{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T07:53:13Z","timestamp":1791186793045,"version":"4.1.0"},"reference-count":35,"publisher":"The Endocrine Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Farnesoid X receptor (FXR) is known to play important regulatory roles in bile acid, lipid, and carbohydrate metabolism. Aged (&amp;gt;12 months old) Fxr\u2212\/\u2212 mice also develop spontaneous liver carcinomas. In this report, we used three mouse models to investigate the role of FXR deficiency in obesity. As compared with low-density lipoprotein receptor (Ldlr) knockout (Ldlr\u2212\/\u2212) mice, the Ldlr\u2212\/\u2212Fxr\u2212\/\u2212 double-knockout mice were highly resistant to diet-induced obesity, which was associated with increased expression of genes involved in energy metabolism in the skeletal muscle and brown adipose tissue. Such a striking effect of FXR deficiency on obesity on an Ldlr\u2212\/\u2212 background led us to investigate whether FXR deficiency alone is sufficient to affect obesity. As compared with wild-type mice, Fxr\u2212\/\u2212 mice showed resistance to diet-induced weight gain. Interestingly, only female Fxr\u2212\/\u2212 mice showed significant resistance to diet-induced obesity, which was accompanied by increased energy expenditure in these mice. Finally, we determined the effect of FXR deficiency on obesity in a genetically obese and diabetic mouse model. We generated ob\u2212\/\u2212Fxr\u2212\/\u2212 mice that were deficient in both Leptin and Fxr. On a chow diet, ob\u2212\/\u2212Fxr\u2212\/\u2212 mice gained less body weight and had reduced body fat mass as compared with ob\/ob mice. In addition, we observed liver carcinomas in 43% of young (&amp;lt;11 months old) Ob\u2212\/\u2212Fxr\u2212\/\u2212 mice. Together these data indicate that loss of FXR prevents diet-induced or genetic obesity and accelerates liver carcinogenesis under diabetic conditions.<\/jats:p>","DOI":"10.1210\/me.2011-1157","type":"journal-article","created":{"date-parts":[[2012,1,20]],"date-time":"2012-01-20T06:14:50Z","timestamp":1327040090000},"page":"272-280","source":"Crossref","is-referenced-by-count":115,"title":["Loss of FXR Protects against Diet-Induced Obesity and Accelerates Liver Carcinogenesis in ob\/ob Mice"],"prefix":"10.1210","volume":"26","author":[{"given":"Yanqiao","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Integrative Medical Sciences (Y.Z., X.G., W.-D.C., J.X., H.M.), Northeast Ohio Medical University, Rootstown, Ohio 44272;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuemei","family":"Ge","sequence":"first","affiliation":[{"name":"Department of Integrative Medical Sciences (Y.Z., X.G., W.-D.C., J.X., H.M.), Northeast Ohio Medical University, Rootstown, Ohio 44272;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lydia A.","family":"Heemstra","sequence":"first","affiliation":[{"name":"Department of Biological Sciences (L.A.H., J.L.S., N.K., C.M.N.), Kent State University, Kent, Ohio 44242;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Dong","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Integrative Medical Sciences (Y.Z., X.G., W.-D.C., J.X., H.M.), Northeast Ohio Medical University, Rootstown, Ohio 44272;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiesi","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Integrative Medical Sciences (Y.Z., X.G., W.-D.C., J.X., H.M.), Northeast Ohio Medical University, Rootstown, Ohio 44272;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph L.","family":"Smith","sequence":"first","affiliation":[{"name":"Department of Biological Sciences (L.A.H., J.L.S., N.K., C.M.N.), Kent State University, Kent, Ohio 44242;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiyan","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Integrative Medical Sciences (Y.Z., X.G., W.-D.C., J.X., H.M.), Northeast Ohio Medical University, Rootstown, Ohio 44272;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neda","family":"Kasim","sequence":"first","affiliation":[{"name":"Department of Integrative Medical Sciences (Y.Z., X.G., W.-D.C., J.X., H.M.), Northeast Ohio Medical University, Rootstown, Ohio 44272;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter A.","family":"Edwards","sequence":"first","affiliation":[{"name":"Departments of Biological Chemistry and Medicine (P.A.E.), University of California, Los Angeles, Los Angeles, California 90095"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colleen M.","family":"Novak","sequence":"first","affiliation":[{"name":"Department of Biological Sciences (L.A.H., J.L.S., N.K., C.M.N.), Kent State University, Kent, Ohio 44242;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071613171377600_B1","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.febslet.2007.11.015","article-title":"FXR signaling in metabolic disease.","volume":"582","author":"Zhang","year":"2008","journal-title":"FEBS Lett"},{"key":"2020071613171377600_B2","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1152\/physrev.00010.2008","article-title":"Role of bile acids and bile acid receptors in metabolic regulation.","volume":"89","author":"Lefebvre","year":"2009","journal-title":"Physiol Rev"},{"key":"2020071613171377600_B3","doi-asserted-by":"crossref","first-page":"H272","DOI":"10.1152\/ajpheart.01075.2008","article-title":"Antiatherosclerotic effect of farnesoid X receptor.","volume":"296","author":"Mencarelli","year":"2009","journal-title":"Am J Physiol Heart Circ 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