The expressions of nuclear receptor subfamily 1 group D member 1 (NR1D1) and UNC-51-like kinase 1 (ULK1) are significantly reduced in an in vitro obesity model established using mouse preadipocyte (3T3-L1) differentiation, and increased NR1D1 could rapidly bind to the ULK1 promoter, thus significantly up-regulating the expression of ULK1, Parkin and PINK1 and down-regulating that of TOM20, increasing mitophagy levels, enhancing 3T3-L1 cell viability and triglyceride (TG) content, reducing lipid droplet production, and attenuating obesity. This evidence concerns the gene NR1D1 and obesity due to melanocortin 4 receptor deficiency.