Maternal hypothyroidism in mice influences glucose metabolism in adult offspring

Kemkem, Y.; Nasteska, D.; Hodson, D.; Guillou, A.; Mollard, P.; Bargi-Souza, P.; Peliciari-Garcia, R. A.; De Bray, A.; Schaeffer, M.

doi:10.1101/785030

bioRxiv · 10.1101/785030

Maternal hypothyroidism in mice influences glucose metabolism in adult offspring

Kemkem, Y.·Nasteska, D.·Hodson, D.·Guillou, A.·Mollard, P.·Bargi-Souza, P.·Peliciari-Garcia, R. A.·De Bray, A.·Schaeffer, M.

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Abstract

During pregnancy, maternal metabolic diseases and hormonal imbalance may alter fetal beta cell development and/or proliferation, thus leading to an increased risk for developing type 2 diabetes in adulthood. Although thyroid hormones play an important role in fetal endocrine pancreas development, the impact of maternal hypothyroidism on glucose homeostasis in adult offsprings remains poorly understood. Here, we show that when fed normal chow, adult mice born to hypothyroid mothers were more glucose-tolerant due to beta cell hyperproliferation and increased insulin sensitivity. However, following high fat feeding, these offsprings became profoundly hyperinsulinemic, insulin-resistant and glucose-intolerant compared to controls from euthyroid mothers. Suggesting presence of epigenetic changes, altered glucose metabolism was maintained in a second generation of animals. As such, gestational hypothyroidism induces long-term and persistent alterations in endocrine pancreas function, which may have important implications for type 2 diabetes prevention in affected individuals.\n\nSIGNIFICANCEDiabetes and hypothyroidism are two major public health issues, affecting [~] 9 and 2 % of the population worldwide, respectively. As master metabolic gatekeepers, the thyroid hormones play an essential role in metabolism and fetal development. However, gestation increases demand on the thyroid axis in the mother, leading to hypothyroidism in 0.5 % of pregnancies. Maternal hypothyroidism is associated with deficits in fetal growth that may lead to long-term alterations in metabolism in the offspring. We therefore sought to investigate the effects of gestational hypothyroidism on glucose metabolism in adult offspring and their descendants, and how this may predispose to diabetes development.

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Kemkem, Y., Nasteska, D., Hodson, D., Guillou, A., Mollard, P., Bargi-Souza, P., Peliciari-Garcia, R. A., De Bray, A., Schaeffer, M.. 2019-09-28. Maternal hypothyroidism in mice influences glucose metabolism in adult offspring. https://doi.org/10.1101/785030

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