Galanin and the orexin 2 receptor as possible regulators of enkephalin in the paraventricular nucleus of the hypothalamus: relation to dietary fat

Recent studies show that the non-opioid peptides, galanin (GAL) and orexin (OX), are similar to the opioid enkephalin (ENK) in being stimulated by dietary fat and also in enhancing the consumption of a high-fat diet (HFD). This suggests that, when an HFD is provided, these non-opioids may stimulate the opioid system to promote excess consumption of this diet. Using single- and double-labeling immunohistochemistry, the present study sought to identify possible neuroanatomical substrates for this close relationship. Focusing on the hypothalamic paraventricular nucleus (PVN), and particularly its anterior (aPVN), middle (mPVN) and posterior (pPVN) parts, the experiments examined whether GAL itself or the receptors for GAL and OX are stimulated by an HFD in the same areas and possibly the same neurons as ENK. Compared to animals fed a standard chow diet, rats consuming an HFD exhibited an increased density of medial parvocellular neurons immunoreactive (IR) for GAL in the mPVN and aPVN and for ENK in the mPVN and pPVN, distinguishing the mPVN as an area where both peptides were affected. While showing little evidence for GAL and ENK colocalization with a chow diet, double-labeling studies in HFD-fed rats revealed significant colocalization specifically in medial parvocellular neurons of the mPVN. Immediately posterior to this site, further analyses revealed a similar relationship between the OX 2 receptor (OX2R) and ENK in HFD-treated animals. While increasing the density of neurons immunoreactive for OX2R as well as for the GAL 1 receptor but not OX 1 receptor, HFD consumption increased the colocalization only of OX2R and ENK, specifically in the medial parvocellular neurons of the pPVN. These changes in HFD-fed rats, showing GAL and OX2R to colocalize with ENK exclusively in neurons of the medial parvocellular mPVN and pPVN, respectively, suggest possible neural substrates through which the non-opioid peptides may functionally interact with ENK when exposed to an HFD.

▶Fat increases galanin and enkephalin in the same area of paraventricular nucleus. ▶Fat increases galanin 1 and orexin 2 receptor levels in the paraventricular nucleus. ▶Enkephalin and galanin colocalize in the paraventricular nucleus after fat intake. ▶Enkephalin and orexin 2 receptors colocalize in the paraventricular nucleus with fat. ▶Galanin and orexin may act through enkephalin to exert their effects on fat intake.