JOURNAL ARTICLE

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

M Dahlhoff, S Pfister, A Blutke, J Rozman, M Klingenspor, M J Deutsch, B Rathkolb, B Fink, M Gimpfl, M Hrabě de Angelis, A A Roscher, E Wolf, R Ensenauer
Biochimica et Biophysica Acta 2014, 1842 (2): 304-17
24275555
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.

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