{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T02:55:41Z","timestamp":1763348141125,"version":"build-2065373602"},"reference-count":29,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2018,8,16]],"date-time":"2018-08-16T00:00:00Z","timestamp":1534377600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["No. 2009-0083538"],"award-info":[{"award-number":["No. 2009-0083538"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>This study investigated the effects of 2-(4-(5-chlorobenzo[d]thiazol-2-yl)phenoxy)-2,2-difluoroacetic acid (MHY3200) on high-fat diet (HFD)-induced hepatic lipid accumulation and inflammation. The measurement of peroxisome proliferator-activated receptor (PPAR)\u03b1 activity by using a luciferase assay indicated that MHY3200 was more potent than a known PPAR\u03b1 agonist, WY14643, in AC2F cells. Six-month-old male SD rats were fed chow or HFD for 1 month, and after, with or without added MHY3200 (1 or 2 mg\/kg\/day) for 4 weeks. The oral administration of MHY3200 caused a significant decrease in serum triglyceride (TG), glucose, alanine aminotransferase, and insulin, as well as a slight decrease in the level of free fatty acid and aspartate transaminase. No weight gain was detected when compared with HFD rats, and hepatic TG content was also attenuated by the administration of MHY3200. Furthermore, phosphorylation of the ER stress marker, inositol-requiring kinase 1 and its downstream gene, c-Jun N-terminal kinase, in addition to serine phosphorylation of insulin receptor substrate 1 were suppressed by MHY3200. Consistent with these results, MHY3200 administration reduced the levels of activation of protein-1, cyclooxygenase-2, and inducible nitric oxide synthase. Our results suggested that MHY3200 ameliorated HFD-induced hepatic lipid accumulation and inflammation, and improved insulin resistance through PPAR\u03b1 activation.<\/jats:p>","DOI":"10.3390\/molecules23082057","type":"journal-article","created":{"date-parts":[[2018,8,16]],"date-time":"2018-08-16T11:39:08Z","timestamp":1534419548000},"page":"2057","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Hepatoprotective Effects of MHY3200 on High-Fat, Diet-Induced, Non-Alcoholic Fatty Liver Disease in Rats"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2049-9411","authenticated-orcid":false,"given":"Min Jo","family":"Kim","sequence":"first","affiliation":[{"name":"Molecular Inflammation Research Center for Aging Intervention (MRCA), College of Pharmacy, Pusan National University, Busan 609-735, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1183-7159","authenticated-orcid":false,"given":"Chan Hum","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Medicinal Crop Research, National Institute of Horticultural and Herbal Science Rural Development Administration, Eumseong 27709, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dae Hyun","family":"Kim","sequence":"additional","affiliation":[{"name":"Molecular Inflammation Research Center for Aging Intervention (MRCA), College of Pharmacy, Pusan National University, Busan 609-735, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min Hi","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Irma Lerma Rangel College of Pharmacy, Texas A&amp;M Health Science Center, College Station, TX 77843, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyung Chul","family":"Park","sequence":"additional","affiliation":[{"name":"Molecular Inflammation Research Center for Aging Intervention (MRCA), College of Pharmacy, Pusan National University, Busan 609-735, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min Kyung","family":"Hyun","sequence":"additional","affiliation":[{"name":"Molecular Inflammation Research Center for Aging Intervention (MRCA), College of Pharmacy, Pusan National University, Busan 609-735, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A Kyoung","family":"Lee","sequence":"additional","affiliation":[{"name":"Molecular Inflammation Research Center for Aging Intervention (MRCA), College of Pharmacy, Pusan National University, Busan 609-735, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1119-7112","authenticated-orcid":false,"given":"Hyung Ryong","family":"Moon","sequence":"additional","affiliation":[{"name":"Molecular Inflammation Research Center for Aging Intervention (MRCA), College of Pharmacy, Pusan National University, Busan 609-735, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hae Young","family":"Chung","sequence":"additional","affiliation":[{"name":"Molecular Inflammation Research Center for Aging Intervention (MRCA), College of Pharmacy, Pusan National University, Busan 609-735, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2018,8,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1053\/jhep.2003.50161","article-title":"Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome","volume":"37","author":"Marchesini","year":"2003","journal-title":"Hepatology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1002\/oby.20426","article-title":"Racial differences in nonalcoholic fatty liver disease in the U.S. population","volume":"22","author":"Schneider","year":"2014","journal-title":"Obesity"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1053\/jhep.2000.17894","article-title":"Prevalence of obesity and diabetes in patients with cryptogenic cirrhosis: A case-control study","volume":"32","author":"Poonawala","year":"2000","journal-title":"Hepatology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1038\/nm1166","article-title":"Local and systemic insulin resistance resulting from hepatic activation of IKK-beta and NF-kappaB","volume":"11","author":"Cai","year":"2005","journal-title":"Nat. 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