Post-prandial cardiac hypertrophy is sustained by mechanics, epigenetic, and metabolic reprogramming in pythons [ATAC-Seq]

Constricting pythons, known for their ability to consume infrequent, massive meals, exhibit rapid and reversible cardiac hypertrophy following feeding. Our primary goal was to investigate how python hearts achieve this adaptive response after feeding. Isolated myofibrils increased force after feeding without changes in sarcomere ultrastructure and without increasing energy cost. Ca2+ transients were prolonged after feeding with no changes in myofibril Ca2+ sensitivity. Feeding reduced titin-based tension, resulting in decreased cardiac tissue stiffness. Feeding also reduced the activity of sirtuins, a metabolically-linked class of histone deacetylases, and increased chromatin accessibility. A transcription factor enrichment analysis on transposase-accessible chromatin with sequencing (ATAC-Seq) revealed the prominent role of transcription factors YY1 and NRF1 in post-feeding cardiac adaptation. Gene expression was also changed in favor of translation and metabolism. Finally, metabolomics analysis and ATP production assay demonstrated that cardiac adaptation after feeding not only increased energy demand but also energy production. These findings have broader implications for our understanding of cardiac adaptation across species and hold promise for the development of innovative approaches to address cardiovascular diseases. Overall design: To determine the chromatin accessibility profile of post-prandial python hearts, the cardiomyocytes of fasted and 24 post fed Python regius were extracted for ATAC-sequencing analysis. The cardiomyocytes from three fasted and three fed pythons were included in the study. Transcription factor expression analysis (TFEA) was performed between fasted and 24 hour post fed python cardiomyocytes.