Absence of adipose differentiation related protein upregulates hepatic VLDL secretion, relieves hepatosteatosis, and improves whole body insulin resistance in leptin-deficient mice
Absence of adipose differentiation related protein upregulates hepatic VLDL secretion, relieves hepatosteatosis, and improves whole body insulin resistance in leptin-deficient mice
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DOI：
10.1194/jlr.m004515
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发表时间：
2010-08-01
影响因子：
6.5
通讯作者：
Chan, Lawrence
中科院分区：
文献类型：
--
作者：
Chang, Benny Hung-Junn;Li, Lan;Chan, Lawrence
我们先前表明，脂肪分化相关蛋白（Adfp）缺陷小鼠显示肝脏甘油三酯（TG）含量减少60%。在这项研究中，我们研究了ADFP在遗传性肥胖模型Lep（ob/ob）小鼠的脂质和葡萄糖稳态中的作用。我们将Adfp（-/-）小鼠与Lep（ob/ob）小鼠交配，建立Lep（ob/ob）/Adfp（-/-）和Lep（ob/ob）/Adfp（+/+）小鼠，并分析两组小鼠的肝脏脂质、脂滴（LD）形态、LD蛋白组成和分布、脂肪生成基因表达、VLDL分泌以及胰岛素敏感性。与Lep（ob/ob）/Adfp（+/+）小鼠相比，Lep（ob/ob）/Adfp（-/-）小鼠表现出VLDL分泌率增加，肝脏TG降低25%，与大体和显微镜下脂肪肝改善相关，部分肝细胞中LD大小发生变化，主要LD相关蛋白从细胞质室重新分布至LD表面。在脂肪生成基因表达中没有检测到变化。Lep（ob/ob）/Adfp（-/-）小鼠在肝脏和肌肉中也具有改善的葡萄糖耐量和胰岛素敏感性。尽管其它LDP重新定位到LD，但Lep（ob/ob）/Adfp（-/-）小鼠肝脏中LD大小的改变表明ADFP在确定肝脏LD的大小和分布中的非冗余作用。张，B。H-J L. Li，P. Saha，and L.陈。脂肪分化相关蛋白的缺乏上调肝脏VLDL分泌，减轻肝脂肪变性，并改善瘦素缺乏小鼠的全身胰岛素抵抗。J. Lipid Res. 2010. 51：2132-2142
We previously showed that adipose differentiation related protein (Adfp)-deficient mice display a 60% reduction in hepatic triglyceride (TG) content. In this study, we investigated the role of ADFP in lipid and glucose homeostasis in a genetic obesity model, Lep(ob/ob) mice. We bred Adfp(-/-) mice with Lep(ob/ob) mice to create Lep(ob/ob) /Adfp(-/-) and Lep(ob/ob) /Adfp(+/+) mice and analyzed the hepatic lipids, lipid droplet (LD) morphology, LD protein composition and distribution, lipogenic gene expression, and VLDL secretion, as well as insulin sensitivity of the two groups of mice. Compared with Lep(ob/ob) /Adfp(+/+) mice, Lep(ob/ob) /Adfp(-/-) mice displayed an increased VLDL secretion rate, a 25% reduction in hepatic TG associated with improvement in fatty liver grossly and microscopically with a change of the size of LDs in a proportion of the hepatocytes and a redistribution of major LD-associated proteins from the cytoplasmic compartment to the LD surface. There was no detectable change in lipogenic gene expression. Lep(ob/ob) /Adfp(-/-) mice also had improved glucose tolerance and insulin sensitivity in both liver and muscle.jlr The alteration of LD size in the liver of Lep(ob/ob) /Adfp(-/-) mice despite the relocation of other LDPs to the LD indicates a nonredundant role for ADFP in determining the size and distribution of hepatic LDs.-Chang, B. H-J., L. Li, P. Saha, and L. Chan. Absence of adipose differentiation related protein upregulates hepatic VLDL secretion, relieves hepatosteatosis, and improves whole body insulin resistance in leptin-deficient mice. J. Lipid Res. 2010. 51: 2132-2142