MT-ND6 and obesity due to melanocortin 4 receptor deficiency: As a common energy sensor, AMPK has been demonstrated to play a vital role in a range of diseases including obesity and T2DM.[45, 46] Of note, the crosstalk between AMPK and epigenetic events has been uncovered recently.[41, 47] Evidence showed that the activity of DNMT1 might be regulated by AMPK.[41] Here we fill in the gap by showing that free fatty acid could promote DNMT1 mitochondrial translocation via activation of AMPK, thereby induce ND6 hypermethylation, mitochondrial dysfunction and IR.