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In the present study, we investigate the ameliorative effects of PCM, a combination of Diospyros kaki fruit and Citrus unshiu peel mixture, on high-fat diet- (HFD-) induced NAFLD and clarify the potential mechanisms. PCM in HFD-fed mice was orally administered at a dose of 50 or 100\u2009mg\/kg subsequently for 2 months. Thereafter, lipid metabolism parameters and fat synthesis-related genes in the mouse liver were evaluated. Subsequently, body weight changes, liver weight, serum liver function and lipid profiles, and liver pathology were examined, and the relative levels of fatty acid synthesis and \u03b2-oxidation gene expression were evaluated by western blot. Serum AST, ALT, and TG levels in the HFD control mice were significantly higher than those of normal mice. Compared with HFD control mice, PCM supplementation increased phosphorylation of AMP-activated protein kinase (AMPK). Peroxisome proliferator-activated receptor (PPAR) \u03b1 was significantly increased by PCM administration. Continuously, the activation of PPAR\u03b1 significantly elevated carnitine palmitoyltransferase 1 (CPT-1), a key enzyme in fatty acid \u03b2-oxidation, and mitochondrial uncoupling protein 2 (UCP-2), thermogenic regulatory genes, in PCM-treated mice compared with those of HFD control mice. Moreover, PCM inhibits lipogenesis and cholesterol synthesis via suppression of sterol regulatory element binding protein-1 (SREBP-1) and SREBP-2 and its target genes such as acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), stearoyl-CoA desaturase-1 (SCD-1), and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR). Taken together, these effects were mediated through activation of AMPK. In the conclusion, PCM improved liver damage in HFD-fed mice and attenuated NAFLD by the activation of PPAR\u03b1 and the inhibition of SREBPs expression via AMPK-dependent pathways.<\/jats:p>","DOI":"10.1155\/2020\/8812634","type":"journal-article","created":{"date-parts":[[2020,12,25]],"date-time":"2020-12-25T00:06:13Z","timestamp":1608854773000},"page":"1-12","source":"Crossref","is-referenced-by-count":21,"title":["Diospyros kaki and Citrus unshiu Mixture Improves Disorders of Lipid Metabolism in Nonalcoholic Fatty Liver Disease"],"prefix":"10.1155","volume":"2020","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4365-6988","authenticated-orcid":true,"given":"Mi-Rae","family":"Shin","sequence":"first","affiliation":[{"name":"Department of Herbology, Korean Medicine of College, Daegu Haany University, Daegu 42158, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung Ho","family":"Shin","sequence":"additional","affiliation":[{"name":"Foot-and-Mouth Disease Vaccine Research Center, Animal and Plant Quarantine Agency, Gyeongsangbuk-do 39660, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4162-6849","authenticated-orcid":true,"given":"Seong-Soo","family":"Roh","sequence":"additional","affiliation":[{"name":"Department of Herbology, Korean Medicine of College, Daegu Haany University, Daegu 42158, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","reference":[{"key":"1","doi-asserted-by":"publisher","DOI":"10.4162\/nrp.2015.9.4.350"},{"key":"2","doi-asserted-by":"publisher","DOI":"10.4103\/2156-7514.157860"},{"key":"3","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1746.2012.07222.x"},{"key":"4","doi-asserted-by":"publisher","DOI":"10.1111\/liv.12454"},{"issue":"4","key":"5","first-page":"671","article-title":"The effect of dietary lipid manipulation on hepatic mitochondrial phospholipid fatty acid composition and carnitine palmitoyltransferase I activity","volume":"34","author":"G. 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