β2-Adrenergic receptor ablation modulates hepatic lipid accumulation and glucose tolerance in aging mice

Catecholamines acting through β-adrenergic receptors (β(1)-, β(2)-, β(3)-AR subtypes) modulate important biological responses in various tissues. Our previous studies suggest a role for increased hepatic β-AR-mediated signaling during aging as a mediator of hepatic steatosis, liver glucose output, and insulin resistance in rodents. In the current study, we have utilized β(2)-AR knockout (KO) and wildtype (WT) control mice to define further the role of β(2)-AR signaling during aging on lipid and glucose metabolism. Our results demonstrate for the first time that age-related increases in hepatic triglyceride accumulation and body weight are attenuated upon β(2)-AR ablation. Although no differences in plasma triglyceride, non-esterified fatty acids or insulin levels were detected between old WT and KO animals, an age-associated increase in hepatic expression of lipid homeostasis regulator Cidea was significantly reduced in old KO mice. Interestingly, we also observed a shift from reduced glucose tolerance in young adult KO animals to significantly improved glucose tolerance in old KO when compared to age-matched WT mice. These results provide evidence for an important role played by β(2)-ARs in the regulation of lipid and glucose metabolism during aging. The effect of β(2)-AR ablation on caloric intake during aging is currently not known and requires investigation. Future studies are also warranted to delineate the β(2)-AR-mediated mechanisms involved in the control of lipid and glucose homeostasis, especially in the context of a growing aging population.