title: Secretome-derived isotope tags (SDIT) reveal adipocyte-derived apolipoprotein C-I as a predictive marker for cardiovascular disease.
abstract: We developed a quantitative strategy, named secretome-derived isotopic tag (SDIT), to concurrently identify and quantify the adipocyte-secreted plasma proteins from normal and high-fat-diet (HFD) induced obese mice, based on the application of isotope-labeled secreted proteins from cultured mouse adipocytes as internal standards. We detected 197 proteins with significant changes between normal and obese mice plasma. Importantly, a novel adipocyte-secreted plasma protein, apolipoprotein C-I (apoC-I), significantly increased in the obese mice plasma. The expression and secretion of adipocyte apoC-I was detected in differentiated 3T3-L1 and primary rat adipocytes. Our in vitro experiments proved that functional Golgi apparatus was required for apoC-I secretion. Additionally, obese mice had increased apoC-I production in adipose tissue. Population survey of 367 participants showed that the plasma level of apoC-I was significantly increased in obese individuals compared with healthy individuals. After multiple adjustments for age and sex, the odds ratios for risk factors of cardiovascular disease including high LDL cholesterol, hypercholesterolemia, and hypertriglyceridemia, respectively, were used to compare the highest with the lowest apoC-I quartile. Taken together, our studies provide a novel strategy to concurrently identify and quantify tissue-specific secreted proteins. This strategy can be used to identify the largest global characterization of adipocyte-derived plasma proteome and provides a potential disease-related biomarker for clinical diagnoses. By selectively analyzing adipocyte-secreted proteins in plasma from obese vs lean murine and/or human subjects, we discovered that apoC-I is an adipocyte-secreted plasma protein and a predictive marker for cardiovascular disease.
authors.affiliation: Key Laboratory of Systems Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Rong-Xia
authors.initials: RX
authors.lastname: Li
authors.forename: Yu-Bo
authors.initials: YB
authors.lastname: Ding
authors.forename: Shi-Lin
authors.initials: SL
authors.lastname: Zhao
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Xiao
authors.forename: Qing-run
authors.initials: QR
authors.lastname: Li
authors.forename: Fang-Ying
authors.initials: FY
authors.lastname: Xia
authors.forename: Liang
authors.initials: L
authors.lastname: Sun
authors.forename: Xu
authors.initials: X
authors.lastname: Lin
authors.forename: Jia-Rui
authors.initials: JR
authors.lastname: Wu
authors.forename: Kan
authors.initials: K
authors.lastname: Liao
authors.forename: Rong
authors.initials: R
authors.lastname: Zeng
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism*; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D053302:Apolipoprotein C-I / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood* / Q000473:pathology; D016022:Case-Control Studies; D008078:Cholesterol, LDL / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects; D005260:Female; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D015228:Hypertriglyceridemia / Q000175:diagnosis / Q000473:pathology; D007553:Isotope Labeling / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D008875:Middle Aged; D016017:Odds Ratio; D061251:Primary Cell Culture; D020543:Proteome / Q000032:analysis / Q000378:metabolism; D040901:Proteomics / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012307:Risk Factors
chemical_list: D053302:Apolipoprotein C-I; D015415:Biomarkers; D008078:Cholesterol, LDL; D020543:Proteome