Genetic, dietary, and sex-specific regulation of hepatic ceramides and the relationship between hepatic ceramides and IR [S]
Elevated hepatic ceramide levels have been implicated in both insulin resistance (IR) and hepatic steatosis. To understand the factors contributing to hepatic ceramide levels in mice of both sexes, we have quantitated ceramides in a reference population of mice, the Hybrid Mouse Diversity Panel that...
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Elsevier
2018-01-01
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| Series: | Journal of Lipid Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520330753 |
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doaj-f06455053a49487895841ef47b2899312021-04-29T04:36:19ZengElsevierJournal of Lipid Research0022-22752018-01-0159711641174Genetic, dietary, and sex-specific regulation of hepatic ceramides and the relationship between hepatic ceramides and IR [S]Frode Norheim0Thomas Bjellaas1Simon T. Hui2Karthickeyan Chella Krishnan3Jakleen Lee4Sonul Gupta5Calvin Pan6Yehudit Hasin-Brumshtein7Brian W. Parks8Daniel Y. Li9Hai H. Bui10Marian Mosier11Yuping Wu12Adriana Huertas-Vazquez13Stanley L. Hazen14Thomas E. Gundersen15Margarete Mehrabian16W.H.Wilson Tang17Andrea L. Hevener18Christian A. Drevon19Aldons J. Lusis20Division of Cardiology University of California at Los Angeles, Los Angeles, CAVITAS Analytical Services, Oslo, NorwayDivision of Cardiology University of California at Los Angeles, Los Angeles, CADivision of Cardiology University of California at Los Angeles, Los Angeles, CADivision of Cardiology University of California at Los Angeles, Los Angeles, CADivision of Cardiology University of California at Los Angeles, Los Angeles, CADivision of Cardiology University of California at Los Angeles, Los Angeles, CADivision of Cardiology University of California at Los Angeles, Los Angeles, CADepartment of Nutritional Sciences, University of Wisconsin-Madison, Madison, WIDivision of Cardiology University of California at Los Angeles, Los Angeles, CA; Cleveland Clinic Lerner College of Medicine of Case Western University, Cleveland, OHLilly Research Laboratories, Indianapolis, INLilly Research Laboratories, Indianapolis, INDepartment of Mathematics, Cleveland State University, Cleveland OHDivision of Cardiology University of California at Los Angeles, Los Angeles, CADepartment of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OHVITAS Analytical Services, Oslo, NorwayDivision of Cardiology University of California at Los Angeles, Los Angeles, CADepartment of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OHDivision of Endocrinology, Diabetes, and Hypertension, Department of Medicine, University of California at Los Angeles, Los Angeles, CAVITAS Analytical Services, Oslo, Norway; Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, NorwayDivision of Cardiology University of California at Los Angeles, Los Angeles, CA; To whom correspondence should be addressed.Elevated hepatic ceramide levels have been implicated in both insulin resistance (IR) and hepatic steatosis. To understand the factors contributing to hepatic ceramide levels in mice of both sexes, we have quantitated ceramides in a reference population of mice, the Hybrid Mouse Diversity Panel that has been previously characterized for a variety of metabolic syndrome traits. We observed significant positive correlations between Cer(d18:1/16:0) and IR/hepatic steatosis, consistent with previous findings, although the relationship broke down between sexes, as females were less insulin resistant, but had higher Cer(d18:1/16:0) levels than males. The sex difference was due in part to testosterone-mediated repression of ceramide synthase 6. One ceramide species, Cer(d18:1/20:0), was present at higher levels in males and was associated with IR only in males. Clear evidence of gene-by-sex and gene-by-diet interactions was observed, including sex-specific genome-wide association study results. Thus, our studies show clear differences in how hepatic ceramides are regulated