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Gene expression profiling of subcutaneous adipose tissue in morbid obesity using a focused microarray: Distinct expression of cell-cycle- and differentiation-related genes

BACKGROUND: Obesity results from an imbalance between food intake and energy expenditure, which leads to an excess of adipose tissue. The excess of adipose tissue and adipocyte dysfunction associated with obesity are linked to the abnormal regulation of adipogenesis. The objective of this study was...

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Autores principales: Rodríguez-Acebes, Sara, Palacios, Nuria, Botella-Carretero, José I, Olea, Nuria, Crespo, Lorena, Peromingo, Roberto, Gómez-Coronado, Diego, Lasunción, Miguel A, Vázquez, Clotilde, Martínez-Botas, Javier
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3022546/
https://www.ncbi.nlm.nih.gov/pubmed/21182758
http://dx.doi.org/10.1186/1755-8794-3-61
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author Rodríguez-Acebes, Sara
Palacios, Nuria
Botella-Carretero, José I
Olea, Nuria
Crespo, Lorena
Peromingo, Roberto
Gómez-Coronado, Diego
Lasunción, Miguel A
Vázquez, Clotilde
Martínez-Botas, Javier
author_facet Rodríguez-Acebes, Sara
Palacios, Nuria
Botella-Carretero, José I
Olea, Nuria
Crespo, Lorena
Peromingo, Roberto
Gómez-Coronado, Diego
Lasunción, Miguel A
Vázquez, Clotilde
Martínez-Botas, Javier
author_sort Rodríguez-Acebes, Sara
collection PubMed
description BACKGROUND: Obesity results from an imbalance between food intake and energy expenditure, which leads to an excess of adipose tissue. The excess of adipose tissue and adipocyte dysfunction associated with obesity are linked to the abnormal regulation of adipogenesis. The objective of this study was to analyze the expression profile of cell-cycle- and lipid-metabolism-related genes of adipose tissue in morbid obesity. METHODS: We used a custom-made focused cDNA microarray to determine the adipose tissue mRNA expression profile. Gene expression of subcutaneous abdominal fat samples from 15 morbidly obese women was compared with subcutaneous fat samples from 10 nonobese control patients. The findings were validated in an independent population of 31 obese women and 9 obese men and in an animal model of obesity (Lep(ob/ob )mice) by real-time RT-PCR. RESULTS: Microarray analysis revealed that transcription factors that regulate the first stages of adipocyte differentiation, such as CCAAT/enhancer binding protein beta (C/EBPβ) and JUN, were upregulated in the adipose tissues of morbidly obese patients. The expression of peroxisome proliferator-activated receptor gamma (PPARγ), a transcription factor which controls lipid metabolism and the final steps of preadipocyte conversion into mature adipocytes, was downregulated. The expression of three cyclin-dependent kinase inhibitors that regulate clonal expansion and postmitotic growth arrest during adipocyte differentiation was also altered in obese subjects: p18 and p27 were downregulated, and p21 was upregulated. Angiopoietin-like 4 (ANGPTL4), which regulates angiogenesis, lipid and glucose metabolism and it is know to increase dramatically in the early stages of adipocyte differentiation, was upregulated. The expression of C/EBPβ, p18, p21, JUN, and ANGPTL4 presented similar alterations in subcutaneous adipose tissue of Lep(ob/ob )mice. CONCLUSIONS: Our microarray gene profiling study revealed that the expression of genes involved in adipogenesis is profoundly altered in the subcutaneous adipose tissue of morbidly obese subjects. This expression pattern is consistent with an immature adipocyte phenotype that could reflect the expansion of the adipose tissue during obesity.
