{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:59:43Z","timestamp":1787029183197,"version":"build-2736575974"},"reference-count":42,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2018,11,9]],"date-time":"2018-11-09T00:00:00Z","timestamp":1541721600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"a National Research Foundation (NRF) of Korea grant funded by the Korea government","award":["2015R1C1A2A01051533, 2016R1A2B4011329 and 2018R1D1A1B07043068"],"award-info":[{"award-number":["2015R1C1A2A01051533, 2016R1A2B4011329 and 2018R1D1A1B07043068"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>The aim of the current study was to elucidate the effects of long-term supplementation with dietary ursolic acid (UR) on obesity and associated comorbidities by analyzing transcriptional and metabolic responses, focusing on the role of UR in the modulation of the circadian rhythm pathway in particular. C57BL\/6J mice were divided into three groups and fed a normal diet, high-fat diet, or high-fat + 0.05% (w\/w) UR diet for 16 weeks. Oligonucleotide microarray profiling revealed that UR is an effective regulator of the liver transcriptome, and canonical pathways associated with the \u201ccircadian rhythm\u201d and \u201cextracellular matrix (ECM)\u2013receptor interactions\u201d were effectively regulated by UR in the liver. UR altered the expression of various clock and clock-controlled genes (CCGs), which may be linked to the improvement of hepatic steatosis and fibrosis via lipid metabolism control and detoxification enhancement. UR reduced excessive reactive oxygen species production, adipokine\/cytokine dysregulation, and ECM accumulation in the liver, which also contributed to improve hepatic lipotoxicity and fibrosis. Moreover, UR improved pancreatic islet dysfunction, and suppressed hepatic gluconeogenesis, thereby reducing obesity-associated insulin resistance. Therapeutic approaches targeting hepatic circadian clock and CCGs using UR may ameliorate the deleterious effects of diet-induced obesity and associated complications such as hepatic fibrosis.<\/jats:p>","DOI":"10.3390\/nu10111719","type":"journal-article","created":{"date-parts":[[2018,11,13]],"date-time":"2018-11-13T03:27:31Z","timestamp":1542079651000},"page":"1719","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Ursolic Acid Attenuates Hepatic Steatosis, Fibrosis, and Insulin Resistance by Modulating the Circadian Rhythm Pathway in Diet-Induced Obese Mice"],"prefix":"10.3390","volume":"10","author":[{"given":"Eun-Young","family":"Kwon","sequence":"first","affiliation":[{"name":"Department of Food Science and Nutrition, Kyungpook National University, 1370 San-Kyuk Dong Puk-Ku, Daegu 41566, Korea"},{"name":"Center for Food and Nutritional Genomics Research, Kyungpook National University, 1370 San-Kyuk Dong Puk-Ku, Daegu 41566, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su-Kyung","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Physiology &amp; Obesity-Mediated Disease Research Center, Keimyung University School of Medicine, Daegu 82601, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myung-Sook","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Food Science and Nutrition, Kyungpook National University, 1370 San-Kyuk Dong Puk-Ku, Daegu 41566, Korea"},{"name":"Center for Food and Nutritional Genomics Research, Kyungpook National University, 1370 San-Kyuk Dong Puk-Ku, Daegu 41566, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,11,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Guh, D.P., Zhang, W., Bansback, N., Amarsi, Z., Birmingham, C.L., and Anis, A.H. 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