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

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 met...

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Bibliographic Details
Published in:Journal of diabetes research 2017-01, Vol.2017 (2017), p.1-8
Main Authors: Sutterlüty-Fall, Hedwig, Gossens, Klaus, Todoric, Jelena, Jais, Alexander, Noebauer, Britta, Einwallner, Elisa
Format: Article
Language:English
Subjects:
Adenoviruses
Animals
Antibodies
Blood Glucose - metabolism
Cardiovascular disease
Cholesterol
Diabetes
Diabetes Mellitus, Type 2 - genetics
Diabetes Mellitus, Type 2 - metabolism
Disease Progression
Experiments
Glucose
Insulin
Insulin resistance
Insulin Resistance - genetics
Laboratories
Lipids
Liver
Liver - metabolism
Male
Metabolism
Mice
Mice, Transgenic
Obesity
Obesity - genetics
Obesity - metabolism
Proteins
Steroid Hydroxylases - genetics
Steroid Hydroxylases - metabolism
Triglycerides
Veins & arteries
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Summary: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.
ISSN:2314-6745
2314-6753
DOI:10.1155/2017/4108768