Targeted disruption of steroidogenic acute regulatory protein D4 leads to modest weight reduction and minor alterations in lipid metabolism[S]
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 die...
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| Format: | Article |
| Language: | English |
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Elsevier
2010-05-01
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| Series: | Journal of Lipid Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520410697 |
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| author | Joshua J. Riegelhaupt Marc P. Waase Jeanne Garbarino Daniel E. Cruz Jan L. Breslow |
| author_facet | Joshua J. Riegelhaupt Marc P. Waase Jeanne Garbarino Daniel E. Cruz Jan L. Breslow |
| author_sort | Joshua J. Riegelhaupt |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-20T04:06:53Z |
| format | Article |
| id | doaj.art-7033c10501ba431cb8cfae82f51cfd46 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-20T04:06:53Z |
| publishDate | 2010-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-7033c10501ba431cb8cfae82f51cfd462022-12-21T19:54:01ZengElsevierJournal of Lipid Research0022-22752010-05-0151511341143Targeted disruption of steroidogenic acute regulatory protein D4 leads to modest weight reduction and minor alterations in lipid metabolism[S]Joshua J. Riegelhaupt0Marc P. Waase1Jeanne Garbarino2Daniel E. Cruz3Jan L. Breslow4Laboratory of Mammalian GeneticsMetabolism, Rockefeller University, New York, NY 10021Laboratory of Mammalian GeneticsMetabolism, Rockefeller University, New York, NY 10021Laboratory of Mammalian GeneticsMetabolism, Rockefeller University, New York, NY 10021Laboratory of Mammalian GeneticsMetabolism, Rockefeller University, New York, NY 10021To whom correspondence should be addressed; Laboratory of Mammalian GeneticsMetabolism, Rockefeller University, New York, NY 10021Steroidogenic 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.http://www.sciencedirect.com/science/article/pii/S0022227520410697StARD4mouse knockoutintracellular cholesterol transportStAR related lipid transfer |
| spellingShingle | Joshua J. Riegelhaupt Marc P. Waase Jeanne Garbarino Daniel E. Cruz Jan L. Breslow Targeted disruption of steroidogenic acute regulatory protein D4 leads to modest weight reduction and minor alterations in lipid metabolism[S] Journal of Lipid Research StARD4 mouse knockout intracellular cholesterol transport StAR related lipid transfer |
| title | Targeted disruption of steroidogenic acute regulatory protein D4 leads to modest weight reduction and minor alterations in lipid metabolism[S] |
| title_full | Targeted disruption of steroidogenic acute regulatory protein D4 leads to modest weight reduction and minor alterations in lipid metabolism[S] |
| title_fullStr | Targeted disruption of steroidogenic acute regulatory protein D4 leads to modest weight reduction and minor alterations in lipid metabolism[S] |
| title_full_unstemmed | Targeted disruption of steroidogenic acute regulatory protein D4 leads to modest weight reduction and minor alterations in lipid metabolism[S] |
| title_short | Targeted disruption of steroidogenic acute regulatory protein D4 leads to modest weight reduction and minor alterations in lipid metabolism[S] |
| title_sort | targeted disruption of steroidogenic acute regulatory protein d4 leads to modest weight reduction and minor alterations in lipid metabolism s |
| topic | StARD4 mouse knockout intracellular cholesterol transport StAR related lipid transfer |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520410697 |
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