Study On The Inhibiting Feeding Effect Of Nesfatin-1 By Affecting Dopamine Secretion In Mice

Objective: Energy intake exceeds energy consumption for a long time,leading to energy imbalance and excessive accumulation of body fat,resulting in the emergence of metabolic diseases such as obesity,which seriously threaten the health of animal organisms.Research has found that Nesfatin-1 is closely related to obesity and obesity related diseases,and as a neuropeptide,the inhibitory effect of Nesfatin-1 on feeding and the regulation of lipid metabolism has received much attention in recent years.To explore the inhibitory mechanism of Nesfatin-1 on feeding,this study investigated the effect of Nesfatin-1 on dopamine secretion in starved mice by blocking energy intake and analyzed the effect on the rewarding effect of the organism.Method: Forty C57BL/6 mice were randomly divided into negative control group(n=8)and fasting group(n=32).The mice in the starvation group were starved for 24 h and48 h to establish a fasting model,and 1.25 nmol/g Nesfatin-1 was injected intraperitoneally to establish the Nesfatin-1 group(including fasting 24 h+Nesfatin-1 and fasting 48h+Nesfatin-1 groups);the mice in the negative control group were injected intraperitoneally with the same dose of PBS buffer.The mice in each group were weighed and blood was collected from the tail vein for blood glucose measurement to determine whether the fasting mouse model was established.Then they were anesthetized,blood was taken from their eyes and brain tissue was collected after they were killed.ELISA was used to detect the levels of Nesfatin-1 and dopamine in the serum of each group of mice,while q RT-PCR was used to detect the relative expression levels of tyrosine hydroxylase(TH)and c-FOS m RNA in the brain tissue of each group of mice.Western Blot was also used to detect the relative expression levels of TH and c-FOS proteins in the brain tissue of each group of mice.Result:(1)Compared with the negative control group,the body weight and blood glucose of mice in the fasting group were highly significantly decreased(P<0.01),indicating successful modeling.(2)Compared with the negative control group,the serum levels of Nesfatin-1 and dopamine in the fasting group mice were significantly reduced(P<0.05);after Nesfatin-1 intervention,the levels of Nesfatin-1 and dopamine in the serum of fasting mice highly significantly increased(P<0.01).(3)Compared with the negative control group,the relative expression of TH m RNA in the brain tissue of the fasting group mice was extremely significant reduced(P<0.01),while the relative expression of c-FOS m RNA was highly significantly increased(P<0.01);after Nesfatin-1 intervention,the relative expression levels of TH and c-FOS m RNA in the brain tissue of fasting mice significantly increased(P<0.05).(4)Compared with the negative control group,the relative expression of TH protein in brain tissue of the fasting group mice was highly significantly reduced(P<0.01),while the relative expression of c-FOS protein was highly significantly increased(P<0.01);after Nesfatin-1 intervention,the relative expression levels of TH and c-FOS proteins in brain tissue of fasting mice significantly increased(P<0.05).Conclusion:(1)Nesfatin-1 can promote the release of dopamine in fasting mice,which may stimulate their brain reward system.(2)Nesfatin-1 can promote the expression of TH in the brain tissue of fasting mice,thereby promoting the release of dopamine.(3)Nesfatin-1 was able to promote the expression of c-FOS in the brain tissue of fasting mice,indicating that Nesfatin-1 can stimulate the activation of neurons in fasting mice.Therefore,Nesfatin-1 may activate the rewarding effect of the body’s nervous system by stimulating the secretion of dopamine,and achieve energy regulation and inhibition of food intake.This study provides an important foundation for the application research of Nesfatin-1.