(3) Environmental factors play an important role in the development of disease caused by genetic variants (Hazebroek et al., 2015; Thomas, 2004), and studies have reported that young Prdm16 cKO mice exhibit normal cardiac function, but metabolic stress interventions induce heart failure and cardiac hypertrophy (Cibi et al., 2020). Here, PRDM16 is linked to heart failure.