Although SFA has been shown to downregulate the expressions of INSR and IRS-1 via multiple mechanisms, this study demonstrates that SFA-inducible miR-183-5p contributes to IRS-1 reduction in hepatocytes and suggests that induction of miR-183-5p contributes toward hepatic insulin resistance in a background of obesity. Here, INSR is linked to obesity due to melanocortin 4 receptor deficiency.