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

Abstract

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.

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Acknowledgements

We thank Simon Auer, MBA, for his technical assistance. This study was supported by grants from the Fonds zur Förderung der wissenschaftlichen Forschung (FWF, Project P19893-B05), the Land Salzburg and the Verein für Medizinische Forschung Salzburg, Austria.

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Correspondence to W Patsch.

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Felder, T., Hahne, P., Soyal, S. et al. Hepatic adiponectin receptors (ADIPOR) 1 and 2 mRNA and their relation to insulin resistance in obese humans. Int J Obes 34, 846–851 (2010). https://doi.org/10.1038/ijo.2010.7

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