Abstract
The obesity-associated inflammation of white adipose tissue (WAT) is one of the factors leading to the development of related diseases such as insulin resistance and liver steatosis. Recently, microRNAs (miRNAs) were identified as important regulators of WAT functions. Herein, we cultured human Simpson-Golabi-Behmel syndrome (SGBS) adipocytes with macrophage-conditioned medium (MacCM) and performed an Affimetrix miRNA array to identify miRNAs differentially expressed under inflammatory conditions. We identified 24 miRNAs differentially expressed upon inflammation in human adipocytes and miR-146a was the most up-regulated miRNA species. In subcutaneous WAT, miR-146a was elevated in both human and murine obesity. Transfection of miR-146a mimics prevented the MacCM-induced inflammatory response in SGBS adipocytes as seen by reduced levels of IL-8 and MCP-1 mRNA and protein. We identified IRAK1 and TRAF6 as targets of miR-146a in human adipocytes and detected a reduced inflammation-induced activation of JNK and p38 upon miR-146a transfection. Taken together, we could show that miR-146a reduces the inflammatory response in human adipocytes. In a negative feedback loop miR-146a might contribute to the regulation of inflammatory processes in WAT and possibly prevent an overwhelming inflammatory response.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adipocytes, White / drug effects
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Adipocytes, White / metabolism*
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Adipocytes, White / pathology
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Adipose Tissue, White / drug effects
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Adipose Tissue, White / metabolism
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Adipose Tissue, White / pathology
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Arrhythmias, Cardiac / genetics*
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Arrhythmias, Cardiac / metabolism
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Arrhythmias, Cardiac / pathology
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Chemokine CCL2 / genetics
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Chemokine CCL2 / metabolism
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Culture Media, Conditioned / pharmacology
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Feedback, Physiological
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Female
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Gene Expression Regulation
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Genetic Diseases, X-Linked / genetics*
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Genetic Diseases, X-Linked / metabolism
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Genetic Diseases, X-Linked / pathology
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Gigantism / genetics*
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Gigantism / metabolism
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Gigantism / pathology
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Heart Defects, Congenital / genetics*
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Heart Defects, Congenital / metabolism
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Heart Defects, Congenital / pathology
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Humans
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Inflammation
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Intellectual Disability / genetics*
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Intellectual Disability / metabolism
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Intellectual Disability / pathology
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Interleukin-1 Receptor-Associated Kinases / genetics*
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Interleukin-1 Receptor-Associated Kinases / metabolism
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Interleukin-8 / genetics
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Interleukin-8 / metabolism
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Intracellular Signaling Peptides and Proteins
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MAP Kinase Kinase 4 / genetics
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MAP Kinase Kinase 4 / metabolism
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Macrophages / cytology
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Macrophages / metabolism
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MicroRNAs / agonists
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MicroRNAs / antagonists & inhibitors
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MicroRNAs / genetics*
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MicroRNAs / metabolism
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Molecular Mimicry
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Oligonucleotide Array Sequence Analysis
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Oligoribonucleotides / genetics
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Oligoribonucleotides / metabolism
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Primary Cell Culture
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RNA, Small Interfering / genetics
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RNA, Small Interfering / metabolism
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Signal Transduction
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TNF Receptor-Associated Factor 6 / genetics*
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TNF Receptor-Associated Factor 6 / metabolism
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Transfection
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p38 Mitogen-Activated Protein Kinases / genetics
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p38 Mitogen-Activated Protein Kinases / metabolism
Substances
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CCL2 protein, human
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Chemokine CCL2
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Culture Media, Conditioned
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Interleukin-8
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Intracellular Signaling Peptides and Proteins
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MIRN146 microRNA, human
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MicroRNAs
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Oligoribonucleotides
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RNA, Small Interfering
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TNF Receptor-Associated Factor 6
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Tifab protein, human
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IRAK1 protein, human
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Interleukin-1 Receptor-Associated Kinases
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p38 Mitogen-Activated Protein Kinases
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MAP Kinase Kinase 4
Supplementary concepts
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Simpson-Golabi-Behmel syndrome