Molecular Analyses of Metabolic Abnormalities in PDIP-1 Null Mice

PDIP-1 无效小鼠代谢异常的分子分析

基本信息

批准号：
18590975
负责人：
SATOH Tetsurou
金额：
$ 2.41万
依托单位：
Gunma University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18590975/
关键词：
PPARγ PDIP1 transcriptional cofactor metabolic syndrome high-fat diet-induced obesity fatty liver fatty acid β oxidation PPARγ メタボリック症候群脂肪酸β酸化 PRIC285 ノックアウトマウス脂質代謝肥満症生活習慣病

项目摘要

Nuclear receptor PPARγ is the master regulator of adipocyte differentiation and facilitates lipid reserve in a body. Using yeast two-hybrid screen, we recently isolated a novel coactivator of PPARγ, PDIP1 also known as PRIC285. To elucidate physiological function of PDIP1, mice lacking PDIP1 were generated using homologous recombination. Brown adipose tissues in PDIP1-/- mice revealed inappropriate phenotype containing larger fat droplets with reduced expression of uncoupling protein-1 (UCP-1), aP2 and calnitin palmitoyle transferase-la genes. Although white adipose tissues (WAT) appeared morphologically normal, serum triglyceride and very low density lipoprotein in PDIP1^<-/-> mice were significantly decreased. Causatively, expression of a subset of genes enhancing fatty-acid oxidation in liver and WAT were significantly upregulated. When fed a high-fat diet (HFD), PDIP1^<-/-> mice showed resistance to obesity with reduced adiposity and hepatic steatosis and improved glucose and insulin tolerance. These findings suggest that PDIP1 is deleteriously involved in development of HFD-induced obesity and dyslipidemia, thus representing a potential target treating for metabolic syndrome with lipotoxicity.

核受体PPARγ是脂肪细胞分化的主要调节剂，并促进体内脂质储备。使用酵母两杂交筛网，我们最近分离了PPARγ的新型共激活因子，PDIP1也称为Pric285。为了阐明PDIP1的身体功能，使用同源重组产生缺乏PDIP1的小鼠。 PDIP1 - / - 小鼠中的棕色脂肪组织揭示了不适当的表型，其中含有较大的脂肪液滴，降低了解偶偶联蛋白-1（UCP-1），AP2和Calnitin Palmitoyle转移酶LA基因的表达。尽管白色脂肪组织（WAT）在形态上似乎正常，但血清甘油三酸酯和PDIP1^< - / - >小鼠中非常低的密度脂蛋白得到显着改善。因果关系，基因的一部分表达增强了肝脏和WAT中脂肪酸氧化的表达显着更新。当喂养高脂饮食（HFD）时，PDIP1^< - / - >小鼠表现出对肥胖症的抗性，其肥胖和肝炎脂肪变性降低，以及改善的葡萄糖和胰岛素耐受性。这些发现表明，PDIP1与HFD诱导的肥胖症和血脂异常的发展相关，因此代表了具有脂毒性代谢综合征的潜在靶标。