Pattern of expression of adiponectin receptors in human adipose tissue depots and its relation to the metabolic state.

OBJECTIVE: To investigate whether adiponectin receptor genes (AdipoR1 and AdipoR2) expression in human subcutaneous (SAT) and visceral (VAT) adipose tissue in severely obese patients with or without diabetes is related to adiponectin gene (APM1) expression and in vivo metabolic parameters.

DESIGN: Cross-sectional, clinical research study.

SUBJECTS: Total RNA was extracted from SAT and VAT tissue obtained during surgery from 13 lean controls, 30 obese diabetic patients, 19 obese glucose-intolerant patients and 54 obese subjects with normal glucose tolerance.

MEASUREMENTS: Tissue expression of APM1, AdipoR1 and AdipoR2, tissue concentration of adiponectin (ApN), and metabolic variables.

RESULTS: APM1 expression was higher in SAT than VAT (1.06+/-0.76 vs 0.69+/-0.52, P<0.0001) as was AdipoR1 (1.17+/-0.70 vs 0.66+/-0.38, P<0.0001) and AdipoR2 (7.02+/-6.19 vs 0.75+/-0.64, P<0.0001). In SAT, APM1 and AdipoR1 expression tended to be lower - by 0.38+/-0.22 and 0.35+/-0.22, respectively - and AdipoR2 expression was markedly depressed - by 4.82+/-1.93 - in association with obesity, whereas presence of diabetes had no additional effect. In VAT, APM1 and AdipoR1 expressions were also reduced - by 0.36+/-0.16 and 0.30+/-0.11, respectively - in association with obesity. Within both SAT and VAT, expression levels of APM1, AdipoR1 and AdipoR2 were all positively interrelated. Tissue ApN concentrations in SAT were similar across groups, whereas ApN levels in VAT were substantially lower in association with obesity (by an average of 63+/-12 ng/mg total protein, P<0.0001). In multivariate models adjusting for sex, age and obesity, serum triglyceride concentrations were reciprocally related to APM1 (r=-0.27, P<0.02), AdipoR1 (r=-0.37, P<0.002 and AdipoR2 expression (r=-0.37, P<0.002) in VAT. Likewise, plasma insulin concentrations were inversely related only to APM1 in VAT (r=-0.25, P<0.03).

CONCLUSIONS: Severe obesity is associated with suppressed expression of both ApN and its receptors in both SAT and VAT, the expression levels in VAT are specifically linked with hyperinsulinemia and dyslipidemia.