NEGR1 and obesity due to melanocortin 4 receptor deficiency: Previous studies have shown that metabolic stress, such as high glucose-induced reactive oxygen species (ROS), can trigger a compensatory increase in mtDNA-encoded electron transport subunit expression.78 Since NEGR1 deficiency is associated with obesity and Type II diabetes,79 metabolic stress may similarly influence mitochondrial genome-encoded gene expression in Negr1 KO mice.