To better clarify the direct role of IRF1 in HP-induced alterations, we fed IRF1 knockout (IRF1−/−) mice with HPD for 12 weeks and found that HPD-induced cardiac hypertrophy, HF, downregulated PGC1α expression and energy metabolism remodeling were significantly attenuated in IRF1−/− mice (Supplementary Fig. 14A–J). The gene discussed is PPARGC1A; the disease is cardiac hypertrophy.