About this Journal Submit a Manuscript Table of Contents
Cholesterol
Volume 2014 (2014), Article ID 843468, 11 pages
http://dx.doi.org/10.1155/2014/843468
Research Article

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

1Division of Atherosclerosis and Vascular Medicine, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA
2Department of Kinesiology and Health Education, Southern Illinois University Edwardsville, Campus Box 1126, Edwardsville, IL 62026-1126, USA

Received 26 October 2013; Revised 18 December 2013; Accepted 21 December 2013; Published 5 February 2014

Academic Editor: Francisco Blanco-Vaca

Copyright © 2014 Joshua S. Wooten et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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 ( ) increased. In the liver and adipose tissue of the obese mice, 4β-hydroxycholesterol was significantly ( ) 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 ( ) 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.