Asnicar M A, Smith D P, Yang D D, Heiman M L, Fox N, Chen Y F, Hsiung H M, Köster A
Division of Endocrine Research, Eli Lilly & Co., Indianapolis, Indiana 46285, USA.
Endocrinology. 2001 Oct;142(10):4394-400. doi: 10.1210/endo.142.10.8416.
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.
可卡因和苯丙胺调节转录肽（CART）最初被鉴定为一种主要的脑信使核糖核酸，受可卡因和苯丙胺上调。CART蛋白已被确认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，我们通过基因打靶产生了CART基因缺陷小鼠。在高脂饮食条件下，与野生型同窝小鼠相比，CART基因缺陷小鼠和雌性杂合子小鼠（而非雄性杂合子小鼠）的每周食物摄入量、体重和脂肪量均有统计学意义的显著增加。此外，在17周龄以及喂养研究的第14周时，喂食高脂饮食的CART基因缺陷小鼠和雌性杂合子小鼠比喂食常规食物的它们更重。然而，野生型或雄性杂合子小鼠在那个年龄并未表现出因饮食热量含量导致的体重变化。与促黑素细胞皮质激素原、阿黑皮素原或瘦素基因缺陷小鼠所呈现的肥胖表型相反,我们的结果表明CART基因缺陷使小鼠在高热量饮食下易患肥胖症。结果还表明，在能量平衡调节方面，与促黑素细胞皮质激素原或瘦素相比，CART可能不是主要的厌食信号。
