{"id":2548,"date":"2015-06-30T00:00:00","date_gmt":"2015-06-30T07:00:00","guid":{"rendered":"https:\/\/vermont.salk.edu\/news-release\/a-high-fat-diet-may-alleviate-mitochondrial-disease\/"},"modified":"2015-11-15T08:19:09","modified_gmt":"2015-11-15T16:19:09","slug":"a-high-fat-diet-may-alleviate-mitochondrial-disease","status":"publish","type":"disclosure","link":"https:\/\/www.salk.edu\/zh\/news-release\/a-high-fat-diet-may-alleviate-mitochondrial-disease\/","title":{"rendered":"A high-fat diet may alleviate mitochondrial disease"},"content":{"rendered":"

\nLA JOLLA\u2013Mice that have a genetic version of mitochondrial disease can easily be mistaken for much older animals by the time they are nine months old: they have thinning grey hair, osteoporosis, poor hearing, infertility, heart problems and have lost weight. Despite having this disease at birth, these mice have a \u201csecret weapon\u201d in their youth that staves off signs of aging for a time.\n<\/p>\n

\nNew research from the Salk Institute reveals how a longevity hormone helps these mice\u2013born with thousands of mutations in their energy-generating mitochondria\u2013maintain metabolic homeostasis at a young age. This work provides insight into potential new therapies for mitochondrial and metabolic diseases in humans.\n<\/p>\n

\n\u201cThese findings help us understand the link between diet, health and aging, and they give us the potential to dissect these connections in a molecular way that could lead to therapeutics,\u201d says \u7f57\u7eb3\u5fb7\u00b7\u57c3\u6587\u65af<\/a>, director of Salk\u2019s \u57fa\u56e0\u8868\u8fbe\u5b9e\u9a8c\u5ba4<\/a> and senior author of the new paper, published June 29, 2015 in Proceedings of the National Academy of Sciences<\/a><\/em>.\n<\/p>\n

\nWhen Evans and collaborators studied these mice, they found that the longevity-promoting endocrine hormone FGF21 was highly active, even though these mice display hallmarks of accelerated aging.\n<\/p>\n

\n\u201cFGF21 is classically thought of as an anti-aging gene, turned on by exercise or fasting and suspected to extend lifespan,\u201d says Christopher Wall, a graduate student in the Evans lab at the time of the study and first author of the new paper. \u201cYet these mice ultimately age prematurely, despite having high levels of this hormone.\u201d\n<\/p>\n

\nTo explain this paradox, the team found that FGF21 actually assists stressed mitochondria and reprograms the metabolic state of these mice. In the paper, Evans and collaborators describe how FGF21 appears to switch tissues with important metabolic functions from burning sugar to burning fat\u2013which is easier fuel for the dysfunctional mitochondria to process.\n<\/p>\n

\"\"<\/p>\n

In young but rapidly aging mice, high-fat diet feeding (right) ramps up heat production and metabolic activity relative to cooler mice fed a normal chow diet (left).<\/p>\n

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

\nImage: Courtesy of the Salk Institute for Biological Studies\n<\/p>\n<\/div>\n

\n\u201cThis works for a while in these mice, but eventually their bodies run out of fat to burn,\u201d says Michael Downes, a senior staff scientist at Salk involved in the new study. \u201cFGF21 needs some additional fat from the diet to keep working.\u201d The team also found that feeding the mice a high-fat diet amplifies the effects of FGF21, granting them complete resistance to diet-induced obesity and many of its associated diseases.\n<\/p>\n

\n\u201cWhat we believe now is that turning on FGF21 is an adaptation to help this animal maintain its metabolic health,\u201d says Evans, a Howard Hughes Medical Institute investigator and the March of Dimes Chair in Molecular and Developmental Biology. \u201cIf the mice didn\u2019t have this hormonal \u2018fountain of youth,\u2019 they might age even more quickly than they already do.\u201d\n<\/p>\n

\nThe new observation has the potential to impact human health in multiple ways, says Evans. Elevated FGF21 levels have previously been observed in people with mitochondrial diseases, so increasing dietary fat intake could potentially ease their symptoms by helping the hormone reduce the strain on the mitochondria. At the same time, these findings suggest that using drugs to mildly stress mitochondria could activate a beneficial FGF21-dependent metabolic shift in patients suffering from obesity and other metabolic diseases.\n<\/p>\n

\n\u201cWe want to look at the interaction between FGF21 and dietary fat in human patients with mitochondrial disease now,\u201d says Downes, \u201cand start to see how we can manipulate this dynamic in different ways.\u201d\n<\/p>\n

\nOther researchers on the study were Jamie Whyte, Jae M. Suh, Weiwei Fan, Brett Collins, Ruth Yu, and Annette R. Atkins of the Salk Institute; Christopher Liddle of the University of Sydney<\/a>; and Jane C. Naviaux, Kefeng Li, Andrew Taylor Bright, William A. Alaynick, and Robert K. Naviaux of the University of California, San Diego School of Medicine<\/a>.\n<\/p>\n

\nThe research was supported by the Howard Hughes Medical Institute<\/a>, the National Institutes of Health<\/a>, the Glenn Foundation for Medical Research<\/a>, the Leona M. and Harry B. Helmsley Charitable Trust<\/a>, Ipsen\/Biomeasure<\/a>, the Ellison Medical Foundation<\/a>, the Samuel Waxman Cancer Research Foundation<\/a>, the Jane Botsford Johnson Foundation, the University of California, San Diego (UCSD) Christini Foundation, the UCSD Mitochondrial Research Fund<\/a>, and the Wright Family Foundation<\/a>.<\/p>","protected":false},"featured_media":0,"template":"","faculty":[91],"disease-research":[123,176],"class_list":["post-2548","disclosure","type-disclosure","status-publish","hentry","faculty-ronald-evans","disease-research-metabolism-and-diabetes","disease-research-mitochondrial-disease"],"acf":[],"yoast_head":"\nA high-fat diet may alleviate mitochondrial disease - 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\/a-high-fat-diet-may-alleviate-mitochondrial-disease\/\" \/>\n<meta property=\"og:locale\" content=\"zh_CN\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"A high-fat diet may alleviate mitochondrial disease - Salk Institute for Biological Studies\" \/>\n<meta property=\"og:description\" content=\"LA JOLLA\u2013Mice that have a genetic version of mitochondrial disease can easily be mistaken for much older animals by the time they are nine months old: they have thinning grey hair, osteoporosis, poor hearing, infertility, heart problems and have lost weight. 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