title: Peri-conceptional obesogenic exposure induces sex-specific programming of disease susceptibilities in adult mouse offspring.
abstract: Vulnerability of the fetus upon maternal obesity can potentially occur during all developmental phases. We aimed at elaborating longer-term health outcomes of fetal overnutrition during the earliest stages of development. We utilized Naval Medical Research Institute (NMRI) mice to induce pre-conceptional and gestational obesity and followed offspring outcomes in the absence of any postnatal obesogenic influences. Male adult offspring developed overweight, insulin resistance, hyperleptinemia, hyperuricemia and hepatic steatosis; all these features were not observed in females. Instead, they showed impaired fasting glucose and a reduced fat mass and adipocyte size. Influences of the interaction of maternal diet∗sex concerned offspring genes involved in fatty liver disease, lipid droplet size regulation and fat mass expansion. These data suggest that a peri-conceptional obesogenic exposure is sufficient to shape offspring gene expression patterns and health outcomes in a sex- and organ-specific manner, indicating varying developmental vulnerabilities between sexes towards metabolic disease in response to maternal overnutrition.
authors.affiliation: Institute of Molecular Animal Breeding and Biotechnology, Gene Center, Ludwig-Maximilians-Universität München, Feodor-Lynen-Strasse 25, 81377 Munich, Germany. Electronic address: dahlhoff@lmb.uni-muenchen.de.
authors.forename: M
authors.initials: M
authors.lastname: Dahlhoff
authors.affiliation: Research Center, Dr. von Hauner Children's Hospital, Ludwig-Maximilians-Universität München, Lindwurmstrasse 4, 80337 Munich, Germany. Electronic address: Sabine_Pfister@gmx.de.
authors.forename: S
authors.initials: S
authors.lastname: Pfister
authors.affiliation: Institute of Veterinary Pathology at the Centre for Clinical Veterinary Medicine, Ludwig-Maximilians-Universität München, Veterinärstrasse 13, 80539 Munich, Germany. Electronic address: blutke@patho.vetmed.uni-muenchen.de.
authors.forename: A
authors.initials: A
authors.lastname: Blutke
authors.affiliation: German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, Ingolstädter Landstrasse 1, 85764 München-Neuherberg, Germany; Molecular Nutritional Medicine, Else-Kröner Fresenius Center, Technische Universität München, Gregor-Mendel-Strasse 2, 85350 Freising-Weihenstephan, Germany. Electronic address: jan.rozman@helmholtz-muenchen.de.
authors.forename: J
authors.initials: J
authors.lastname: Rozman
authors.affiliation: Molecular Nutritional Medicine, Else-Kröner Fresenius Center, Technische Universität München, Gregor-Mendel-Strasse 2, 85350 Freising-Weihenstephan, Germany. Electronic address: martin.klingenspor@wzw.tum.de.
authors.forename: M
authors.initials: M
authors.lastname: Klingenspor
authors.affiliation: Research Center, Dr. von Hauner Children's Hospital, Ludwig-Maximilians-Universität München, Lindwurmstrasse 4, 80337 Munich, Germany. Electronic address: manuel_deutsch@hotmail.com.
authors.forename: M J
authors.initials: MJ
authors.lastname: Deutsch
authors.affiliation: Institute of Molecular Animal Breeding and Biotechnology, Gene Center, Ludwig-Maximilians-Universität München, Feodor-Lynen-Strasse 25, 81377 Munich, Germany; German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, Ingolstädter Landstrasse 1, 85764 München-Neuherberg, Germany. Electronic address: birgit.rathkolb@helmholtz-muenchen.de.
authors.forename: B
authors.initials: B
authors.lastname: Rathkolb
authors.affiliation: Research Center, Dr. von Hauner Children's Hospital, Ludwig-Maximilians-Universität München, Lindwurmstrasse 4, 80337 Munich, Germany. Electronic address: bafink@web.de.
authors.forename: B
authors.initials: B
authors.lastname: Fink
authors.affiliation: Research Center, Dr. von Hauner Children's Hospital, Ludwig-Maximilians-Universität München, Lindwurmstrasse 4, 80337 Munich, Germany. Electronic address: Martina.Gimpfl@med.uni-muenchen.de.
authors.forename: M
authors.initials: M
authors.lastname: Gimpfl
authors.affiliation: German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, Ingolstädter Landstrasse 1, 85764 München-Neuherberg, Germany; Lehrstuhl für Experimentelle Genetik, Wissenschaftszentrum Weihenstephan, Technische Universität München, Alte Akademie 8, 85354 Freising, Germany; Member of German Center for Diabetes Research (DZD), Ingolstädter Landstrasse 1, 85764 München-Neuherberg, Germany. Electronic address: hrabe@helmholtz-muenchen.de.
