Ronald Evans<\/a> and his postdoctoral fellow Yong-Xu Wang, appears in the September issue of the Public Library of Science Biology journal (PLoS Biology). Evans is also an Investigator of the Howard Hughes Medical Institute.<\/p>\nEvans, Wang and team discovered that activation of the switch, a receptor called PPAR-delta, increases the rate at which the body burns fat. This makes PPAR-delta an exciting potential target for drugs that treat diabetes and lipid disorders.<\/p>\n
The team produced a genetically engineered mouse endowed with the activated form of PPAR-delta in its skeletal muscles. The result was a dramatic increase in “non-fatiguing” or “slow twitch” muscle cells and a mouse capable of running up to twice the distance of a normal littermate without training.<\/p>\n
By expressing genes for an activated form of the receptor PPAR-delta, we created a mouse that could, compared to normal mice, run marathons, said Evans. The activated form of PPAR-delta produced muscle fibers that enhanced endurance exercise.”<\/p>\n
By turning on PPAR-delta, the team had produced highly efficient muscle fibers that burned fat more rapidly. As a result, the mice were almost unable to gain weight even in the absence of exercise. <\/p>\n
“These muscles also provided resistance to obesity, despite the level of exercise,” said Evans. “By manipulating this receptor, it is possible to design treatments that change our muscle makeup and help resist obesity and associated metabolic disorders.<\/p>\n
To test the concept, Evans and his team treated normal mice with an experimental drug called GW501516 that activates PPAR-delta. These mice also expressed genes for slow-twitch muscles and gained less weight when given a high-fat diet. This drug is now in the earliest stages of being tested on people for its effects on obesity and other disorders of fat metabolism such as high blood cholesterol.<\/p>\n
This experiment underscores the importance of metabolism in fighting obesity and improving fitness, said Evans. Activating the PPAR switch may prevent physical fatigue and enhance the quality of exercise, which may lead to a new class of drugs to promote weight loss and treat diseases arising from an overweight population.<\/p>\n
Das Salk Institute for Biological Studies in La Jolla, Kalifornien, ist eine unabh\u00e4ngige gemeinn\u00fctzige Organisation, die sich der Grundlagenforschung in den Biowissenschaften, der Verbesserung der menschlichen Gesundheit und der Lebensbedingungen sowie der Ausbildung zuk\u00fcnftiger Forschergenerationen widmet. Jonas Salk, M.D., gr\u00fcndete das Institut 1960 mit einem Grundst\u00fccksgeschenk der Stadt San Diego und der finanziellen Unterst\u00fctzung der March of Dimes Birth Defects Foundation. <\/p>","protected":false},"featured_media":0,"template":"","faculty":[91],"disease-research":[],"class_list":["post-2254","disclosure","type-disclosure","status-publish","hentry","faculty-ronald-evans"],"acf":[],"yoast_head":"\n
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