While previous reports implicate a molecular mechanism involving KLFs and NRs in the context of, but not limited to, neuronal differentiation and ischemic stroke [44, 45], smooth muscle biology [46], prenatal lung differentiation [47, 48], hepatic steatosis [49], endometriosis [50], and browning of adipocytes [51], this report is the first demonstration that KLFs and NRs, in general, and KLF15 and PPARα, in particular, coordinate metabolic gene expression and function in the cardiomyocyte. Here, KLF15 is linked to ischemic stroke.