Role of ENPP1 on adipocyte maturation.

Role of ENPP1 on adipocyte maturation.
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DOI:
10.1371/journal.pone.0000882
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发表时间:
2007-09-12
期刊:
影响因子:
3.7
通讯作者:
Abate N
Abate N
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Liang J;Fu M;Ciociola E;Chandalia M;Abate N

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人们认识到,脂肪组织响应于能量过剩而扩张的能力,即脂肪细胞成熟,在确定葡萄糖和脂质代谢的全身异常中是重要的。外核苷酸焦磷酸酶磷酸二酯酶1(ENPP 1,又称PC-1)参与胰岛素抵抗及相关疾病的发病机制。然而,其在脂肪组织生理学中作为全身性胰岛素抵抗机制的作用尚不清楚。本研究旨在评估ENPP 1在脂肪形成过程中是否受到调节,以及脂肪细胞中的过度表达是否会影响脂肪细胞成熟,这是ENPP 1相关胰岛素抵抗的潜在新机制。在3T3-L1成熟过程中发现ENPP 1表达下调,并且在3T3-L1(pQCXIP-ENPP 1载体)中过表达人ENPP 1导致脂肪细胞胰岛素抵抗和脂肪细胞成熟缺陷。脂肪细胞成熟在ENPP 1基因敲除小鼠的间充质胚胎细胞中比野生型更有效。我们确定ENPP 1作为一种新的机制,有缺陷的脂肪细胞成熟。这种机制可能有助于在没有肥胖的情况下胰岛素抵抗的发病机制。
It is recognized that the ability of adipose tissue to expand in response to energy excess, i.e. adipocyte maturation, is important in determining systemic abnormalities in glucose and lipid metabolism. Ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1, also known as PC-1) has been recently reported to be involved in the pathogenesis of insulin resistance and related diseases. However, its role on adipose tissue physiology as a mechanism of systemic insulin resistance is not understood. This study was performed to evaluate whether ENPP1 is regulated during adipogenesis and whether over-expression in adipocytes can affect adipocyte maturation, a potential novel mechanism of ENPP1-related insulin resistance. ENPP1 expression was found down-regulated during 3T3-L1 maturation, and over-expression of human ENPP1 in 3T3-L1 (pQCXIP-ENPP1 vector) resulted in adipocyte insulin resistance and in defective adipocyte maturation. Adipocyte maturation was more efficient in mesenchymal embryonal cells from ENPP1 knockout mice than from wild-type. We identify ENPP1 as a novel mechanism of defective adipocyte maturation. This mechanism could contribute to the pathogenesis of insulin resistance in absence of obesity.
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