title: Potential involvement of adipocyte insulin resistance in obesity-associated up-regulation of adipocyte lysophospholipase D/autotaxin expression.
abstract: OBJECTIVE
  Autotaxin is a lysophospholipase D that is secreted by adipocytes and whose expression is substantially up-regulated in obese, diabetic db/db mice. The aim of the present study was to depict the physiopathological and cellular mechanisms involved in regulation of adipocyte autotaxin expression.
  
  
  METHODS
  Autotaxin mRNAs were quantified in adipose tissue from db/db mice (obese and highly diabetic type 2), gold-thioglucose-treated (GTG) mice (highly obese and moderately diabetic type 2), high-fat diet-fed (HFD) mice (obese and moderately diabetic type 2), streptozotocin-treated mice (thin and diabetic type 1), and massively obese humans with glucose intolerance.
  
  
  RESULTS
  When compared to non-obese controls, autotaxin expression in db/db mice was significantly increased, but not in GTG, HFD, or streptozotocin-treated mice. During db/db mice development, up-regulation of autotaxin occurred only 3 weeks after the emergence of hyperinsulinaemia, and simultaneously with the emergence of hyperglycaaemia. Adipocytes from db/db mice exhibited a stronger impairment of insulin-stimulated glucose uptake than non-obese and HFD-induced obese mice. Autotaxin expression was up-regulated by treatment with TNFalpha (insulin resistance-promoting cytokine), and down-regulated by rosiglitazone treatment (insulin-sensitising compound) in 3T3F442A adipocytes. Finally, adipose tissue autotaxin expression was significantly up-regulated in patients exhibiting both insulin resistance and impaired glucose tolerance.
  
  
  CONCLUSIONS
  The present work demonstrates the existence of a db/db-specific up-regulation of adipocyte autotaxin expression, which could be related to the severe type 2 diabetes phenotype and adipocyte insulin resistance, rather than excess adiposity in itself. It also showed that type 2 diabetes in humans is also associated with up-regulation of adipocyte autotaxin expression.
authors.affiliation: INSERM U586, Institut Louis Bugnard, Rangueil Hospital, TSA 50032, 31059, Toulouse Cedex 9, France.
authors.forename: J
authors.initials: J
authors.lastname: Boucher
authors.forename: D
authors.initials: D
authors.lastname: Quilliot
authors.forename: J P
authors.initials: JP
authors.lastname: Pradères
authors.forename: M F
authors.initials: MF
authors.lastname: Simon
authors.forename: S
authors.initials: S
authors.lastname: Grès
authors.forename: C
authors.initials: C
authors.lastname: Guigné
authors.forename: D
authors.initials: D
authors.lastname: Prévot
authors.forename: G
authors.initials: G
authors.lastname: Ferry
authors.forename: J A
authors.initials: JA
authors.lastname: Boutin
authors.forename: C
authors.initials: C
authors.lastname: Carpéné
authors.forename: P
authors.initials: P
authors.lastname: Valet
authors.forename: J S
authors.initials: JS
authors.lastname: Saulnier-Blache
mesh_terms: D017667:Adipocytes / Q000201:enzymology / Q000502:physiology*; D000818:Animals; D001692:Biological Transport; D003847:Deoxyglucose / Q000493:pharmacokinetics; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology / Q000503:physiopathology; D005786:Gene Expression Regulation; D015971:Gene Expression Regulation, Enzymologic; D005956:Glucose-6-Phosphate Isomerase / Q000235:genetics*; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D015187:Lipectomy; D051379:Mice; D008810:Mice, Inbred C57BL; D009097:Multienzyme Complexes / Q000235:genetics*; D009765:Obesity / Q000503:physiopathology*; D043264:Phosphodiesterase I; D010727:Phosphoric Diester Hydrolases / Q000235:genetics*; D011755:Pyrophosphatases; D000099189:Lysophospholipase D
chemical_list: D003847:Deoxyglucose; D005956:Glucose-6-Phosphate Isomerase; D006023:Glycoproteins; D009097:Multienzyme Complexes; D043264:Phosphodiesterase I; D010727:Phosphoric Diester Hydrolases; D011755:Pyrophosphatases; D000099189:Lysophospholipase D