MTII attenuates ghrelin- and food deprivation-induced increases in food hoarding and food intake

Abstract

Food deprivation triggers a constellation of physiological and behavioral changes including increases in peripherally-produced ghrelin and centrally-produced agouti-related protein (AgRP). Upon refeeding, food intake is increased in most species, however hamsters primarily increase food hoarding. Food deprivation-induced increases in food hoarding by Siberian hamsters are mimicked by peripheral ghrelin and central AgRP injections. Because food deprivation stimulates ghrelin as well as AgRP synthesis/release, food deprivation-induced increases in hoarding may be mediated by melanocortin 3 or 4 receptor (MC3/4-R) antagonism via AgRP, the MC3/4-R inverse agonist. Therefore, we asked: Can a MC3/4-R agonist block food deprivation- or ghrelin-induced increases in foraging, food hoarding and food intake? This was accomplished by injecting melanotan II (MTII), a synthetic MC3/4-R agonist, into the 3rd ventricle in food deprived, fed or peripheral ghrelin injected hamsters and housed in a running wheel-based food delivery foraging system. Three foraging conditions were used: a) no running wheel access, non-contingent food, b) running wheel access, non-contingent food or c) a foraging requirement for food (10 revolutions/pellet). Food deprivation was a more potent stimulator of foraging and hoarding than ghrelin. Concurrent injections of MTII completely blocked food deprivation- and ghrelin-induced increases in food intake and attenuated, but did not always completely block, food deprivation- and ghrelin-induced increases in food hoarding. Collectively, these data suggest that the MC3/4-R are involved in ghrelin- and food deprivation-induced increases in food intake, but other neurochemical systems, such as previously demonstrated with neuropeptide Y, also are involved in increases in food hoarding as well as foraging.

Figure 1

Mean ± SEM of food intake as a percentage of the intracerebroventricularly (icv) and intraperitoneally (ip) saline-injected controls (dashed reference line) for the effects of ip ghrelin treatment with icv saline (black bars), ip saline treatment with icv melanotan II (MTII; gray bars) and ip ghrelin treatment with icv MTII (striped bars) on hamsters without a foraging requirement and a stationary wheel (Blocked Wheel), hamsters with no foraging requirement and a freely moving wheel (Free Wheel) and hamsters with a foraging requirements (10 Revolutions/pellet). *=p<0.05 compared to the saline control condition

Figure 2

Mean ± SEM of food hoarding as a percentage of the intracerebroventricularly (icv) and intraperitoneally (ip) saline-injected controls (dashed reference line) for the effects of ip ghrelin treatment with icv saline (black bars), ip saline treatment with icv melanotan II (MTII; gray bars) and ip ghrelin treatment with icv MTII (striped bars) on hamsters without a foraging requirement and a stationary wheel (Blocked Wheel), hamsters with no foraging requirement and a freely moving wheel (Free Wheel) and hamsters with a foraging requirements (10 Revolutions/pellet). *=p<0.05 compared to the saline control condition

Figure 3

Mean ± SEM food intake as a percentage of the saline-injected ad libitum fed control condition for the effects of food deprivation with intracerebroventricular (icv) saline injection (black bars) and food deprivation with icv melanotan II (MTII; gray bars) on hamsters without a foraging requirement and a stationary wheel (Blocked Wheel), hamsters with no foraging requirement and a freely moving wheel (Free Wheel) and hamsters with a foraging requirement (10 Revolutions/pellet) *=p<0.05 compared to saline injected ad libitum control condition.

Figure 4

Mean ± SEM food hoarding as a percentage of the saline-injected ad libitum fed control condition for the effects of food deprivation with intracerebroventricular (icv) saline injection (black bars) and food deprivation with icv melanotan II (MTII; white bars) on hamsters without a foraging requirement and a stationary wheel (Blocked Wheel), hamsters with no foraging requirement and a freely moving wheel (Free Wheel) and hamsters with a foraging requirements (10 Revolutions/pellet) *=p<0.05 compared to saline injected ad libitum fed control condition.