title: Dexamethasone treatment alters insulin, leptin, and adiponectin levels in male mice as observed in DIO but does not lead to alterations of metabolic phenotypes in the offspring.
abstract: Epigenetic inheritance (EI) of metabolic phenotypes via the paternal lineage has been shown in rodent models of diet-induced obesity (DIO). However, the factors involved in soma-to-germline information transfer remain elusive. Here, we address the role of alterations in insulin, leptin, and adiponectin levels for EI of metabolic phenotypes by treating C57BL/6NTac male mice (F0) with the synthetic glucocorticoid dexamethasone and generating offspring (F1) either by in vitro fertilization or by natural fecundation. Dexamethasone treatment slightly alters F0 body composition by increasing fat mass and decreasing lean mass, and significantly improves glucose tolerance. Moreover, it increases insulin and leptin levels and reduces adiponectin levels in F0 fathers as observed in mouse models of DIO. However, these paternal changes of metabolic hormones do not alter metabolic parameters, such as body weight, body composition and glucose homeostasis in male and female F1 mice even when these are challenged with a high-fat diet. Accordingly, sperm transcriptomes are not altered by dexamethasone treatment. Our results suggest that neither increased glucocorticoid, insulin, and leptin levels, nor decreased adiponectin levels in fathers are sufficient to confer soma-to-germline information transfer in EI of obesity via the paternal lineage.
authors.affiliation: Institute of Experimental Genetics and German Mouse Clinic, Helmholtz Zentrum München GmbH - German Research Center for Environmental Health, Ingolstädter Landstr. 1, 85764, Neuherberg, Germany.
authors.forename: Clemens
authors.initials: C
authors.lastname: Bönisch
authors.affiliation: Institute of Experimental Genetics and German Mouse Clinic, Helmholtz Zentrum München GmbH - German Research Center for Environmental Health, Ingolstädter Landstr. 1, 85764, Neuherberg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Irmler
authors.affiliation: Institute of Experimental Genetics and German Mouse Clinic, Helmholtz Zentrum München GmbH - German Research Center for Environmental Health, Ingolstädter Landstr. 1, 85764, Neuherberg, Germany.|Institute of Pathology, Helmholtz Zentrum München GmbH - German Research Center for Environmental Health, 85764, Neuherberg, Germany.
authors.forename: Laura
authors.initials: L
authors.lastname: Brachthäuser
authors.affiliation: Institute of Experimental Genetics and German Mouse Clinic, Helmholtz Zentrum München GmbH - German Research Center for Environmental Health, Ingolstädter Landstr. 1, 85764, Neuherberg, Germany.|Institute of Pathology, Helmholtz Zentrum München GmbH - German Research Center for Environmental Health, 85764, Neuherberg, Germany.
authors.forename: Frauke
authors.initials: F
authors.lastname: Neff
authors.affiliation: Institute of Experimental Genetics and German Mouse Clinic, Helmholtz Zentrum München GmbH - German Research Center for Environmental Health, Ingolstädter Landstr. 1, 85764, Neuherberg, Germany.
authors.forename: Mareike T
authors.initials: MT
authors.lastname: Bamberger
authors.affiliation: Institute of Experimental Genetics and German Mouse Clinic, Helmholtz Zentrum München GmbH - German Research Center for Environmental Health, Ingolstädter Landstr. 1, 85764, Neuherberg, Germany.
authors.forename: Susan
authors.initials: S
authors.lastname: Marschall
authors.affiliation: Institute of Experimental Genetics and German Mouse Clinic, Helmholtz Zentrum München GmbH - German Research Center for Environmental Health, Ingolstädter Landstr. 1, 85764, Neuherberg, Germany.|Chair of Experimental Genetics, Technische Universität München, 85354, Freising, Germany.|German Center for Diabetes Research (DZD), 85764, Neuherberg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Hrabě de Angelis
authors.affiliation: Institute of Experimental Genetics and German Mouse Clinic, Helmholtz Zentrum München GmbH - German Research Center for Environmental Health, Ingolstädter Landstr. 1, 85764, Neuherberg, Germany. beckers@helmholtz-muenchen.de.|Chair of Experimental Genetics, Technische Universität München, 85354, Freising, Germany. beckers@helmholtz-muenchen.de.|German Center for Diabetes Research (DZD), 85764, Neuherberg, Germany. beckers@helmholtz-muenchen.de.
authors.forename: Johannes
authors.initials: J
authors.lastname: Beckers
mesh_terms: D052242:Adiponectin / Q000235:genetics* / Q000378:metabolism; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001823:Body Composition / Q000187:drug effects / Q000235:genetics; D003907:Dexamethasone / Q000494:pharmacology*; D059305:Diet, High-Fat / Q000009:adverse effects; D044127:Epigenesis, Genetic; D005260:Female; D005307:Fertilization in Vitro; D005951:Glucose Tolerance Test; D040582:Inheritance Patterns; D007328:Insulin / Q000235:genetics* / Q000378:metabolism; D020738:Leptin / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000209:etiology / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D015398:Signal Transduction; D013094:Spermatozoa / Q000187:drug effects / Q000378:metabolism; D059467:Transcriptome
chemical_list: D052242:Adiponectin; C499919:Adipoq protein, mouse; D007328:Insulin; D020738:Leptin; D003907:Dexamethasone