Hypothalamic CART and serum leptin levels are reduced in the anorectic (anx/anx) mouse

Cocaine- and amphetamine-regulated transcript (CART) is expressed in the hy pothalamus, 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 im munohistochemistry to study CART expression in mice homozygous for the anor exia (anx) mutation which are characterized by a much reduced food intake a nd premature death, anx/anx mice had significantly decreased levels of CART mRNA label and peptide-immunoreactive cell bodies and fibers in the arcuat e nucleus and a lower number of detectable CART-expressing cells in the dor somedial hypothalamic nucleus/lateral hypothalamic area. Moreover, serum le ptin levels were significantly lower in anx/anx mice compared to normal lit termates, most likely due to the prominent depletion of body fat in these a nimals. The decrease in the anorexigenic agents leptin and CART, may reflec t a compensatory down-regulation in response to the energy-deprived state o f anx/anx mice. Alternatively, the reduced arcuate CART expression may be a consequence of a molecular defect in the arcuate nucleus of these animals. (C) 2000 Elsevier Science B.V. All rights reserved.