authors.forename: M
authors.initials: M
authors.lastname: Hrabě de Angelis
authors.affiliation: Research Center, Dr. von Hauner Children's Hospital, Ludwig-Maximilians-Universität München, Lindwurmstrasse 4, 80337 Munich, Germany. Electronic address: Adelbert.Roscher@med.uni-muenchen.de.
authors.forename: A A
authors.initials: AA
authors.lastname: Roscher
authors.affiliation: Institute of Molecular Animal Breeding and Biotechnology, Gene Center, Ludwig-Maximilians-Universität München, Feodor-Lynen-Strasse 25, 81377 Munich, Germany. Electronic address: ewolf@lmb.uni-muenchen.de.
authors.forename: E
authors.initials: E
authors.lastname: Wolf
authors.affiliation: Research Center, Dr. von Hauner Children's Hospital, Ludwig-Maximilians-Universität München, Lindwurmstrasse 4, 80337 Munich, Germany. Electronic address: Regina.Ensenauer@med.uni-muenchen.de.
authors.forename: R
authors.initials: R
authors.lastname: Ensenauer
mesh_terms: D017667:Adipocytes / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001835:Body Weight / Q000502:physiology; D048429:Cell Size; D059305:Diet, High-Fat / Q000009:adverse effects*; D004198:Disease Susceptibility / Q000209:etiology / Q000503:physiopathology*; D005234:Fatty Liver / Q000209:etiology / Q000503:physiopathology; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005951:Glucose Tolerance Test; D033461:Hyperuricemia / Q000209:etiology / Q000503:physiopathology; D007333:Insulin Resistance / Q000502:physiology; D020738:Leptin / Q000097:blood; D008297:Male; D008815:Mice, Inbred Strains; D009765:Obesity / Q000209:etiology / Q000235:genetics / Q000503:physiopathology*; D050177:Overweight / Q000209:etiology / Q000503:physiopathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000209:etiology / Q000235:genetics / Q000503:physiopathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012737:Sex Factors; D050151:Subcutaneous Fat / Q000378:metabolism; D013997:Time Factors
chemical_list: D020738:Leptin
keywords: ANOVA; ATP citrate lyase; AUC; Acaca; Acetyl-Coenzyme A carboxylase 1; Acly; Actb; Analysis of variance; Area under the curve; B cell leukemia/lymphoma 2; BW; Bax; Bcl2; Bcl2-associated X protein; Berardinelli–Seip congenital lipodystrophy 2 (also known as seipin); Beta-actin; Body weight; Bscl2; CD; CET; CT; Carbon dioxide production; Carnitine palmitoyltransferase 1; Cd36; Cd36 antigen; Cell death-inducing DNA fragmentation factor, alpha subunit-like effector A; Central European Time; Cidea; Computed tomography; Control diet; Cpt1; Day post coitum; EEC; European Economic Commission; Exposure to maternal control diet; Exposure to maternal high-fat, high-calorie diet; FA; Fabp4; Fasn; Fatty acid; Fatty acid binding protein 4; Fatty acid synthase; GR; GTT; Glucocorticoid receptor; Glucose tolerance test; H&E; HFD; HMW; HOMA-IR; HP; Hairy and enhancer of split 1; Heat production; Hematoxylin–eosin; Hes1; High-fat, high-calorie diet; High-molecular-weight; Homeostatic model assessment of insulin resistance; Lep; Leptin; MD; MDA; MRI; Magnetic resonance imaging; Maintenance diet; Malic enzyme 1; Malondialdehyde; Me1; Mesoderm-specific transcript/imprinted paternally expressed gene 1 (also known as Peg1); Mest; N; NAFLD; NEFA; NMRI; NRL; Naval Medical Research Institute; Nitrogen; Non-alcoholic fatty liver disease; Non-esterified fatty acid; Nose–rump-length; Nr1h3; Nr3c1; Nuclear receptor subfamily 1, group H, member 3 (also known as Lxra, liver X receptor alpha); Nuclear receptor subfamily 3, group C, member 1 (also known as Gr, glucocorticoid receptor); Obesity; Offspring; Oxygen consumption; PFA; Paraformaldehyde; Patatin-like phospholipase domain-containing protein 2 (also known as Atgl, adipose triglyceride lipase); Peptidylprolyl isomerase A; Peri-conceptional; Perilipin 2; Peroxisome proliferator activated receptor alpha; Peroxisome proliferator activated receptor gamma; Plin2; Pnpla2; Ppara; Pparg; Ppia; Pregnancy; Programming; RER; ROI; Region of interest; Respiratory exchange ratio; S.e.m.; Scd2; Secreted frizzled-related sequence protein 5; Sex-specificity; Sfrp5; Srebf1; Standard error of the mean; Stearoyl-Coenzyme A desaturase 2; Sterol regulatory element binding transcription factor 1; TBARS; Thiobarbituric acid-reactive substances; Ube2d2; Ubiquitin-conjugating enzyme E2D 2; VCO(2); VO(2); dpc; mat-CD; mat-HFD