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Groundbreaking discovery of mechanism that controls obesity, atherosclerosis
Date:7/5/2012

A*STAR scientists from the Institute of Molecular and Cell Biology (IMCB) and the Singapore Bioimaging Consortium (SBIC) have discovered a new signalling pathway that controls both obesity and atherosclerosis. The team demonstrated, for the first time, that mice deficient in the Wip1 gene were resistant to weight gain and atherosclerosis via regulation of the Ataxia telangiectasia mutated gene (ATM) and its downstream signalling molecule mTor. These groundbreaking findings were published in the journal Cell Metabolism on 3rd July and may provide significant new avenues for therapeutic interventions for obesity and atherosclerosis.

Obesity and atherosclerosis-related diseases account for over one-third of deaths in the Western world. Controlling these conditions remains a major challenge due to an incomplete understanding of the molecular pathways involved. Atherosclerosis, a progressive disease of the large arteries, is an underlying cause of many cardiovascular diseases. In Singapore, 10.8% of our population is obese and cardiovascular disease accounted for 31.9% of all deaths in 2010.

Obesity and atherosclerosis are accompanied by the accumulation of lipid droplets in adipocytes (fat cells) and in foam cells respectively. Foam cells can subsequently rupture, damaging blood vessels, and contributing to further progression of atherosclerosis. The scientists discovered that Wip1 deficient mice, even when fed a high-fat diet, were resistant to obesity and atherosclerosis by preventing the accumulation of lipid droplets. This appeared to be through increased autophagy, the normal process by which the body degrades its own cellular components. They showed that the Wip1 deficient mice exhibited increased activity of ATM which decreased mTor signalling, resulting in increased autophagy. This degraded the lipid droplets and suppressed obesity and atherosclerosis.

"This is the first time that Wip1-dependent regulation of ATM-mTor pa
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Contact: Ong Siok Ming
ong_siok_ming@a-star.edu.sg
65-682-66254
Agency for Science, Technology and Research (A*STAR), Singapore
Source:Eurekalert

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