In summary, we propose for the first time a new working model showing that transcription factors, such as STAT3, NFκB and EGR1, increase transcript levels of various miRNAs that are unique to the four HRDs (atherosclerosis, NAFLD, obesity, and T2DM/IR) as well as shared among the HRDs. The gene discussed is STAT3; the disease is obesity due to melanocortin 4 receptor deficiency.