Hepatic adiponectin receptors (ADIPOR) 1 and 2 mRNA and their relation to insulin resistance in obese humans

Objective: Adiponectin signalling attenuates insulin resistance (IR) and steatosis hepatis in animal models. As adiponectin receptor (ADIPOR) 1 and ADIPOR2 are critical components in the adiponectin signalling cascade, we studied hepatic ADIPOR1/2 mRNA levels in humans and their relation to IR. Design: We determined metabolic risk factors and levels of hepatic mRNA transcribed from ADIPOR1, ADIPOR2 and FOXO1, a putative up-stream regulator, in 43 and 34 obese subjects with low and high homeostasis model assessment-IR, respectively. Results: Plasma adiponectin and metabolic risk factors showed associations with IR as expected. Both hepatic ADIPOR1 and ADIPOR2 mRNA expression levels were higher in insulin-resistant subjects (P < 0.0035). ADIPOR1 mRNA correlated with FOXO1 mRNA in obese insulin resistant (P=0.0034), but not insulin-sensitive subjects, while no correlations of ADIPOR2 with FOXO1 mRNA were noted. FOXO1 enhanced transcription from the ADIPOR1, but not the ADIPOR2 promoter in HepG2 cells. Conclusion: Increased hepatic ADIPOR1 and ADIPOR2 mRNA in insulin-resistant obese subjects may, at least in part, reflect a compensatory mechanism for reduced plasma adiponectin. FOXO1 may contribute to enhanced ADIPOR1, but not ADIPOR2 transcription in IR. International Journal of Obesity (2010) 34, 846-851; doi: 10.1038/ijo.2010.7; published online 2 February 2010