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Submitted on June 19, 2006
Accepted on October 27, 2006
The Central Arkansas Veterans Healthcare System, and the Department of Medicine, Division of Endocrinology, and The Department of Biostatistics, and the Department of PediatricsUniversity of Arkansas for Medical Sciences, Little Rock, AR 72205; Department of Medicine, University of Maryland, Baltimore, MD 21201
* To whom correspondence should be addressed. E-mail: KernPhilipA{at}uams.edu.
Context: Visfatin (VF) is a recently described adipokine preferentially secreted by visceral adipose tissue (VAT) with insulin mimetic properties.
Objective: To examine the association of VF with insulin sensitivity, intramyocellular lipid (IMCL) and inflammation in humans.
Design and patients: VF mRNA was examined in paired samples of VAT and abdominal sc adipose tissue (SAT) obtained from subjects undergoing surgery. Plasma VF and VF mRNA was also examined in SAT and muscle tissue, obtained by biopsy from well characterized subjects with normal (NGT) or impaired glucose tolerance (IGT), with a wide range in BMI and SI.
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 pioglitazone or metformin.
Main outcome measures: The relationship between VF and obesity, insulin sensitivity, adipose tissue inflammation, IMCL and response to insulin sensitizers.
Results: No significant difference in VF mRNA was seen between SAT and VAT depots. VAT VF mRNA associated positively with BMI whereas, SAT VF mRNA decreased with BMI. SAT VF correlated positively with SI, and the association of SAT VF mRNA with SI was independent of BMI. IMCL and markers of inflammation (adipose CD68 and plasma TNF
) were negatively associated with SAT VF. IGT subjects treated with pioglitazone, showed no change in SAT VF mRNA despite a significant increase in SI. Plasma VF and muscle VF mRNA did not correlate with BMI or SI or IMCL and there was no change in muscle VF with either pioglitazone or metformin treatments.
Conclusion: SAT VF is highly expressed in lean, more insulin sensitive subjects, and is attenuated in subjects with high IMCL, low SI, and high levels of inflammatory markers. VAT VF and SAT VF are regulated oppositely with BMI.
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