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MicroRNA-146b promotes adipogenesis by suppressing the SIRT1-FOXO1 cascade

Sirtuin 1 (SIRT1) plays a critical role in the maintenance of metabolic homeostasis and promotes fat mobilization in white adipose tissue. However, regulation of SIRT1 during adipogenesis, particularly through microRNAs, remains unclear. We observed that miR-146b expression was markedly increased du...

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Autores principales: Ahn, Jiyun, Lee, Hyunjung, Jung, Chang Hwa, Jeon, Tae Il, Ha, Tae Youl
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3799582/
https://www.ncbi.nlm.nih.gov/pubmed/24009212
http://dx.doi.org/10.1002/emmm.201302647
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author Ahn, Jiyun
Lee, Hyunjung
Jung, Chang Hwa
Jeon, Tae Il
Ha, Tae Youl
author_facet Ahn, Jiyun
Lee, Hyunjung
Jung, Chang Hwa
Jeon, Tae Il
Ha, Tae Youl
author_sort Ahn, Jiyun
collection PubMed
description Sirtuin 1 (SIRT1) plays a critical role in the maintenance of metabolic homeostasis and promotes fat mobilization in white adipose tissue. However, regulation of SIRT1 during adipogenesis, particularly through microRNAs, remains unclear. We observed that miR-146b expression was markedly increased during adipogenesis in 3T3-L1 cells. Differentiation of 3T3-L1 was induced by overexpression of miR-146b. Conversely, inhibition of miR-146b decreased adipocyte differentiation. Bioinformatics-based studies suggested that SIRT1 is a target of miR-146b. Further analysis confirmed that SIRT1 was negatively regulated by miR-146b. We also observed that miR-146b bound directly to the 3′-untranslated region of SIRT1 and inhibited adipogenesis through SIRT1 downregulation. The miR-146b/SIRT1 axis mediates adipogenesis through increased acetylation of forkhead box O1 (FOXO1). Expression of miR-146b was increased and SIRT1 mRNA subsequently decreased in the adipose tissues of diet-induced and genetically obese mice. Furthermore, in vivo knockdown of miR-146b by a locked nucleic acid miR-146b antagomir significantly reduced body weight and fat volume in accordance with upregulation of SIRT1 and subsequent acetylation of FOXO1. Therefore, the miR-146b/SIRT1 pathway could be a potential target for obesity prevention and treatment.
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spelling pubmed-37995822013-10-23 MicroRNA-146b promotes adipogenesis by suppressing the SIRT1-FOXO1 cascade Ahn, Jiyun Lee, Hyunjung Jung, Chang Hwa Jeon, Tae Il Ha, Tae Youl EMBO Mol Med Research Articles Sirtuin 1 (SIRT1) plays a critical role in the maintenance of metabolic homeostasis and promotes fat mobilization in white adipose tissue. However, regulation of SIRT1 during adipogenesis, particularly through microRNAs, remains unclear. We observed that miR-146b expression was markedly increased during adipogenesis in 3T3-L1 cells. Differentiation of 3T3-L1 was induced by overexpression of miR-146b. Conversely, inhibition of miR-146b decreased adipocyte differentiation. Bioinformatics-based studies suggested that SIRT1 is a target of miR-146b. Further analysis confirmed that SIRT1 was negatively regulated by miR-146b. We also observed that miR-146b bound directly to the 3′-untranslated region of SIRT1 and inhibited adipogenesis through SIRT1 downregulation. The miR-146b/SIRT1 axis mediates adipogenesis through increased acetylation of forkhead box O1 (FOXO1). Expression of miR-146b was increased and SIRT1 mRNA subsequently decreased in the adipose tissues of diet-induced and genetically obese mice. Furthermore, in vivo knockdown of miR-146b by a locked nucleic acid miR-146b antagomir significantly reduced body weight and fat volume in accordance with upregulation of SIRT1 and subsequent acetylation of FOXO1. Therefore, the miR-146b/SIRT1 pathway could be a potential target for obesity prevention and treatment. Blackwell Publishing Ltd 2013-10 2013-09-06 /pmc/articles/PMC3799582/ /pubmed/24009212 http://dx.doi.org/10.1002/emmm.201302647 Text en © 2013 The Authors. Published by John Wiley and Sons, Ltd on behalf of EMBO http://creativecommons.org/licenses/by/2.5/ Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation.
spellingShingle Research Articles
Ahn, Jiyun
Lee, Hyunjung
Jung, Chang Hwa
Jeon, Tae Il
Ha, Tae Youl
MicroRNA-146b promotes adipogenesis by suppressing the SIRT1-FOXO1 cascade
title MicroRNA-146b promotes adipogenesis by suppressing the SIRT1-FOXO1 cascade
title_full MicroRNA-146b promotes adipogenesis by suppressing the SIRT1-FOXO1 cascade
title_fullStr MicroRNA-146b promotes adipogenesis by suppressing the SIRT1-FOXO1 cascade
title_full_unstemmed MicroRNA-146b promotes adipogenesis by suppressing the SIRT1-FOXO1 cascade
title_short MicroRNA-146b promotes adipogenesis by suppressing the SIRT1-FOXO1 cascade
title_sort microrna-146b promotes adipogenesis by suppressing the sirt1-foxo1 cascade
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3799582/
https://www.ncbi.nlm.nih.gov/pubmed/24009212
http://dx.doi.org/10.1002/emmm.201302647
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