{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T19:21:10Z","timestamp":1792264870530,"version":"4.4.0"},"reference-count":37,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T00:00:00Z","timestamp":1779408000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T00:00:00Z","timestamp":1779408000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100008967","name":"Bilim Akademisi","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008967","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004410","name":"T\u00fcrkiye Bilimsel ve Teknolojik Ara\u015ft\u0131rma Kurumu","doi-asserted-by":"publisher","award":["121Z911"],"award-info":[{"award-number":["121Z911"]}],"id":[{"id":"10.13039\/501100004410","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004410","name":"European Molecular Biology Organization","doi-asserted-by":"publisher","award":["4162"],"award-info":[{"award-number":["4162"]}],"id":[{"id":"10.13039\/100004410","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FEBS Journal"],"abstract":"<jats:p>Nuclear factor \u03baB (NF\u2010\u03baB)\u2010inducing kinase (NIK) is a critical component of the noncanonical NF\u2010\u03baB pathway and an important regulator of immune response. NIK deficiency causes loss of lymph nodes, disruption of lymphoid organ structure and deficits in B\u2010cell formation and immunoglobulin production. In this study, we generated adipocyte\u2010specific NIK\u2010knockout (Adipo\u2010NIK\u2010KO) mice to study the role of this protein in adipose tissue metabolism. We found that NIK depletion in mouse primary adipocytes potentiates thermogenic capacity without altering the differentiation of these cells. Loss of NIK in adipocytes stimulated Fibroblast growth factor 21 (FGF21)\u2010induced expression of thermogenic genes, including Uncoupling protein 1 (UCP1) and mitochondrial uncoupled respiration. In fact, enhanced browning of subcutaneous fat depots was detected in Adipo\u2010NIK\u2010KO mice, which also had elevated energy expenditure. These mice exhibited improved glucose tolerance and insulin sensitivity and reduced hepatic lipid deposition upon diet\u2010induced obesity. Similarly, inhibition of NIK by a specific small molecule enhanced metabolic rate and glucose homeostasis in obese mice. Therefore, NIK inhibition holds therapeutic potential for reversing glucose intolerance and insulin resistance associated with obesity.<\/jats:p>","DOI":"10.1111\/febs.70600","type":"journal-article","created":{"date-parts":[[2026,5,23]],"date-time":"2026-05-23T06:31:43Z","timestamp":1779517903000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Adipocyte\u2010specific\n                    <scp>NIK<\/scp>\n                    depletion enhances energy metabolism and glucose tolerance in mice"],"prefix":"10.1111","author":[{"given":"Atakan","family":"Ozcan","sequence":"first","affiliation":[{"name":"Department of Molecular Biology and Genetics Koc University  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Uslucan","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics Koc University  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleyna","family":"Kizilyer","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics Koc University  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samet","family":"Agca","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics Koc University  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aylin","family":"Karatas","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Beykoz Institute of Life Sciences and Biotechnology Bezmialem Vakif University  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanaz","family":"Naghizadeh","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics Koc University  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bahar Zehra Camurdanoglu","family":"Weber","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics Koc University  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1800-2923","authenticated-orcid":false,"given":"Sukru Anil","family":"Dogan","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Beykoz Institute of Life Sciences and Biotechnology Bezmialem Vakif University  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8722-9913","authenticated-orcid":false,"given":"Serkan","family":"Kir","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics Koc University  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,22]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1111\/jpi.12137","article-title":"Melatonin, energy metabolism, and obesity: a review","volume":"56","author":"Cipolla\u2010Neto J","year":"2014","journal-title":"J Pineal Res"},{"key":"e_1_2_10_3_1","doi-asserted-by":"crossref","first-page":"1899","DOI":"10.1053\/j.gastro.2019.12.054","article-title":"Adipose tissue\u2010liver cross talk in the control of whole\u2010body metabolism: implications in nonalcoholic fatty liver disease","volume":"158","author":"Azzu V","year":"2020","journal-title":"Gastroenterology"},{"key":"e_1_2_10_4_1","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1172\/JCI78362","article-title":"Brown and beige fat in humans: thermogenic adipocytes that control energy and glucose homeostasis","volume":"125","author":"Sidossis 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FOXP3\u2010dependent regulatory T\u00a0cell program","volume":"9","author":"Sato Y","year":"2023","journal-title":"Heliyon"},{"key":"e_1_2_10_20_1","doi-asserted-by":"crossref","first-page":"953","DOI":"10.4049\/jimmunol.1401514","article-title":"Conditional deletion of NF\u2010kappaB\u2010inducing kinase (NIK) in adult mice disrupts mature B cell survival and activation","volume":"195","author":"Brightbill HD","year":"2015","journal-title":"J Immunol"},{"key":"e_1_2_10_21_1","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1002\/eji.1830240224","article-title":"A new mutation, aly, that induces a generalized lack of lymph nodes accompanied by immunodeficiency in mice","volume":"24","author":"Miyawaki S","year":"1994","journal-title":"Eur J Immunol"},{"key":"e_1_2_10_22_1","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1084\/jem.20150218","article-title":"Nuclear factor kappaB\u2010inducing kinase activation as a mechanism of pancreatic beta cell failure in 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J"}],"container-title":["The FEBS 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