Kristensen P, Judge M E, Thim L, Ribel U, Christjansen K N, Wulff B S, Clausen J T, Jensen P B, Madsen O D, Vrang N, Larsen P J, Hastrup S
Health Care Discovery, Novo Nordisk, Bagsvaerd, Denmark.
Nature. 1998 May 7;393(6680):72-6. doi: 10.1038/29993.
The mammalian hypothalamus strongly influences ingestive behaviour through several different signalling molecules and receptor systems. Here we show that CART (cocaine- and amphetamine-regulated transcript), a brain-located peptide, is a satiety factor and is closely associated with the actions of two important regulators of food intake, leptin and neuropeptide Y. Food-deprived animals show a pronounced decrease in expression of CART messenger RNA in the arcuate nucleus. In animal models of obesity with disrupted leptin signalling, CART mRNA is almost absent from the arcuate nucleus. Peripheral administration of leptin to obese mice stimulates CART mRNA expression. When injected intracerebroventricularly into rats, recombinant CART peptide inhibits both normal and starvation-induced feeding, and completely blocks the feeding response induced by neuropeptide Y. An antiserum against CART increases feeding in normal rats, indicating that CART may be an endogenous inhibitor of food intake in normal animals.
哺乳动物的下丘脑通过几种不同的信号分子和受体系统对摄食行为产生强烈影响。我们在此表明，可卡因和苯丙胺调节转录物（CART），一种存在于大脑中的肽，是一种饱腹感因子，并且与食物摄入的两个重要调节因子瘦素和神经肽Y的作用密切相关。食物匮乏的动物弓状核中CART信使核糖核酸的表达明显下降。在瘦素信号传导受损的肥胖动物模型中，弓状核中几乎不存在CART信使核糖核酸。向肥胖小鼠外周给予瘦素可刺激CART信使核糖核酸的表达。当将重组CART肽脑室内注射到大鼠体内时，它会抑制正常和饥饿诱导的进食，并完全阻断神经肽Y诱导的进食反应。一种针对CART的抗血清会增加正常大鼠的进食量，这表明CART可能是正常动物体内食物摄入的内源性抑制剂。
