MicroRNA-22 Is a Key Regulator of Lipid and Metabolic Homeostasis.
Riccardo PanellaAndreas PetriBhavna N DesaiSharmila FagooneeCody A CottonPiercen K NguyenEric M LundinAlexandre WagshalDa-Zhi WangAnders M NäärIoannis S VlachosEleftheria Maratos-FlierFiorella AltrudaSakari KauppinenPier Paolo PandolfiPublished in: International journal of molecular sciences (2023)
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.
Keyphrases
- cell proliferation
- type diabetes
- high fat diet induced
- insulin resistance
- long non coding rna
- weight loss
- long noncoding rna
- metabolic syndrome
- cardiovascular disease
- public health
- adipose tissue
- weight gain
- mouse model
- transcription factor
- glycemic control
- skeletal muscle
- gene expression
- coronary artery disease
- genome wide
- squamous cell carcinoma
- copy number
- body mass index
- young adults
- papillary thyroid
- atrial fibrillation
- radiofrequency ablation
- smoking cessation
- lymph node metastasis
- liver fibrosis
- childhood cancer