Protection against fatty liver but normal adipogenesis in mice lacking adipose differentiation-related protein
Protection against fatty liver but normal adipogenesis in mice lacking adipose differentiation-related protein
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DOI：
10.1128/mcb.26.3.1063-1076.2006
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发表时间：
2006-02-01
影响因子：
5.3
通讯作者：
Chan, L
中科院分区：
文献类型：
--
作者：
Chang, BHJ;Li, L;Chan, L
脂肪分化相关蛋白（ADFP，又称ADRP或亲脂蛋白）是一种存在于大多数细胞和组织中的脂滴蛋白。在脂质负荷增加的细胞中，ADFP的表达被强烈诱导。我们灭活了小鼠的Adfp基因，以便更好地了解它在脂质积累中的作用。adfp缺陷小鼠的脂肪分化和脂肪分解在体内和体外均未发生改变。重要的是，它们显示出肝脏甘油三酯（TG）降低60%，并对饮食诱导的脂肪肝有抵抗力。为了确定肝脏TG含量降低的机制，我们测量了肝脏脂肪生成、极低密度脂蛋白（VLDL）分泌、脂质摄取和利用，所有这些参数在突变型和野生型小鼠之间都是相似的。在adfp缺陷的肝脏中，在总TG减少的情况下，发现相似的VLDL输出，这可以解释为TG保留在VLDL组装的微粒体中。考虑到脂滴被认为是由微粒体膜的外小叶形成的，细胞质中TG的减少与Adfp（-/-）细胞微粒中TG的积累表明Adfp可能促进新ld的形成。在缺乏ADFP的情况下，LD形成的损害与微粒体TG的积累有关，但与其他亚细胞区室TG的减少有关。
Adipose differentiation-related protein (ADFP; also known as ADRP or adipophilin), is a lipid droplet (LD) protein found in most cells and tissues. ADFP expression is strongly induced-in cells with increased lipid load. We have inactivated the Adfp gene in mice to better understand its role in lipid accumulation. The Adfp-deficient mice have unaltered adipose differentiation or lipolysis in vitro or in vivo. Importantly, they display a 60% reduction in hepatic triglyceride (TG) and are resistant to diet-induced fatty liver. To determine the mechanism for the reduced hepatic TG content, we measured hepatic lipogenesis, very-low-density lipoprotein (VLDL) secretion, and lipid uptake and utilization, all of which parameters were shown to be similar between mutant and wild-type mice. The finding of similar VLDL output in the presence of a reduction in total TG in the Adfp-deficient liver is explained by the retention of TG in the microsomes where VLDL is assembled. Given that lipid droplets are thought to form from the outer leaflet of the microsomal membrane, the reduction of TG in the cytosol with concomitant accumulation of TG in the microsome of Adfp(-/-) cells suggests that ADFP may facilitate the formation of new LDs. In the absence of ADFP, impairment of LD formation is associated with the accumulation of microsomal TG but a reduction in TG in other subcellular compartments.