Mutant PNPLA2 and PNPLA8 are causal for neutral lipid storage- or mitochondria-associated cardiomyopathies.66,67 Supplementing palmitate, which compensates for serum deficiency due to FGF21 loss (Fig. 1a), increased HR in both genotypes; however, after 12-h fasting, Fgf21-/- mice showed much less effective recovery during the awakening phase (Fig. 5c, supplementary Fig. 19a), which was consistent with reduced FAO enzymes due to FGF21 deficiency. This evidence concerns the gene PNPLA8 and cardiomyopathy.