MicroRNA-22 Is a Key Regulator of Lipid and Metabolic Homeostasis
Riccardo Panella, Andreas Petri, Bhavna N. Desai, Sharmila Fagoonee, Cody A. Cotton, Piercen K. Nguyen, Eric M. Lundin, Alexandre Wagshal, Da‐Zhi Wang, Anders M. Näär, Ioannis S. Vlachos, Eleftheria Maratos–Flier, Fiorella Altruda, Sakari Kauppinen, Pier Paolo Pandolfi
Abstract
Obesity is a growing public health problem associated with increased risk of type 2 diabetes, cardiovascular disease, nonalcoholic fatty liver disease (NAFLD) and cancer. Here, we identify microRNA-22 (miR-22) as an essential rheostat involved in the control of lipid and energy homeostasis as well as the onset and maintenance of obesity. We demonstrate through knockout and transgenic mouse models that miR-22 loss-of-function protects against obesity and hepatic steatosis, while its overexpression promotes both phenotypes even when mice are fed a regular chow diet. Mechanistically, we show that miR-22 controls multiple pathways related to lipid biogenesis and differentiation. Importantly, genetic ablation of miR-22 favors metabolic rewiring towards higher energy expenditure and browning of white adipose tissue, suggesting that modulation of miR-22 could represent a viable therapeutic strategy for treatment of obesity and other metabolic disorders.