Li, Jiawei; (2019) The immune mechanism of developmental programming in non-alcoholic fatty liver disease. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Previously, it was shown that maternal obesity before pregnancy, during pregnancy and lactation predisposes adult offspring for obesity and NAFLD, with the possible mechanism involving the breast milk. It was later shown that there is an interaction between maternal obesity and post-weaning diet, with alteration in Kupffer (liver macrophage) cells and natural killer cells in the liver. As a sequel to previous findings in our groups, this project focuses on the programming effect of maternal obesity at earlier time points of development. We found that embryos from obese mothers had significantly lower body mass comparing to embryos from the lean mothers, accompanied by an increase in transforming growth factor- (Tgf-) and Glioma-associated (Gli) gene, and altered immune profile. Gli3 is a Hedgehog (Hh) responsive transcription factor, suggesting an involvement of the Hedgehog (Hh) Signalling Pathway in the developmental programming effect of NAFLD. Further investigation and published literature show that Hh is a crucial factor in modulating organ development and immune development. An adult mouse model in this project investigates the relationship between Hh and NAFLD. Taking all the factors together, this thesis demonstrates that there is an interactive effect between the Hh and obesity, which may be the underlying mechanism for the developmental programming effect seen in NAFLD.

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