The discoveries that miR-182–5 p is associated with T2D and NAFLD via LRP6 downregulation in liver of obese subjects and the reversibility by weight loss in DIO mice offer unique mechanistic insight into diabetes pathology and point towards promising future anti-diabetic strategies, built either on antagonizing miR-182–5 p activity or reducing hepatic miR-182–5 p expression by pharmacological or dietary means. Here, LRP6 is linked to metabolic dysfunction-associated steatotic liver disease.