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Journal of Diabetes Research
Volume 2017, Article ID 4108768, 8 pages
https://doi.org/10.1155/2017/4108768
Research Article

Hepatic Cholesterol-25-Hydroxylase Overexpression Improves Systemic Insulin Sensitivity in Mice

1Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
2Laboratory of Gene Regulation and Signal Transduction, Departments of Pharmacology and Pathology, UCSD School of Medicine, San Diego, CA, USA
3Max Planck Institute for Immunobiology and Epigenetics, Freiburg, Germany
4Institute of Cancer Research, Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria

Correspondence should be addressed to Elisa Einwallner; ta.ca.neiwinudem@renllawnie.asile

Received 13 November 2016; Revised 4 January 2017; Accepted 31 January 2017; Published 19 February 2017

Academic Editor: Toshiyasu Sasaoka

Copyright © 2017 Britta Noebauer 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

Obesity is a major risk factor for several diseases including diabetes, heart disease, and some forms of cancer and due to its rapidly increasing prevalence it has become one of the biggest problems medicine is facing today. All the more surprising, a substantial percentage of obese patients are metabolically healthy when classified based on insulin resistance and systemic inflammation. Oxysterols are naturally occurring molecules that play important role in various metabolic and inflammatory processes and their levels are elevated in patients suffering from obesity and diabetes. 25-Hydroxycholesterol (25-OHC) is produced in cells from cholesterol by the enzyme cholesterol 25-hydroxylase (Ch25h) and is involved in lipid metabolism, inflammatory processes, and cell proliferation. Here, we investigated the role of hepatic Ch25h in the transition from metabolically healthy obesity to insulin resistance and diabetes. Using several different experimental approaches, we demonstrated the significance of Ch25h on the border of “healthy” and “diseased” states of obesity. Adenovirus-mediated Ch25h overexpression in mice improved glucose tolerance and insulin sensitivity and lowered HOMA-IR. Our data suggest that low hepatic Ch25h levels could be considered a risk marker for unhealthy obesity.