alive and functioning even when they\u2019re running low on fuel. In different tissues throughout the body and at different time points in development, AMPK likely has varying effects. Until now, the only way to study the specific impact of genetically increasing AMPK activity was to change its activity in an organism for its entire life, starting at embryogenesis.\r\n\r\n\u201cWhen AMPK is overactivated from the very beginning of embryogenesis, we don\u2019t know what effects it\u2019s having on normal development,\u201d says Daniel Garcia, a senior research associate at Salk and first author of the new paper.\r\n\r\nSo Garcia, Shaw and their colleagues enabled a mouse to have a special version of AMPK that lets the researchers activate the gene by feeding the adult mouse an antibiotic.\r\n\r\n\u201cThe model we\u2019ve developed is much more similar to what you would see in a clinic if you target AMPK with drugs,\u201d says Garcia.\r\n\r\nMoreover, by double-engineering the inducible AMPK gene in the mice, the researchers can also control where in the body this AMPK activation happens\u2014everywhere, or just in a select tissue or tissues.\r\n\r\nTo test the utility of the new model, the researchers developed mice that could have AMPK activated in the liver. Then, they fed a subset of these mice high-fat diets leading to diet-induced obesity and an excess accumulation of fats in the liver. This condition is equivalent to nonalcoholic fatty liver disease (NAFLD) in humans, the leading form of chronic liver disease in American adults.\r\n\r\n
\"From
From left: Reuben Shaw and Daniel Garcia, after notification of their paper's acceptance.

Click here<\/a> for a high-resolution image.

Credit: Salk Institute<\/figcaption><\/figure>\r\n\r\nIn both mice with and without NAFLD, levels of fats in the liver dropped when AMPK was activated\u2014new fat production was slowed and existing fats were metabolized. Moreover, when AMPK was activated in mice that were fed a high-fat diet, the mice were protected against weight gain and obesity and had fewer signs of liver inflammation.\r\n\r\n\u201cThis paper confirms that AMPK is a good target for treating NAFLD,\u201d says Garcia. \u201cIt\u2019s further confirmation that AMPK activators should be tested clinically.\u201d\r\n\r\nIn addition to the effects on liver fat, AMPK activation\u2014even though it was limited to the liver\u2014also lowered levels of fats elsewhere in the body, suggesting that hormones released by the liver into the rest of the body were affected.\r\n\r\n\u201cThese results indicate that AMPK could potentially be a powerful treatment to a host of diseases in humans,\u201d says Shaw, who holds the William R. Brody Chair.\r\n\r\nThe researchers next plan to study AMPK activation in a plethora of other tissues, including muscles, where scientists have hypothesized AMPK could have a dramatic effect.\r\n\r\n\u201cThere are broader questions beyond NAFLD to ask about whether genetic activation of AMPK in muscle mimics exercise and whether activation of AMPK later in an organism's life can promote life span,\u201d says Shaw.\r\n\r\nOther researchers on the study were Kristina Hellberg, Amandine Chaix, Sebastien Herzig, Terry Lin, Maxim Shokhirev, Antonio Pinto, Debbie Ross, Alan Saghatelian and Satchidananda Panda of the Salk Institute; Martina Wallace, Mehmet Badur and Christian Metallo of the University of California San Diego; and Lukas Dow of Weill Cornell Medicine.\r\n\r\nThe work and the researchers involved were supported by grants from the National Institutes of Health, the Leona M. and Harry B. Helmsley Charitable Trust, the American Cancer Society, the Glenn Center for Aging Research, the American Heart Association and Philippe Foundation Inc.","protected":false},"featured_media":21371,"template":"","faculty":[45],"disease-research":[46,446,123],"class_list":["post-21368","disclosure","type-disclosure","status-publish","has-post-thumbnail","hentry","faculty-reuben-shaw","disease-research-cancer-biology","disease-research-cardiovascular-disease","disease-research-metabolism-and-diabetes"],"acf":[],"yoast_head":"\nSalk scientists uncover the health effects of metabolic \u201cmagic bullet\u201d protein - 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\/zh\/news-release\/salk-scientists-uncover-the-health-effects-of-metabolic-magic-bullet-protein\/\" \/>\n<meta property=\"og:locale\" content=\"zh_CN\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Salk scientists uncover the health effects of metabolic \u201cmagic bullet\u201d protein - 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