アディポネクチン・アディポネクチン受容体の生理的意義

抄録

Adiponectin/Acrp30 is a hormone secreted by adipocytes that acts as an antidiabetic and anti-atherogenic adipokine. We reported that AdipoR1/R2 serve as receptors for adiponectin and mediate increased fatty-acid oxidation and glucose uptake by adiponectin. Moreover, obesity was associated with decreased plasma adiponectin levels as well as decreased expression levels of AdipoR1/R2, the latter reduced adiponectin sensitivity, both of which finally lead to insulin resistance. In this study, to clarify the physiological and pathophysiological roles of AdipoRs in vivo, we studied the effects of adenovirus-mediated upregualtion of AdipoRs in the mice liver. Here we show that adenovirus-mediated expression of AdipoR1 in the liver of db/db mice increased adiponectin effect such as increased activation of AMP kinase by adiponectin, decreased molecules involved in gluconeogenesis and increased fatty-acid oxidation, thereby ameliorating diabetes. Moreover, adenovirus-mediated expression of AdipoR2 in the liver of db/db mice increased adiponectin effect such as increased PPARalpha target genes including molecules involved in fatty acid oxidation and energy dissipation, thereby ameliorating diabetes. These data raised the possibility that AdipoR1 may be more tightly linked to activation of AMP kinase pathway, while AdipoR2 may be more tightly linked to activation of PPARalpha pathway. Adiponectin receptor agonists and adiponectin sensitizers should serve as versatile treatment strategies for obesity-linked diseases such as diabetes and metabolic syndrome. [J Physiol Sci. 2006;56 Suppl:S27]