Human visfatin expression: relationship to insulin sensitivity, intramyocellular lipids, and inflammation.
BACKGROUND
Visfatin (VF) is a recently described adipokine preferentially secreted by visceral adipose tissue (VAT) with insulin mimetic properties.


OBJECTIVE
The aim of this study was to examine the association of VF with insulin sensitivity, intramyocellular lipids (IMCL), and inflammation in humans.


METHODS
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 or impaired glucose tolerance, with a wide range in body mass index (BMI) and insulin sensitivity (S(I)).


METHODS
The study was conducted at a University Hospital and General Clinical Research Center.


METHODS
S(I) was measured, and fat and muscle biopsies were performed. In impaired glucose tolerance subjects, these procedures were performed before and after treatment with pioglitazone or metformin.


METHODS
We measured the relationship between VF and obesity, S(I), 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 S(I), and the association of SAT VF mRNA with S(I) was independent of BMI. IMCL and markers of inflammation (adipose CD68 and plasma TNFalpha) were negatively associated with SAT VF. Impaired glucose tolerance subjects treated with pioglitazone showed no change in SAT VF mRNA despite a significant increase in S(I). Plasma VF and muscle VF mRNA did not correlate with BMI or S(I) or IMCL, and there was no change in muscle VF with either pioglitazone or metformin treatments.


CONCLUSIONS
SAT VF is highly expressed in lean, more insulin-sensitive subjects and is attenuated in subjects with high IMCL, low S(I), and high levels of inflammatory markers. VAT VF and SAT VF are regulated oppositely with BMI.
Varma
Vijayalakshmi
V
The Central Arkansas Veterans Healthcare System, 598/151 LR, 4300 West 7th Street, Little Rock, Arkansas 72205, USA.
Yao-Borengasser
Aiwei
A
Rasouli
Neda
N
Bodles
Angela M
AM
Phanavanh
Bounleut
B
Lee
Mi-Jeong
MJ
Starks
Tasha
T
Kern
Leslie M
LM
Spencer
Horace J
HJ
McGehee
Robert E
RE
Fried
Susan K
SK
Kern
Philip A
PA
D050153:Abdominal Fat / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers; D001706:Biopsy; D015992:Body Mass Index; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression / Q000502:physiology; D018149:Glucose Intolerance / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007249:Inflammation / Q000378:metabolism / Q000503:physiopathology*; D007333:Insulin Resistance / Q000502:physiology*; D050356:Lipid Metabolism / Q000276:immunology; D008687:Metformin / Q000494:pharmacology; D018482:Muscle, Skeletal / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D054409:Nicotinamide Phosphoribosyltransferase; D009765:Obesity / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology*; D000077205:Pioglitazone; D012333:RNA, Messenger / Q000378:metabolism; D045162:Thiazolidinediones / Q000494:pharmacology
D015415:Biomarkers; D016207:Cytokines; D007004:Hypoglycemic Agents; D012333:RNA, Messenger; D045162:Thiazolidinediones; D008687:Metformin; C089946:2,4-thiazolidinedione; D054409:Nicotinamide Phosphoribosyltransferase; C085455:nicotinamide phosphoribosyltransferase, human; D000077205:Pioglitazone