Evidence is seen by the fact that strong expression of Ob-Rb is seen in all the above hypothalamic nuclei, of which the ARC seems to be the most sensitive to leptin. Furthermore, after injection of leptin into ob/ob mice, Fos-like immunoreactivity was observed in the PVN. While there are differences in opinion about the sites of action of leptin, such as extra-hypothalamic sites and in different levels in different hypothalamic studies in different studies, further evidence that lesions of the hypothalamus also causing leptin-resistance confirm leptin acts in the hypothalamus. Also, central injection of leptin reduces food intake at doses that have no effect in the periphery. How so?.
The most revealing finding of the adipocyte-hypothalamic signalling pathway is that it appears that NPY-producing neurons appear to be one of the main targets for leptin, seen by the fact that ob/ob mice that also have an complete knockout for NPY are much less obese than normal ob mice. It has been speculated that in fact the action of leptin in acting as an appetite suppressant is due to its downregulation of NPY expression (Erickson et al, 1996). These less fat mice that lack both leptin and NPY suggests that NPY is a central effector of leptin deficiency. .
Furthermore, this is supported by observations that Ob-Rb and NPY are coexpressed in the ARC. Also, leptin inhibited NPY expression in ob/ob mice and in normal mice as well as possibly regulating the availability of NPY for release. Not only in NPY neurons, but the OB-Rb receptor has also be located on POMC (precursor forendorphin)- and galanin-containing neurons. This raises the possibility that if the observed anti-appetite effects seen with leptin are due to it disrupting orexigenic signal transmission. Leptin receptors are also co-expressed on many anorexigenic neurons, such as GLP-1 andMSH, where the administration of leptin appeared to increase their release.