Adenosine A 1 receptors regulate lipolysis and lipogenesis in mouse adipose tissue — Interactions with insulin

Abstract

Adenosine acting at adenosine A 1 receptors is considered to be one major regulator of adipose tissue physiology. We have examined the role of adenosine and its interactions with insulin in adipose tissue by using A 1R knock out (−/−) mice. Removal of endogenous adenosine with adenosine deaminase caused lipolysis in A 1R (+/+), but not A 1R (−/−) adipocytes. The adenosine analogue, 2-chloroadenosine, inhibited noradrenaline-stimulated lipolysis and cAMP accumulation in A 1R (+/+), but not in A 1R (−/−) adipocytes. Insulin reduces lipolysis and cAMP via another mechanism than adenosine and acted additively, but not synergistically, with adenosine. Plasma levels of free fatty acids, glycerol and triglycerides were significantly lower in A 1R (+/+) than in A 1R (−/−) mice after administration of an adenosine analogue. 2-chloroadenosine induced lipogenesis in presence of insulin in A 1R (+/+), but not in A 1R (−/−) adipocytes. There were no changes in mRNA levels for several genes involved in fat synthesis in adipose tissue between genotypes. Body weight was similar in young A 1R (+/+) and A 1R (−/−) mice, but old male A 1R (−/−) mice were heavier than wild type controls. In conclusion, adenosine inhibits lipolysis via the adenosine A 1 receptor and other adenosine receptors play no significant role. Adenosine and insulin mediate additive but not synergistic antilipolytic effects and 2-chloroadenosine stimulates lipogenesis via adenosine A 1 receptors. Thus deletion of adenosine A 1 receptors should increase lipolysis and decrease lipogenesis, but in fact an increased fat mass was observed, indicating that other actions of adenosine A 1 receptors, possibly outside adipose tissue, are also important.