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Extracellular fatty acid synthase: a possible surrogate biomarker of insulin resistance.

Fernandez-Real JM, Menendez JA, Moreno-Navarrete JM, Blüher M, Vazquez-Martin A, Vázquez MJ, Ortega F, Diéguez C, Frühbeck G, Ricart W, Vidal-Puig A - Diabetes (2010)

Bottom Line: Circulating fatty acid synthase (FASN) is a biomarker of metabolically demanding human diseases.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.Rosiglitazone did not lead to significant changes in circulating FASN concentration.

View Article: PubMed Central - PubMed

Affiliation: Department of Diabetes, Endocrinology and Nutrition, Institutd' Investigació Biomédica de Girona, CIBEROBN Fisiopatología de la Obesidad y Nutrición CB06/03/010, Girona, Catalonia, Spain. jmfernandezreal.girona.ics@gencat.cat

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.

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Related in: MedlinePlus

Summary of the studies performed on circulating FASN levels.
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Figure 1: Summary of the studies performed on circulating FASN levels.

Mentions: To test the main hypothesis, we evaluated circulating FASN in different cohorts of subjects, summarized in Fig. 1. The cross-sectional association of circulating FASN with insulin sensitivity was studied in two independent cohorts and the relationship with adipose tissue FASN gene expression in one cohort. Furthermore, we evaluated the effects of diet-induced weight loss (cohort 1), exercise improvement of insulin sensitivity (cohort 2), bariatric surgery–induced weight loss (cohort 3), and rosiglitazone-associated improvement of insulin sensitivity (cohort 4).


Extracellular fatty acid synthase: a possible surrogate biomarker of insulin resistance.

Fernandez-Real JM, Menendez JA, Moreno-Navarrete JM, Blüher M, Vazquez-Martin A, Vázquez MJ, Ortega F, Diéguez C, Frühbeck G, Ricart W, Vidal-Puig A - Diabetes (2010)

Summary of the studies performed on circulating FASN levels.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2874712&req=5

Figure 1: Summary of the studies performed on circulating FASN levels.
Mentions: To test the main hypothesis, we evaluated circulating FASN in different cohorts of subjects, summarized in Fig. 1. The cross-sectional association of circulating FASN with insulin sensitivity was studied in two independent cohorts and the relationship with adipose tissue FASN gene expression in one cohort. Furthermore, we evaluated the effects of diet-induced weight loss (cohort 1), exercise improvement of insulin sensitivity (cohort 2), bariatric surgery–induced weight loss (cohort 3), and rosiglitazone-associated improvement of insulin sensitivity (cohort 4).

Bottom Line: Circulating fatty acid synthase (FASN) is a biomarker of metabolically demanding human diseases.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.Rosiglitazone did not lead to significant changes in circulating FASN concentration.

View Article: PubMed Central - PubMed

Affiliation: Department of Diabetes, Endocrinology and Nutrition, Institutd' Investigació Biomédica de Girona, CIBEROBN Fisiopatología de la Obesidad y Nutrición CB06/03/010, Girona, Catalonia, Spain. jmfernandezreal.girona.ics@gencat.cat

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.

Show MeSH
Related in: MedlinePlus