THU135 Maternal Obesogenic Diet Exposure Affects Post-natal And Pathologic Hepatocyte Proliferation In Offspring

Abstract

Abstract Disclosure: N. Ramavath: None. H. Hinrichs: None. M. Young: None. M. Thompson: None. Background: Obesity is a complex metabolic syndrome associated with a wide range of abnormalities in liver known as non-alcoholic fatty liver diseases (NAFLD). Evidence supports that maternal obesity/obesogenic diet exposure programs increased NAFLD offspring. The liver responds to lipotoxic hepatocyte injury through hepatocyte proliferation. It is not clear whether maternal obesogenic diet exposure affects the capacity of offspring hepatocytes to proliferate. We hypothesized that early impact of maternal/ obesogenic diet exposure in early life or utero exposure enhances hepatocyte proliferation capacity in offspring. Methods: Female mice were fed chow or high fat-fructose-cholesterol (HFFC) diet for 6 weeks and bred with lean males Liver and serum samples were collected at different postnatal time periods 5, 10, 15, 20, 25, and 30 days to analyze histological and molecular markers for liver proliferation. In addition, a small group of offspring from each group were weaned to the HFFC diet for 7 weeks to analyze progression of NAFLD (non -alcoholic fatty liver diseases). Results: No significant difference between neonatal body weight and liver weight was observed; however, the liver weight/body weight was increased at day 20 in HFFC offspring compared to chow offspring. The number of ki-67 positive hepatocytes peaked in both groups at day 15. An increase in ki-67 positive hepatocytes was observed at 15, 20, and 30 days in HFFC offspring compared to chow offspring. After 7 weeks of HFFC diet feeding, the number of Ki-67 positive hepatocytes was higher in HFFC offspring in comparison with Chow offspring. Conclusion: Maternal obesogenic diet exposure affected post-natal and NAFLD-associated hepatocyte proliferation in offspring with an increase in hepatocyte proliferative capacity. This could have implications for the ability of maternal obesity exposed offspring to respond to hepatic injury and potential for development of hepatic cancer. Presentation: Thursday, June 15, 2023