Down regulation of the prepro-orexin gene expression in genetically obese mice.

The gene expression of prepro-orexin, the precursor of orexin-A and orexin-B which are hypothalamic pepetides that are associated with feeding behavior, were examined in control (C57B1/6J) and obese (ob/ob and db/db) mice using in situ hybridization histochemistry. Orexins are identical with hypocretins that have been identified by directional tag PCR subtractive hybridization method. In situ hybridization histochemistry revealed that the expression of the prepro-orexin gene was significantly decreased in ob/ob and db/db mice compared with control mice. The gene expression of neuropeptide Y (NPY), a potent feeding stimulant, is known to be increased in ob/ob and db/db mice. The expression of the NPY gene in the arcuate nucleus was increased remarkably in ob/ob and db/db mice compared to that of control mice. An immunohistochemical study showed that orexin-A and orexin-B immunoreactive neurons exhibited in the lateral and posterior hypothalamic areas and the perifornical nucleus were distributed similarly in control, ob/ob and db/db mice. These results suggest that the regulatory mechanism of orexins/hypocretins may be different from that of NPY in genetically obese mice.