MiR-337-3p Promotes Adipocyte Browning by Inhibiting TWIST1
Indira G.C. Vonhögen,
Hamid el Azzouzi,
Servé Olieslagers,
Aliaksei Vasilevich,
Jan de Boer,
Francisco J. Tinahones,
Paula A. da Costa Martins,
Leon J. de Windt,
Mora Murri
Affiliations
Indira G.C. Vonhögen
Department of Molecular Genetics, Faculty of Sciences and Engineering, CARIM School for Cardiovascular Diseases, Faculty of Health, Medicine and Life Sciences, Maastricht University, 6200 MD Maastricht, The Netherlands
Hamid el Azzouzi
Department of Molecular Genetics, Faculty of Sciences and Engineering, CARIM School for Cardiovascular Diseases, Faculty of Health, Medicine and Life Sciences, Maastricht University, 6200 MD Maastricht, The Netherlands
Servé Olieslagers
Department of Molecular Genetics, Faculty of Sciences and Engineering, CARIM School for Cardiovascular Diseases, Faculty of Health, Medicine and Life Sciences, Maastricht University, 6200 MD Maastricht, The Netherlands
Aliaksei Vasilevich
BioInterface Science Group, Department of Biomedical Engineering and Institute for Complex Molecular Systems, Eindhoven University of Technology, 5600 MB Eindhoven, The Netherlands
Jan de Boer
BioInterface Science Group, Department of Biomedical Engineering and Institute for Complex Molecular Systems, Eindhoven University of Technology, 5600 MB Eindhoven, The Netherlands
Francisco J. Tinahones
Unidad de Gestión Clínica de Endocrinología y Nutrición, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Clínico Virgen de la Victoria, 29010 Málaga, Spain
Paula A. da Costa Martins
Department of Molecular Genetics, Faculty of Sciences and Engineering, CARIM School for Cardiovascular Diseases, Faculty of Health, Medicine and Life Sciences, Maastricht University, 6200 MD Maastricht, The Netherlands
Leon J. de Windt
Department of Molecular Genetics, Faculty of Sciences and Engineering, CARIM School for Cardiovascular Diseases, Faculty of Health, Medicine and Life Sciences, Maastricht University, 6200 MD Maastricht, The Netherlands
Mora Murri
Unidad de Gestión Clínica de Endocrinología y Nutrición, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Clínico Virgen de la Victoria, 29010 Málaga, Spain
The prevalence of metabolic syndrome (MetS) and obesity is an alarming health issue worldwide. Obesity is characterized by an excessive accumulation of white adipose tissue (WAT), and it is associated with diminished brown adipose tissue (BAT) activity. Twist1 acts as a negative feedback regulator of BAT metabolism. Therefore, targeting Twist1 could become a strategy for obesity and metabolic disease. Here, we have identified miR-337-3p as an upstream regulator of Twist1. Increased miR-337-3p expression paralleled decreased expression of TWIST1 in BAT compared to WAT. Overexpression of miR-337-3p in brown pre-adipocytes provoked a reduction in Twist1 expression that was accompanied by increased expression of brown/mitochondrial markers. Luciferase assays confirmed an interaction between the miR-337 seed sequence and Twist1 3′UTR. The inverse relationship between the expression of TWIST1 and miR-337 was finally validated in adipose tissue samples from non-MetS and MetS subjects that demonstrated a dysregulation of the miR-337-Twist1 molecular axis in MetS. The present study demonstrates that adipocyte miR-337-3p suppresses Twist1 repression and enhances the browning of adipocytes.
