Background:Previous studies have revealed obesity is an important risk factor for depression,but further research is needed to clarify the underlying mechanisms.In particular,whether adiponectin and leptin,two important hormones secreted by adipose tissue,are associated with obesityrelated depression still remains controversial.Besides,it is unclear whether obesity causes brain metabolic disorder and their association with depression.Objective:To study the correlation between obesity and depress...更多
Background:Previous studies have revealed obesity is an important risk factor for depression,but further research is needed to clarify the underlying mechanisms.In particular,whether adiponectin and leptin,two important hormones secreted by adipose tissue,are associated with obesityrelated depression still remains controversial.Besides,it is unclear whether obesity causes brain metabolic disorder and their association with depression.Objective:To study the correlation between obesity and depressive disorders,and to explore the underling mechanisms.Methods:Male C57 BL/6 J mice were randomly divided into two groups and fed with high-fat diet(HFD,45%kcal)or standard chow for 8 weeks,respectively.The body weight was detected every week.At the end of the diet regimen,behavioral changes were assessed by sucrose preference test(SPT)and forced swimming test(FST).In addition,total cholesterol in blood,as well as adiponectin and leptin levels in blood or brain were assessed by enzyme-linked immunoassay.Furthermore,the brain metabolome was analyzed by 1H nuclear magnetic resonance(NMR)spectroscopic analysis.Results:After given high-fat diet for 4 weeks,the body weight of most of the mice increased by 20%more than that of the control group,which was considered to meet the obesity standard,and the rest of the mice were ruled out.After another 4 weeks,obese mice displayed a significant decline in sucrose preference in SPT and dramatically prolonged immobility time in FST.Compared with the control group,the levels of total cholesterol,adiponectin and leptin in blood obviously rose up in obesity model mice,however,there was no significant difference in adiponectin and leptin content in the brain.Additionally,twelve metabolites signifi cantly changed in the brain of obese mice,which were primarily involved in energy metabolism,amino acid metabolism,lipid metabolism and the tricarboxylic acid cycle(TCA)cycle.Conclusion:The results demonstrated that diet-induced obesity led to depression,which may be related to metabolomic disorder收起