Peri-conceptional obesogenic exposure induces sex-specific programming of disease susceptibilities in adult mouse offspring

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1842

Article

Dahlhoff, M.²  Pfister, S.¹  Blutke, A.³  Rozman, J.^4,5  Klingenspor, M.⁵  Deutsch, M. J.¹  Rathkolb, B.^2,4  Fink, B.¹  Gimpfl, M.¹  de Angelis, M. Hrabe^4,6  Roscher, A. A.¹  Wolf, E.²  Ensenauer, R.¹ 

[1] Univ Munich, Res Ctr, Dr von Hauner Childrens Hosp, D-80337 Munich, Germany

[2] Univ Munich, Gene Ctr, Inst Mol Anim Breeding & Biotechnol, D-81377 Munich, Germany

[3] Univ Munich, Ctr Clin Vet Med, Inst Vet Pathol, D-80539 Munich, Germany

[4] Helmholtz Zentrum Munchen, Inst Expt Genet, German Mouse Clin, D-85764 Munich, Germany

[5] Tech Univ Munich, Else Kroner Fresenius Ctr, D-85350 Freising Weihenstephan, Germany

[6] Tech Univ Munich, Wissensch Zentrum Weihenstephan, Lehrstuhl Expt Genet, D-85354 Freising Weihenstephan, Germany

关键词: Obesity;    Peri-conceptional;    Pregnancy;    Offspring;    Programming;    Sex-specificity;   

DOI  :  10.1016/j.bbadis.2013.11.021

来源: Elsevier

【 摘 要 】

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. (C) 2013 Elsevier B.V. All rights reserved.

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