The Influence of an Obesogenic Diet on Oxysterol Metabolism in C57BL/6J Mice

Our current understanding of oxysterol metabolism during different disease states such as obesity and dyslipidemia is limited. Therefore, the aim of this study was to determine the effect of diet-induced obesity on the tissue distribution of various oxysterols and the mRNA expression of key enzymes...

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Published in:Cholesterol 2014-01, Vol.2014 (2014), p.g1-11
Main Authors: Wooten, Joshua S., Wu, Huaizhu, Raya, Joe, Perrard, Xiaoyuan Dai, Gaubatz, John, Hoogeveen, Ron C.
Format: Article
Language:English
Subjects:
Apoptosis
Atherosclerosis
Cholesterol
Cholesterol metabolism
Cytotoxicity
Development and progression
Diabetes
Enzymes
Genetic aspects
Lipids
Medicine
Metabolism
Metabolites
Obesity
Oxidative stress
Physiological aspects
Rodents
Studies
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container_title Cholesterol
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creator Wooten, Joshua S.
Wu, Huaizhu
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description Our current understanding of oxysterol metabolism during different disease states such as obesity and dyslipidemia is limited. Therefore, the aim of this study was to determine the effect of diet-induced obesity on the tissue distribution of various oxysterols and the mRNA expression of key enzymes involved in oxysterol metabolism. To induce obesity, male C57BL/6J mice were fed a high fat-cholesterol diet for 24 weeks. Following diet-induced obesity, plasma levels of 4β-hydroxycholesterol, 5,6α-epoxycholesterol, 5,6β-epoxycholesterol, 7α-hydroxycholesterol, 7β-hydroxycholesterol, and 27-hydroxycholesterol were significantly (P
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Therefore, the aim of this study was to determine the effect of diet-induced obesity on the tissue distribution of various oxysterols and the mRNA expression of key enzymes involved in oxysterol metabolism. To induce obesity, male C57BL/6J mice were fed a high fat-cholesterol diet for 24 weeks. Following diet-induced obesity, plasma levels of 4β-hydroxycholesterol, 5,6α-epoxycholesterol, 5,6β-epoxycholesterol, 7α-hydroxycholesterol, 7β-hydroxycholesterol, and 27-hydroxycholesterol were significantly (P&lt;0.05) increased. In the liver and adipose tissue of the obese mice, 4β-hydroxycholesterol was significantly (P&lt;0.05) increased, whereas 27-hydroxycholesterol was increased only in the adipose tissue. No significant changes in either hepatic or adipose tissue mRNA expression were observed for oxysterol synthesizing enzymes 4β-hydroxylase, 27-hydroxylase, or 7α-hydroxylase. Hepatic mRNA expression of SULT2B1b, a key enzyme involved in oxysterol detoxification, was significantly (P&lt;0.05) elevated in the obese mice. Interestingly, the appearance of the large HDL1 lipoprotein was observed with increased oxysterol synthesis during obesity. In diet-induced obese mice, dietary intake and endogenous enzymatic synthesis of oxysterols could not account for the increased oxysterol levels, suggesting that nonenzymatic cholesterol oxidation pathways may be responsible for the changes in oxysterol metabolism.</description><identifier>ISSN: 2090-1283</identifier><identifier>EISSN: 2090-1291</identifier><identifier>DOI: 10.1155/2014/843468</identifier><identifier>PMID: 24672716</identifier><language>eng</language><publisher>Cairo, Egypt: Hindawi Limiteds</publisher><subject>Apoptosis ; Atherosclerosis ; Cholesterol ; Cholesterol metabolism ; Cytotoxicity ; Development and progression ; Diabetes ; Enzymes ; Genetic aspects ; Lipids ; Medicine ; Metabolism ; Metabolites ; Obesity ; Oxidative stress ; Physiological aspects ; Rodents ; Studies</subject><ispartof>Cholesterol, 2014-01, Vol.2014 (2014), p.g1-11</ispartof><rights>Copyright © 2014 Joshua S. 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subjects Apoptosis
Atherosclerosis
Cholesterol
Cholesterol metabolism
Cytotoxicity
Development and progression
Diabetes
Enzymes
Genetic aspects
Lipids
Medicine
Metabolism
Metabolites
Obesity
Oxidative stress
Physiological aspects
Rodents
Studies
title The Influence of an Obesogenic Diet on Oxysterol Metabolism in C57BL/6J Mice
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