Maternal obesity or weight loss around conception impacts hepatic fatty acid metabolism in the offspring

Abstract

OBJECTIVE: To determine the impact of maternal obesity or weight loss during the periconceptional period on programming of lipid metabolism in the liver of the offspring. METHODS: An embryo transfer model was used to investigate the effects of exposure to either maternal obesity and/or weight loss before and for 1-week post-conception on the abundance of key molecules regulating hepatic fatty acid oxidation and lipid synthesis in the 4-month-old lamb. RESULTS: Periconceptional maternal obesity resulted in decreased hepatic PPARα, PGC1α and GCN5 abundance and increased hepatic SIRT1 and AMPKα1, AMPKα2 and SREBP1 abundance in the offspring. Maternal weight loss in obese ewes did not ablate all of these effects of maternal obesity on hepatic metabolism in the lamb. Weight loss in normal weight ewes also resulted in decreased hepatic PGC1α and GCN5 and increased AMPKα2 abundance in the offspring. CONCLUSIONS: Exposure of the oocyte/embryo to either maternal obesity or weight loss during the periconceptional period has long term consequences for hepatic lipid metabolism. These findings highlight the sensitivity of the early embryo to maternal nutrition and the need for dietary interventions which maximize metabolic benefits and minimize metabolic costs for the next generation.