Effects Of Ghrelin On Selective Food Intake In Rats And Its Mechanism

Objective: To investigate the effect of central ghrelin on selective food intake in rats and its underlying mechanism.Methods: Rats were fed basal diet for 14 days.The lateral ventricle(ICV)or the ventral tegmental area(VTA)were placed in the tube,and microinjection of ghrelin to observe the energy intake of selective food(chow,sucrose and lard)in 3h,6h and 0-24 h.Rats were fasting and intraperitoneal injection of ghrelin receptor antagonist JMV 2959,observing the energy intake of chow,sucrose and lard in 3h,6h and 0-24 h after fasting or intraperitoneal injection of JMV 2959 in rats.Fasting of GHSR gene knockout mice,and observed the energy intake of chow,sucrose and lard in 3h,6h and 0-24 h.Results: ICV injection of 3 ug ghrelin,the energyintake of chow in 3h,6h and 0-24 h increased significantly of rats compared with the control group of artificial cerebrospinal fluid(a CSF)(P < 0.01-0.001),the intake energy of lard at 3 h and 6 h was also significantly increased in rats(P < 0.05),however,the energy intake of sucrose at 3 h,6 h and 0-24 h did not change significantly(P > 0.05).The total energy intake of rats in 3h after ICV injection of ghrelinsignificantly increased,which was 2 times as high as that of the control group(P < 0.001).The effect of ghrelin on appetite was still obvious in rats while injected with ghrelin 6h in ICV,the total energy intake was significantly higher than the a CSF control group(P < 0.05).The 24 h cumulative energy intake(0-24h)of ICV injected with ghrelin did not change significantly(P > 0.05).Injection of 2 ug ghrelin in the VTA,the chow energy intake in 3 h and 6 h increased significantly(P < 0.01),and total energy intake significantly higher than the a CSF control group(P < 0.01).However,there was no significant difference in the 0-24 h energy intake between the groups of the VTA injection of ghrelin(P > 0.05).The fasting rats(fasting + intraperitoneal injection of NS)the 0-24 h total energy intake increased by 24%(P<0.001),the chow energy intake was significantly increased by 26%(P<0.001),lard energy intake increased by 29% (P<0.001),but sucrose energy intake remained unchanged(P>0.05)compared with fourteenth days of free choice feeding.Compared with the NS control group,the total energy intake of rats in 3h,6h and 0-24 h were significantly reduced by 26%(P < 0.01),16%(P < 0.01)and 14%(P < 0.001)respectively while intraperitoneal injection of ghrelin receptor antagonist JMV2959.The energy intake in 3 h and 6 h reduced by 25%(P<0.01)and 22%(P<0.01)respectively.The energy intake of lardhas a decreasing trend,but no statistical significance(P > 0.05).Compared with the NS control group,the 0-24 h energy intake by intraperitoneal injection of JMV2959 decreased by 12%(P < 0.001).The energy intake of lard was also significantly reduced by 20%(P < 0.001,P< 0.001),but there was no significant change in the energy consumption of sucrose in 0-24h(P > 0.05).Compared with wild type controls,fasting overnight GHSR knockout mice have a significant reduction in the chow energy intake in 0-24 h by 14%(P < 0.01),but the sucrose and lard energy intake in 0-24 h is no significant change(P > 0.05).The chow,lard or sucrose energy intake of 3 h and 6 h in GHSR knockout mice were not significantly different from those in the control group(P>0.05).Conclusion: Ghrelin,a brain gut hunger hormone,is involved in the regulation of selective food intake in rats.The ghrelin effect may be mediated by its receptor signaling pathway.Ghrelin has the function of promoting "healthy" food intake,and VTA may be the neurobiological basis for ghrelin to exert this effect.