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Submitted on April 14, 2006
Accepted on April 10, 2007
The Central Arkansas Veterans Healthcare System, and the Department of Medicine, Division of Endocrinology, and The Department of Biostatistics, and the Department of Pediatrics University of Arkansas for Medical Sciences, Little Rock, AR 72205 and Department of Medicine, University of Maryland, Baltimore, MD 21201
* To whom correspondence should be addressed. E-mail: KernPhilipA{at}uams.edu.
Context: Retinol binding protein 4 (RBP4) was recently found to be expressed and secreted by adipose tissue and was strongly associated with insulin resistance.
Objective: To determine the relationship between RBP4 and obesity, insulin resistance, and other markers of insulin resistance in humans.
Design and patients: RBP4 mRNA levels in adipose tissue and muscle of non-diabetic human subjects with either normal (NGT) or impaired glucose tolerance (IGT) were studied, along with plasma RBP4. RBP4 gene expression was also measured in adipose tissue fractions and from visceral (VAT) and subcutaneous adipose tissue (SAT) from surgical patients.
Setting: University Hospital and General Clinical Research Center
Intervention: Insulin sensitivity was measured, and fat and muscle biopsies were performed. In IGT subjects, these procedures were performed before and after treatment with metformin or pioglitazone.
Main outcome measures: The relationship between RBP4 expression and obesity, insulin sensitivity, adipose tissue inflammation, and intramyocellular lipid (IMCL) level, and response to insulin sensitizers.
Results: RBP4 was expressed predominantly from the adipocyte fraction of SAT. Although SAT RBP4 expression and plasma RBP4 level demonstrated no significant relationship with BMI or SI, there was a strong positive correlation between RBP4 mRNA and adipose inflammation (MCP1 and CD68), and GLUT4 mRNA. Treatment of IGT subjects with pioglitazone resulted in an increase in SI and an increase in RBP4 gene expression in both adipose tissue and muscle, but not in plasma RBP4 level, and the in vitro treatment of cultured adipocytes with pioglitazone yielded a similar increase in RBP4 mRNA.
Conclusion: RBP4 gene expression in humans is associated with inflammatory markers, but not with insulin resistance. The increase in RBP4 mRNA following pioglitazone treatment is unusual, suggesting a complex regulation of this novel adipokine.
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