Differences in GIP Receptor Expression by Feeding Status in the Mouse Brain

Gastric inhibitory polypeptide (GIP) contributes to energy metabolism regulation. We investigated differences in GIP receptor expression in the brain by feeding status among lean and obese mice and the effect of acute central GIP administration on the expression of appetite-regulating hypothalamic neuropeptides. We divided the mice into four groups: fed/lean, fasted/lean, fed/obese, and fasted/obese. The arcuate nucleus (ARC), paraventricular nucleus of the hypothalamus, and nucleus of the solitary tract in the brainstem were harvested. GIP (6 nmol) or saline was injected for the acute intracerebroventricular administration test, followed by the collection of hypothalamic tissue after 2 h. Fed/obese mice had higher ARC GIP receptor mRNA levels than fasted/obese and lean mice. This difference was not observed among lean mice by feeding status. Obese mice had higher blood GIP levels than lean mice. Fed/obese mice had higher blood GIP levels than fasted/obese mice. This difference was not observed among lean mice by feeding status. GIP administration significantly increased proopiomelano-cortin (Pomc) mRNA levels (GIP: 7.59 ± 0.14; saline: 3.44 ± 1.38 arbitrary units; p = 0.030). Increased GIP receptor expression in the ARC in obese mice indicates its central nervous system involvement in energy balance regulation. GIP potentially regulates POMC-mediated appetite regulation in the hypothalamus. It is possible that POMC neurons are targets of GIP action in the brain.