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Báo cáo khoa học: Adipocyte hyperplasia and RMI1 in the treatment of obesity

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The escalating prevalence of obesity is one of the most pressing health concerns of the modern era, yet existing medicines to combat this global pandemic are disappointingly limited in terms of safety and effectiveness. The inadequacy of currently available therapies for obesity has made new drug development crucial. | IFEBS Journal MINIREVIEW Adipocyte hyperplasia and RMI1 in the treatment of obesity Akira Suwa Takeshi Kurama and Teruhiko Shimokawa Drug Discovery Research Astellas Pharma Inc. Ibaraki Japan Keywords adipocyte hyperplasia adipogenesis cell cycle obesity E2F energy homeostasis high-fat diet metabolic disorders RMI1 therapeutic target Correspondence A. Suwa Pharmacology Research Labs Drug Discovery Research Astellas Pharma Inc. 21 Miyukigaoka Tsukuba-shi Ibaraki 305-8585 Japan Fax 81 29 852 5391 Tel 81 29 863 6417 E-mail akira.suwa@jp.astellas.com Received 26 July 2010 revised 29 November 2010 accepted 3 December 2010 doi 10.1111 j.1742-4658.2010.07980.x The escalating prevalence of obesity is one of the most pressing health concerns of the modern era yet existing medicines to combat this global pandemic are disappointingly limited in terms of safety and effectiveness. The inadequacy of currently available therapies for obesity has made new drug development crucial. In the past several decades however major progress has been achieved in understanding adipocyte hyperplasia associated with the pathogenesis of obesity and consequently new potential targets for the medical treatment of obesity have been identified. We primarily review recent progress in the regulation of adipocyte hyperplasia as a novel emerging nontraditional approach. In this minireview we focus on recQ-mediated genome instability 1 RMI1 a recently identified novel molecular target for obesity treatment. RMI1-deficient mice have been found to be resistant to high-fat diet- and genetics-related obesity. Expression of this protein is regulated by E2F transcription factors and recent studies have suggested that RMI1 plays an important role in the control of energy homeostasis during the development of obesity with a mode of action based on the regulation of adipocyte hyperplasia. Introduction Obesity is a complex disorder and a major risk factor for metabolic diseases such as type 2 diabetes mellitus .