In general, chronic lipid overload, such as HFD feeding, elicits lipid redistribution between adipose tissue and liver, resulting in a similar metabolic phenotype in both organs through lipid homeostasis; however, the contrasting effects (protective or non-protective) of Redd1 deficiency on metabolic dysregulation i.e., obesity in an HFD-fed mouse model could arise from complex interactions among genetic background, nutrient composition, and environmental stress44–47. The gene discussed is DDIT4; the disease is obesity due to melanocortin 4 receptor deficiency.