Energy restriction lowers the expression of genes linked to inflammation, the cytoskeleton, the extracellular matrix, and angiogenesis in mouse adipose tissue
Energy restriction lowers the expression of genes linked to inflammation, the cytoskeleton, the extracellular matrix, and angiogenesis in mouse adipose tissue
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DOI：
10.1093/jn/136.2.343
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发表时间：
2006-02-01
影响因子：
4.2
通讯作者：
Weindruch, R
中科院分区：
文献类型：
--
作者：
Higami, Y;Barger, JL;Weindruch, R
利用高密度寡核苷酸芯片，我们研究了能量限制（ER）对10- 11月龄雄性C57 B16小鼠附睾白色脂肪组织（WAT）中> 11，000个基因表达的作用。研究了四组：对照组不限食（CO）、处死前18 h限食（FR）、短期ER 23 d（SER）和长期ER 9 mo（LER）。正如我们先前报道的，与CO小鼠相比，FR和SER对基因表达谱的影响最小;然而，确定在WAT中表达的6266个基因中有345个转录本被LER显著改变。我们在这里集中在这些基因中的109个（31%）参与炎症（56个基因），细胞骨架（16个基因），细胞外基质（23个基因），或血管生成（14个基因）。在这109个基因中，104个转录本（95%）被LER下调。热休克蛋白47和骨粘连蛋白的蛋白质印迹，以及缺氧诱导因子（HIF-1 α）的免疫组织化学染色，证实了LER下调这些基因表达的微阵列数据。此外，LER使脂肪细胞大小减少75%反映了参与细胞形态的基因表达的变化。我们的研究结果提供的证据表明，LER抑制WAT中编码炎症分子的基因的表达，同时促进细胞骨架、细胞外基质和血管的结构重塑。这些改变可能在防止WAT衍生的炎症和LER延长寿命方面发挥重要作用。
Using high-density oligonucleotide microarrays, we examined the actions of energy restriction (ER) on the expression of > 11,000 genes in epididymal white adipose tissue (WAT) of 10- to 11-mo-old male C57B16 mice. Four groups were studied: controls not subjected to food restriction (CO), food-restricted 18 h before being killed (FR), short-term ER for 23 d (SER), and long-term ER for 9 mo (LER). As we reported previously, compared with CO mice, FR and SER minimally influenced the gene expression profiles; however, 345 transcripts of 6266 genes determined to be expressed in WAT were significantly altered by LER. We focus here on the 109 (31%) of these genes that were involved in either inflammation (56 genes), cytoskeleton (16 genes), extracellular matrix (23 genes), or angiogenesis (14 genes). Among these 109 genes, 104 transcripts (95%) were downregulated by LER. Western blotting for heat shook protein 47 and osteonectin, and immunohistochemical staining for hypoxia inducible factor (HIF-1 alpha), supportec the microarray data that LER downregulated the expressions of these genes. Additionally, a 75% reduction in adipocyte size with LER reflected the change in the expression of genes involved in cell morphology. Our findings provide evidence that LER suppresses the expression of genes encoding inflammatory molecules in WAT while promoting structural remodeling of the cytoskeleton, extracellular matrix, and vasculature. These alterations may play an important role in the protection against WAT-derived inflammation and in lifespan extension by LER.