Leptin responsiveness in mice that ectopically express agouti protein

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• 作者：Harris ; Ruth B.S. ; Mitchell ; Tiffany D. ; Mynatt ; Randall L.
• 关键词：BAPa mice ; Gender ; Weight loss ; Thermogenesis
• 刊名：Physiology and Behavior
• 出版年：2002
• 出版时间：February 1 - 15 2002
• 年：2002
• 卷：75
• 期：1-2
• 页码：159-167
• 全文大小：353 K

文摘

Agouti protein is an endogenous antagonist of melanocortin receptors (MCR), including MCR3 and MCR4, which have been implicated as part of the hypothalamic mechanism that mediates leptin-induced hypophagia. In this experiment we examined the effects of peripheral and central leptin administration in male and female β-actin promoter (BAPa) mice that express agouti protein ectopically and have a phenotype that includes obesity and diabetes which is exaggerated in males compared with females. Intraperitoneal infusion of 10 μg leptin/day for 13 days caused weight loss and a transient inhibition of food intake in wild-type mice, with a greater effect in males than females. Male BAPa mice were resistant to leptin infusion whereas female mice lost weight. All of the mice lost body weight following a single intracerebroventricular injection of leptin but the effect was greater in female BAPa mice than any other group. There also was a delayed suppression of food intake that was the same for wild-type and BAPa female mice, whereas food intake recovered faster in BAPa than wild-type males. The dissociation between food intake and body weight loss implies a significant effect of leptin on energy expenditure in BAPa mice. These results demonstrate that the effect of leptin on energy balance is not entirely dependent upon the melanocortin system.