Program in Integrative Cell Signalling and Neurobiology of Metabolism, Section of Comparative Medicine, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Nat Rev Drug Discov. 2012 Sep;11(9):675-91. doi: 10.1038/nrd3739. Epub 2012 Aug 3.
Current anti-obesity drugs aim to reduce food intake by either curbing appetite or suppressing the craving for food. However, many of these agents have been associated with severe psychiatric and/or cardiovascular side effects, highlighting the need for alternative therapeutic strategies. Emerging knowledge on the role of the hypothalamus in enabling the central nervous system to adapt to the changing environment - by managing peripheral tissue output and by regulating higher brain functions - may facilitate the discovery of new agents that are more effective and have an acceptable benefit-risk profile. Targeting the molecular pathways that mediate the beneficial effects of calorie restriction and exercise may represent an alternative therapeutic approach for the treatment of chronic metabolic disorders such as obesity.
目前的抗肥胖药物旨在通过抑制食欲或抑制对食物的渴望来减少食物摄入。然而，许多这些药物与严重的精神和/或心血管副作用有关，这突出表明需要替代治疗策略。新兴的下丘脑在使中枢神经系统适应不断变化的环境方面的作用的知识——通过管理外周组织输出和调节更高的大脑功能——可能有助于发现更有效且具有可接受的获益-风险特征的新药物。针对介导热量限制和运动的有益效果的分子途径可能代表治疗肥胖等慢性代谢疾病的另一种治疗方法。
