Prolonged AICAR-induced AMP-kinase activation promotes energy dissipation in white adipocytes: novel mechanisms integrating HSL and ATGL
Prolonged AICAR-induced AMP-kinase activation promotes energy dissipation in white adipocytes: novel mechanisms integrating HSL and ATGL
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DOI：
10.1194/jlr.m800480-jlr200
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发表时间：
2009-04-01
影响因子：
6.5
通讯作者：
Ceddia, Rolando B.
中科院分区：
文献类型：
--
作者：
Gaidhu, Mandeep P.;Fediuc, Sergiu;Ceddia, Rolando B.
本研究旨在探讨AMP激活蛋白激酶(AMPK)的长时间激活对白色脂肪组织(WAT)脂质分配的影响及其可能的分子机制。将大鼠附睾脂肪细胞与5‘-氨基咪唑-4-甲酰胺-1-β-D-呋喃核苷(AICAR；0.5 mM)孵育15h，并于注射AICAR后15h分离附睾腺脂肪细胞(I.P.0.7g/kg体重)。脂肪细胞用于各种代谢分析以及基因表达和蛋白质含量的测定。测定了体内NEFA浓度随时间的变化。AICAR处理显著增加了AMPK活性，抑制了脂肪生成，增加了FA的氧化。伴随而来的是过氧化体增殖物激活受体(PPAR)α、PPAR-γ和PPAR-γ-辅活化子-1α(PGC-1α)mRNA水平的上调。在体外和体内，随着AICAR治疗时间的延长，脂解作用先是被抑制，但后来又增加了。暴露于AICAR可增加脂肪甘油三酯脂肪酶(ATGL)的含量和FA的释放，尽管基础和肾上腺素刺激的激素敏感脂肪酶(HSL)活性受到抑制。在这里，我们提供了证据表明，延长AICAR诱导的AMPK激活可以通过上调WAT中有利于能量消耗而不是脂肪储存的途径来重塑脂肪细胞的新陈代谢。此外，我们还展示了AICAR诱导的AMPK激活对脂解作用的新的时间依赖效应，其中包括对HSL和ATGL的拮抗调节。-Gaidhu，M.P.，S.Fediuc，N.M.Anthony，M.So，M.Mirpourian，R.L.S.Perry和R.B.Ceddia。AICAR诱导的长时间AMP-激酶激活促进白色脂肪细胞的能量消耗：整合HSL和ATGL的新机制。J.Lipid Res.2009年。50：704-715。
This study was designed to investigate the effects of prolonged activation of AMP-activated protein kinase (AMPK) on lipid partitioning and the potential molecular mechanisms involved in these processes in white adipose tissue (WAT). Rat epididymal adipocytes were incubated with 5'-aminoimidasole-4- carboxamide-1-beta-D-ribofuranoside (AICAR; 0.5 mM) for 15 h. Also, epididymal adipocytes were isolated 15 h after AICAR was injected (i.p. 0.7 g/kg body weight) in rats. Adipocytes were utilized for various metabolic assays and for determination of gene expression and protein content. Time-dependent in vivo plasma NEFA concentrations were determined. AICAR treatment significantly increased AMPK activation, inhibited lipogenesis, and increased FA oxidation. This was accompanied by upregulation of peroxisome proliferator-activated receptor (PPAR)alpha, PPAR gamma, and PPAR gamma-coactivator-1 alpha (PGC-1 alpha) mRNA levels. Lipolysis was first suppressed, but then increased, both in vitro and in vivo, with prolonged AICAR treatment. Exposure to AICAR increased adipose triglyceride lipase (ATGL) content and FA release, despite inhibition of basal and epinephrine-stimulated hormone-sensitive lipase (HSL) activity. Here, we provide evidence that prolonged AICAR-induced AMPK activation can remodel adipocyte metabolism by upregulating pathways that favor energy dissipation versus lipid storage in WAT. Additionally, we show novel time-dependent effects of AICAR-induced AMPK activation on lipolysis, which involves antagonistic modulation of HSL and ATGL.-Gaidhu, M. P., S. Fediuc, N. M. Anthony, M. So, M. Mirpourian, R. L. S. Perry, and R. B. Ceddia. Prolonged AICAR-induced AMP-kinase activation promotes energy dissipation in white adipocytes: novel mechanisms integrating HSL and ATGL. J. Lipid Res. 2009. 50 : 704-715.