Ghrelin通过下丘脑外侧核CART神经元影响小鼠采食和体质量

Ghrelin affects feed intake and body weight of mice through CART neurons in lateral hypothalamic nucleus

生长素释放肽(ghrelin)是一种胃产生的激素,作用于中枢后调节机体能量代谢。可卡因苯丙胺调节转录肽(CART)神经元参与摄食行为和能量平衡调节过程。已知CART神经元受激素影响调节能量稳态,但Ghrelin是否通过影响CART神经元发挥促食欲功能尚不清楚。因此,本研究重点关注了Ghrelin调节摄食和体质量过程中下丘脑背内侧核(DMH)CART神经元的作用。首先通过免疫荧光确定CART的全脑表达。然后评估了腹腔注射Ghrelin后对DMHCART神经元表达的影响,最后将Ghrelin注射到DMH后测量了小鼠摄食量和体质量变化。结果显示,在内侧视前核(MPA)、弓状核(ARC)、下丘脑背内侧核(DMH)、丘脑室旁核(PVT)和中缝核(ROb)检测到CART免疫阳性神经元和纤维。与对照组相比,外周注射Ghrelin显著增加DMHCART免疫阳性神经元表达(P=0.0373)。DMH注射Ghrelin导致体质量(P=0.0040)和采食(P=0.0231)增加。该研究证实了DMHCART神经元受Ghrelin调控,并有望为代谢紊乱及肥胖症疾病的临床干预提供新的调控靶点。

Ghrelin is a hormone produced by the stomach that regulates energy metabolism after acting on the central nervous system.Cocaine amphetamine-regulated transcriptional peptide(CART)neurons participate in the regulation of feeding behavior and energy balance.It is known that CART neurons are influenced by hormones to regulate energy homeostasis,but whether ghrelin exerts its pro-appetite function by influencing CART neurons is unknown.Therefore,this study focuses on the role of VMHCART neurons in the regulation of feeding and relative body weight by ghrelin.Firstly,the whole brain expression of CART was determined by immunofluorescence.Then the effect of intraperitoneal injection of ghrelin on the expression of DMH~(CART)neurons was evaluated.Finally,the ghrelin was delivered to DMH and the changes of food intake and relative body weight of mice were measured.CART immunoreactive neurons were detected in medial preoptic nucleus(MPA),arcuate nucleus(ARC),dorsomedial hypothalamic nucleus(DMH),thalamic paraventricular nucleus(PVT)and raphe nucleus(ROb).Compared with the control group,peripheral injection of ghrelin significantly increased the expression of DMHCART immunoreactive neurons(P=0.0373).DMH long-term injection of ghrelin resulted in an increase in body weight(P=0.0040)and feed intake(P=0.0231).The results provide anatomical evidence for the whole brain distribution of CART,which proves that ghrelin affects feed intake and body weight of mice through CART neurons in DMH,suggesting that specific neuron types and regional specificity are involved in ghrelin regulation of feed intake and energy homeostasis.