{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T01:16:21Z","timestamp":1774574181426,"version":"3.50.1"},"reference-count":49,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2020,12,28]],"date-time":"2020-12-28T00:00:00Z","timestamp":1609113600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"by a National Research Foundation (NRF) of Korea grant funded by the Korean government (MSIP)","award":["NRF-2020R1I1A3074694"],"award-info":[{"award-number":["NRF-2020R1I1A3074694"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Obesity, a characteristic of metabolic syndrome, is also associated with chronic inflammation and the development of autoimmune diseases. However, the relationship between obesity and autoimmune diseases remains to be investigated in depth. Here, we compared hepatic gene expression profiles among high-fat diet (HFD) mice using the primary biliary cholangitis (PBC) mouse model based on the chronic expression of interferon gamma (IFN\u03b3) (ARE-Del-\/- mice). The top differentially expressed genes affected by upstream transcriptional regulators IFN\u03b3, LPS, and TNF\u03b1 displayed an overlap in HFD and ARE-Del-\/- mice, indicating that obesity-induced liver inflammation may be dependent on signaling via IFN\u03b3. The top pathways altered in HFD mice were mostly involved in the innate immune responses, which overlapped with ARE-Del-\/- mice. In contrast, T cell-mediated signaling pathways were exclusively altered in ARE-Del-\/- mice. We further evaluated the therapeutic effect of luteolin, known as anti-inflammatory flavonoid, in HFD and ARE-Del-\/- mice. Luteolin strongly suppressed the MHC I and II antigen presentation pathways, which were highly activated in both HFD and ARE-Del-\/- mice. Conversely, luteolin increased metabolic processes of fatty acid oxidation and oxidative phosphorylation in the liver, which were suppressed in ARE-Del-\/- mice. Luteolin also strongly induced PPAR signaling, which was downregulated in HFD and ARE-Del-\/- mice. Using human GWAS data, we characterized the genetic interaction between significant obesity-related genes and IFN\u03b3 signaling and demonstrated that IFN\u03b3 is crucial for obesity-mediated inflammatory responses. Collectively, this study improves our mechanistic understanding of the relationship between obesity and autoimmune diseases. Furthermore, it provides new methodological insights into how immune network-based analyses effectively integrate RNA-seq and microarray data.<\/jats:p>","DOI":"10.3390\/ijms22010208","type":"journal-article","created":{"date-parts":[[2020,12,28]],"date-time":"2020-12-28T10:33:56Z","timestamp":1609151636000},"page":"208","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["IFN\u03b3 Is a Key Link between Obesity and Th1-Mediated AutoImmune Diseases"],"prefix":"10.3390","volume":"22","author":[{"given":"Heekyong R.","family":"Bae","sequence":"first","affiliation":[{"name":"Omixplus, LLC., Gaithersburg, MD 20885, USA"},{"name":"Laboratory of Cancer Immunometabolism, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute-Frederick, Frederick, MD 21701, USA"},{"name":"Department of Food Science and Nutrition, Center for Food and Nutritional Genomics Research, Kyungpook National University, Daegu 41566, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Myung-Sook","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Food Science and Nutrition, Center for Food and Nutritional Genomics Research, Kyungpook National University, Daegu 41566, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suntae","family":"Kim","sequence":"additional","affiliation":[{"name":"Omixplus, LLC., Gaithersburg, MD 20885, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Howard A.","family":"Young","sequence":"additional","affiliation":[{"name":"Laboratory of Cancer Immunometabolism, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute-Frederick, Frederick, MD 21701, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. Eric","family":"Gershwin","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis, Davis, CA 95616, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seon-Min","family":"Jeon","sequence":"additional","affiliation":[{"name":"R&amp;D Center, APtechnologies Corp., Gyeonggi-do, Hwaseong-si 18469, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eun-Young","family":"Kwon","sequence":"additional","affiliation":[{"name":"Department of Food Science and Nutrition, Center for Food and Nutritional Genomics Research, Kyungpook National University, Daegu 41566, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,28]]},"reference":[{"key":"ref_1","first-page":"123","article-title":"Interferon-gamma and systemic autoimmunity","volume":"16","author":"Pollard","year":"2013","journal-title":"Discov. 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