Veyrat-Durebex Christelle, Montet Xavier, Vinciguerra Manlio, Gjinovci Asllan, Meda Paolo, Foti Michelangelo, Rohner-Jeanrenaud Françoise
Department of Internal Medicine, Centre Médical Universitaire, 1211 Geneva 4, Switzerland.
Am J Physiol Endocrinol Metab. 2009 May;296(5):E1120-32. doi: 10.1152/ajpendo.90592.2008. Epub 2009 Feb 10.
The inbred Lou/C rat, originating from the Wistar strain, has been described as a model of resistance to diet-induced obesity, but little is known about its metabolism. Since this knowledge could provide some clues about the etiology of obesity/insulin resistance, this study aimed at characterizing glucose and lipid metabolism in Lou/C vs. Wistar rats. This was achieved by performing glucose and insulin tolerance tests, euglycemic hyperinsulinemic clamps, and characterization of intracellular insulin signaling in skeletal muscle. Substrate-induced insulin secretion was evaluated using perfused pancreas and isolated islets. Finally, body fat composition and the expression of various factors involved in lipid metabolism were determined. Body weight and caloric intake were lower in Lou/C than in Wistar rats, whereas food efficiency was similar. Improved glucose tolerance of Lou/C rats was not related to increased insulin output but was related to improved insulin sensitivity/responsiveness in the liver and in skeletal muscles. In the latter tissue, this was accompanied by improved insulin signaling, as suggested by higher activation of the insulin receptor and of the Akt/protein kinase B pathway. Fat deposition was markedly lower in Lou/C than in Wistar rats, especially in visceral adipose tissue. In the inguinal adipose depot, expression of uncoupling protein-1 was detected in Lou/C but not in Wistar rats, in keeping with a higher expression of peroxisome proliferator-activated receptor-gamma coactivator-1 in these animals. The Lou/C rat is a valuable model of spontaneous food restriction with associated improved insulin sensitivity. Independently from its reduced caloric intake, it also exhibits a preferential channeling of nutrients toward utilization rather than storage.
近交系Lou/C大鼠源自Wistar品系，已被描述为对饮食诱导肥胖具有抗性的模型，但其代谢情况鲜为人知。由于这方面的知识可能为肥胖/胰岛素抵抗的病因提供一些线索，本研究旨在表征Lou/C大鼠与Wistar大鼠的葡萄糖和脂质代谢。这是通过进行葡萄糖和胰岛素耐量试验、正常血糖高胰岛素钳夹试验以及骨骼肌细胞内胰岛素信号的表征来实现的。使用灌注胰腺和分离的胰岛评估底物诱导的胰岛素分泌。最后，测定身体脂肪组成以及脂质代谢中各种相关因子的表达。Lou/C大鼠的体重和热量摄入低于Wistar大鼠，而食物效率相似。Lou/C大鼠改善的葡萄糖耐量与胰岛素分泌增加无关，而是与肝脏和骨骼肌中胰岛素敏感性/反应性的改善有关。在后者组织中，这伴随着胰岛素信号的改善，胰岛素受体和Akt/蛋白激酶B途径的更高激活表明了这一点。Lou/C大鼠的脂肪沉积明显低于Wistar大鼠，尤其是在内脏脂肪组织中。在腹股沟脂肪库中，Lou/C大鼠检测到解偶联蛋白-1的表达，而Wistar大鼠未检测到，这与这些动物中过氧化物酶体增殖物激活受体-γ共激活因子-1的更高表达一致。Lou/C大鼠是自发食物限制并伴有胰岛素敏感性改善的有价值模型。独立于其减少的热量摄入，它还表现出营养物质优先向利用而非储存的方向分配。
