title: Esculetin prevents non-alcoholic fatty liver in diabetic mice fed high-fat diet.
abstract: This study investigated the effects and mechanism of esculetin (6,7-dihydroxycoumarin) on non-alcoholic fatty liver in diabetic mice fed high-fat diet (HFD). The diabetic mice model was induced by injection of streptozotocin, after which they were fed HFD diet with or without esculetin for 11 weeks. Non-diabetic mice were provided a normal diet. Diabetes induced hepatic hypertrophy, lipid accumulation and droplets; however, esculetin reversed these changes. Esculetin treatment in diabetic mice fed HFD significantly down-regulated expression of lipid synthesis genes (Fasn, Dgat2 and Plpp2) and inflammation genes (Tlr4, Myd88, Nfkb, Tnfα and Il6). Moreover, the activities of hepatic lipid synthesis enzymes (fatty acid synthase and phosphatidate phosphohydrolase) and gluconeogenesis enzyme (glucose-6-phosphatase) in the esculetin group were decreased compared with the diabetic group. In addition, esculetin significantly reduced blood HbA1c, serum cytokines (TNF-α and IL-6) and chemokine (MCP-1) levels compared with the diabetic group without changing the insulin content in serum and the pancreas. Hepatic SOD activity was lower and lipid peroxidation level was higher in the diabetic group than in the normal group; however, esculetin attenuates these differences. Overall, these results demonstrated that esculetin supplementation could protect against development of non-alcoholic fatty liver in diabetes via regulation of lipids, glucose and inflammation.
authors: Department of Food and Nutrition, Sunchon National University, Suncheon, 57922, Republic of Korea.
authors: Ra-Yeong
authors: RY
authors: Choi
authors: Department of Food and Nutrition, Sunchon National University, Suncheon, 57922, Republic of Korea.
authors: Ju Ri
authors: JR
authors: Ham
authors: Department of Food and Nutrition, Sunchon National University, Suncheon, 57922, Republic of Korea. Electronic address: leemk@sunchon.ac.kr.
authors: Mi-Kyung
authors: MK
authors: Lee
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D018925:Chemokines / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000150:complications* / Q000188:drug therapy*; D059305:Diet, High-Fat / Q000009:adverse effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D007249:Inflammation / Q000473:pathology; D007328:Insulin / Q000097:blood; D050356:Lipid Metabolism / Q000187:drug effects / Q000235:genetics; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000517:prevention & control*; D013482:Superoxide Dismutase / Q000378:metabolism; D014468:Umbelliferones / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D001786:Blood Glucose; D018925:Chemokines; D007328:Insulin; D014468:Umbelliferones; D013482:Superoxide Dismutase; C007628:esculetin
keywords: Diabetes; Esculetin; High-fat diet; Inflammation; Non-alcoholic fatty liver