Previous studies investigating the effects of exogenous growth hormone (GH) on the expression of adiponectin and the adiponectin receptors have generated seemingly conflicting results. Here, to determine the effects of chronic exogenous GH levels, we investigated the expression of adiponectin receptor R1 (adipoR1) in skeletal muscle and adiponectin receptor R2 (adipoR2) in the liver of normal C57BL/6 adult male mice 24 weeks after a single injection of rAAV2/1-CMV-GH1 viral particles. AdipoR1 and adipoR2 mRNA expression levels were determined by quantitative real-time reverse transcription-polymerase chain reaction. AdipoR1 and adipoR2 proteins were analyzed by Western blotting. Serum total and high molecular weight (HMW) adiponectin concentrations were measured by enzyme-linked immunosorbent assay (ELISA) kits for mice. The results demonstrated that the injection of rAAV2/1-CMV-GH1 within the concentration range of 1.0x1011 to 4.0x1011 viral particles significantly up-regulated hepatic adipoR2 gene expression. The serum HMW adiponectin level increased significantly with the concentration range of 2.0x1011 to 4.0x1011 rAAV2/1-CMV-GH1 viral particles. The injection of 4.0x1011 rAAV2/1-CMV-GH1 viral particles induced a significant increase in both serum glucose and insulin concentrations (p<0.05), and the homeostasis model assessment of insulin resistance (p<0.01). This may decrease body insulin sensitivity and therefore raise the potential risk of insulin resistance. However, exogenous GH levels did not significantly affect adipoR1 expression in skeletal muscle. In conclusion, chronic exogenous GH up-regulates hepatic adipoR2, rather than adipoR1, in vivo, and raises the serum HMW adiponectin level. However, the elevation of exogenous GH concentrations may increase the risk of insulin resistance.

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