Himms-Hagen J
Department of Biochemistry, Microbiology and Immunology, Faculyt of Medicine, University of Ottawa, 451 Smyth Road, Ottawa ON K1H 8M5, Canada.
Curr Drug Targets CNS Neurol Disord. 2004 Oct;3(5):389-409. doi: 10.2174/1568007043337076.
The possibility of developing a pill to increase energy expenditure is explored by examining the metabolic processes involved. Such a pill should be targeted at organ systems involved in facultative thermogenesis. In rodents, these are brown adipose tissue (BAT) and skeletal muscle. Since BAT-mediated thermogenesis is not available in adult humans, emphasis here is on skeletal muscle. A hypothesis is presented based on three known facts: (1) plasticity of skeletal muscle, with interconversion of fiber types that differ in their fuel efficiency; (2) presence of thyroxine 5'-deiodinase type 2 (TD2) in human skeletal muscle; (3) gradual increase in thermogenesis that occurs during rehabilitation after starvation, probably in muscle. A low capacity thermogenic system, muscle efficiency thermogenesis (MET), is proposed to occur as adipose stores refill during the transition from famine to feasting to obesity. This system involves increased activity of TD2 and a T3-induced increase in proportion of type II fibers, less efficient at rest and during activity. The protective effect of this system is probably overwhelmed by long-term eating in excess of energy needs. Better understanding of the complex remodeling of differentiated muscle fibers in the conversions proposed and of the regulation of TD2 activity in human skeletal muscle may reveal targets for increasing energy expenditure in humans. In addition, the possibility of exploiting the plasticity of the adipose organ, with conversion of white adipocytes in white adipose tissue to atypical brown adipocytes and increasing thermogenesis in them is considered as another potential target for increasing energy expenditure in humans.
通过研究相关代谢过程，探索开发一种可增加能量消耗的药丸的可能性。这种药丸应以参与适应性产热的器官系统为靶点。在啮齿动物中，这些器官系统是棕色脂肪组织（BAT）和骨骼肌。由于成年人体内不存在BAT介导的产热，因此这里重点关注骨骼肌。基于三个已知事实提出了一个假设：（1）骨骼肌具有可塑性，不同燃料效率的纤维类型可相互转换；（2）人类骨骼肌中存在2型甲状腺素5'-脱碘酶（TD2）；（3）饥饿后康复期间产热逐渐增加，可能发生在肌肉中。提出了一种低容量产热系统，即肌肉效率产热（MET），它在从饥荒到盛宴再到肥胖的转变过程中随着脂肪储备的重新填充而出现。该系统涉及TD2活性增加以及T3诱导的II型纤维比例增加，II型纤维在休息和活动时效率较低。长期摄入能量超过需求可能会掩盖该系统的保护作用。更好地理解所提出的分化肌纤维转换过程中的复杂重塑以及人类骨骼肌中TD2活性的调节，可能会揭示增加人类能量消耗的靶点。此外，利用脂肪器官的可塑性，将白色脂肪组织中的白色脂肪细胞转化为非典型棕色脂肪细胞并增加其中的产热，被认为是增加人类能量消耗的另一个潜在靶点。
