Figure 8. The proposed model for the metabolic regulation of miR-181a-SIRT1.

Excess NEFA in the liver increases miR-181a expression, which in turn decreases SIRT1 expression and activity via translation inhibition, resulting in reduced lipidolysis, impaired insulin sensitivity, and increased gluconeogenesis and lipid synthesis. Therefore, inhibiting miR-181a or increasing SIRT1 expression and activity may contribute to reductions in metabolic dysfunction in dairy cows or patients with NAFLD.