Activation of NRF2 results in beneficial effects similar to those obtained with dietary MR; NRF2 activators prevent HFD-induced obesity and adiposity46, increased energy expenditure, reduced blood glucose, insulin, and plasma lipid levels47, and reduce liver lipid accumulation in DIO and diabetic mice46,47. Here, NFE2L2 is linked to obesity due to melanocortin 4 receptor deficiency.