Extracellular fatty acid synthase: A possible surrogate biomarker of insulin resistance
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Output type: Journal article
Author list: Fernandez-Real J., Menendez J., Moreno-Navarrete J., Blüher M., Vazquez-Martin A., Vázquez M., Ortega F., Diéguez C., Frühbeck G., Ricart W., Vidal-Puig A.
Publisher: American Diabetes Association
Publication year: 2010
Volume number: 59
Issue number: 6
Start page: 1506
End page: 1511
Number of pages: 6
ISSN: 0012-1797
URL: http://api.elsevier.com/content/abstract/scopus_id:77953187835
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Open access status: hybrid
Full text URL: https://doi.org/10.2337/db09-1756
Abstract
CONTEXT - Circulating fatty acid synthase (FASN) is a biomarker of metabolically demanding human diseases. The aim of this study was to determine whether circulating FASN could be a biomarker of overnutrition-induced metabolic stress and insulin resistance in common metabolic disorders. RESEARCH DESIGN AND METHODS - Circulating FASN was evaluated in two cross-sectional studies in association with insulin sensitivity and in four longitudinal studies investigating the effect of diet- and surgery-induced weight loss, physical training, and adipose tissue expansion using peroxisome proliferator-activated receptor agonist rosiglitazone on circulating FASN. RESULTS - Age- and BMI-adjusted FASN concentrations were significantly increased in association with obesity-induced insulin resistance in two independent cohorts. Both visceral and subcutaneous FASN expression and protein levels correlated inversely with extracellular circulating FASN (P = -0.63; P < 0.0001), suggesting that circulating FASN is linked to depletion of intracellular FASN. Improved insulin sensitivity induced by therapeutic strategies that decreased fat mass (diet induced, surgery induced, or physical training) all led to decreased FASN levels in blood (P values between 0.02 and 0.04). To discriminate whether this was an effect related to insulin sensitization, we also investigated the effects of rosiglitazone. Rosiglitazone did not lead to significant changes in circulating FASN concentration. CONCLUSIONS - Our results suggest that circulating FASN is a biomarker of overnutrition-induced insulin resistance that could provide diagnostic and prognostic advantages by providing insights on the individualized metabolic stress. © 2010 by the American Diabetes Association.
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