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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| Format: | Article |
| Language: | English |
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Wiley
2017-01-01
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| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/2017/4108768 |
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| author | Britta Noebauer Alexander Jais Jelena Todoric Klaus Gossens Hedwig Sutterlüty-Fall Elisa Einwallner |
| author_facet | Britta Noebauer Alexander Jais Jelena Todoric Klaus Gossens Hedwig Sutterlüty-Fall Elisa Einwallner |
| author_sort | Britta Noebauer |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-21285082752d476695349bba1c8080f0 |
| institution | Kabale University |
| issn | 2314-6745 2314-6753 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Research |
| spelling | doaj-art-21285082752d476695349bba1c8080f02025-02-03T05:59:46ZengWileyJournal of Diabetes Research2314-67452314-67532017-01-01201710.1155/2017/41087684108768Hepatic Cholesterol-25-Hydroxylase Overexpression Improves Systemic Insulin Sensitivity in MiceBritta Noebauer0Alexander Jais1Jelena Todoric2Klaus Gossens3Hedwig Sutterlüty-Fall4Elisa Einwallner5Department of Laboratory Medicine, Medical University of Vienna, Vienna, AustriaDepartment of Laboratory Medicine, Medical University of Vienna, Vienna, AustriaLaboratory of Gene Regulation and Signal Transduction, Departments of Pharmacology and Pathology, UCSD School of Medicine, San Diego, CA, USAMax Planck Institute for Immunobiology and Epigenetics, Freiburg, GermanyInstitute of Cancer Research, Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Vienna, AustriaDepartment of Laboratory Medicine, Medical University of Vienna, Vienna, AustriaObesity 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.http://dx.doi.org/10.1155/2017/4108768 |
| spellingShingle | Britta Noebauer Alexander Jais Jelena Todoric Klaus Gossens Hedwig Sutterlüty-Fall Elisa Einwallner Hepatic Cholesterol-25-Hydroxylase Overexpression Improves Systemic Insulin Sensitivity in Mice Journal of Diabetes Research |
| title | Hepatic Cholesterol-25-Hydroxylase Overexpression Improves Systemic Insulin Sensitivity in Mice |
| title_full | Hepatic Cholesterol-25-Hydroxylase Overexpression Improves Systemic Insulin Sensitivity in Mice |
| title_fullStr | Hepatic Cholesterol-25-Hydroxylase Overexpression Improves Systemic Insulin Sensitivity in Mice |
| title_full_unstemmed | Hepatic Cholesterol-25-Hydroxylase Overexpression Improves Systemic Insulin Sensitivity in Mice |
| title_short | Hepatic Cholesterol-25-Hydroxylase Overexpression Improves Systemic Insulin Sensitivity in Mice |
| title_sort | hepatic cholesterol 25 hydroxylase overexpression improves systemic insulin sensitivity in mice |
| url | http://dx.doi.org/10.1155/2017/4108768 |
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