PMID- 32437400 OWN - NLM STAT- MEDLINE DCOM- 20200812 LR - 20200812 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 15 IP - 5 DP - 2020 TI - Interferon regulatory factor 7 mediates obesity-associated MCP-1 transcription. PG - e0233390 LID - 10.1371/journal.pone.0233390 [doi] LID - e0233390 AB - Hypertrophy, associated with adipocyte dysfunction, causes increased pro-inflammatory adipokine, and abnormal glucose and lipid metabolism, leading to insulin resistance and obesity-related-health problems. By combining DNA microarray and genomic data analyses to predict DNA binding motifs, we identified the transcription factor Interferon Regulatory Factor 7 (IRF7) as a possible regulator of genes related to adipocyte hypertrophy. To investigate the role of IRF7 in adipocytes, we examined gene expression patterns in 3T3-L1 cells infected with a retrovirus carrying the IRF7 gene and found that enforced IRF7 expression induced the expression of monocyte chemoattractant protein-1 (MCP-1), a key initial adipokine in the chronic inflammation of obesity. CRISPR/Cas9 mediated-suppression of IRF7 significantly reduced MCP-1 mRNA. Luciferase assays, chromatin immunoprecipitation PCR analysis and gel shift assay showed that IRF7 transactivates the MCP-1 gene by binding to its proximal Interferon Stimulation Response Element (ISRE), a putative IRF7 binding motif. IRF7 knockout mice exhibited lower expression of MCP-1 in epidydimal white adipose tissue under high-fat feeding conditions, suggesting the transcription factor is physiologically important for inducing MCP-1. Taken together, our results suggest that IRF7 transactivates MCP-1 mRNA in adipocytes, and it may be involved in the adipose tissue inflammation associated with obesity. FAU - Kuroda, Masashi AU - Kuroda M AD - Department of Nutrition and Metabolism, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima-city, Tokushima, Japan. FAU - Nishiguchi, Misa AU - Nishiguchi M AD - Department of Nutrition and Metabolism, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima-city, Tokushima, Japan. FAU - Ugawa, Naho AU - Ugawa N AD - Department of Nutrition and Metabolism, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima-city, Tokushima, Japan. FAU - Ishikawa, Etsuko AU - Ishikawa E AD - Department of Nutrition and Metabolism, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima-city, Tokushima, Japan. FAU - Kawabata, Yasuyo AU - Kawabata Y AD - Department of Nutrition and Metabolism, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima-city, Tokushima, Japan. FAU - Okamoto, Saya AU - Okamoto S AD - Department of Nutrition and Metabolism, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima-city, Tokushima, Japan. FAU - Sasaki, Waka AU - Sasaki W AD - Department of Nutrition and Metabolism, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima-city, Tokushima, Japan. FAU - Miyatake, Yumiko AU - Miyatake Y AD - Department of Nutrition and Metabolism, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima-city, Tokushima, Japan. FAU - Sebe, Mayu AU - Sebe M AD - Department of Nutrition and Metabolism, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima-city, Tokushima, Japan. FAU - Masumoto, Saeko AU - Masumoto S AD - Faculty of Food and Agricultural Sciences, Fukushima University, Fukushima-city, Fukushima, Japan. FAU - Tsutsumi, Rie AU - Tsutsumi R AD - Department of Nutrition and Metabolism, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima-city, Tokushima, Japan. FAU - Harada, Nagakatsu AU - Harada N AD - Department of Health and Nutrition, Faculty of Nursing and Nutrition, The University of Shimane, Izumo-city, Shimane, Japan. FAU - Sakaue, Hiroshi AU - Sakaue H AUID- ORCID: 0000-0002-2468-2363 AD - Department of Nutrition and Metabolism, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima-city, Tokushima, Japan. AD - Diabetes Therapeutics and Research Center, Tokushima University, Tokushima-city, Tokushima, Japan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200521 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Chemokine CCL2) RN - 0 (Interferon Regulatory Factor-7) SB - IM MH - 3T3-L1 Cells MH - Adipocytes/*metabolism MH - Adipose Tissue, White/metabolism MH - Animals MH - Chemokine CCL2/*genetics/metabolism MH - Gene Expression Regulation MH - HEK293 Cells MH - Humans MH - Interferon Regulatory Factor-7/*genetics/metabolism MH - Mice MH - Mice, Knockout MH - Obesity/*genetics/metabolism MH - Promoter Regions, Genetic PMC - PMC7241760 COIS- The authors have declared that no competing interests exist. EDAT- 2020/05/22 06:00 MHDA- 2020/08/13 06:00 PMCR- 2020/05/21 CRDT- 2020/05/22 06:00 PHST- 2019/12/05 00:00 [received] PHST- 2020/05/04 00:00 [accepted] PHST- 2020/05/22 06:00 [entrez] PHST- 2020/05/22 06:00 [pubmed] PHST- 2020/08/13 06:00 [medline] PHST- 2020/05/21 00:00 [pmc-release] AID - PONE-D-19-33716 [pii] AID - 10.1371/journal.pone.0233390 [doi] PST - epublish SO - PLoS One. 2020 May 21;15(5):e0233390. doi: 10.1371/journal.pone.0233390. eCollection 2020.