Low-abundant Adiponectin Receptors in Visceral Adipose Tissue of Humans and Rats Are Further Reduced in Diabetic Animals

Background And Aims: Adipose tissue is an endocrine organ that releases various proteins that may also exert autocrine/paracrine effects. The antidiabetic adipokine adiponectin acts through two receptors, AdipoR1 and AdipoR2, but so far mainly mRNA expression has been measured in adipocytes and adipose tissues. Therefore, we aimed to analyze AdipoR1 and AdipoR2 proteins in adipocytes and paired samples of subcutaneous and visceral adipocytes/adipose tissue.

Methods: AdipoR1 and AdipoR2 mRNA and protein expression were determined in adipocytes and paired samples of subcutaneous and visceral adipose tissue of humans and rats.

Results: AdipoR1 and AdipoR2 proteins were similarly abundant in preadipocytes and mature adipocytes despite an induction of mRNA expression during differentiation. Differentiation of 3T3-L1 cells in the presence of palmitic acid did not alter adiponectin receptor proteins but metformin and fenofibrate upregulated AdipoR2 within 24 h of incubation. AdipoR2 protein was significantly lower in human visceral compared to subcutaneous fat, and both receptors were reduced in visceral adipocytes. In rat tissues both receptors were reduced in visceral fat. In diabetic animals AdipoR2 protein, but not mRNA, was lower in both fat depots compared to similarly obese rats with normal glucose disposal. AdipoR1 was only reduced in subcutaneous adipose tissue of diabetic animals where mRNA expression was induced.

Conclusions: These data indicate that mRNA expression is not suitable to predict adiponectin receptor protein. Low adiponectin receptors in visceral adipocytes and adipose tissue and further suppression in adipose tissue of insulin-resistant animals indicate disturbed adiponectin bioactivity.