Levian Candace, Ruiz Esmeralda, Yang Xia
Department of Integrative Biology and Physiology, University of California, Los Angeles.
Yale J Biol Med. 2014 Jun 6;87(2):113-26. eCollection 2014 Jun.
The recent obesity epidemic has imposed significant health, economical, and societal concerns. However, effective preventive and therapeutic strategies are currently lacking, primarily due to a lack of comprehensive understanding of the underlying molecular mechanisms. Recent genome-wide scans of genetic variants, transcriptome, and epigenome have uncovered >50 genetic loci that predispose individuals to obesity and revealed hundreds of genes with altered transcriptional activity and/or epigenetic variations in obesity-related tissues upon various environmental challenges such as high caloric diets, lack of physical activity, and environmental chemicals. These discoveries highlight the importance of genes involved in the control of energy homeostasis and food intake by the central nervous system, as well as genes contributing to lipid metabolism, adipogenesis, fat cell differentiation, and immune response in peripheral tissues, in obesity development. Future studies that are directed to obtain a more comprehensive, systems-level understanding of disease mechanisms and that test novel therapeutic strategies aiming at systems-level normalization of the obesity-related molecular alterations are warranted.
近期肥胖症的流行引发了重大的健康、经济和社会问题。然而，目前缺乏有效的预防和治疗策略，主要原因是对潜在分子机制缺乏全面了解。最近对基因变异、转录组和表观基因组进行的全基因组扫描发现了50多个使个体易患肥胖症的基因位点，并揭示了数百个基因在高热量饮食、缺乏体育活动和环境化学物质等各种环境挑战下，其转录活性和/或表观遗传变异在肥胖相关组织中发生改变。这些发现凸显了中枢神经系统中参与能量稳态和食物摄入控制的基因，以及在外周组织中对脂质代谢、脂肪生成、脂肪细胞分化和免疫反应有贡献的基因在肥胖症发展中的重要性。有必要开展未来研究，以更全面、系统层面地了解疾病机制，并测试旨在使肥胖相关分子改变实现系统层面正常化的新型治疗策略。
