Johansson Stina M, Lindgren Eva, Yang Jiang-Ning, Herling Andreas W, Fredholm Bertil B
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Eur J Pharmacol. 2008 Nov 12;597(1-3):92-101. doi: 10.1016/j.ejphar.2008.08.022. Epub 2008 Aug 31.
Adenosine acting at adenosine A1 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 A1R knock out (-/-) mice. Removal of endogenous adenosine with adenosine deaminase caused lipolysis in A1R (+/+), but not A1R (-/-) adipocytes. The adenosine analogue, 2-chloroadenosine, inhibited noradrenaline-stimulated lipolysis and cAMP accumulation in A1R (+/+), but not in A1R (-/-) 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 A1R (+/+) than in A1R (-/-) mice after administration of an adenosine analogue. 2-chloroadenosine induced lipogenesis in presence of insulin in A1R (+/+), but not in A1R (-/-) 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 A1R (+/+) and A1R (-/-) mice, but old male A1R (-/-) mice were heavier than wild type controls. In conclusion, adenosine inhibits lipolysis via the adenosine A1 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 A1 receptors. Thus deletion of adenosine A1 receptors should increase lipolysis and decrease lipogenesis, but in fact an increased fat mass was observed, indicating that other actions of adenosine A1 receptors, possibly outside adipose tissue, are also important.
作用于腺苷A1受体的腺苷被认为是脂肪组织生理功能的一个主要调节因子。我们通过使用A1R基因敲除（-/-）小鼠研究了腺苷在脂肪组织中的作用及其与胰岛素的相互作用。用腺苷脱氨酶去除内源性腺苷会导致A1R（+/+）脂肪细胞发生脂解，但不会导致A1R（-/-）脂肪细胞发生脂解。腺苷类似物2-氯腺苷可抑制去甲肾上腺素刺激的A1R（+/+）脂肪细胞的脂解和cAMP积累，但对A1R（-/-）脂肪细胞无此作用。胰岛素通过与腺苷不同的机制降低脂解和cAMP，且与腺苷起相加作用而非协同作用。给予腺苷类似物后，A1R（+/+）小鼠血浆中游离脂肪酸、甘油和甘油三酯的水平显著低于A1R（-/-）小鼠。2-氯腺苷在胰岛素存在的情况下可诱导A1R（+/+）脂肪细胞发生脂肪生成，但对A1R（-/-）脂肪细胞无此作用。不同基因型之间，参与脂肪合成的几个基因在脂肪组织中的mRNA水平没有变化。年轻的A1R（+/+）和A1R（-/-）小鼠体重相似，但老年雄性A1R（-/-）小鼠比野生型对照更重。总之，腺苷通过腺苷A1受体抑制脂解，其他腺苷受体无显著作用。腺苷和胰岛素介导相加而非协同的抗脂解作用，2-氯腺苷通过腺苷A1受体刺激脂肪生成。因此，腺苷A1受体的缺失应会增加脂解并减少脂肪生成，但实际上观察到脂肪量增加，这表明腺苷A1受体的其他作用（可能在脂肪组织之外）也很重要。
