Importantly, we implicate a putative role for the hepatic innate immune

system. The experimental design allowed us to investigate the relative influence of maternal obesity versus a postnatal obesogenic environment on progression of the NAFLD phenotype. The postweaning learn more obesogenic diet had the greater influence on adiposity, hepatosteatosis, and markers of liver injury and fibrosis; however, there was an independent effect of maternal diet and a significant interaction between maternal and postweaning environments, which led to the most profound degree of liver injury observed. Moreover, we also observed that this disorder progressed with age. At 3 months, there was evidence of offspring obesity, adiposity, hepatosteatosis, and up-regulation of IL-6, TNF-α, and α-SMA as biochemical

markers of liver injury and fibrosis. By 12 months, there was more-profound evidence of hepatosteatosis, as assessed by the biochemical Sorafenib molecular weight markers and histological evidence of liver injury and fibrosis. We previously reported that offspring of obese mouse dams, when weaned onto standard chow, despite displaying hypertensive and dysmetabolic characteristics, did not exhibit a robust fatty liver phenotype.3 Here, we report similar hepatic tissue TG content Buspirone HCl in OffOb-SC, compared to controls, corroborated by histological steatosis assessment. Our findings parallel the findings of Bruce et al.,5 who reported hepatosteatosis in offspring exposed to maternal high-fat diet and weaned onto high-fat chow. OffOb-OD display

an accelerated and exaggerated liver phenotype, compared to offspring exposed only to a postweaning obesogenic diet. Therefore, taken together, the evidence suggests that developmental programming by diet-induced maternal obesity sensitizes the liver to the deleterious consequences of a second postnatal dietary challenge. Whereas Bruce et al. implicated phenotypic propagation of the liver phenotype by hepatic mitochondrial dysfunction and lipogenesis gene priming, we now suggest that maternal diet-induced obesity may also program offspring susceptibility to NAFLD by perturbation of the innate immune system. Offspring of obese dams reared on a hypercalorific diet, despite demonstrating increased KC numbers, showed impaired KC phagocytic activity and increased KC ROS production, which also revealed an apparent interaction between the maternal and postnatal environments. The current paradigm for the pathogenesis of NAFLD holds fat accumulation as a prerequisite for disease development.