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Dahlhoff, M.* ; Pfister, S.* ; Blutke, A.* ; Rozman, J. ; Klingenspor, M.* ; Deutsch, M.J.* ; Rathkolb, B. ; Fink, B.* ; Gimpfl, M.* ; Hrabě de Angelis, M. ; Roscher, A.A.* ; Wolf, E.* ; Ensenauer, R.*

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

Biochim. Biophys. Acta-Mol. Basis Dis. 1842, 304–317 (2014)

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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 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 not being observed in females. Instead, those 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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