Long-term disruption of glucose homeostasis in a rodent model of preterm birth.

Diao, S.; Guenoun, D.; Chen, S.-P.; CRUCIANI-GUGLIELMACCI, C.; Pansiot, J.; Laforge, M.; Raho, I.; Faivre, V.; Degos, V.; Gressens, P.; Nadjar, A.; Van Steenwinckel, J.; Adle-Biasette, H.; Magnan, C.; Jacquens, A.; Bokobza, C.

doi:10.1101/2024.02.07.579307

bioRxiv · 10.1101/2024.02.07.579307

Long-term disruption of glucose homeostasis in a rodent model of preterm birth.

Diao, S.·Guenoun, D.·Chen, S.-P.·CRUCIANI-GUGLIELMACCI, C.·Pansiot, J.·Laforge, M.·Raho, I.·Faivre, V.·Degos, V.·Gressens, P.·Nadjar, A.·Van Steenwinckel, J.·Adle-Biasette, H.·Magnan, C.·Jacquens, A.·Bokobza, C.

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Abstract

Around 1 of every 10 babies is born preterm, and the incidence of preterm birth has been rising. The long-term consequences of preterm survivors are not fully understood. Preterm birth is proven to be associated with metabolic diseases and related disorders later in life. Preterm newborns are susceptible to perinatal inflammatory events such as chorioamnionitis, hypoxia-ischemia, and sepsis. We hypothesized that perinatal inflammation has a role in the developmental programming of metabolic diseases and related disorders. In the present study, perinatal inflammation was modeled by systemic administration of IL-1{beta} in mice. We observed a pronounced sexual dimorphism where only the males presented significant insulin resistance and glucose intolerance accompanied by leptin resistance in the long term following perinatal inflammation exposure. Adiposity and energy homeostasis were intact. It showed that perinatal inflammation selectively contributes to the long-term dysregulation of glucose metabolism in a sex-dependent manner. The underlying mechanism might be linked with hypothalamic inflammation and upregulated circulating CCL5. Metformin treatment might be optional to treat insulin resistance resulting from perinatal inflammation. HighlightsO_LIPerinatal inflammation is common in preterm infants, often leading to perinatal brain injuries. However, the long-term metabolic outcomes of these infants are not fully revealed. C_LIO_LIWe explored the long-term metabolic outcomes in mice with perinatal IL-1{beta} exposure and sought its association with inflammation. C_LIO_LIPerinatal inflammation has a profound and deleterious role in glucose metabolism in a sex-dependent and time-dependent manner. C_LIO_LIPerinatal inflammation might be a risk factor for metabolic disorders in preterm survivors. C_LI

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Diao, S., Guenoun, D., Chen, S.-P., CRUCIANI-GUGLIELMACCI, C., Pansiot, J., Laforge, M., Raho, I., Faivre, V., Degos, V., Gressens, P., Nadjar, A., Van Steenwinckel, J., Adle-Biasette, H., Magnan, C., Jacquens, A., Bokobza, C.. 2024-02-07. Long-term disruption of glucose homeostasis in a rodent model of preterm birth.. https://doi.org/10.1101/2024.02.07.579307

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