This systematic review aims to summarize and reassess the data from past studies, investigate the changes in adipose tissue DNA methylation in obesity and IR, and assess whether adipose tissue DNA methylation can be used as a risk factor, possible biomarker, or prognostic marker for obesity and insulin, and to provide new ideas for revealing the underlying mechanisms of obesity and IR and for treatment and prevention. Here, INS is linked to obesity due to melanocortin 4 receptor deficiency.