NDLI: Targeted disruption of steroidogenic acute regulatory protein D4 leads to modest weight reduction and minor alterations in lipid metabolism.

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Targeted disruption of steroidogenic acute regulatory protein D4 leads to modest weight reduction and minor alterations in lipid metabolism.

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Targeted disruption of steroidogenic acute regulatory protein D4 leads to modest weight reduction and minor alterations in lipid metabolism.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Riegelhaupt, Joshua J. Waase, Marc P. Garbarino, Jeanne Cruz, Daniel E. Breslow, Jan L.
Description	Country affiliation: United States Author Affiliation: Riegelhaupt JJ ( Laboratory of Mammalian GeneticsMetabolism, Rockefeller University, New York, NY 10021, USA.)
Abstract	Steroidogenic acute regulatory protein (StAR)D4 is a member of the StAR related lipid transfer family. Homology comes from the approximately 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% lova-statin 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 approximately 2.5-fold in knockouts. These observations suggest that StARD4's role can largely be compensated for by other intracellular cholesterol transporters.
File Format	HTM / HTML
ISSN	00222275
e-ISSN	15397262
DOI	10.1194/jlr.M003095
Journal	The Journal of Lipid Research
Issue Number	5
Volume Number	51
Language	English
Publisher	American Society for Biochemistry and Molecular Biology
Publisher Date	2010-05-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Discipline Biochemistry Gene Knockout Techniques Lipid Metabolism Genetics Membrane Transport Proteins Deficiency Weight Loss Absorptiometry, Photon Animals Body Mass Index Cholesterol Pharmacology Dietary Fats Fertility Gallbladder Metabolism Gene Expression Profiling Gene Expression Regulation Glucose Tolerance Test Liver Lovastatin Chemistry Mice Organ Size Protein Structure, Tertiary Rna, Messenger Sterols Time Factors
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Endocrinology

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Targeted disruption of steroidogenic acute regulatory protein D4 leads to modest weight reduction and minor alterations in lipid metabolism.

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Targeted disruption of steroidogenic acute regulatory protein D4 leads to modest weight reduction and minor alterations in lipid metabolism.