title: Increased subcutaneous adipose tissue expression of genes involved in glycerolipid-fatty acid cycling in obese insulin-resistant versus -sensitive individuals.
abstract: BACKGROUND
  A subpopulation of obese individuals remains insulin sensitive (ISO). They represent a unique human model to investigate factors underlying insulin resistance (IR) without the confounding effect of major differences in weight/adiposity. Altered fatty-acid (FA) metabolism in sc adipose tissue (SAT) contributes to obesity-associated IR.
  
  
  OBJECTIVE
  To test the hypothesis that ISO and body mass index-matched insulin-resistant obese (IRO) patients demonstrate differential SAT expression profiles of genes involved in glycerolipid-FA metabolism and that weight loss-induced improvement of IR ameliorates these changes.
  
  
  METHODS
  A cross-sectional and longitudinal study.
  
  
  METHODS
  Thirty-eight nondiabetic obese women were stratified into ISO (n = 25) or IRO (n = 13) groups based on hyperinsulinemic-euglycemic clamp results. Subjects were studied before and after a 6-month hypocaloric diet intervention.
  
  
  METHODS
  mRNA (quantitative RT-PCR) and protein (mass spectrometry and immunoblots) levels were measured in SAT biopsies.
  
  
  RESULTS
  Despite having age, body mass index, and fat mass similar to ISO individuals, IRO patients had lower insulin sensitivity and glucose tolerance (P < .05). Baseline SAT mRNA and protein levels of genes involved in both the synthesis and lipolysis of glycerolipid-FAs were higher in IRO individuals (P < .05), even when groups were matched for visceral adipose tissue content. The dietary intervention resulted in approximately 6% weight loss in both the IRO and ISO groups (P < .05) but only ameliorated insulin sensitivity in IRO individuals (P < .05). Likewise, the intervention reduced the expression of most glycerolipid-FA metabolism genes (P < .05), with expression levels in IRO individuals being restored to ISO levels.
  
  
  CONCLUSIONS
  Increased SAT expression of genes involved in both the synthesis and hydrolysis of glycerolipid-FAs is closely associated with IR in obese women. The results suggest that enhanced glycerolipid-FA cycling in SAT contributes to obesity-associated IR.
authors.affiliation: Institut de recherches cliniques de Montréal (M.-S.G., J.R.P., M.-E.L., B.C., R.R.-L.), Montréal, QC H2W 1R7, Canada; Montreal Diabetes Research Center at the Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM) (M.-S.G., M.-E.L., R.S., S.R.M.M., M.P., R.R.-L.), Montréal, QC H2X 0A9, Canada; McGill University and Centre d'Innovation Génome Québec (R.S.), Montréal, QC H3A 0G1, Canada; Molecular Nutrition Unit at the CRCHUM (S.R.M.M., M.P.), Montréal, QC H2X 0A9, Canada; Diabetes and Metabolism Research Unit (N.B.R.), and Department of Medicine and Section of Endocrinology (N.B.R.), Boston University School of Medicine, Boston, Massachusetts 02118; Departments of Biochemistry (B.C., M.P.) and Nutrition (M.-E.L., M.P., R.R.-L.), Faculty of Medicine, Université de Montréal, Montréal, QC H3C 3J7, Canada.
authors.forename: Marie-Soleil
authors.initials: MS
authors.lastname: Gauthier
authors.forename: Joelle R
authors.initials: JR
authors.lastname: Pérusse
authors.forename: Marie-Ève
authors.initials: MÈ
authors.lastname: Lavoie
authors.forename: Robert
authors.initials: R
authors.lastname: Sladek
authors.forename: S R Murthy
authors.initials: SR
authors.lastname: Madiraju
authors.forename: Neil B
authors.initials: NB
authors.lastname: Ruderman
authors.forename: Benoit
authors.initials: B
authors.lastname: Coulombe
authors.forename: Marc
authors.initials: M
authors.lastname: Prentki
authors.forename: Rémi
authors.initials: R
authors.lastname: Rabasa-Lhoret
mesh_terms: D000368:Aged; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D004038:Diet, Reducing; D005227:Fatty Acids / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D006017:Glycolipids / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D008137:Longitudinal Studies; D008875:Middle Aged; D009765:Obesity / Q000178:diet therapy / Q000235:genetics* / Q000378:metabolism*; D017698:Postmenopause / Q000235:genetics; D050151:Subcutaneous Fat / Q000378:metabolism*
chemical_list: D005227:Fatty Acids; D006017:Glycolipids