Colombo Carlo, Cutson Jaime J, Yamauchi Toshimasa, Vinson Charles, Kadowaki Takashi, Gavrilova Oksana, Reitman Marc L
Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Diabetes. 2002 Sep;51(9):2727-33. doi: 10.2337/diabetes.51.9.2727.
Severe adipose tissue deficiency (lipoatrophy) causes insulin-resistant diabetes, elevated serum triglyceride and fatty acid levels, and massive triglyceride deposition in the liver. In lipoatrophic A-ZIP/F-1 mice, transplantation of normal adipose tissue greatly improved these parameters, whereas 1 week of leptin infusion had more modest effects. In contrast, leptin infusion was strikingly more effective in the aP2-n sterol response element binding protein 1 lipoatrophic mouse. Here we show that a longer duration of leptin infusion further improves the metabolic status of the A-ZIP/F-1 mice and that genetic background does not make a major contribution to the effect of leptin on glucose and insulin levels. Adipose transplantation using leptin-deficient ob/ob fat had no effect on the phenotype of the A-ZIP/F-1 mice. Moreover, the presence of ob/ob adipose tissue did not enhance the effects of leptin infusion. Serum adiponectin levels were 2% of control levels in the A-ZIP/F-1 mouse and increased only twofold with adipose transplantation and not at all after leptin infusion, suggesting that adiponectin deficiency is not a major contributor to the diabetic phenotype. Taken together, these results suggest that sequestration of triglycerides into fat may not be enough to restore a nondiabetic phenotype and that leptin deficiency plays a major role in causing the metabolic complications of lipoatrophy.
严重的脂肪组织缺乏（脂肪萎缩）会导致胰岛素抵抗性糖尿病、血清甘油三酯和脂肪酸水平升高，以及肝脏中大量甘油三酯沉积。在脂肪萎缩的A-ZIP/F-1小鼠中，移植正常脂肪组织可显著改善这些指标，而输注瘦素1周的效果则较为有限。相比之下，在aP2-核甾醇反应元件结合蛋白1脂肪萎缩小鼠中，输注瘦素的效果则显著更佳。在此我们表明，延长瘦素输注时间可进一步改善A-ZIP/F-1小鼠的代谢状况，且遗传背景对瘦素对血糖和胰岛素水平的影响并无重大作用。使用瘦素缺乏的ob/ob脂肪进行脂肪移植对A-ZIP/F-1小鼠的表型没有影响。此外，ob/ob脂肪组织的存在并未增强瘦素输注的效果。A-ZIP/F-1小鼠血清脂联素水平仅为对照水平的2%，脂肪移植后仅增加两倍，而瘦素输注后则完全没有增加，这表明脂联素缺乏并非糖尿病表型的主要促成因素。综上所述，这些结果表明，将甘油三酯隔离到脂肪中可能不足以恢复非糖尿病表型，且瘦素缺乏在导致脂肪萎缩的代谢并发症中起主要作用。
