{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T07:56:37Z","timestamp":1791186997850,"version":"4.1.0"},"reference-count":33,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2015,5,13]],"date-time":"2015-05-13T00:00:00Z","timestamp":1431475200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Major Research plan of the Natural Science Foundation of China","award":["81473461"],"award-info":[{"award-number":["81473461"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>There is strong evidence to suggest that inflammatory responses link obesity and diseases, and the understanding of obesity-induced inflammatory mechanisms is central to the pathogenesis of diseases such asnonalcoholic fatty liver disease(NAFLD) and atherosclerosis that are modified by obesity. Based on this, anti-inflammatory treatments become a potential therapies for obesity-related diseases like NAFLD.A critical role of toll-like receptor (TLR) and its downstream molecules such as tumor necrosis factor receptor-associated factor 6(TRAF6) has been documented in inflammatory response induced by fatty acid. TLR pathway regulation provides a new insight to controlling the inflammatory response induced by fatty acid. Taken together, our study was aimed to understand the mechanism of fatty acid-mediated inflammation and look for an effective target which can prevent the inflammatory response induced by obesity. In this study, we used the saturated fatty acid palmitic acid (PA) to activate TLR4 signal pathway in human monocyte cells THP-1 that established an intracellular inflammatory model. Followed with activated TLR4, downstream molecular TRAF6 was upregulated and ultimately induced proinflammatory cytokine production. Based on this model, we also found that PA downregulated miR-194 expression with TLR4 activation. Moreover, our results showed that key signal molecular TRAF6 is a target of miR-194, overexpression of miR-194 directly decreased TRAF6 expression and attenuated the release of proinflammatory cytokine TNF-\u03b1 in PA-activated monocyte THP-1. We conclude that miR-194 negatively regulates the TLR4 signal pathway which is activated by PA through directly negative TRAF6 expression.<\/jats:p>","DOI":"10.3390\/nu7053483","type":"journal-article","created":{"date-parts":[[2015,5,13]],"date-time":"2015-05-13T12:42:07Z","timestamp":1431520927000},"page":"3483-3496","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":66,"title":["MiRNA-194 Regulates Palmitic Acid-Induced Toll-Like Receptor 4 Inflammatory Responses in THP-1 Cells"],"prefix":"10.3390","volume":"7","author":[{"given":"Huiqun","family":"Tian","sequence":"first","affiliation":[{"name":"Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, Yichang 443002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaoqi","family":"Liu","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, Yichang 443002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohua","family":"Zou","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, Yichang 443002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wu","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, Yichang 443002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changcheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Medical College, China Three Gorges University, Yichang 443002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ding","family":"Yuan","sequence":"additional","affiliation":[{"name":"Medical College, China Three Gorges University, Yichang 443002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2015,5,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1210\/er.2011-0013","article-title":"Emerging role of mast cells and macrophages in cardiovascular and metabolic diseases","volume":"33","author":"Xu","year":"2012","journal-title":"Endocr. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1016\/j.cmet.2008.04.003","article-title":"Alternative M2 activation of Kupffer cells by PPAR\u03b4ameliorates obesity-induced insulin resistance","volume":"7","author":"Odegaard","year":"2008","journal-title":"Cell Metab."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.freeradbiomed.2009.09.026","article-title":"Oxidative stress and glutathione in TGF-\u03b2-mediated fibrogenesis","volume":"48","author":"Liu","year":"2010","journal-title":"Free Radic. Biol. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"603","DOI":"10.3389\/fimmu.2014.00603","article-title":"TH1\/TH2 paradigm extended: Macrophage polarization as an unappreciated pathogen-driven escape mechanism","volume":"5","author":"Muraille","year":"2014","journal-title":"Front. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"16","DOI":"10.3109\/08830185.2010.529976","article-title":"Pathogen recognition by the innate immune system","volume":"30","author":"Kumar","year":"2011","journal-title":"Int. Rev. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"379","DOI":"10.3109\/08830185.2012.706761","article-title":"Toll-like receptor signaling pathways in cardiovascular disease: Challenges and opportunities","volume":"31","author":"Vallejo","year":"2012","journal-title":"Int. Rev. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1172\/JCI29881","article-title":"Obesity induces a phenotypic switch in adipose tissue macrophage polarization","volume":"117","author":"Lumeng","year":"2007","journal-title":"J. Clin. Investig."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"16683","DOI":"10.1074\/jbc.M011695200","article-title":"Saturated fatty acids, but not unsaturated fatty acids, induce the expression of cyclooxygenase-2 mediated through Toll-like receptor 4","volume":"276","author":"Lee","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1189\/jlb.0210072","article-title":"Adipose tissue macrophages: Their role in adipose tissue remodeling","volume":"88","author":"Suganami","year":"2010","journal-title":"J. Leukoc. Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"237613","DOI":"10.5402\/2012\/237613","article-title":"Octanoylated Ghrelin Inhibits the Activation of the Palmitic Acid-Induced TLR4\/NF-\u03baB Signaling Pathway in THP-1 Macrophages","volume":"2012","author":"Liu","year":"2012","journal-title":"ISRN Endocrinol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1016\/j.jhep.2007.04.019","article-title":"Toll-like receptor-4 signaling and Kupffer cells play privotal roles in the pathogenesis of non-alcoholic steatohepatitis","volume":"47","author":"Rivera","year":"2007","journal-title":"J. Hepatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1986","DOI":"10.2337\/db06-1595","article-title":"Loss-of-function mutation in Toll-like receptor 4 prevents diet-induced obesity and insulin resistance","volume":"56","author":"Tsukumo","year":"2007","journal-title":"Diabetes"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1038\/nature07228","article-title":"Widespread changes in protein synthesis induced by microRNAs","volume":"455","author":"Selbach","year":"2008","journal-title":"Nature"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1101\/gr.082701.108","article-title":"Moat mammalian mRNAs are conserved targets of microRNAs","volume":"19","author":"Friedman","year":"2009","journal-title":"Genome Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e101530","DOI":"10.1371\/journal.pone.0101530","article-title":"miR-146a ameliorates liver ischemia\/reperfusion injury by suppressing IRAK1and TRAF6","volume":"2","author":"Jiang","year":"2014","journal-title":"PLoS ONE"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1097\/MOL.0b013e32832fa5c4","article-title":"Toll-like receptor signaling links dietary fatty acids to the metabolic syndrome","volume":"20","author":"Fessler","year":"2009","journal-title":"Curr. Opin. Lipidol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.jinf.2013.07.016","article-title":"Toll like receptor (TLR)-induced differential expression of microRNAs (MiRs) and immune response against infection: A systematic review","volume":"67","author":"Nima","year":"2013","journal-title":"J. Infect."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1261\/rna.031831.111","article-title":"miR-Sens-a retroviral dual-luciferase reporter to detect microRNA activity in primary cells","volume":"18","author":"Beillard","year":"2012","journal-title":"RNA"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.smim.2003.10.003","article-title":"TLR signaling pathways","volume":"16","author":"Takeda","year":"2004","journal-title":"Semin. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1564","DOI":"10.1161\/01.CIR.0000142055.53122.FA","article-title":"Circulating monounuclear cells in the obese are in a proinflammatory state","volume":"110","author":"Ghanim","year":"2004","journal-title":"Circulation"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.it.2003.10.013","article-title":"Inflammation: The link between insulin resistance, obesity and diabetes","volume":"25","author":"Dandona","year":"2004","journal-title":"Trends Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1016\/j.bbrc.2009.08.062","article-title":"Toll-like receptors and innate immunity","volume":"388","author":"Kumar","year":"2009","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.jhep.2012.02.028","article-title":"Toxic lipids stored by Kupffer cells correlates with their pro-inflammatory phenotype at an early stage of steatohepatitis","volume":"57","author":"Leroux","year":"2012","journal-title":"J. Hepatol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1038\/nature10809","article-title":"Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity","volume":"482","author":"Elinav","year":"2012","journal-title":"Nature"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"362847","DOI":"10.1155\/2010\/362847","article-title":"Role of toll-like receptors and their downstream molecules in the development of nonalcoholic Fatty liver disease","volume":"2010","author":"Miura","year":"2010","journal-title":"Gastroenterol. Res. Pract."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1111\/jgh.12019","article-title":"Toll-like receptors in alcoholic liver disease, non-alcoholic steatohepatitis and carcinogenesis","volume":"28","author":"Roh","year":"2013","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2062","DOI":"10.1161\/01.ATV.0000183883.72263.13","article-title":"A paracrine loop between adipocytes and macrophages aggravates inflammatory changes: Role of free fatty acids and tumor necrosis factor alpha","volume":"25","author":"Suganami","year":"2005","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1046\/j.1440-1711.2000.00875.x","article-title":"Modulatory effects of dietary lipids on immune system function","volume":"78","year":"2000","journal-title":"Immunol. Cell Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.ajpath.2012.09.007","article-title":"Toll-like receptor 4 signaling augments transforming growth factor-\u03b2 responses: A novel mechanism for maintaining and amplifying fibrosis in scleroderma","volume":"182","author":"Bhattacharyya","year":"2013","journal-title":"Am. J. Pathol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.jhep.2009.03.008","article-title":"Kupffer cells in non-alcoholic fatty liver disease: The emerging view","volume":"51","author":"Baffy","year":"2009","journal-title":"J. Hepatol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"G101","DOI":"10.1152\/ajpgi.00220.2009","article-title":"Liver fibrosis causes downregulation of miRNA-150 and miRNA-194 in hepatic stellate cells, and their overexpression causes decreased stellate cell activation","volume":"298","author":"Venugopal","year":"2010","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1172\/JCI200522675","article-title":"Selective depletion of macrophages reveals distinct, opposing roles during liver injury and repair","volume":"115","author":"Duffield","year":"2005","journal-title":"J. Clin. Investig."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1038\/nm1663","article-title":"TLR4 enhances TGF-beta signaling and hepatic fibrosis","volume":"13","author":"Seki","year":"2007","journal-title":"Nat. Med."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/7\/5\/3483\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T20:46:13Z","timestamp":1760215573000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/7\/5\/3483"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,5,13]]},"references-count":33,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2015,5]]}},"alternative-id":["nu7053483"],"URL":"https:\/\/doi.org\/10.3390\/nu7053483","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,5,13]]}}}