Costford Sheila, Gowing Adrienne, Harper Mary-Ellen
Department of Biochemistry Microbiology and Immunology, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada K1H 8M5.
Curr Opin Clin Nutr Metab Care. 2007 Nov;10(6):671-8. doi: 10.1097/MCO.0b013e3282f0dbe4.
Obesity is associated with many health problems and its prevalence is rapidly increasing worldwide. Very few pharmaceutical compounds are available for obesity treatment. Strategies for the development of compounds can be targeted to the outcomes of reduced dietary energy intake and/or increased energy expenditure/thermogenesis. In this review, we focus on recent discoveries that advance our understanding of mitochondrial uncoupling as a target for the treatment of obesity. There are various mechanisms whereby uncoupling can occur and for the purpose of this review, we elaborate upon the uncoupling that can occur (1) through the original uncoupling protein, UCP1, in brown adipocytes, or in 'converted' white adipose tissue, and (2) in skeletal muscle.
Studies have identified a number of novel receptors and regulatory proteins involved in the emergence of brown adipocytes in white adipose tissue. Molecular and pharmacologic approaches in knockout and transgenic mice have demonstrated their relevance to obesity treatment. Recent research into uncoupling mechanisms in skeletal muscle indicates that uncoupling can occur through basal and inducible processes.
Uncoupling is a naturally occurring phenomenon whose underlying mechanisms require substantial further study for the development of antiobesity therapies.
肥胖与许多健康问题相关，且在全球范围内其患病率正在迅速上升。可用于肥胖治疗的药物化合物极少。化合物开发策略可针对减少膳食能量摄入和/或增加能量消耗/产热的结果。在本综述中，我们聚焦于最近的发现，这些发现推进了我们对线粒体解偶联作为肥胖治疗靶点的理解。解偶联可通过多种机制发生，出于本综述的目的，我们详细阐述可发生解偶联的情况：(1) 通过棕色脂肪细胞或“转化”白色脂肪组织中的原始解偶联蛋白UCP1，以及(2) 在骨骼肌中。
研究已鉴定出一些参与白色脂肪组织中棕色脂肪细胞出现的新型受体和调节蛋白。基因敲除和转基因小鼠的分子及药理学方法已证明它们与肥胖治疗相关。最近对骨骼肌解偶联机制的研究表明，解偶联可通过基础和诱导过程发生。
解偶联是一种自然发生的现象，其潜在机制在抗肥胖疗法开发方面还需要大量进一步研究。
