Surgery-Induced Weight Loss Is Associated With the Downregulation of Genes Targeted by MicroRNAs in Adipose Tissue
Francisco J. Ortega, Josep M. Mercader, José M. Moreno-Navarrete, Lara Nonell, Eulàlia Puigdecanet, José I. Rodriquez-Hermosa, Oscar Rovira, Gemma Xifra, Ester Guerra, María Moreno, Dolores Mayas, Natalia Moreno-Castellanos
(+6 others)
2015
Journal of Clinical Endocrinology and Metabolism
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
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... 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 ϭ 2 ϫ 10 Ϫ181 ) and inflamed adipocytes (P value ϭ 4 ϫ 10 Ϫ61 ), 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. (J Clin Endocrinol Metab 100: A dipose tissue (AT) is a critical player in systemic inflammation and insulin resistance through the secretion of hormones, adipocytokines (1), fatty acids (2), and (potentially) noncoding RNAs (3) that modulate insulin signaling in AT itself, liver, skeletal muscle, and the vasculature. Deregulated AT expression and secretion participate in systemic insulin resistance and the inflammatory and atherogenic state that contributes to (or even accounts for) in-creased risk of diseases in obesity (4). Molecular changes in adipocytes and increased infiltration and activation of nonfat immune cells such as macrophages (5) and lymphocytes (6) are believed to promote local inflammation and the subsequent deleterious consequences. MicroRNAs (miRNAs) are small noncoding RNAs that modulate gene expression by binding complementary regions in coding messenger RNAs (mRNAs), leading to b Results assessed in controls versus severe obese women (baseline) were compared by Student t test.
doi:10.1210/jc.2015-2357
pmid:26252355
fatcat:qgkuxemwjjfcriyj5drozmz7fy
