IRS1 and obesity due to melanocortin 4 receptor deficiency: By upregulating secreted frizzled-related protein 4 (SFRP4)—an adipokine which increases insulin resistance by decreasing the abundance of insulin receptor substrate 1 (IRS1) and the FOXO1 transcription factor—these two miRNAs can aggravate insulin resistance in the course of human obesity [149,150].