between the sexes, which again suggests that the physiological roles of certain hepatic ceramides differ between the sexes.http://www.sciencedirect.com/science/article/pii/S0022227520330753animal modelsdiabeteslipidomicsmass spectrometrysphingolipidsgonadectomy |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Frode Norheim Thomas Bjellaas Simon T. Hui Karthickeyan Chella Krishnan Jakleen Lee Sonul Gupta Calvin Pan Yehudit Hasin-Brumshtein Brian W. Parks Daniel Y. Li Hai H. Bui Marian Mosier Yuping Wu Adriana Huertas-Vazquez Stanley L. Hazen Thomas E. Gundersen Margarete Mehrabian W.H.Wilson Tang Andrea L. Hevener Christian A. Drevon Aldons J. Lusis |
| spellingShingle |
Frode Norheim Thomas Bjellaas Simon T. Hui Karthickeyan Chella Krishnan Jakleen Lee Sonul Gupta Calvin Pan Yehudit Hasin-Brumshtein Brian W. Parks Daniel Y. Li Hai H. Bui Marian Mosier Yuping Wu Adriana Huertas-Vazquez Stanley L. Hazen Thomas E. Gundersen Margarete Mehrabian W.H.Wilson Tang Andrea L. Hevener Christian A. Drevon Aldons J. Lusis Genetic, dietary, and sex-specific regulation of hepatic ceramides and the relationship between hepatic ceramides and IR [S] Journal of Lipid Research animal models diabetes lipidomics mass spectrometry sphingolipids gonadectomy |
| author_facet |
Frode Norheim Thomas Bjellaas Simon T. Hui Karthickeyan Chella Krishnan Jakleen Lee Sonul Gupta Calvin Pan Yehudit Hasin-Brumshtein Brian W. Parks Daniel Y. Li Hai H. Bui Marian Mosier Yuping Wu Adriana Huertas-Vazquez Stanley L. Hazen Thomas E. Gundersen Margarete Mehrabian W.H.Wilson Tang Andrea L. Hevener Christian A. Drevon Aldons J. Lusis |
| author_sort |
Frode Norheim |
| title |
Genetic, dietary, and sex-specific regulation of hepatic ceramides and the relationship between hepatic ceramides and IR [S] |
| title_short |
Genetic, dietary, and sex-specific regulation of hepatic ceramides and the relationship between hepatic ceramides and IR [S] |
| title_full |
Genetic, dietary, and sex-specific regulation of hepatic ceramides and the relationship between hepatic ceramides and IR [S] |
| title_fullStr |
Genetic, dietary, and sex-specific regulation of hepatic ceramides and the relationship between hepatic ceramides and IR [S] |
| title_full_unstemmed |
Genetic, dietary, and sex-specific regulation of hepatic ceramides and the relationship between hepatic ceramides and IR [S] |
| title_sort |
genetic, dietary, and sex-specific regulation of hepatic ceramides and the relationship between hepatic ceramides and ir [s] |
| publisher |
Elsevier |
| series |
Journal of Lipid Research |
| issn |
0022-2275 |
| publishDate |
2018-01-01 |
| description |
Elevated hepatic ceramide levels have been implicated in both insulin resistance (IR) and hepatic steatosis. To understand the factors contributing to hepatic ceramide levels in mice of both sexes, we have quantitated ceramides in a reference population of mice, the Hybrid Mouse Diversity Panel that has been previously characterized for a variety of metabolic syndrome traits. We observed significant positive correlations between Cer(d18:1/16:0) and IR/hepatic steatosis, consistent with previous findings, although the relationship broke down between sexes, as females were less insulin resistant, but had higher Cer(d18:1/16:0) levels than males. The sex difference was due in part to testosterone-mediated repression of ceramide synthase 6. One ceramide species, Cer(d18:1/20:0), was present at higher levels in males and was associated with IR only in males. Clear evidence of gene-by-sex and gene-by-diet interactions was observed, including sex-specific genome-wide association study results. Thus, our studies show clear differences in how hepatic ceramides are regulated between the sexes, which again suggests that the physiological roles of certain hepatic ceramides differ between the sexes. |
| topic |
animal models diabetes lipidomics mass spectrometry sphingolipids gonadectomy |
| url |
http://www.sciencedirect.com/science/article/pii/S0022227520330753 |
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