title: IL-17 axis accelerates the inflammatory progression of obese in mice via TBK1 and IKBKE pathway.
abstract: Obesity mediates immune inflammatory response and induces IL-17 expression. Adipgenesis can be regulated by IL-17 and it causes TBK1 activation. The inhibition of TBK1 and the inhibition of I IKBKE reduces inflammatory response and improves obesity. It is hypothesized that IL-17 deficiency inhibits obesity progression and inflammation. 3T3-L1 preadipocytes were differentiated in vitro and treated with IL-17. RAW264.7 cells and differentiated 3T3-L1 were pretreated with TBK1 inhibitor and then stimulated with IL-17. Wild-type and IL-17 knock out mice were fed with high-fat diet. IL-17 inhibits adipocyte differentiation from mouse-derived 3T3-L1 preadipocytes and reduces mRNA expression of proadipogenic transcription factors and adipokines in adipocyte cells. IL-17 also showed up-regulation of mRNA levels of inflammatory cytokines in RAW cells. The inhibitor of TBK1 and IKBKE attenuates the effect of IL-17. Loss of IL-17 deficiency improves diet-induced obesity, fatty liver, glucose and lipid metabolism in mice. The expression of TBK1 and IKBKE decreased in the spleen and liver of IL-17 deficiency mice. Moreover, the inflammatory response within the visceral adipose tissue and Th1 cells were inhibited, however, M2 macrophage and Th2 cells increased in IL-17 deficiency mice. IL-17 inhibits adipogenesis where a lack of IL-17 ameliorates glucose metabolism. As well, the inhibition of TBK1 reduces inflammation induced by IL-17. Therefore, IL-17 may be involved in the development of obesity and metabolic dysfunction in a TBK1-dependent manner.
authors.affiliation: The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, South Korea. Electronic address: redcap817@catholic.ac.kr.
authors.forename: Seung Hoon
authors.initials: SH
authors.lastname: Lee
authors.affiliation: The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, South Korea. Electronic address: jhunjy@catholic.ac.kr.
authors.forename: JooYeon
authors.initials: J
authors.lastname: Jhun
authors.affiliation: The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, South Korea. Electronic address: jkbyun0228@catholic.ac.kr.
authors.forename: Jae-Kyung
authors.initials: JK
authors.lastname: Byun
authors.affiliation: The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, South Korea. Electronic address: mnikek@catholic.ac.kr.
authors.forename: Eun-Kyung
authors.initials: EK
authors.lastname: Kim
authors.affiliation: Impact Biotech, Seoul, 137-040, South Korea. Electronic address: chu4222@catholic.ac.kr.
authors.forename: KyoungAh
authors.initials: K
authors.lastname: Jung
authors.affiliation: The Catholic University of Korea, School of Medicine, Seoul, 137-040, South Korea. Electronic address: jieunlee@catholic.ac.kr.
authors.forename: Ji Eun
authors.initials: JE
authors.lastname: Lee
authors.affiliation: Division of Hepatology, Department of Internal Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, 505 Banpo-Dong, Seocho-Ku, Seoul, 137-040, South Korea. Electronic address: jychoi@catholic.ac.kr.
authors.forename: Jong Young
authors.initials: JY
authors.lastname: Choi
authors.affiliation: The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, South Korea; Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, 137-701, South Korea. Electronic address: rapark@catholic.ac.kr.
authors.forename: Sung-Hwan
authors.initials: SH
authors.lastname: Park
authors.affiliation: The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, South Korea; Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, 137-701, South Korea. Electronic address: iammila@catholic.ac.kr.
authors.forename: Mi-La
authors.initials: ML
authors.lastname: Cho
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D050156:Adipogenesis; D000818:Animals; D015415:Biomarkers; D002454:Cell Differentiation; D002460:Cell Line; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression; D051550:I-kappa B Kinase / Q000378:metabolism*; D056747:Immunomodulation; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018836:Inflammation Mediators; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators; D020381:Interleukin-17; C498588:Tbk1 protein, mouse; D017346:Protein Serine-Threonine Kinases; D051550:I-kappa B Kinase; C496566:Ikbke protein, mouse
keywords: IL-17; Obesity; TBK1