文章基本信息

标题：Targeted disruption of steroidogenic acute regulatory protein D4 leads to modest weight reduction and minor alterations in lipid metabolism
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作者：Joshua J. Riegelhaupt ; Marc P. Waase ; Jeanne Garbarino 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2010
卷号：51
期号：5
页码：1134-1143
DOI：10.1194/jlr.M003095
语种：English
出版社：American Society for Biochemistry and Molecular Biology
摘要：Steroidogenic acute regulatory protein (StAR)D4 is a member of the StAR related lipid transfer family. Homology comes from the ∼210 amino acid lipid binding domain implicated in intracellular transport, cell signaling, and lipid metabolism. StARD4 was identified as a gene downregulated 2-fold by dietary cholesterol (Soccio, R. E., R. M. Adams, K. N. Maxwell, and J. L. Breslow. 2005. Differential gene regulation of StarD4 and StarD5 cholesterol transfer proteins. Activation of StarD4 by sterol regulatory element-binding protein-2 and StarD5 by endoplasmic reticulum stress. J. Biol. Chem . 280: 19410–19418). A mouse knockout was created to investigate StARD4’s functionality and role in lipid metabolism. Homozygous knockout mice exhibited normal Mendelian mating genetics, but weighed less than wild-type littermates, an effect not accounted for by energy metabolism or food intake. Body composition as analyzed by DEXA scan showed no significant difference. No significant alterations in plasma or liver lipid content were observed on a chow diet, but female knockout mice showed a decrease in gallbladder bile cholesterol and phospholipid concentration. When challenged with a 0.2% lovastatin diet, StARD4 homozygous mice exhibited no changes. However, when challenged with a 0.5% cholesterol diet, female StARD4 homozygous mice showed a moderate decrease in total cholesterol, LDL, and cholesterol ester concentrations. Microarray analysis of liver RNA found few changes. However, NPC1’s expression, a gene not on the microarray, was decreased ∼2.5-fold in knockouts. These observations suggest that StARD4’s role can largely be compensated for by other intracellular cholesterol transporters.
关键词：StARD4 ; mouse knockout ; intracellular cholesterol transport ; StAR related lipid transfer