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The disruption of hepatic cytochrome P450 reductase afters mouse lipid metabolism

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The disruption of hepatic cytochrome P450 reductase afters mouse lipid metabolism. / Mutch, David M.; Klocke, Bernward; Morrison, Peter; Murray, Carol A.; Henderson, Colin J.; Seifert, Martin; Williamson, Gary.

In: Journal of Proteome Research, Vol. 6, No. 10, 10.2007, p. 3976-3984.

Research output: Contribution to journalArticle

Harvard

Mutch, DM, Klocke, B, Morrison, P, Murray, CA, Henderson, CJ, Seifert, M & Williamson, G 2007, 'The disruption of hepatic cytochrome P450 reductase afters mouse lipid metabolism' Journal of Proteome Research, vol 6, no. 10, pp. 3976-3984., 10.1021/pr0700448

APA

Mutch, D. M., Klocke, B., Morrison, P., Murray, C. A., Henderson, C. J., Seifert, M., & Williamson, G. (2007). The disruption of hepatic cytochrome P450 reductase afters mouse lipid metabolism. Journal of Proteome Research, 6(10), 3976-3984. 10.1021/pr0700448

Vancouver

Mutch DM, Klocke B, Morrison P, Murray CA, Henderson CJ, Seifert M et al. The disruption of hepatic cytochrome P450 reductase afters mouse lipid metabolism. Journal of Proteome Research. 2007 Oct;6(10):3976-3984. Available from: 10.1021/pr0700448

Author

Mutch, David M.; Klocke, Bernward; Morrison, Peter; Murray, Carol A.; Henderson, Colin J.; Seifert, Martin; Williamson, Gary / The disruption of hepatic cytochrome P450 reductase afters mouse lipid metabolism.

In: Journal of Proteome Research, Vol. 6, No. 10, 10.2007, p. 3976-3984.

Research output: Contribution to journalArticle

Bibtex - Download

@article{b92209152aff46ef82d15853949ea3e8,
title = "The disruption of hepatic cytochrome P450 reductase afters mouse lipid metabolism",
author = "Mutch, {David M.} and Bernward Klocke and Peter Morrison and Murray, {Carol A.} and Henderson, {Colin J.} and Martin Seifert and Gary Williamson",
year = "2007",
doi = "10.1021/pr0700448",
volume = "6",
number = "10",
pages = "3976--3984",
journal = "Journal of Proteome Research",
issn = "1535-3893",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - The disruption of hepatic cytochrome P450 reductase afters mouse lipid metabolism

A1 - Mutch,David M.

A1 - Klocke,Bernward

A1 - Morrison,Peter

A1 - Murray,Carol A.

A1 - Henderson,Colin J.

A1 - Seifert,Martin

A1 - Williamson,Gary

AU - Mutch,David M.

AU - Klocke,Bernward

AU - Morrison,Peter

AU - Murray,Carol A.

AU - Henderson,Colin J.

AU - Seifert,Martin

AU - Williamson,Gary

PY - 2007/10

Y1 - 2007/10

N2 - <p>To elucidate the role of hepatic cytochrome P450 oxidoreductase (POR) in lipid metabolism, we characterized perturbations in lipid homeostasis in a mouse model deficient in liver POR. Using an integrative approach in which transcriptomics, lipidomics, and various bioinformatic algorithms were employed, a disruption in liver lipid mobilization, oxidation, and electron transport functions were identified. Analyzing the promoters of genes in these biological processes identified common binding motifs for nuclear receptors sensitive to lipid status, while Srebp-1c binding sites were only identified in genes involved in lipid metabolism. POR-null mice had drastic increases in hepatic lipid content (diacylglycerols, triacylglycerols, phosphatidylcholine, and cholesterol esters) and a specific enrichment in n-7 and n-9 monounsaturated fatty acids (FAs). It was found that while transporters involved in peroxisomal FA oxidation were induced, mitochondrial oxidation appeared to be more tightly controlled, supporting the increase in monounsaturated FAs. Genes coding for hepatic transporters were differentially expressed, where lipid uptake was induced and efflux repressed, indicating that in the absence of hepatic POR the liver serves as a lipid reservoir. Furthermore, while significant changes in intestinal gene expression were found in POR-deficient mice, only minor changes to plasma and intestinal lipid content were observed. Thus, while liver POR plays an important role regulating gene expression and lipid metabolism locally, the hepatic deficiency of this enzyme reverberates throughout the biological system and produces a coordinated response to the low levels of circulating cholesterol and bile.</p>

AB - <p>To elucidate the role of hepatic cytochrome P450 oxidoreductase (POR) in lipid metabolism, we characterized perturbations in lipid homeostasis in a mouse model deficient in liver POR. Using an integrative approach in which transcriptomics, lipidomics, and various bioinformatic algorithms were employed, a disruption in liver lipid mobilization, oxidation, and electron transport functions were identified. Analyzing the promoters of genes in these biological processes identified common binding motifs for nuclear receptors sensitive to lipid status, while Srebp-1c binding sites were only identified in genes involved in lipid metabolism. POR-null mice had drastic increases in hepatic lipid content (diacylglycerols, triacylglycerols, phosphatidylcholine, and cholesterol esters) and a specific enrichment in n-7 and n-9 monounsaturated fatty acids (FAs). It was found that while transporters involved in peroxisomal FA oxidation were induced, mitochondrial oxidation appeared to be more tightly controlled, supporting the increase in monounsaturated FAs. Genes coding for hepatic transporters were differentially expressed, where lipid uptake was induced and efflux repressed, indicating that in the absence of hepatic POR the liver serves as a lipid reservoir. Furthermore, while significant changes in intestinal gene expression were found in POR-deficient mice, only minor changes to plasma and intestinal lipid content were observed. Thus, while liver POR plays an important role regulating gene expression and lipid metabolism locally, the hepatic deficiency of this enzyme reverberates throughout the biological system and produces a coordinated response to the low levels of circulating cholesterol and bile.</p>

U2 - 10.1021/pr0700448

DO - 10.1021/pr0700448

M1 - Article

JO - Journal of Proteome Research

JF - Journal of Proteome Research

SN - 1535-3893

IS - 10

VL - 6

SP - 3976

EP - 3984

ER -

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