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The Fto Gene Regulates the Proliferation and Differentiation of Pre-Adipocytes in Vitro

The highly regulated differentiation and proliferation of pre-adipocytes play a key role in the initiation of obesity. Fat mass and obesity associated (FTO) is a novel gene strongly associated with the risk of obesity. A deficiency of FTO may cause growth retardation in addition to fat mass and adip...

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Autores principales: Jiao, Yang, Zhang, Jingying, Lu, Lunjie, Xu, Jiaying, Qin, Liqiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4772064/
https://www.ncbi.nlm.nih.gov/pubmed/26907332
http://dx.doi.org/10.3390/nu8020102
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author Jiao, Yang
Zhang, Jingying
Lu, Lunjie
Xu, Jiaying
Qin, Liqiang
author_facet Jiao, Yang
Zhang, Jingying
Lu, Lunjie
Xu, Jiaying
Qin, Liqiang
author_sort Jiao, Yang
collection PubMed
description The highly regulated differentiation and proliferation of pre-adipocytes play a key role in the initiation of obesity. Fat mass and obesity associated (FTO) is a novel gene strongly associated with the risk of obesity. A deficiency of FTO may cause growth retardation in addition to fat mass and adipocyte size reduction in vivo. To investigate the potential role of Fto gene on the proliferation and differentiation of pre-adipocytes, we generated Fto-knockdown and overexpressed 3T3-L1 cells. Using numerous proliferation assays our results suggest that Fto knockdown leads to suppression of proliferation, lower mitochondrial membrane potential, less cellular ATP, and decreased and smaller intracellular lipid droplets compared with controls (p < 0.05). Western blot analysis demonstrated that Fto knockdown can significantly suppress peroxisome proliferator-activated receptor gamma (PPARγ) and glucose transporter type 4 (GLUT4) expression and inhibit Akt phosphorylation. By contrast, overexpression of Fto had the opposing effect on proliferation, mitochondrial membrane potential, ATP generation, in vitro differentiation, Akt phosphorylation, and PPARγ and GLUT4 expression. Moreover, we demonstrated that Wortmannin, a phosphoinositide 3-kinase (PI3K) inhibitor, could inhibit phospho-Akt in Fto overexpressed 3T3-L1 cells. Taken together, the results suggest that Fto regulates the proliferation and differentiation of 3T3-L1 cells via multiple mechanisms, including PPARγ and PI3K/Akt signaling.
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spelling pubmed-47720642016-03-08 The Fto Gene Regulates the Proliferation and Differentiation of Pre-Adipocytes in Vitro Jiao, Yang Zhang, Jingying Lu, Lunjie Xu, Jiaying Qin, Liqiang Nutrients Article The highly regulated differentiation and proliferation of pre-adipocytes play a key role in the initiation of obesity. Fat mass and obesity associated (FTO) is a novel gene strongly associated with the risk of obesity. A deficiency of FTO may cause growth retardation in addition to fat mass and adipocyte size reduction in vivo. To investigate the potential role of Fto gene on the proliferation and differentiation of pre-adipocytes, we generated Fto-knockdown and overexpressed 3T3-L1 cells. Using numerous proliferation assays our results suggest that Fto knockdown leads to suppression of proliferation, lower mitochondrial membrane potential, less cellular ATP, and decreased and smaller intracellular lipid droplets compared with controls (p < 0.05). Western blot analysis demonstrated that Fto knockdown can significantly suppress peroxisome proliferator-activated receptor gamma (PPARγ) and glucose transporter type 4 (GLUT4) expression and inhibit Akt phosphorylation. By contrast, overexpression of Fto had the opposing effect on proliferation, mitochondrial membrane potential, ATP generation, in vitro differentiation, Akt phosphorylation, and PPARγ and GLUT4 expression. Moreover, we demonstrated that Wortmannin, a phosphoinositide 3-kinase (PI3K) inhibitor, could inhibit phospho-Akt in Fto overexpressed 3T3-L1 cells. Taken together, the results suggest that Fto regulates the proliferation and differentiation of 3T3-L1 cells via multiple mechanisms, including PPARγ and PI3K/Akt signaling. MDPI 2016-02-19 /pmc/articles/PMC4772064/ /pubmed/26907332 http://dx.doi.org/10.3390/nu8020102 Text en © 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons by Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Jiao, Yang
Zhang, Jingying
Lu, Lunjie
Xu, Jiaying
Qin, Liqiang
The Fto Gene Regulates the Proliferation and Differentiation of Pre-Adipocytes in Vitro
title The Fto Gene Regulates the Proliferation and Differentiation of Pre-Adipocytes in Vitro
title_full The Fto Gene Regulates the Proliferation and Differentiation of Pre-Adipocytes in Vitro
title_fullStr The Fto Gene Regulates the Proliferation and Differentiation of Pre-Adipocytes in Vitro
title_full_unstemmed The Fto Gene Regulates the Proliferation and Differentiation of Pre-Adipocytes in Vitro
title_short The Fto Gene Regulates the Proliferation and Differentiation of Pre-Adipocytes in Vitro
title_sort fto gene regulates the proliferation and differentiation of pre-adipocytes in vitro
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4772064/
https://www.ncbi.nlm.nih.gov/pubmed/26907332
http://dx.doi.org/10.3390/nu8020102
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