Adipose hypothermia in obesity and its association with period homolog 1, insulin sensitivity, and inflammation in fat.

Adipose hypothermia in obesity and its association with period homolog 1, insulin sensitivity, and inflammation in fat.
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DOI:
10.1371/journal.pone.0112813
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Shimomura I
Shimomura I
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Yamaoka M;Maeda N;Takayama Y;Sekimoto R;Tsushima Y;Matsuda K;Mori T;Inoue K;Nishizawa H;Tominaga M;Funahashi T;Shimomura I

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内脏脂肪肥胖在代谢综合征的发展中起着重要作用。我们以前报道过人类内脏脂肪肥胖对外周血细胞基因表达谱的影响。昼夜节律相关基因与内脏脂肪面积高度相关,周期同源物1 (PER1)与内脏脂肪面积负相关最显著。然而,对脂肪Per1的调控仍然知之甚少。本研究旨在了解Per1在脂肪组织中的调节作用。25和35周龄ob/ob小鼠脂肪Per1 mRNA水平明显降低。在25周龄和35周龄的ob/ob小鼠中,白色脂肪组织的其他核心时钟基因水平也很低。Per1 mRNA主要在成熟脂肪细胞(MAF)中表达,在ob/ob小鼠的MAF中表达量明显较低。为了研究可能的机制,我们用H2O2、肿瘤坏死因子-α (TNF-α)、S100A8和脂多糖(LPS)处理3T3-L1脂肪细胞。然而,这些药物未观察到Per1 mRNA水平的显著变化。将培养的3T3-L1脂肪细胞暴露在低温(33℃)下,Per1和过氧化氢酶降低,单核细胞趋化蛋白-1 (Mcp-1) mRNA水平升高。低温也使胰岛素介导的3T3-L1脂肪细胞Akt磷酸化恶化。最后,遥测分析显示ob/ob小鼠脂肪组织温度较低。在肥胖中,脂肪低温似乎会加速脂肪细胞功能障碍。
Visceral fat adiposity plays an important role in the development of metabolic syndrome. We reported previously the impact of human visceral fat adiposity on gene expression profile of peripheral blood cells. Genes related to circadian rhythm were highly associated with visceral fat area and period homolog 1 (PER1) showed the most significant negative correlation with visceral fat area. However, regulation of adipose Per1 remains poorly understood. The present study was designed to understand the regulation of Per1 in adipose tissues. Adipose Per1 mRNA levels of ob/ob mice were markedly low at 25 and 35 weeks of age. The levels of other core clock genes of white adipose tissues were also low in ob/ob mice at 25 and 35 weeks of age. Per1 mRNA was mainly expressed in the mature adipocyte fraction (MAF) and it was significantly low in MAF of ob/ob mice. To examine the possible mechanisms, 3T3-L1 adipocytes were treated with H2O2, tumor necrosis factor-α (TNF-α), S100A8, and lipopolysaccharide (LPS). However, no significant changes in Per1 mRNA level were observed by these agents. Exposure of cultured 3T3-L1 adipocytes to low temperature (33°C) decreased Per1 and catalase, and increased monocyte chemoattractant protein-1 (Mcp-1) mRNA levels. Hypothermia also worsened insulin-mediated Akt phosphorylation in 3T3-L1 adipocytes. Finally, telemetric analysis showed low temperature of adipose tissues in ob/ob mice. In obesity, adipose hypothermia seems to accelerate adipocyte dysfunction.
DOI: 10.1371/journal.pone.0087661
发表时间: 2014
期刊: PloS one
影响因子: 3.7
作者:
Inoue K;Maeda N;Mori T;Sekimoto R;Tsushima Y;Matsuda K;Yamaoka M;Suganami T;Nishizawa H;Ogawa Y;Funahashi T;Shimomura I
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期刊: ENDOCRINOLOGY
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DOI: 10.1126/science.1195027
发表时间: 2010-12-03
期刊: Science (New York, N.Y.)
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通讯作者: Weaver DR