title: Proteome changes in rat plasma in response to sibutramine.
abstract: Sibutramine is an anti-obesity agent that induces weight loss by selective inhibition of neuronal reuptake of serotonin and norepinephrine; however, it is associated with the risk of cardiovascular diseases (CVD), including heart attack and stroke. Here, we analyzed global protein expression patterns in plasma of control and sibutramine-treated rats using proteomic analysis for a better understanding of the two conflicting functions of this drug, appetite regulation, and cardiovascular risk. The control (n=6) and sibutramine-treated groups (n=6) were injected by vehicle and sibutramine, respectively, and 2-DE combined with MALDI-TOF/MS were performed. Compared to control rats, sibutramine-administered rats gained approximately 18% less body weight and consumed about 13% less food. Plasma leptin and insulin levels also showed a significant decrease in sibutramine-treated rats. As a result of proteomic analysis, 23 differentially regulated proteins were discovered and were reconfirmed by immunoblot analysis. Changed proteins were classified into appetite regulation and cardiovascular risk, according to their regulation pattern. Because the differential levels of proteins that have been well recognized as predictors of CVD risk were not well matched with the results of our proteomic analysis, this study does not conclusively prove that sibutramine has an effect on CVD risk.
authors.affiliation: Department of Biotechnology, Daegu University, Kyungsan, Kyungbuk, Republic of Korea.
authors.forename: Jung-Won
authors.initials: JW
authors.lastname: Choi
authors.forename: Jeong In
authors.initials: JI
authors.lastname: Joo
authors.forename: Dong Hyun
authors.initials: DH
authors.lastname: Kim
authors.forename: Xia
authors.initials: X
authors.lastname: Wang
authors.forename: Tae Seok
authors.initials: TS
authors.lastname: Oh
authors.forename: Duk Kwon
authors.initials: DK
authors.lastname: Choi
authors.forename: Jong Won
authors.initials: JW
authors.lastname: Yun
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects; D000818:Animals; D001067:Appetite Depressants / Q000008:administration & dosage* / Q000009:adverse effects; D001069:Appetite Regulation / Q000187:drug effects / Q000235:genetics; D001798:Blood Proteins / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000139:chemically induced; D002853:Chromatography, Liquid; D003503:Cyclobutanes / Q000008:administration & dosage* / Q000009:adverse effects; D015180:Electrophoresis, Gel, Two-Dimensional; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood; D008297:Male; D009765:Obesity / Q000097:blood / Q000188:drug therapy / Q000235:genetics; D020543:Proteome / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012307:Risk Factors; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods; D015431:Weight Loss / Q000187:drug effects
chemical_list: D001067:Appetite Depressants; D001798:Blood Proteins; D003503:Cyclobutanes; D007328:Insulin; D020738:Leptin; D020543:Proteome; C058254:sibutramine