Dietary β-Cryptoxanthin Inhibits High-Refined Carbohydrate Diet–Induced Fatty Liver via Differential Protective Mechanisms Depending on Carotenoid Cleavage Enzymes in Male Mice. Issue 9 (18th June 2019)

• Record Type: Journal Article
• Authors: Lim, Ji Ye; Liu, Chun; Hu, Kang-Quan; Smith, Donald E; Wu, Dayong; Lamon-Fava, Stefania; Ausman, Lynne M; Wang, Xiang-Dong
• Is Part Of: Journal of nutrition. Volume 149:Issue 9(2019)
• Page Start: 1553
• Page End: 1564
• Publication Date: 2019-06-18
• Subjects: NAFLD -- high-refined carbohydrate diet -- β-cryptoxanthin -- carotenoid cleavage enzymes -- sirtuin 1 -- nuclear receptors; Nutrition -- Periodicals; Diet -- Periodicals; 613.205
• DOI: 10.1093/jn/nxz106
• Languages: English
• ISSNs: 0022-3166

Abstract

ABSTRACT: Background: β-Cryptoxanthin (BCX), a provitamin A carotenoid shown to protect against nonalcoholic fatty liver disease (NAFLD), can be cleaved by β-carotene-15, 15′-oxygenase (BCO1) to generate vitamin A, and by β-carotene-9′, 10′-oxygenase (BCO2) to produce bioactive apo-carotenoids. BCO1/BCO2 polymorphisms have been associated with variations in plasma carotenoid amounts in both humans and animals. Objectives: We investigated whether BCX feeding inhibits high refined-carbohydrate diet (HRCD)-induced NAFLD, dependent or independent of BCO1/BCO2. Methods: Six-week-old male wild-type (WT) and BCO1 −/− /BCO2 −/− double knockout (DKO) mice were randomly fed HRCD (66.5% of energy from carbohydrate) with or without BCX (10 mg/kg diet) for 24 wk. Pathological and biochemical variables were analyzed in the liver and mesenteric adipose tissues (MATs). Data were analyzed by 2-factor ANOVA. Results: Compared to their respective HRCD controls, BCX reduced hepatic steatosis severity by 33‒43% and hepatic total cholesterol by 43‒70% in both WT and DKO mice ( P < 0.01). Hepatic concentrations of BCX, but not retinol and retinyl palmitate, were 33-fold higher in DKO mice than in WT mice ( P < 0.001). BCX feeding increased the hepatic fatty acid oxidation protein peroxisome proliferator-activated receptor-α, and the cholesterol efflux gene ATP-binding cassette transporter5, and suppressed the lipogenesis gene acetyl-CoA carboxylase 1 ( Acc1 ) in the MAT of WT mice but not DKO mice ( P < 0.05). BCX feeding decreased the hepatic lipogenesis proteins ACC and stearoyl-CoA desaturase-1 (3-fold and 5-fold) and the cholesterol synthesis genes 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase and HMG-CoA synthase 1 (2.7-fold and 1.8-fold) and increased the cholesterol catabolism gene cholesterol 7α-hydroxylase (1.9-fold) in the DKO but not WT mice ( P < 0.05). BCX feeding increased hepatic protein sirtuin1 (2.5-fold) and AMP-activated protein kinase (9-fold) and decreased hepatic farnesoid X receptor protein (80%) and the inflammatory cytokine gene Il6 (6-fold) in the MAT of DKO mice but not WT mice ( P < 0.05). Conclusion: BCX feeding mitigates HRCD-induced NAFLD in both WT and DKO mice through different mechanisms in the liver-MAT axis, depending on the presence or absence of BCO1/BCO2.