Differential transcriptional modulation of biological processes in adipocyte triglyceride lipase and hormone-sensitive lipase-deficient mice
Differential transcriptional modulation of biological processes in adipocyte triglyceride lipase and hormone-sensitive lipase-deficient mice
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DOI：
10.1016/j.ygeno.2008.03.010
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发表时间：
2008-07-01
期刊：
影响因子：
4.4
通讯作者：
Strauss, Juliane Gertrude
中科院分区：
文献类型：
--
作者：
Pinent, Montserrat;Hackl, Hubert;Strauss, Juliane Gertrude
脂肪细胞甘油三酸酯脂肪酶（ATGL）和激素敏感脂肪酶（HSL）是细胞内脂肪酶，可动员哺乳动物的主要能量来源甘油三酸酯。在小鼠中缺失编码ATGL（Pnpla 2）或HSL（Lipe）的基因导致显著的表型差异，表明这些脂肪酶的不同作用。本研究的目的是确定在ATGL-和HSL-缺陷小鼠的代谢组织中调节的生物过程。DNA微阵列被用来提供全基因组覆盖的类型的基因，在野生型和突变型小鼠的差异表达。对于两种小鼠模型，在白色脂肪组织、棕色脂肪组织（BAT）、骨骼肌（SM）、心肌（CM）和肝脏中鉴定转录物标签。ATGL和HSL的基因切除改变了代谢组织中大量基因的转录水平。然而，这两种模型中受影响的基因在很大程度上是不同的。事实上，在两种小鼠模型中，只有一种生物过程以相同的方式进行调节，即BAT中脂肪酸代谢的下调。在ATGL（-/-）CM中观察到生物过程的最显著调节，其中观察到与氧化途径相关的转录物的协同下调。相反，在HSL-/-小鼠中，SM中观察到最显著的变化，即转录水平的改变反映了能量来源从脂质到碳水化合物的变化。转录物特征还为ATGL（-/-）小鼠特有的代谢紊乱提供了新的见解。我们的研究结果表明，ATGL和HSL差异调节代谢组织中的生物过程。我们假设，脂肪分解途径的中间代谢产物是哺乳动物中广泛的生化和细胞过程的信号分子和激活剂。(C)2008年爱思唯尔公司All rights reserved.
Adipocyte triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) are intracellular lipases that mobilize triglycerides, the main energy source in mammals. Deletion of genes encoding ATGL (Pnpla2) or HSL (Lipe) in mice results in striking phenotypic differences, suggesting distinct roles for these lipases. The goal of the present study was to identify the biological processes that are modulated in the metabolic tissues of ATGL- and HSL-deficient mice. DNA microarrays were employed to provide full genome coverage concerning the types of genes that are differentially expressed in wild-type and mutant mice. For both mouse models, transcript signatures were identified in white adipose tissue, brown adipose tissue (BAT), skeletal muscle (SM), cardiac muscle (CM), and liver. Genetic ablation of ATGL and HSL alters the transcript levels of a large number of genes in metabolic tissues. The genes affected in the two models are, however, largely different ones. Indeed, only one biological process was modulated in the same way in both mouse models, namely the down-regulation of fatty acid metabolism in BAT. The most pronounced modulation of biological processes was observed in ATGL(-/-) CM, in which a concerted down-regulation of transcripts associated with oxidative pathways was observed. In HSL-/- mice, in contrast, the most marked changes were seen in SM, namely, alterations in transcript levels reflecting a change of energy source from lipid to carbohydrate. The transcript signatures also provided novel insights into the metabolic derangements that are characteristic of ATGL(-/-) mice. Our findings suggest that ATGL and HSL differentially modulate biological processes in metabolic tissues. We hypothesize that the intermediary metabolites of the lipolytic pathways are signaling molecules and activators of a wide range of biochemical and cellular processes in mammals. (C) 2008 Elsevier Inc. All rights reserved.