| Objective: To investigate the effects of CTRP4 on feeding behavior and body weight and the potential molecular mechanisms through up-regulating the expression of CTRP4 gene.Methods: 1.The N2 a cells were divided into blank group(Control group),negative group(Ad-GFP group),and CTRP4 overexpression group(Ad-CTRP4 group).After 72 h of infecting with Ad-GFP and Ad-CTRP4,qPCR was performed to determine the level of CTRP4 mRNA in N2 a cells.Western blot was performed to determine the expressions of CTRP4,TNF-α,SOCS3,p-STAT3/t-STAT3,Pomc and Npy at the protein level in N2 a cell.2.The mice were divided into NCD-saline group(NCS group),NCD-Ad-GFP group(NCG group),NCD-Ad-CTRP4 group(NCC group),HFD-saline group(HFS group),HFD-Ad-GFP group(HFG group),HFD-Ad-CTRP4 group(HFC group).After ICV injection with saline,Ad-GFP and Ad-CTRP4,the daily food intake and body weight of mice in each group were monitored for 7 consecutive days.Western blot was performed to determine the expressions of CTRP4,TNF-α,SOCS3,p-STAT3/t-STAT3 and Pomc at the protein level in hypothalamus.Result: 1.Compared with the control group,the levels of CTRP4 mRNA and protein were significantly increased in N2 A cells of the CTRP4 overexpression group(P<0.01).Besides,the levels of p-STAT3/t-STAT3 and Pomc were markedly increased in Ad-CTRP4 group(P<0.01).And the expressions of SOCS3(P<0.01),IL-6(P<0.01),TNF-α(P<0.05)and Npy(P<0.05)were obviously decreased.2.Compared with the control group,the ICV injection of Ad-CTRP4 could significantly reduce the food intake in both normal diet and high-fat diet obese mice,which lasted from the second day to the seventh day.There was no significant difference in body weight between the groups.3.Compared to contemporary NCD mice,the levels of hypothalamus CTRP4 were significantly reduced in HFD obese mice(P<0.01),whlie the levels of IL-6 and SOCS3 were significantly increased(P<0.05).In NCD mice,compared to control group,the levels of p-STAT3/t-STAT3(P<0.01)and Pomc(P<0.05)were markedly increased,while the expressions of SOCS3(P<0.05),IL-6(P<0.01)and TNF-α(P<0.05)were obviously decreased in NCC group.In HFD mice,compared to control group,the levels of p-STAT3/t-STAT3(P<0.05)and Pomc(P<0.01)were markedly increased,while the expressions of SOCS3(P<0.05),IL-6(P<0.05)and TNF-α(P<0.05)were obviously decreased in HFC group.Conclusion: Increased level of the hypothalamic CTRP4 can inhibit the food intake in mice,but has no significant inhibitory effect on body weight.Increased CTRP4 level could inhibit inflammatory factors asTNF-α and IL-6,reduce the expression of negative regulator SOCS3,increase p-STAT3/t-STAT3 level,so as to regulate appetite-regulating protein and finally suppresse food intake. |
