Our previous and other studies have revealed that activation of the HSF1/PGC-1α axis could enhance mitochondrial homeostasis and adaptive oxidation as well as induce a thermogenic program in adipose tissues, leading to ameliorations of metabolic disorders, including obesity and metabolic associated fatty liver disease (MAFLD) (Ma et al., 2015; Li et al., 2022a; Rao et al., 2022). The gene discussed is PPARGC1A; the disease is obesity due to melanocortin 4 receptor deficiency.