INS and obesity due to melanocortin 4 receptor deficiency: Overall, we demonstrate a potential causal link from adipose tissue mitochondrial metabolism to DNA methylation and expression of SH3BP4. In addition, this connection holds significance in obesity, where certain outcomes related to insulin sensitivity and intra-abdominal fat were seen to contribute to SH3BP4 methylation, influenced either by mtDNAq or through alternative pathways.