title: Dietary umbelliferone attenuates alcohol-induced fatty liver via regulation of PPARα and SREBP-1c in rats.
abstract: This study investigated the effects of umbelliferone (UF) on alcoholic fatty liver and its underlying mechanism. Rats were fed a Lieber-DeCarli liquid diet with 36% of calories as alcohol with or without UF (0.05 g/L) for 8 weeks. Pair-fed rats received an isocaloric carbohydrate liquid diet. UF significantly reduced the severity of alcohol-induced body weight loss, hepatic lipid accumulation and droplet formation, and dyslipidemia. UF decreased plasma AST, ALT, and γGTP activity. UF significantly reduced hepatic cytochrome P450 2E1 activities and increased alcohol dehydrogenase and aldehyde dehydrogenase 2 activities compared to the alcohol control group, which resulted in a lower plasma acetaldehyde level in the rats that received UF. Chronic alcohol exposure inhibited hepatic AMPK activation compared to the pair-fed rats, which was reversed by UF supplementation. UF also significantly suppressed the lipogenic gene expression (SREBP-1c, SREBP-2, FAS, CIDEA, and PPARγ) and elevated the fatty acid oxidation gene expression (PPARα, Acsl1, CPT, Acox, and Acaa1a) compared to the alcohol control group, which could lead to inhibition of FAS activity and stimulation of CPT and fatty acid β-oxidation activities in the liver of chronic alcohol-fed rats. These results indicated that UF attenuated alcoholic steatosis through down-regulation of SREBP-1c-mediated lipogenesis and up-regulation of PPARα-mediated fatty acid oxidation. Therefore, UF may provide a promising natural therapeutic strategy against alcoholic fatty liver.
authors.affiliation: Department of Hotel Cuisine, Suseong College, Daegu, 706-022, Republic of Korea.
authors.forename: Myung-Joo
authors.initials: MJ
authors.lastname: Kim
authors.affiliation: Jeollanamdo Development Institute of Korean Traditional Medicine, Jangheung, 529-851, Republic of Korea.
authors.forename: Mi-Ok
authors.initials: MO
authors.lastname: Sim
authors.affiliation: Department of Food and Nutrition, Sunchon National University, 255 Jungang-ro, Suncheon, Jeonnam, 540-950, Republic of Korea.
authors.forename: Hae-In
authors.initials: HI
authors.lastname: Lee
authors.affiliation: Department of Food and Nutrition, Sunchon National University, 255 Jungang-ro, Suncheon, Jeonnam, 540-950, Republic of Korea.
authors.forename: Ju Ri
authors.initials: JR
authors.lastname: Ham
authors.affiliation: Department of Food and Nutrition, Sunchon National University, 255 Jungang-ro, Suncheon, Jeonnam, 540-950, Republic of Korea.
authors.forename: Kwon-Il
authors.initials: KI
authors.lastname: Seo
authors.affiliation: Department of Food and Nutrition, Sunchon National University, 255 Jungang-ro, Suncheon, Jeonnam, 540-950, Republic of Korea. Electronic address: leemk@sunchon.ac.kr.
authors.forename: Mi-Kyung
authors.initials: MK
authors.lastname: Lee
mesh_terms: D000426:Alcohol Dehydrogenase / Q000378:metabolism; D000444:Aldehyde Dehydrogenase / Q000378:metabolism; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000818:Animals; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D019587:Dietary Supplements; D005235:Fatty Liver, Alcoholic / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D007069:Ifosfamide / Q000031:analogs & derivatives / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D024101:Mitochondrial Proteins / Q000378:metabolism; D047493:PPAR alpha / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D051780:Sterol Regulatory Element Binding Protein 1 / Q000187:drug effects* / Q000502:physiology; D014468:Umbelliferones / Q000627:therapeutic use*
chemical_list: D000960:Hypolipidemic Agents; D024101:Mitochondrial Proteins; D047493:PPAR alpha; D051780:Sterol Regulatory Element Binding Protein 1; D014468:Umbelliferones; C064634:acetaldoifosphamide; C031477:7-hydroxycoumarin; D000426:Alcohol Dehydrogenase; D019392:Cytochrome P-450 CYP2E1; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; C505112:Aldh2 protein, rat; D007069:Ifosfamide
keywords: Alcoholic fatty liver; Lipid metabolism; PPARα; SREBP-1c; Umbelliferone