Johansen J E, Broberger C, Lavebratt C, Johansson C, Kuhar M J, Hökfelt T, Schalling M
Neurogenetics Unit, Department of Molecular Medicine, Karolinska Hospital, S-171 76 Stockholm, Sweden.
Brain Res Mol Brain Res. 2000 Dec 8;84(1-2):97-105. doi: 10.1016/s0169-328x(00)00228-x.
Cocaine- and amphetamine-regulated transcript (CART) is expressed in the hypothalamus, and putative peptides encoded by CART potently inhibit feeding when administered centrally. CART is strongly down-regulated in the lateral hypothalamic area and the arcuate nucleus in animal models of obesity with disrupted leptin signaling. Here we have used in situ hybridization and immunohistochemistry to study CART expression in mice homozygous for the anorexia (anx) mutation which are characterized by a much reduced food intake and premature death. anx/anx mice had significantly decreased levels of CART mRNA label and peptide-immunoreactive cell bodies and fibers in the arcuate nucleus and a lower number of detectable CART-expressing cells in the dorsomedial hypothalamic nucleus/lateral hypothalamic area. Moreover, serum leptin levels were significantly lower in anx/anx mice compared to normal littermates, most likely due to the prominent depletion of body fat in these animals. The decrease in the anorexigenic agents leptin and CART, may reflect a compensatory down-regulation in response to the energy-deprived state of anx/anx mice. Alternatively, the reduced arcuate CART expression may be a consequence of a molecular defect in the arcuate nucleus of these animals.
可卡因和苯丙胺调节转录物（CART）在下丘脑中表达，当向中枢给药时，由CART编码的假定肽可有效抑制进食。在瘦素信号传导中断的肥胖动物模型中，下丘脑外侧区和弓状核中的CART被强烈下调。在这里，我们使用原位杂交和免疫组织化学来研究厌食（anx）突变纯合小鼠中的CART表达，这些小鼠的特征是食物摄入量大幅减少和过早死亡。anx/anx小鼠弓状核中CART mRNA标记和肽免疫反应性细胞体及纤维的水平显著降低，在背内侧下丘脑核/下丘脑外侧区中可检测到的表达CART的细胞数量也较少。此外，与正常同窝小鼠相比，anx/anx小鼠的血清瘦素水平显著降低，这很可能是由于这些动物体内脂肪显著减少所致。厌食性因子瘦素和CART的减少，可能反映了对anx/anx小鼠能量缺乏状态的一种代偿性下调。或者，弓状核中CART表达的降低可能是这些动物弓状核分子缺陷的结果。
