High-fat intake during lactation ameliorates cardiac fatty acid metabolic disorders and dysfunction in mouse offspring undergoing prenatal poly (I:C) stimulation.

Prenatal inflammation exposure (PIE) is associated with increased prevalence of cardiovascular diseases (CVDs) in offspring, including heart failure and hypertension. In this study, we investigated the molecular mechanisms underlying the prenatal programming of cardiac function. Pregnant mice were injected with poly (I:C) (20 mg/kg, i.p.) on day 10.5 of gestation. Mothers and pubs were fed with high-fat diet during lactation. Cardiac tissues of the offspring were collected for analysis. We found that prenatal poly (I:C) exposure significantly reduced fatty acid metabolism and impaired the homeostasis of energy metabolism in the heart tissues of offspring at the age of 4 weeks. RNA-sequencing analysis of the heart tissues revealed that prenatal poly (I:C) exposure resulted in decreased expression of the fatty acid oxidation-related enzymes and increased expression of glycolysis-related enzymes, enabling rewiring of energy metabolism. High-fat intake during lactation partially ameliorated cardiac fatty acid metabolism in the heart tissues and prevented cardiac dysfunction in offspring mice exposed to prenatal poly (I:C) at the age of 16 weeks. Collectively, abnormal cardiac fatty acid metabolism accounts for the prenatal poly (I:C) exposure-induced cardiac dysfunction, highlighting the potential of dietary interventions to prevent cardiac dysfunction for PIE offspring.