Multi-omics insight into cardiac myofibril remodeling in post-prandial Burmese pythons

Burmese pythons exhibit cardiac remodeling in response to increased metabolic rate during digestion. Here, we performed single-myofibril mechanics measurements and myosin biochemical assays to evaluate the impact of feeding on the cardiomyocyte sarcomere in two experimental paradigms: normal feeding (one meal per month) and frequent feeding (eight meals per month). Myofibril tension and rate of relaxation increased during digestion in both paradigms, while frequent feeding was further associated with slower myofibril activation. To gain potential mechanistic insight, we performed multi-omics analyses. RNA sequencing identified increased relative concentration of some sarcomeric mRNAs during digestion; however, proteomics suggested a delay in sarcomere protein synthesis at the peak of remodeling, as the relative abundance of most sarcomere proteins declined. Analysis of post-translational modifications identified hundreds of sites on sarcomere proteins, including on the tension-regulating proteins titin and myosin. Our results detail the molecular underpinnings of cardiac remodeling in digesting Burmese pythons and suggest the mechanism for rapidly increasing myofibril function is a post-translational program.