title: Coordinated regulation of scopoletin at adipose tissue-liver axis improved alcohol-induced lipid dysmetabolism and inflammation in rats.
abstract: There is increasing evidence that alcohol-induced white adipose tissue (WAT) dysfunction contributes to disturbance of hepatic lipid metabolism. This study investigated the effects of scopoletin on lipid homeostasis and inflammation at the WAT and liver in chronic alcohol-fed rats. Rats were fed a liquid diet containing 5% alcohol with or without two doses of scopoletin (0.001% and 0.005%) for 8 weeks. Scopoletin decreased serum triglyceride and cytokines (TNFα and IL-6) levels and hepatic and WAT lipid levels, whereas it increased WAT adiponectin mRNA and serum adiponectin levels, up-regulated hepatic gene and protein expression of AdipoR2 and activated AMPK. Additionally, scopoletin inhibited the expression of lipogenic genes (SREBP-1c and Fasn) and increased the expression of fatty acid oxidative genes (PPARα, Acsl1, CPT, Acox, and Acaa1a) in both WAT and liver. Alcohol led to significant up-regulation of WAT lipolysis and hepatic Cidea gene expression, whereas it decreased the WAT Cidea gene level; however, scopoletin reversed these changes. Scopoletin significantly down-regulated TLR4 signaling genes such as MyD88, TRIF, NFκB, TNFα and IL-6 in WAT and liver. These results indicated that coordinated regulation of scopoletin at the WAT-liver axis may play an important role in improvement of alcohol-induced lipid dysregulation and inflammation.
authors.affiliation: Department of Food and Nutrition, Sunchon National University, Suncheon, 540-950, South Korea. Electronic address: leemk@sunchon.ac.kr.
authors.forename: Hae-In
authors.initials: HI
authors.lastname: Lee
authors.affiliation: Department of Food and Nutrition, Sunchon National University, Suncheon, 540-950, South Korea.
authors.forename: Mi-Kyung
authors.initials: MK
authors.lastname: Lee
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000378:metabolism; D052242:Adiponectin / Q000097:blood; D000273:Adipose Tissue / Q000187:drug effects*; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D000431:Ethanol / Q000009:adverse effects; D007249:Inflammation / Q000188:drug therapy*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects*; D008099:Liver / Q000187:drug effects*; D008297:Male; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D054419:Receptors, Adiponectin / Q000235:genetics / Q000378:metabolism; D012603:Scopoletin / Q000494:pharmacology*; D015398:Signal Transduction; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D005723:gamma-Glutamyltransferase / Q000097:blood
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D052242:Adiponectin; D015850:Interleukin-6; C507781:Myd88 protein, rat; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D047493:PPAR alpha; D054419:Receptors, Adiponectin; D051780:Sterol Regulatory Element Binding Protein 1; C523075:Ticam1 protein, rat; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; C506573:adiponectin receptor 2, rat; D000431:Ethanol; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D055372:AMP-Activated Protein Kinases; D012603:Scopoletin
keywords: Adipose tissue; Alcohol; Inflammation; Liver; Scopoletin