Gnudi L, Shepherd P R, Kahn B B
Harvard Thorndike Research Laboratory, Harvard Medical School, Boston, MA, USA.
Proc Nutr Soc. 1996 Mar;55(1B):191-9. doi: 10.1079/pns19960020.
In summary, over-expression of GLUT4 selectively in fat causes increased flux of glucose into adipocytes and leads to increases in either the replication of immature pre-adipocytes or their differentiation into mature adipocytes resulting in an increase in fat cell number. This is the first model in which obesity is accounted for entirely by adipocyte hyperplasia and, therefore, is useful for studying the mechanisms involved in controlling fat cell number in vivo. GLUT4 over-expression in adipocytes of transgenic animals also increased whole- body insulin sensitivity. However, GLUT4 over-expression exclusively in adipocytes did not protect them from insulin resistance in vivo induced by high-fat feeding, in spite of the fact that insulin resistance was prevented at the level of the adipocyte. Interestingly, GLUT4 over-expression in fat protected the animals from developing further obesity when fed on a high-fat diet. It is possible that this failure to increase adiposity further is due to enhanced partitioning of glucose into fat, which may result in decreased glucose supply to muscle. This in turn may cause diversion of lipid to muscle to be oxidized as fatty acid. This diversion of lipid could result in protection against increased fat deposition in adipocytes. Further studies will be required in order to understand the molecular mechanisms by which GLUT4 over-expression in adipose tissues affects nutrient partitioning between muscle and adipose tissue and what the consequences of this are for whole-body fuel metabolism.
总之，在脂肪组织中选择性地过表达葡萄糖转运蛋白4（GLUT4）会导致进入脂肪细胞的葡萄糖通量增加，并导致未成熟前脂肪细胞的复制增加或其分化为成熟脂肪细胞，从而使脂肪细胞数量增加。这是第一个完全由脂肪细胞增生导致肥胖的模型，因此，对于研究体内控制脂肪细胞数量的机制很有用。转基因动物脂肪细胞中GLUT4的过表达也提高了全身胰岛素敏感性。然而，尽管在脂肪细胞水平上预防了胰岛素抵抗，但仅在脂肪细胞中过表达GLUT4并不能保护它们免受高脂喂养诱导的体内胰岛素抵抗。有趣的是，在高脂肪饮食喂养时，脂肪组织中GLUT4的过表达保护动物免于进一步肥胖。可能进一步增加肥胖失败的原因是葡萄糖更多地分配到脂肪中，这可能导致肌肉的葡萄糖供应减少。这反过来可能导致脂质转向肌肉，作为脂肪酸被氧化。这种脂质的转移可能导致防止脂肪细胞中脂肪沉积增加。为了理解脂肪组织中GLUT4过表达影响肌肉和脂肪组织之间营养分配的分子机制以及这对全身燃料代谢的后果，还需要进一步的研究。
