title: ApoB-lipoproteins and dysfunctional white adipose tissue: Relation to risk factors for type 2 diabetes in humans.
abstract: Elevated plasma apoB is an independent predictor of T2D; however, underlying mechanisms remain unclear. Chronic reduction in white adipose tissue (WAT) function promotes T2D. We reported that differentiation of preadipocytes and acute incubation of human WAT with LDL induce their dysfunction (decreased hydrolysis and storage of triglyceride-rich lipoproteins [TRL]).
  
  
  
  To examine the hypothesis that the association of plasma apoB with T2D risk factors, hypertriglyceridemia (hyperTG), insulin resistance (IR), and hyperinsulinemia, was dependent on WAT dysfunction.
  
  
  
  Thirty normoglycemic subjects were enrolled (≥27 kg/m2, 45-74 years). Fasting gynoid WAT biopsy was obtained followed by the ingestion of a13C-triolein-labeled-high-fat meal. WAT function was measured ex vivo as the hydrolysis and storage of3H-triolein-labeled-TRL as3H-lipids over 4 hours. Insulin sensitivity and secretion were measured by Botnia clamps.
  
  
  
  WAT function correlated with higher insulin sensitivity (M/Iclampr = 0.60) and faster plasma clearance of chylomicrons in women (iAUC6hrsapoB48, r = -0.60). Plasma apoB correlated with WAT dysfunction (r = -0.52), postprandial hyperTG (iAUC6hrs-TG, r = 0.51,13C-TG, r = 0.48), IR (M/Iclampr = -0.38) and hyperinsulinemia (second phase-glucose-induced-insulin-secretion, r = 0.41). Co-incubation of subjects' WAT with their LDL increased medium accumulation of3H-TRL and3H-NEFA with no sex differences. Adjusting for WAT function eliminated the association of plasma apoB with IR independent of sex and body fat or adipocyte diameter. Its association with other risk factors was unaffected.
  
  
  
  Association of plasma apoB with IR in obese subjects is dependent on gynoid WAT dysfunction. We propose that targeting hyperapoB, without increasing their uptake into nonhepatic peripheral tissues, ameliorates WAT function and risk for T2D.
authors.affiliation: Nutrition Department, Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada; Institut de recherches cliniques de Montréal (IRCM), Montréal, Québec, Canada; Montreal Diabetes Research Center (MDRC), Montréal, Québec, Canada.
authors.forename: Valérie
authors.initials: V
authors.lastname: Lamantia
authors.affiliation: Nutrition Department, Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada; Institut de recherches cliniques de Montréal (IRCM), 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; 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; Montreal Diabetes Research Center (MDRC), Montréal, Québec, Canada; Molecular Biology Department, Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Cyr
authors.affiliation: Institut de recherches cliniques de Montréal (IRCM), Montréal, Québec, Canada; Division of Experimental Medicine, Faculty of Medicine, McGill University, Montréal, Québec, Canada.
authors.forename: Alexis
authors.initials: A
authors.lastname: Baass
authors.affiliation: Nutrition Department, Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada; Institut de recherches cliniques de Montréal (IRCM), Montréal, Québec, Canada.
authors.forename: Robert
authors.initials: R
authors.lastname: Dufour
authors.affiliation: Nutrition Department, Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada; Institut de recherches cliniques de Montréal (IRCM), Montréal, Québec, Canada; Montreal Diabetes Research Center (MDRC), Montréal, Québec, Canada.
authors.forename: Rémi
authors.initials: R
authors.lastname: Rabasa-Lhoret
authors.affiliation: Nutrition Department, Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada; Institut de recherches cliniques de Montréal (IRCM), Montréal, Québec, Canada; Montreal Diabetes Research Center (MDRC), Montréal, Québec, Canada. Electronic address: may.faraj@umontreal.ca.
authors.forename: May
authors.initials: M
authors.lastname: Faraj
mesh_terms: D052436:Adipose Tissue, White / Q000473:pathology*; D001055:Apolipoproteins B / Q000097:blood*; D048429:Cell Size; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000473:pathology*; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D012307:Risk Factors
chemical_list: D001055:Apolipoproteins B
keywords: Adipose tissue; ApoB; Insulin resistance; Insulin secretion; Remnant accumulation