title: Enrichment of Triglyceride-Rich Lipoproteins with Apolipoprotein C-I Is Positively Associated with Their Delayed Plasma Clearance Independently of Other Transferable Apolipoproteins in Postmenopausal Overweight and Obese Women.
abstract: Background:The role of plasma apolipoprotein (apo) C-I in cardiometabolic risk in humans is unclear. However, in vitro studies showed a dual role for apoC-I, both protective and harmful, depending on the carrier lipoprotein.Objective:We tested the hypothesis that triglyceride (TG)-rich lipoprotein (TRL) apoC-I, not total or HDL apoC-I, is associated with delayed postprandial plasma clearance of TRLs, independently of apoC-II, apoC-III, and apoE.Methods:This cross-sectional study examines the plasma clearance of a13C-triolein-labeled high-fat meal (68% fat energy) in 20 postmenopausal overweight and obese women [body mass index (in kg/m2) ≥27; aged 45-74 y] as the increment change in area under the 6-h postprandial curves (iAUC6h) of TRL parameters. Lipoproteins were fractionated by fast-protein LC. Transferable apolipoproteins were measured by ELISA. TRL enrichment with apolipoproteins was calculated by dividing their TRL concentrations by TRL apoB. The effects of human apoC-I and apoC-III on the hydrolysis and storage of3H-triolein-labeled TRLs were tested in 3T3-L1 adipocytes.Results:TRL apoC-I was positively associated with plasma apo B-48 and total and non-HDL TGs, cholesterol, and apoB (r= 0.52-0.97) and negatively with HDL cholesterol (r= -0.52) and LDL diameter (r= -0.91) (P< 0.05). Total and HDL apoC-I were correlated only with total (r= 0.62) and HDL (r= 0.75) cholesterol. Women with high fasting TRL enrichment with apoC-I (99-365 μmol apoC-I/μmol apoB), but not apoC-II, apoC-III, or apoE, had higher iAUC6hfor TGs (+195%),13C-TGs (+319%), and apo B-48 (+186%) than those with low enrichment (14-97 μmol apoC-I/μmol apoB). The 4-h postprandial increase in TRL apoC-I was associated with a 4-h increase in TRL TGs and iAUC6hfor TGs,13C-TGs, and apo B-48 (r= 0.74-0.86,P< 0.001), independently of 4-h changes in TRL apoB, apoC-II, apoC-III, or apoE. ApoC-I and apoC-III inhibited3H-TRL clearance by adipocytes by >75% (P< 0.001).Conclusions:TRL enrichment with apoC-I is positively associated with postprandial hypertriglyceridemia and remnant accumulation in postmenopausal overweight and obese women, independently of apoC-II, apoC-III, or apoE, which may be due to inhibiting TRL clearance by adipocytes. Reducing TRL apoC-I may ameliorate delayed postprandial plasma clearance of TRLs and associated risks in humans.
authors.affiliation: Montreal Clinical Research Institute, Montreal, Quebec, Canada.|Faculty of Medicine, University of Montreal, Montreal, Quebec, Canada; and.|Montreal Diabetes Research Center, Montreal, Quebec, Canada.
authors.forename: Hanny
authors.initials: H
authors.lastname: Wassef
authors.affiliation: Montreal Clinical Research Institute, Montreal, Quebec, Canada.|Faculty of Medicine, University of Montreal, Montreal, Quebec, Canada; and.|Montreal Diabetes Research Center, Montreal, Quebec, Canada.
authors.forename: Simon
authors.initials: S
authors.lastname: Bissonnette
authors.affiliation: Montreal Clinical Research Institute, Montreal, Quebec, Canada.|Faculty of Medicine, University of Montreal, Montreal, Quebec, Canada; and.
authors.forename: Robert
authors.initials: R
authors.lastname: Dufour
authors.affiliation: Montreal Clinical Research Institute, Montreal, Quebec, Canada.|Faculty of Medicine, University of Montreal, Montreal, Quebec, Canada; and.
authors.forename: Jean
authors.initials: J
authors.lastname: Davignon
authors.affiliation: Montreal Clinical Research Institute, Montreal, Quebec, Canada; may.faraj@umontreal.ca.|Faculty of Medicine, University of Montreal, Montreal, Quebec, Canada; and.|Montreal Diabetes Research Center, Montreal, Quebec, Canada.
authors.forename: May
authors.initials: M
authors.lastname: Faraj
mesh_terms: D041721:3T3-L1 Cells; D000368:Aged; D000818:Animals; D053302:Apolipoprotein C-I / Q000097:blood* / Q000494:pharmacology; D001053:Apolipoproteins / Q000097:blood; D019540:Area Under Curve; D002784:Cholesterol / Q000097:blood*; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D015243:Cholesterol, VLDL / Q000097:blood; D003430:Cross-Sectional Studies; D004032:Diet; D004041:Dietary Fats / Q000097:blood*; D005260:Female; D006801:Humans; D015228:Hypertriglyceridemia / Q000097:blood*; D008074:Lipoproteins / Q000097:blood; D051379:Mice; D008875:Middle Aged; D009765:Obesity / Q000097:blood*; D050177:Overweight; D017698:Postmenopause; D019518:Postprandial Period; D014280:Triglycerides / Q000097:blood*
chemical_list: C505803:APOC1 protein, human; D053302:Apolipoprotein C-I; D001053:Apolipoproteins; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D015243:Cholesterol, VLDL; D004041:Dietary Fats; D008074:Lipoproteins; D014280:Triglycerides; C030087:lipoprotein triglyceride; D002784:Cholesterol
keywords: apoB lipoproteins; chylomicron and VLDL clearance; in situ LPL activity; overweight and obese postmenopausal women; remnants