High-fat diet during mouse pregnancy impairs fetal heart development
Maternal obesity is associated with detrimental outcomes in offspring. However, the specific effects of gestational exposure to a high-fat diet (HFD) on fetal heart development remain poorly understood. In the study, we investigated that maternal overnutrition accounted for defective development in offspring, and cell proliferation was restricted severely in neonatal organ. Starting with this clue, we found decreased cell cycle and similar cross area of cardiomyocytes in offspring exposed to a maternal HFD. Moreover, RNA sequencing analysis detected that HFD diminished fatty acid metabolism, enhanced inflammation response and up-regulated substantially the pathway TP53 regulates transcription of cell cycle genes in postnatal day 0 (P0) cardiomyocytes. Further, normal lactation after delivery not only recovered from growth retardation but also maintained normal cardiac function in offspring. These data demonstrated a potential TP53 pathway-dependent mechanism through which maternal HFD contributed to offspring cardiac defects. Overall design: To investigate the mechanisms through which transcriptional pathway in HFD heart might lead to defective proliferation in cardiomyocytes, we isolated cardiomyocytes from all groups of hearts at P0 followed by RNA-seq.