MiR-337-3p Promotes Adipocyte Browning by Inhibiting TWIST1.
Indira G C VonhögenHamid El AzzouziServé OlieslagersAliaksei VasilevichJan de BoerFrancisco J TinahonesPaula A da Costa MartinsLeon J De WindtMora MurriPublished in: Cells (2020)
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.
Keyphrases
- adipose tissue
- insulin resistance
- epithelial mesenchymal transition
- poor prognosis
- metabolic syndrome
- high fat diet induced
- long non coding rna
- cell proliferation
- high fat diet
- type diabetes
- binding protein
- signaling pathway
- weight gain
- weight loss
- public health
- transcription factor
- oxidative stress
- skeletal muscle
- fatty acid
- long noncoding rna
- risk assessment
- body mass index
- uric acid
- single molecule
- high throughput
- cardiovascular risk factors