Adenosine A1 receptors regulate lipolysis and lipogenesis in mouse adipose tissue - Interactions with insulin
Adenosine A1 receptors regulate lipolysis and lipogenesis in mouse adipose tissue - Interactions with insulin
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DOI：
10.1016/j.ejphar.2008.08.022
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发表时间：
2008-11-12
影响因子：
5
通讯作者：
Fredholm, Bertil B.
中科院分区：
文献类型：
--
作者：
JohanssonA, Stina M.;Lindgren, Eva;Fredholm, Bertil B.
腺苷作用于腺苷A受体，被认为是脂肪组织生理的主要调节因子之一。我们用A，R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可引起A(1)R(+/+)脂肪细胞的脂解，但不能引起A，R(-/-)脂肪细胞的脂解。腺苷类似物2-氯腺苷抑制去甲肾上腺素刺激的A(1)R(+/+)脂肪细胞的脂解和cAMP积聚，但对A(1)R(-/-)脂肪细胞无影响。胰岛素通过腺苷以外的另一种机制减少脂肪分解和cAMP，并且与腺苷是相加的，但不是协同作用。给予腺苷类似物后，A(1)R(+/+)小鼠的血浆游离脂肪酸、甘油和甘油三酯水平显著低于A(1)R(-/-)小鼠。2-氯腺苷诱导A(1)R(+/+)脂肪细胞脂肪生成，但不诱导A(1)R(-/-)脂肪细胞脂肪生成。与脂肪组织中脂肪合成有关的几个基因的基因水平在不同的基因型之间没有变化。年轻A(1)R(+/+)和A(1)R(-/-)小鼠体重相似，但老年A(1)R(-/-)小鼠体重高于野生型对照组。总而言之，腺苷通过腺苷A(1)受体抑制脂解作用，其他腺苷受体没有显著作用。腺苷和胰岛素介导相加而不是协同的降脂作用，2-氯腺苷通过腺苷A受体刺激脂肪生成。因此，腺苷A(1)受体的缺失应该会增加脂肪分解和减少脂肪生成，但实际上观察到了脂肪质量的增加，这表明腺苷A(1)受体的其他作用也很重要，可能是在脂肪组织之外。(C)2008爱思唯尔B.V.保留所有权利。
Adenosine acting at adenosine A, 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, R knock out (-/-) mice. Removal of endogenous adenosine with adenosine deaminase caused lipolysis in A(1)R (+/+), but not A, R (-/-) adipocytes. The adenosine analogue, 2-chloroadenosine, inhibited noradrenaline-stimulated lipolysis and cAMP accumulation in A(1)R (+/+), but not in A(1)R (-/-) 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(1)R (+/+) than in A(1)R (-/-) mice after administration of an adenosine analogue. 2-chloroadenosine induced lipogenesis in presence of insulin in A(1)R (+/+), but not in A(1)R (-/-) 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(1)R (+/+) and A(1)R (-/-) mice, but old mate A(1)R (-/-) 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, 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. (C) 2008 Elsevier B.V. All rights reserved.