The global epidemic of obesity has led to an increasing number of obese women in childbearing age. While it is now understood that maternal obesity may have harmful consequences on fetal and adult metabolic programming of the offspring’s liver, however, the underlying mechanisms remain elusive. Macrophages have been identified as metabolite-sensing cells and are thus essential mediators of pathological conditions caused by intake of a Western diet. The recent discovery that most tissue-resident macrophages have a fetal origin places these cells in a unique position of sensing and responding to metaflammation during embryogenesis. Thus, we hypothesise that fetal macrophages function as messengers of maternal metaflammation, and are key players for the development of metabolic syndromesin the offspring. Based on the latest data on hepatic macrophage ontogeny, we propose to study the intergenerational consequences of maternal obesity on their development and effector function for liver metabolism. Using a maternal obesity mouse model, we aim to characterise the contribution of hepatic macrophages to hepatosteatosis in the offspring. To this end, we aim at dissecting the ontogeny as well as cellular and molecular changes of macrophages and other myeloid cells in the liver from offspring born to obese mothers. Further, we will characterise epigenetic modulators and lipid species driving develop-mental programming events and test whether the systemic metabolic changes in the offspring lead to detrimental effects in tissue regeneration upon inflammation. Finally, we will address whether develop-mental programming of hepatic macrophages is causal for the development of liver steatosis by using conditional knockouts targeting key molecules in hepatic macrophage development, activation and metabolic regulation. In summary, this project will characterise how maternal obesity regulates macrophage-mediated signalling events in the developing fetus that drive pathophysiological mechanisms of liver steatosis in adulthood.