title: Astaxanthin lowers plasma TAG concentrations and increases hepatic antioxidant gene expression in diet-induced obesity mice.
abstract: Non-alcoholic fatty liver disease (NAFLD) is significantly associated with hyperlipidaemia and oxidative stress. We have previously reported that astaxanthin (ASTX), a xanthophyll carotenoid, lowers plasma total cholesterol and TAG concentrations in apoE knockout mice. To investigate whether ASTX supplementation can prevent the development of NAFLD in obesity, male C57BL/6J mice (n 8 per group) were fed a high-fat diet (35%, w/w) supplemented with 0, 0.003, 0.01 or 0.03% of ASTX (w/w) for 12 weeks. The 0.03% ASTX-supplemented group, but not the other groups, exhibited a significant decrease in plasma TAG concentrations, suggesting that ASTX at a 0.03% supplementation dosage exerts a hypotriacylglycerolaemic effect. Although there was an increase in the mRNA expression of fatty acid synthase and diglyceride acyltransferase 2, the mRNA levels of acyl-CoA oxidase 1, a critical enzyme in peroxisomal fatty acid β-oxidation, exhibited an increase in the 0.03% ASTX-supplemented group. There was a decrease in plasma alanine transaminase (ALT) and aspartate transaminase (AST) concentrations in the 0.03% ASTX-supplemented group. There was a significant increase in the hepatic mRNA expression of nuclear factor erythroid 2-related factor 2 and its downstream genes, which are critical for endogenous antioxidant mechanism, in the 0.03% ASTX-supplemented group. Furthermore, there was a significant decrease in the mRNA abundance of IL-6 in the primary splenocytes isolated from the 0.03% ASTX-supplemented group upon lipopolysaccharide (LPS) stimulation when compared with that in the splenocytes isolated from the control group. In conclusion, ASTX supplementation lowered the plasma concentrations of TAG, ALT and AST, increased the hepatic expression of endogenous antioxidant genes, and rendered splenocytes less sensitive to LPS stimulation. Therefore, ASTX may prevent obesity-associated metabolic disturbances and inflammation.
authors.affiliation: Department of Nutritional Sciences,University of Connecticut,Storrs,CT06269,USA.
authors.forename: Yue
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Nutritional Sciences,University of Connecticut,Storrs,CT06269,USA.
authors.forename: Tho X
authors.initials: TX
authors.lastname: Pham
authors.affiliation: Department of Nutritional Sciences,University of Connecticut,Storrs,CT06269,USA.
authors.forename: Casey J
authors.initials: CJ
authors.lastname: Wegner
authors.affiliation: Department of Nutritional Sciences,University of Connecticut,Storrs,CT06269,USA.
authors.forename: Bohkyung
authors.initials: B
authors.lastname: Kim
authors.affiliation: Department of Nutritional Sciences,University of Connecticut,Storrs,CT06269,USA.
authors.forename: Chai Siah
authors.initials: CS
authors.lastname: Ku
authors.affiliation: Department of Nutritional Sciences,University of Connecticut,Storrs,CT06269,USA.
authors.forename: Young-Ki
authors.initials: YK
authors.lastname: Park
authors.affiliation: Department of Nutritional Sciences,University of Connecticut,Storrs,CT06269,USA.
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Lee
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001219:Aspartate Aminotransferases / Q000097:blood; D059305:Diet, High-Fat; D019587:Dietary Supplements; D015870:Gene Expression / Q000187:drug effects; D050356:Lipid Metabolism / Q000187:drug effects; D050155:Lipogenesis / Q000187:drug effects / Q000235:genetics; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D051267:NF-E2-Related Factor 2 / Q000235:genetics; D065626:Non-alcoholic Fatty Liver Disease / Q000517:prevention & control; D009765:Obesity / Q000097:blood* / Q000188:drug therapy* / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013154:Spleen / Q000187:drug effects / Q000378:metabolism; D014280:Triglycerides / Q000097:blood*; D024341:Xanthophylls / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D012333:RNA, Messenger; D014280:Triglycerides; D024341:Xanthophylls; C005948:astaxanthine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase