MiR-337-3p Promotes Adipocyte Browning by Inhibiting TWIST1

Indira G. C. Vonhoegen; Hamid el Azzouzi; Serve Olieslagers; Aliaksei Vasilevich; Jan de Boer; Francisco J. Tinahones; Paula A. da Costa Martins; Leon J. de Windt; Mora Murri

doi:10.3390/cells9041056

MiR-337-3p Promotes Adipocyte Browning by Inhibiting TWIST1

Indira G. C. Vonhoegen, Hamid el Azzouzi, Serve Olieslagers, Aliaksei Vasilevich, Jan de Boer, Francisco J. Tinahones, Paula A. da Costa Martins, Leon J. de Windt^*, Mora Murri

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

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.

Original language	English
Article number	1056
Number of pages	16
Journal	Cells
Volume	9
Issue number	4
DOIs	https://doi.org/10.3390/cells9041056
Publication status	Published - Apr 2020

Keywords

ADIPOSE-TISSUE
FAT
MITOCHONDRIAL DYSFUNCTION
brown adipose tissue
metabolic syndrome
microRNA
mitochondria
obesity

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Cite this

@article{78d617bb7e864cd68709104c7843897f,

title = "MiR-337-3p Promotes Adipocyte Browning by Inhibiting TWIST1",

abstract = "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.",

keywords = "ADIPOSE-TISSUE, FAT, MITOCHONDRIAL DYSFUNCTION, brown adipose tissue, metabolic syndrome, microRNA, mitochondria, obesity",

author = "Vonhoegen, {Indira G. C.} and {el Azzouzi}, Hamid and Serve Olieslagers and Aliaksei Vasilevich and {de Boer}, Jan and Tinahones, {Francisco J.} and Martins, {Paula A. da Costa} and {de Windt}, {Leon J.} and Mora Murri",

year = "2020",

month = apr,

doi = "10.3390/cells9041056",

language = "English",

volume = "9",

journal = "Cells",

issn = "2073-4409",

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T1 - MiR-337-3p Promotes Adipocyte Browning by Inhibiting TWIST1

AU - Vonhoegen, Indira G. C.

AU - el Azzouzi, Hamid

AU - Olieslagers, Serve

AU - Vasilevich, Aliaksei

AU - de Boer, Jan

AU - Tinahones, Francisco J.

AU - Martins, Paula A. da Costa

AU - de Windt, Leon J.

AU - Murri, Mora

PY - 2020/4

Y1 - 2020/4

N2 - 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.

AB - 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.

KW - ADIPOSE-TISSUE

KW - FAT

KW - MITOCHONDRIAL DYSFUNCTION

KW - brown adipose tissue

KW - metabolic syndrome

KW - microRNA

KW - mitochondria

KW - obesity

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DO - 10.3390/cells9041056

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