Adiponectin expression in humans is dependent on differentiation of adipocytes and down-regulated by humoral serum components

Even though adiponectin expression is restricted to adipose tissue, serum levels are paradoxically decreased in obesity. We characterized adiponectin expression during adipocyte differentiation and analyzed the impact of serum and culture conditions on adipocytokine expression.

In the progress of differentiation, expression and secretion of leptin was detected at small amounts in preadipocytes and increased 108fold in differentiated adipocytes. Adiponectin, in contrast, was not expressed by preadipocytes. Differentiation into adipocytes was necessary to induce an increasing expression of adiponectin mRNA (359±64 increase, P<0.001) in parallel with increasing expression of the adipocyte differentiation markers PPARy and aP2. Secretion of adiponectin was restricted to fully differentiated adipocytes as specified by Western blot and immunohistochemistry.

Addition of FCS over the course of differentiation significantly and dose-dependently down-regulated adiponectin to almost undetectable levels, while leptin expression was significantly increased (6.5fold, P<0.001). Also, acute incubation of mature adipocytes with FCS or human serum resulted in a suppression of adiponectin expression to 9.8±0.03% (P=0.0043). Conversely, acute withdrawal of adipogenic ingredients from the culture medium resulted in a marked decrease of leptin and adiponectin production. We identified insulin as a critical component of adipocyte culture medium to maintain adiponectin expression with a down-regulation to 62.2±0.1% (P=0.0011) in the absence of insulin. We did not detect resistin expression or secretion at any point of adipocyte differentiation in SGBS cells or primary cultures.

In conclusion, we show an increasing expression of adiponectin during differentiation of human adipocytes that is down regulated by addition of serum suggesting a strong humoral component of adiponectin regulation. These dynamic changes are of physiological interest in the light of the paradoxical decrease of adiponectin levels and the continuous recruitment of preadipocytes for differentiation in obesity.