Francisco J Ortega1, Josep M Mercader1, José M Moreno-Navarrete1, Lara Nonell1, Eulàlia Puigdecanet1, José I Rodriquez-Hermosa1, Oscar Rovira1, Gemma Xifra1, Ester Guerra1, María Moreno1, Dolores Mayas1, Natalia Moreno-Castellanos1, José A Fernández-Formoso1, Wifredo Ricart1, Francisco J Tinahones1, David Torrents1, María M Malagón1, José M Fernández-Real1. 1. Department of Diabetes, Endocrinology and Nutrition (F.J.O., J.M.M.-N., O.R., G.X., E.G., M.M., W.R., J.M.R.-R.), Institut d'Investigació Biomédica de Girona, Girona, Spain; CIBER de la Fisiopatología de la Obesidad y la Nutrición and Instituto de Salud Carlos III (F.J.O., J.M.M.-N., O.R., D.M., N.M.-C., J.A.F.-F., W.R., F.J.T., M.M.M., J.M.F.-R.), Spain; Joint BSC-CRG-IRB Program on Computational Biology (J.M.M., D.T.), Barcelona Supercomputing Center, Barcelona, Spain; Servei d'Anàlisi de Microarrays (L.N., E.P.), Institut Hospital del Mar d'Investigacions Mèdiques, Barcelona, Spain; Department of Surgery (J.I.R.-H.), Institut d'Investigació Biomédica de Girona, Girona, Spain; Service of Endocrinology and Nutrition (D.M., F.J.T.), Hospital Clínico Universitario Virgen de Victoria de Malaga, Málaga, Spain; Department of Cell Biology, Physiology and Immunology (N.M.-C., M.M.M.), Instituto Maimonides de Investigaciones Biomedicas de Cordoba/Reina Sofia University Hospital, University of Cordoba, Cordoba, Spain; and Institució Catalana de Recerca i Estudis Avançats (D.T.), Barcelona, Spain.
Abstract
CONTEXT: Molecular mechanisms associated with physiological variations in adipose tissue (AT) are not fully recognized. The most recent reports highlight the critical relevance of microRNAs (miRNAs) found in AT. OBJECTIVE: To identify changes in messenger RNA (mRNA) and miRNA expressions and their interaction in human AT before and after surgery-induced weight loss. Research Design and Setting: Genome-wide mRNA and miRNA expressions were assessed by microarrays in abdominal subcutaneous AT of 16 morbidly obese women before and 2 years after laparoscopic Roux-en-Y gastric bypass. The association of changes in miRNAs with their respective mRNA targets was studied. The results were replicated in publicly available microarray datasets. Validation was made by real-time polymerase chain reaction in additional fat samples from 26 age-matched lean women and in isolated human adipocytes. RESULTS: A total of 5018 different mRNA probe sets and 15 miRNAs were differentially expressed after surgery-induced weight loss. The clustering of similar expression patterns for gene products with related functions revealed molecular footprints that elucidate significant changes in cell cycle, development, lipid metabolism, and the inflammatory response. The participation of inflammation was demonstrated by results assessed in isolated adipocytes. Interestingly, when transcriptomes were analyzed taking into account the presence of miRNA target sites, miRNA target mRNAs were upregulated in obese AT (P value = 2 × 10(-181)) and inflamed adipocytes (P value = 4 × 10(-61)), according to the number of target sites harbored by each transcript. CONCLUSIONS: Current findings suggest impaired miRNA target gene expression in obese AT in close association with inflammation, both improving after weight loss.
CONTEXT: Molecular mechanisms associated with physiological variations in adipose tissue (AT) are not fully recognized. The most recent reports highlight the critical relevance of microRNAs (miRNAs) found in AT. OBJECTIVE: To identify changes in messenger RNA (mRNA) and miRNA expressions and their interaction in human AT before and after surgery-induced weight loss. Research Design and Setting: Genome-wide mRNA and miRNA expressions were assessed by microarrays in abdominal subcutaneous AT of 16 morbidly obesewomen before and 2 years after laparoscopic Roux-en-Y gastric bypass. The association of changes in miRNAs with their respective mRNA targets was studied. The results were replicated in publicly available microarray datasets. Validation was made by real-time polymerase chain reaction in additional fat samples from 26 age-matched lean women and in isolated human adipocytes. RESULTS: A total of 5018 different mRNA probe sets and 15 miRNAs were differentially expressed after surgery-induced weight loss. The clustering of similar expression patterns for gene products with related functions revealed molecular footprints that elucidate significant changes in cell cycle, development, lipid metabolism, and the inflammatory response. The participation of inflammation was demonstrated by results assessed in isolated adipocytes. Interestingly, when transcriptomes were analyzed taking into account the presence of miRNA target sites, miRNA target mRNAs were upregulated in obese AT (P value = 2 × 10(-181)) and inflamed adipocytes (P value = 4 × 10(-61)), according to the number of target sites harbored by each transcript. CONCLUSIONS: Current findings suggest impaired miRNA target gene expression in obese AT in close association with inflammation, both improving after weight loss.
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