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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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2016
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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. |
format | Online Article Text |
id | pubmed-4772064 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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