Role of energy charge and AMP-activated protein kinase in adipocytes in the control of body fat stores.

M Rossmeisl, P Flachs, P Brauner, J Sponarova, O Matejkova, T Prazak, J Ruzickova, K Bardova, O Kuda, J Kopecky
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引用次数: 70

Abstract

As indicated by in vitro studies, both lipogenesis and lipolysis in adipocytes depend on the cellular ATP levels. Ectopic expression of mitochondrial uncoupling protein 1 (UCP1) in the white adipose tissue of the aP2-Ucp1 transgenic mice reduced obesity induced by genetic or dietary manipulations. Furthermore, respiratory uncoupling lowered the cellular energy charge in adipocytes, while the synthesis of fatty acids (FA) was inhibited and their oxidation increased. Importantly, the complex metabolic changes triggered by ectopic UCP1 were associated with the activation of AMP-activated protein kinase (AMPK), a metabolic master switch, in adipocytes. Effects of several typical treatments that reduce adiposity, such as administration of leptin, beta-adrenoceptor agonists, bezafibrate, dietary n-3 polyunsaturated FA or fasting, can be compared with a phenotype of the aP2-Ucp1 mice. These situations generally lead to the upregulation of mitochondrial UCPs and suppression of the cellular energy charge and FA synthesis in adipocytes. On the other hand, FA oxidation is increased. Moreover, it has been shown that AMPK in adipocytes can be activated by adipocyte-derived hormones leptin and adiponectin, and also by insulin-sensitizes thiazolidinediones. Thus, it is evident that metabolism of adipose tissue itself is important for the control of body fat content and that the cellular energy charge and AMPK are involved in the control of lipid metabolism in adipocytes. The reciprocal link between synthesis and oxidation of FA in adipocytes represents a prospective target for the new treatment strategies aimed at reducing obesity.

脂肪细胞中能量电荷和amp活化蛋白激酶在控制体脂肪储存中的作用。
体外研究表明,脂肪细胞的脂肪生成和脂肪分解都依赖于细胞ATP水平。在aP2-Ucp1转基因小鼠的白色脂肪组织中,线粒体解偶联蛋白1 (UCP1)的异位表达减少了遗传或饮食操作引起的肥胖。此外,呼吸解偶联降低了脂肪细胞的能量电荷,抑制了脂肪酸(FA)的合成,增加了脂肪酸的氧化。重要的是,异位UCP1引发的复杂代谢变化与脂肪细胞中代谢主开关amp活化蛋白激酶(AMPK)的激活有关。几种典型的减脂治疗的效果,如瘦素、β -肾上腺素受体激动剂、贝扎贝特、饮食n-3多不饱和脂肪酸或禁食,可以与aP2-Ucp1小鼠的表型进行比较。这些情况通常导致线粒体UCPs上调,脂肪细胞能量电荷和FA合成受到抑制。另一方面,FA氧化增加。此外,研究表明,脂肪细胞中的AMPK可以被脂肪细胞来源的激素瘦素和脂联素激活,也可以被胰岛素增敏的噻唑烷二酮激活。由此可见,脂肪组织本身的代谢对机体脂肪含量的控制很重要,细胞能量电荷和AMPK参与了脂肪细胞脂质代谢的控制。脂肪细胞中FA的合成和氧化之间的相互联系代表了旨在减少肥胖的新治疗策略的潜在目标。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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