2. Academic Validation
  3. Potential involvement of adipocyte insulin resistance in obesity-associated up-regulation of adipocyte lysophospholipase D/autotaxin expression

Potential involvement of adipocyte insulin resistance in obesity-associated up-regulation of adipocyte lysophospholipase D/autotaxin expression

  • Diabetologia. 2005 Mar;48(3):569-77. doi: 10.1007/s00125-004-1660-8.
J Boucher 1,  D Quilliot,  J P Pradères,  M F Simon,  S Grès,  C Guigné,  D Prévot,  G Ferry,  J A Boutin,  C Carpéné,  P Valet,  J S Saulnier-Blache
Affiliations

Affiliation

  • 1 INSERM U586, Institut Louis Bugnard, Rangueil Hospital, TSA 50032, 31059, Toulouse Cedex 9, France.
PMID: 15700135 DOI: 10.1007/s00125-004-1660-8
Abstract

Aims/hypothesis: 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/interpretation: 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.

Figures