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spelling pubmed-30225462011-01-19 Gene expression profiling of subcutaneous adipose tissue in morbid obesity using a focused microarray: Distinct expression of cell-cycle- and differentiation-related genes Rodríguez-Acebes, Sara Palacios, Nuria Botella-Carretero, José I Olea, Nuria Crespo, Lorena Peromingo, Roberto Gómez-Coronado, Diego Lasunción, Miguel A Vázquez, Clotilde Martínez-Botas, Javier BMC Med Genomics Research Article BACKGROUND: Obesity results from an imbalance between food intake and energy expenditure, which leads to an excess of adipose tissue. The excess of adipose tissue and adipocyte dysfunction associated with obesity are linked to the abnormal regulation of adipogenesis. The objective of this study was to analyze the expression profile of cell-cycle- and lipid-metabolism-related genes of adipose tissue in morbid obesity. METHODS: We used a custom-made focused cDNA microarray to determine the adipose tissue mRNA expression profile. Gene expression of subcutaneous abdominal fat samples from 15 morbidly obese women was compared with subcutaneous fat samples from 10 nonobese control patients. The findings were validated in an independent population of 31 obese women and 9 obese men and in an animal model of obesity (Lep(ob/ob )mice) by real-time RT-PCR. RESULTS: Microarray analysis revealed that transcription factors that regulate the first stages of adipocyte differentiation, such as CCAAT/enhancer binding protein beta (C/EBPβ) and JUN, were upregulated in the adipose tissues of morbidly obese patients. The expression of peroxisome proliferator-activated receptor gamma (PPARγ), a transcription factor which controls lipid metabolism and the final steps of preadipocyte conversion into mature adipocytes, was downregulated. The expression of three cyclin-dependent kinase inhibitors that regulate clonal expansion and postmitotic growth arrest during adipocyte differentiation was also altered in obese subjects: p18 and p27 were downregulated, and p21 was upregulated. Angiopoietin-like 4 (ANGPTL4), which regulates angiogenesis, lipid and glucose metabolism and it is know to increase dramatically in the early stages of adipocyte differentiation, was upregulated. The expression of C/EBPβ, p18, p21, JUN, and ANGPTL4 presented similar alterations in subcutaneous adipose tissue of Lep(ob/ob )mice. CONCLUSIONS: Our microarray gene profiling study revealed that the expression of genes involved in adipogenesis is profoundly altered in the subcutaneous adipose tissue of morbidly obese subjects. This expression pattern is consistent with an immature adipocyte phenotype that could reflect the expansion of the adipose tissue during obesity. BioMed Central 2010-12-23 /pmc/articles/PMC3022546/ /pubmed/21182758 http://dx.doi.org/10.1186/1755-8794-3-61 Text en Copyright ©2010 Rodríguez-Acebes et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (<url>http://creativecommons.org/licenses/by/2.0</url>), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Rodríguez-Acebes, Sara
Palacios, Nuria
Botella-Carretero, José I
Olea, Nuria
Crespo, Lorena
Peromingo, Roberto
Gómez-Coronado, Diego
Lasunción, Miguel A
Vázquez, Clotilde
Martínez-Botas, Javier
Gene expression profiling of subcutaneous adipose tissue in morbid obesity using a focused microarray: Distinct expression of cell-cycle- and differentiation-related genes
title Gene expression profiling of subcutaneous adipose tissue in morbid obesity using a focused microarray: Distinct expression of cell-cycle- and differentiation-related genes
title_full Gene expression profiling of subcutaneous adipose tissue in morbid obesity using a focused microarray: Distinct expression of cell-cycle- and differentiation-related genes
title_fullStr Gene expression profiling of subcutaneous adipose tissue in morbid obesity using a focused microarray: Distinct expression of cell-cycle- and differentiation-related genes
title_full_unstemmed Gene expression profiling of subcutaneous adipose tissue in morbid obesity using a focused microarray: Distinct expression of cell-cycle- and differentiation-related genes
title_short Gene expression profiling of subcutaneous adipose tissue in morbid obesity using a focused microarray: Distinct expression of cell-cycle- and differentiation-related genes
title_sort gene expression profiling of subcutaneous adipose tissue in morbid obesity using a focused microarray: distinct expression of cell-cycle- and differentiation-related genes
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3022546/
https://www.ncbi.nlm.nih.gov/pubmed/21182758
http://dx.doi.org/10.1186/1755-8794-3-61
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