{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T11:32:01Z","timestamp":1790422321865,"version":"4.1.0"},"reference-count":49,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2019,3,16]],"date-time":"2019-03-16T00:00:00Z","timestamp":1552694400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005795","name":"Chang Gung Memorial Hospital, Linkou","doi-asserted-by":"publisher","award":["CMRPD1D0351, CMRPD1D0352"],"award-info":[{"award-number":["CMRPD1D0351, CMRPD1D0352"]}],"id":[{"id":"10.13039\/501100005795","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ministry of Science and Technology, Taipei, Taiwan","award":["MOST 102-2320-B182-015-MY3, 103-2320-B182-002-MY3, 106-2320-B-182-005-MY3 and 106-2320-B-182-005-MY3"],"award-info":[{"award-number":["MOST 102-2320-B182-015-MY3, 103-2320-B182-002-MY3, 106-2320-B-182-005-MY3 and 106-2320-B-182-005-MY3"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Obesity has been shown to play a role in the pathogenesis of several forms of metabolic syndrome, including non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes. Ursodeoxycholic acid (UDCA) has been shown to possess antioxidant and anti-inflammatory properties and prevents mitochondrial dysfunction in the progression of obesity-associated diseases. The aim of the study was to evaluate the mechanisms of UDCA during obesity-linked hepatic mitochondrial dysfunction and obesity-associated adipose tissue macrophage-induced inflammation in obese mice. UDCA significantly decreased lipid droplets, reduced free fatty acids (FFA) and triglycerides (TG), improved mitochondrial function, and enhanced white adipose tissue browning in ob\/ob mice. This is associated with increased hepatic energy expenditure, mitochondria biogenesis, and incorporation of bile acid metabolism (Abca1, Abcg1 mRNA and BSEP, FGFR4, and TGR5 protein). In addition, UDCA downregulated NF-\u03baB and STAT3 phosphorylation by negative regulation of the expression of SOCS1 and SOCS3 signaling. These changes were accompanied by decreased angiogenesis, as shown by the downregulation of VEGF, VCAM, and TGF-\u03b2RII expression. Importantly, UDCA is equally effective in reducing whole body adiposity. This is associated with decreased adipose tissue expression of macrophage infiltration (CD11b, CD163, and CD206) and lipogenic capacity markers (lipofuscin, SREBP-1, and CD36). Furthermore, UDCA significantly upregulated adipose browning in association with upregulation of SIRT-1-PGC1-\u03b1 signaling in epididymis adipose tissue (EWAT). These results suggest that multi-targeted therapies modulate glucose and lipid biosynthesis fluxes, inflammatory response, angiogenesis, and macrophage differentiation. Therefore, it may be suggested that UDCA treatment may be a novel therapeutic agent for obesity.<\/jats:p>","DOI":"10.3390\/cells8030253","type":"journal-article","created":{"date-parts":[[2019,3,18]],"date-time":"2019-03-18T12:18:53Z","timestamp":1552911533000},"page":"253","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":72,"title":["Ursodeoxycholic Acid Regulates Hepatic Energy Homeostasis and White Adipose Tissue Macrophages Polarization in Leptin-Deficiency Obese Mice"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7158-2114","authenticated-orcid":false,"given":"Yu-Sheng","family":"Chen","sequence":"first","affiliation":[{"name":"Graduate Institute of Clinical Medical Science, College of Medicine, Chang Gung University, No. 259, Wen-Hwa 1st Road, Kwei-Shan, Taoyuan 333, Taiwan"},{"name":"Division of Chinese Acupuncture, Center for Traditional Chinese Medicine, Chang Gung Memorial Hospital, No. 123, Dinghu Road, Guishan District, Taoyuan 333, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsuan-Miao","family":"Liu","sequence":"additional","affiliation":[{"name":"Graduate Institute of Traditional Chinese Medicine, School of Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4097-2085","authenticated-orcid":false,"given":"Tzung-Yan","family":"Lee","sequence":"additional","affiliation":[{"name":"Graduate Institute of Traditional Chinese Medicine, School of Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan"},{"name":"Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Keelung 204, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,3,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Younossi, Z., Tacke, F., Arrese, M., Sharma, B.C., Mostafa, I., Bugianesi, E., Wong, V.W., Yilmaz, Y., George, J., and Fan, J. 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