Genetic, dietary, and sex-specific regulation of hepatic ceramides and the relationship between hepatic ceramides and IR [S]
| Autor: | Andrea L. Hevener, Aldons J. Lusis, Margarete Mehrabian, Simon T. Hui, Stanley L. Hazen, Thomas Bjellaas, Jakleen Lee, Yuping Wu, Karthickeyan Chella Krishnan, Christian A. Drevon, Marian Mosier, Thomas E. Gundersen, Yehudit Hasin-Brumshtein, Daniel Y. Li, Hai H. Bui, Brian W. Parks, W.H. Wilson Tang, Sonul Gupta, Adriana Huertas-Vazquez, Calvin Pan, Frode Norheim |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Medical Biochemistry and Metabolomics Biochemistry chemistry.chemical_compound Mice 0302 clinical medicine Endocrinology insulin resistance 2.1 Biological and endogenous factors Testosterone Aetiology Ceramide synthase Research Articles mass spectrometry Sex Characteristics diabetes Liver Disease animal models Liver Female gonadectomy medicine.medical_specialty Ceramide Biochemistry & Molecular Biology QD415-436 Biology Ceramides sex hormones 03 medical and health sciences Insulin resistance Diabetes mellitus Internal medicine Lipidomics medicine Genetics Animals Nutrition sphingolipids Cell Biology medicine.disease Sphingolipid Diet 030104 developmental biology chemistry genome-wide association studies lipidomics Biochemistry and Cell Biology Insulin Resistance Steatosis Metabolic syndrome Digestive Diseases 030217 neurology & neurosurgery |
| Zdroj: | Journal of Lipid Research, Vol 59, Iss 7, Pp 1164-1174 (2018) Journal of lipid research, vol 59, iss 7 |
| ISSN: | 0022-2275 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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