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In this study, we evaluated the inflammatory cell population in the adipose tissue of MRL\/lpr mice, which could potentially influence their lean phenotype. Furthermore, we compared beige fat activity between the MRL\/MpJ and MRL\/lpr mice. <jats:italic>Fas<\/jats:italic> mutation resulted in high body temperature, improved glucose tolerance, and decreased fat mass and adipocyte size. <jats:italic>Fas<\/jats:italic> mutation prevented high-fat diet-induced obesity and decreased the white adipose tissue M1:M2 ratio. When mice were fed a high-fat diet, <jats:italic>UCP1<\/jats:italic>, <jats:italic>IL-4<\/jats:italic>, <jats:italic>IL-10<\/jats:italic>, and tyrosine hydroxylase genes had significantly higher expression in <jats:italic>Fas<\/jats:italic>-mutant mice than in wild type mice. After a cold challenge, UCP1 expression and browning were also significantly higher in the <jats:italic>Fas<\/jats:italic>-mutant mice. In summary, <jats:italic>Fas<\/jats:italic>-mutant mice are resistant to high-fat diet-induced obesity due to increased IL-4 and IL-10 levels and the promotion of thermogenic protein activity and browning in their adipose tissues. STAT6 activation might contribute to M2 polarisation by increasing IL-4 and IL-10 levels while increases in M2 and tyrosine hydroxylase levels promote browning in response to <jats:italic>Fas<\/jats:italic> mutation.<\/jats:p>","DOI":"10.1038\/s41598-020-68971-7","type":"journal-article","created":{"date-parts":[[2020,7,20]],"date-time":"2020-07-20T10:04:16Z","timestamp":1595239456000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Fas mutation reduces obesity by increasing IL-4 and IL-10 expression and promoting white adipose tissue browning"],"prefix":"10.1038","volume":"10","author":[{"given":"Eun Wha","family":"Choi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minjae","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji Woo","family":"Song","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7545-6366","authenticated-orcid":false,"given":"Kyeongdae","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jungmin","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jehoon","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seo Hyun","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Il Yong","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jae-Hoon","family":"Choi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Je Kyung","family":"Seong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,7,20]]},"reference":[{"key":"68971_CR1","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1056\/NEJMra1514009","volume":"376","author":"SB Heymsfield","year":"2017","unstructured":"Heymsfield, S. 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