Essential role for miR-196a in brown adipogenesis of white fat progenitor cells.

The recent discovery of functional brown adipocytes in adult humans illuminates the potential of these cells in the treatment of obesity and its associated diseases. In rodents, brown adipocyte-like cells are known to be recruited in white adipose tissue (WAT) by cold exposure or β-adrenergic stimul...

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Autores principales:	Masaki Mori, Hironori Nakagami, Gerardo Rodriguez-Araujo, Keisuke Nimura, Yasufumi Kaneda
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/bf29b6e65eca486791145d8e6965bb7c
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spelling	oai:doaj.org-article:bf29b6e65eca486791145d8e6965bb7c2021-11-18T05:36:40ZEssential role for miR-196a in brown adipogenesis of white fat progenitor cells.1544-91731545-788510.1371/journal.pbio.1001314https://doaj.org/article/bf29b6e65eca486791145d8e6965bb7c2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22545021/?tool=EBIhttps://doaj.org/toc/1544-9173https://doaj.org/toc/1545-7885The recent discovery of functional brown adipocytes in adult humans illuminates the potential of these cells in the treatment of obesity and its associated diseases. In rodents, brown adipocyte-like cells are known to be recruited in white adipose tissue (WAT) by cold exposure or β-adrenergic stimulation, but the molecular machinery underlying this phenomenon is not fully understood. Here, we show that inducible brown adipogenesis is mediated by the microRNA miR-196a. We found that miR-196a suppresses the expression of the white-fat gene Hoxc8 post-transcriptionally during the brown adipogenesis of white fat progenitor cells. In mice, miR-196a is induced in the WAT-progenitor cells after cold exposure or β-adrenergic stimulation. The fat-specific forced expression of miR-196a in mice induces the recruitment of brown adipocyte-like cells in WAT. The miR-196a transgenic mice exhibit enhanced energy expenditure and resistance to obesity, indicating the induced brown adipocyte-like cells are metabolically functional. Mechanistically, Hoxc8 targets and represses C/EBPβ, a master switch of brown-fat gene program, in cooperation with histone deacetylase 3 (HDAC3) through the C/EBPβ 3' regulatory sequence. Thus, miR-196a induces functional brown adipocytes in WAT through the suppression of Hoxc8, which functions as a gatekeeper of the inducible brown adipogenesis. The miR-196a-Hoxc8-C/EBPβ signaling pathway may be a therapeutic target for inducing brown adipogenesis to combat obesity and type 2 diabetes.Masaki MoriHironori NakagamiGerardo Rodriguez-AraujoKeisuke NimuraYasufumi KanedaPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Biology, Vol 10, Iss 4, p e1001314 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Masaki Mori Hironori Nakagami Gerardo Rodriguez-Araujo Keisuke Nimura Yasufumi Kaneda Essential role for miR-196a in brown adipogenesis of white fat progenitor cells.
description	The recent discovery of functional brown adipocytes in adult humans illuminates the potential of these cells in the treatment of obesity and its associated diseases. In rodents, brown adipocyte-like cells are known to be recruited in white adipose tissue (WAT) by cold exposure or β-adrenergic stimulation, but the molecular machinery underlying this phenomenon is not fully understood. Here, we show that inducible brown adipogenesis is mediated by the microRNA miR-196a. We found that miR-196a suppresses the expression of the white-fat gene Hoxc8 post-transcriptionally during the brown adipogenesis of white fat progenitor cells. In mice, miR-196a is induced in the WAT-progenitor cells after cold exposure or β-adrenergic stimulation. The fat-specific forced expression of miR-196a in mice induces the recruitment of brown adipocyte-like cells in WAT. The miR-196a transgenic mice exhibit enhanced energy expenditure and resistance to obesity, indicating the induced brown adipocyte-like cells are metabolically functional. Mechanistically, Hoxc8 targets and represses C/EBPβ, a master switch of brown-fat gene program, in cooperation with histone deacetylase 3 (HDAC3) through the C/EBPβ 3' regulatory sequence. Thus, miR-196a induces functional brown adipocytes in WAT through the suppression of Hoxc8, which functions as a gatekeeper of the inducible brown adipogenesis. The miR-196a-Hoxc8-C/EBPβ signaling pathway may be a therapeutic target for inducing brown adipogenesis to combat obesity and type 2 diabetes.
format	article
author	Masaki Mori Hironori Nakagami Gerardo Rodriguez-Araujo Keisuke Nimura Yasufumi Kaneda
author_facet	Masaki Mori Hironori Nakagami Gerardo Rodriguez-Araujo Keisuke Nimura Yasufumi Kaneda
author_sort	Masaki Mori
title	Essential role for miR-196a in brown adipogenesis of white fat progenitor cells.
title_short	Essential role for miR-196a in brown adipogenesis of white fat progenitor cells.
title_full	Essential role for miR-196a in brown adipogenesis of white fat progenitor cells.
title_fullStr	Essential role for miR-196a in brown adipogenesis of white fat progenitor cells.
title_full_unstemmed	Essential role for miR-196a in brown adipogenesis of white fat progenitor cells.
title_sort	essential role for mir-196a in brown adipogenesis of white fat progenitor cells.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/bf29b6e65eca486791145d8e6965bb7c
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Essential role for miR-196a in brown adipogenesis of white fat progenitor cells.

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