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

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.

• Authors: J Boucher, 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
• Journal: Diabetologia (Diabetologia) Vol. 48 Issue 3 Pg. 569-77 (Mar 2005) ISSN: 0012-186X [Print] Germany
• PMID: 15700135 (Publication Type: Journal Article)

Chemical References

• Glycoproteins
• Multienzyme Complexes
• Deoxyglucose
• Phosphoric Diester Hydrolases
• Phosphodiesterase I
• alkylglycerophosphoethanolamine phosphodiesterase
• Pyrophosphatases
• Glucose-6-Phosphate Isomerase

Topics

• Adipocytes (enzymology, physiology)
• Animals
• Biological Transport
• Deoxyglucose (pharmacokinetics)
• Diabetes Mellitus, Experimental (enzymology, physiopathology)
• Diabetes Mellitus, Type 2 (enzymology, physiopathology)
• Gene Expression Regulation
• Gene Expression Regulation, Enzymologic
• Glucose-6-Phosphate Isomerase (genetics)
• Glycoproteins (genetics)
• Humans
• Insulin Resistance (physiology)
• Lipectomy
• Mice
• Mice, Inbred C57BL
• Multienzyme Complexes (genetics)
• Obesity (physiopathology)
• Phosphodiesterase I
• Phosphoric Diester Hydrolases (genetics)
• Pyrophosphatases