Transplantation of adipose tissue lacking leptin is unable to reverse the metabolic abnormalities associated with lipoatrophy
Transplantation of adipose tissue lacking leptin is unable to reverse the metabolic abnormalities associated with lipoatrophy
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DOI：
10.2337/diabetes.51.9.2727
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发表时间：
2002-09-01
期刊：
影响因子：
7.7
通讯作者：
Reitman, ML
中科院分区：
文献类型：
--
作者：
Colombo, C;Cutson, JJ;Reitman, ML
严重的脂肪组织缺乏（脂肪萎缩）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参数，而1周的瘦素输注效果较为温和。相比之下，瘦素输注在aP2-n固醇反应元件结合蛋白1脂肪萎缩小鼠中明显更有效。本研究表明，较长的瘦素输注时间进一步改善了a - zip /F-1小鼠的代谢状态，遗传背景并不是瘦素对葡萄糖和胰岛素水平影响的主要因素。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脂肪组织的存在并没有增强瘦素输注的效果。a - zip /F-1小鼠血清脂联素水平为对照水平的2%，脂肪移植后仅增加两倍，而瘦素输注后则完全没有增加，这表明脂联素缺乏不是糖尿病表型的主要因素。综上所述，这些结果表明，甘油三酯转化为脂肪可能不足以恢复非糖尿病表型，瘦素缺乏在引起脂肪萎缩的代谢并发症中起主要作用。
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.