Adiponectin gene expression and adipocyte NF-kappaB transcriptional activity in elderly overweight and obese women: inter-relationships with fat distribution, hs-CRP, leptin and insulin resistance.
OBJECTIVE
The regulatory processes that modulate adiponectin production and the mechanisms involved in nuclear factor kB (NF-kB) transcriptional activity in human adipocytes are not yet fully known. The aim of our study was to evaluate the inter-relationships between body fat, fat distribution, systemic inflammation, insulin resistance, leptin and the serum and subcutaneous adipose tissue gene expression levels of tumor necrosis factor-alpha (TNF-alpha), adiponectin and the inhibitor kappa B-alpha (IkB-alpha), in subjects with a wide range of body mass index (BMI). We also wanted to determine which of these variables was most closely related to adiponectin gene expression and adipocyte NF-kB transcriptional power.


METHODS
A total of 27 women aged between 50 and 80 years, with BMI ranging from 22.1 to 53.3 kg/m(2), were studied. In all subjects BMI, waist circumference, body composition by dual X-ray absorptometry, triglycerides, cholesterol, high-density lipoprotein cholesterol (HDL-Ch), glucose, insulin, homeostasis model assessment of insulin resistance (HOMA), high-sensitive C-reactive protein (hs-CRP), serum adiponectin, leptin and TNF-alpha were evaluated. Subcutaneous adipose tissue biopsies were taken from the abdomen of all subjects and the mRNA levels of adiponectin, TNF-alpha and IkB-alpha were determined.


RESULTS
BMI and waist circumference were associated positively with leptin, HOMA, and hs-CRP, and negatively with HDL-Ch; waist was also associated with adiponectin and IkB-alpha mRNA. HOMA was negatively associated with serum adiponectin and adiponectin mRNA. Hs-CRP was negatively associated with IkB-alpha mRNA, and was positively associated with HOMA. Step-down multiple regression analysis was performed to determine the joint effects of BMI, waist circumference, triglycerides, HDL-Ch, HOMA, hs-CRP, leptin, serum and TNF-alpha mRNA on adiponectin gene expression: waist circumference and leptin were both included in the best fitting regression equation for predicting adiponectin gene expression (R(2)=0.403, P=0.006). Stepwise multiple regression analysis was performed, considering IkB-alpha mRNA as a dependent variable and BMI, waist, HDL-Ch, HOMA, hs-CRP and adiponectin mRNA as independent variables. Adiponectin mRNA was the only variable to enter the regression (R(2)=0.406, P<0.001).


CONCLUSIONS
Our results suggest that abdominal adiposity and leptin are independent predictors of adiponectin gene expression and that in human adipocytes, adiponectin gene expression is strongly related to IkB-alpha mRNA.
Zamboni
M
M
Geriatric Medicine, University of Verona, Verona, Italy. mauro.zamboni@univr.it
Di Francesco
V
V
Garbin
U
U
Fratta Pasini
A
A
Mazzali
G
G
Stranieri
C
C
Zoico
E
E
Fantin
F
F
Bosello
O
O
Cominacini
L
L
D017667:Adipocytes / Q000502:physiology; D052242:Adiponectin / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D050218:Body Fat Distribution; D002097:C-Reactive Protein / Q000378:metabolism*; D005260:Female; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D020672:I-kappa B Proteins / Q000235:genetics; D007333:Insulin Resistance / Q000502:physiology*; D020738:Leptin / Q000097:blood*; D008875:Middle Aged; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D009765:Obesity / Q000235:genetics* / Q000378:metabolism; D050177:Overweight / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015533:Transcriptional Activation / Q000502:physiology
D052242:Adiponectin; D020672:I-kappa B Proteins; D020738:Leptin; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D012333:RNA, Messenger; D000072000:NF-KappaB Inhibitor alpha; D002097:C-Reactive Protein