Brown adipose tissue development and fetal growth

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SUMMARY Brown adipose tissue (BAT) is developed before birth and exerts the thermogenic function at the maximal level immediately after delivery. Due to the energy-consuming nature of non-shivering thermogenesis, the contribution of BAT activation in energy metabolism and the development of obesity has caught our attention. Our recent study demonstrated that BAT/thermogenesis is significantly reduced during late pregnancy, which actively contributes to maternal metabolic adaptation. In this study, we observed a significant reduction of fetal body weight from UCP1 gene knockout dams. Due to the unique function of BAT in neonatal life, this intriguing phenotype led us to carry out a series of experiments to determine the effect of fetal BAT on fetal development. By knocking out the Ucp1 gene and genetic ablating brown adipocytes in fetuses, our preliminary study generates a shred of solid evidence indicating that fetal BAT development and activation are closely associated with fetal growth. The initial studies also showed that fetal Ucp1 knockout and BAT ablation significantly reduced placenta weight without alternation in placental structure. The metabolic phenotypes of elevated blood glucose concentrations and decreased blood insulin levels in Ucp1-/- and BAT-null fetuses suggest a defect in fetal islet development in these fetuses. Together, these preliminary data led us to hypothesize that there is intra-organ crosstalk between fetal BAT, the placenta, and fetal pancreatic islets at late pregnancy. Through these crosstalks, intrauterine metabolism, fetal tissue development, and growth are regulated. A series of animal studies will be performed to verify this hypothesis. We will use genetic mouse models and in vitro approaches to demonstrate the BAT/Placenta/Islet crosstalk in late pregnancy. The state- of-art system will be employed to determine if fetal brown adipocytes secret unique batokines and through which interact with other fetal organs. This proposal's success will lay down a foundation for future studies to elucidating the function of fetal BAT in intrauterine metabolism and fetal growth.