However, by contrast, although skeletal muscle-specific Fundc1 KO mice also show accumulation of damaged mitochondria and increased levels of reactive oxygen species in skeletal muscle as whole-body and adipose tissue-specific Fundc1 KO mice (Fu et al., 2018), they have ameliorated insulin resistance, hepatic steatosis and obesity in response to high-fat diet challenge, due to enhanced secretion of FGF21 from muscle, a stress-induced metabolically beneficial myokine (muscle-secreted hormone). This evidence concerns the gene FUNDC1 and obesity due to melanocortin 4 receptor deficiency.