Absence of cocaine- and amphetamine-regulated transcript results in obesity in mice fed a high caloric diet
Absence of cocaine- and amphetamine-regulated transcript results in obesity in mice fed a high caloric diet
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DOI：
10.1210/en.142.10.4394
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发表时间：
2001-10-01
期刊：
影响因子：
4.8
通讯作者：
Köster, A
中科院分区：
文献类型：
--
作者：
Asnicar, MA;Smith, DP;Köster, A
Cart（可卡因和安非他明调节转录本）首先被确定为可卡因和安非他明上调的主要大脑 mRNA。 CART 蛋白已被确定为与瘦素作用密切相关的饱腹感因子。为了评估 CART 作为厌食信号的作用，我们通过基因靶向培育了 CART 缺陷小鼠。在高脂肪饮食下，与野生型同窝小鼠相比，CART 缺陷小鼠和雌性杂合小鼠（而非雄性杂合小鼠）每周食物消耗量、体重和脂肪量表现出统计学上显着的增加。此外，在喂养研究的第 17 周和第 14 周，CART 缺陷小鼠和雌性杂合小鼠在接受高脂肪饮食时明显比接受常规饮食的小鼠更重。然而，野生型或雄性杂合小鼠在该年龄没有表现出因饮食热量含量而导致的体重变化。与 MC4R、原阿黑皮质素或瘦素缺陷小鼠中显示的肥胖表型相反，我们的结果表明，CART 缺陷使小鼠在高热量饮食下容易变得肥胖。结果还表明，与阿黑皮素原或瘦素相比，在能量稳态调节方面，CART 可能不是主要的厌食信号。
Cart (cocaine- and amphetamine-regulated transcript) was first identified to be a major brain mRNA up-regulated by cocaine and amphetamine. The CART protein has been established as a satiety factor closely associated with the action of leptin. To assess CART's role as an anorexigenic signal, we have generated CART-deficient mice by gene targeting. On a high fat diet, CART-deficient and female heterozygous mice, but not male heterozygous mice, showed statistically significant increases in weekly food consumption, body weight, and fat mass compared with their wild-type littermates. Furthermore, CART-deficient and female heterozygous mice were significantly heavier when fed a high fat diet than on a regular chow diet at 17 wk of age and at the 14th wk of the feeding studies. However, wild-type or male heterozygous mice showed no weight variations attributable to caloric contents of the diet at that age. Contrary to the obese phenotypes shown in MC4R-, proopiomelanocortin-, or leptin-deficient mice, our results showed that CART deficiency predisposed mice to become obese on a calorically dense diet. The results also show that CART may not be a major anorectic signal compared with proopiomelanocortin or leptin in the regulation of energy homeostasis.