title: WAT apoC-I secretion: role in delayed chylomicron clearance in vivo and ex vivo in WAT in obese subjects.
abstract: Reduced white adipose tissue (WAT) LPL activity delays plasma clearance of TG-rich lipoproteins (TRLs). We reported the secretion of apoC-I, an LPL inhibitor, from WAT ex vivo in women. Therefore we hypothesized that WAT-secreted apoC-I associates with reduced WAT LPL activity and TRL clearance. WAT apoC-I secretion averaged 86.9 ± 31.4 pmol/g/4 h and 74.1 ± 36.6 pmol/g/4 h in 28 women and 11 men with BMI ≥27 kg/m(2), respectively, with no sex differences. Following the ingestion of a (13)C-triolein-labeled high-fat meal, subjects with high WAT apoC-I secretion (above median) had delayed postprandial plasma clearance of dietary TRLs, assessed from plasma (13)C-triolein-labeled TGs and apoB48. They also had reduced hydrolysis and storage of synthetic (3)H-triolein-labeled ((3)H)-TRLs in WAT ex vivo (i.e., in situ LPL activity). Adjusting for WAT in situ LPL activity eliminated group differences in chylomicron clearance; while adjusting for plasma apoC-I, (3)H-NEFA uptake by WAT, or body composition did not. apoC-I inhibited in situ LPL activity in adipocytes in both a concentration- and time-dependent manner. There was no change in postprandial WAT apoC-I secretion. WAT apoC-I secretion may inhibit WAT LPL activity and promote delayed chylomicron clearance in overweight and obese subjects. We propose that reducing WAT apoC-I secretion ameliorates postprandial TRL clearance in humans.
authors.affiliation: Institut de Recherches Cliniques de Montréal (IRCM), Montréal, Québec, Canada Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada Montreal Diabetes Research Center (MDRC), Montréal, Québec, Canada.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Cyr
authors.affiliation: Institut de Recherches Cliniques de Montréal (IRCM), Montréal, Québec, Canada Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada Montreal Diabetes Research Center (MDRC), Montréal, Québec, Canada.
authors.forename: Hanny
authors.initials: H
authors.lastname: Wassef
authors.affiliation: Institut de Recherches Cliniques de Montréal (IRCM), Montréal, Québec, Canada Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada Montreal Diabetes Research Center (MDRC), Montréal, Québec, Canada.
authors.forename: Simon
authors.initials: S
authors.lastname: Bissonnette
authors.affiliation: Institut de Recherches Cliniques de Montréal (IRCM), Montréal, Québec, Canada Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada Montreal Diabetes Research Center (MDRC), Montréal, Québec, Canada.
authors.forename: Valerie
authors.initials: V
authors.lastname: Lamantia
authors.affiliation: Institut de Recherches Cliniques de Montréal (IRCM), Montréal, Québec, Canada Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada Faculty of Medicine, McGill University, Montréal, Québec, Canada.
authors.forename: Jean
authors.initials: J
authors.lastname: Davignon
authors.affiliation: Institut de Recherches Cliniques de Montréal (IRCM), Montréal, Québec, Canada Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada Montreal Diabetes Research Center (MDRC), Montréal, Québec, Canada may.faraj@umontreal.ca.
authors.forename: May
authors.initials: M
authors.lastname: Faraj
mesh_terms: D052436:Adipose Tissue, White / Q000737:chemistry / Q000201:enzymology*; D000368:Aged; D000818:Animals; D053283:Apolipoprotein B-48 / Q000737:chemistry / Q000378:metabolism; D053302:Apolipoprotein C-I / Q000097:blood*; D001057:Apolipoproteins E / Q000737:chemistry / Q000378:metabolism; D015992:Body Mass Index; D002247:Carbon Isotopes / Q000737:chemistry; D002914:Chylomicrons / Q000097:blood; D059305:Diet, High-Fat; D005260:Female; D006801:Humans; D008071:Lipoprotein Lipase / Q000097:blood* / Q000737:chemistry / Q000235:genetics; D008075:Lipoproteins, HDL / Q000097:blood; D008297:Male; D051379:Mice; D008875:Middle Aged; D009765:Obesity / Q000097:blood* / Q000235:genetics / Q000473:pathology; D019518:Postprandial Period; D014280:Triglycerides / Q000097:blood; D014304:Triolein / Q000737:chemistry / Q000378:metabolism
chemical_list: D053283:Apolipoprotein B-48; D053302:Apolipoprotein C-I; D001057:Apolipoproteins E; D002247:Carbon Isotopes; D002914:Chylomicrons; C034396:HDL-triglyceride; D008075:Lipoproteins, HDL; D014280:Triglycerides; D014304:Triolein; D008071:Lipoprotein Lipase
keywords: adipocytes; apolipoprotein C-I; cardiometabolic risk; fat storage; lipase/lipoprotein; lipolysis and fatty acid metabolism; obesity; triglyceride-rich lipoprotein; triglycerides; white adipose tissue