zeaxanthin and Non-alcoholic-Fatty-Liver-Disease

Carotenoids form an important part of the human diet, consumption of which has been associated with many health benefits. With the growing global burden of liver disease, increasing attention has been paid on the possible beneficial role that carotenoids may play in the liver. This review focuses on carotenoid actions in non-alcoholic fatty liver disease (NAFLD), and alcoholic liver disease (ALD). Indeed, many human studies have suggested an association between decreased circulating levels of carotenoids and increased incidence of NAFLD and ALD. The literature describing supplementation of individual carotenoids in rodent models of NAFLD and ALD is reviewed, with particular attention paid to β-carotene and lycopene, but also including β-cryptoxanthin, lutein, zeaxanthin, and astaxanthin. The effect of beta-carotene oxygenase 1 and 2 knock-out mice on hepatic lipid metabolism is also discussed. In general, there is evidence to suggest that carotenoids have beneficial effects in animal models of both NAFLD and ALD. Mechanistically, these benefits may occur via three possible modes of action: 1) improved hepatic antioxidative status broadly attributed to carotenoids in general, 2) the generation of vitamin A from β-carotene and β-cryptoxanthin, leading to improved hepatic retinoid signaling, and 3) the generation of apocarotenoid metabolites from β-carotene and lycopene, that may regulate hepatic signaling pathways. Gaps in our knowledge regarding carotenoid mechanisms of action in the liver are highlighted throughout, and the review ends by emphasizing the importance of dose effects, mode of delivery, and mechanism of action as important areas for further study. This article is part of a Special Issue entitled Carotenoids recent advances in cell and molecular biology edited by Johannes von Lintig and Loredana Quadro.

Topics: Animals; beta-Carotene 15,15'-Monooxygenase; Beta-Cryptoxanthin; Carotenoids; Humans; Liver Diseases, Alcoholic; Lutein; Mice; Mice, Knockout; Non-alcoholic Fatty Liver Disease; Vitamin A; Xanthophylls; Zeaxanthins

Non-alcoholic fatty liver disease (NAFLD) is a common liver disorder worldwide and a risk factor for obesity and diabetes. Emerging evidence has shown that ferroptosis is involved in the progression of NAFLD. Zeaxanthin (ZEA) is a carotenoid found in human serum. It has been reported that ZEA can ameliorate obesity, prevent age-related macular degeneration, and protect against non-alcoholic steatohepatitis. However, no study has focused on the protective effects of ZEA against NAFLD. In this study, free fatty acid (FFA) induced HepG2 cells were used as a cell model for NAFLD. Our results suggest that ZEA exerts antioxidative and anti-inflammatory effects in FFA-induced HepG2 cells. Moreover, ZEA acted as a ferroptosis inhibitor, significantly reducing reactive oxygen species (ROS) generation and iron overload and improving mitochondrial dysfunction in FFA-induced HepG2 cells. In addition, ZEA downregulated the expression of p53 and modulated downstream targets, such as GPX4, SLC7A11, SAT1, and ALOX15, which contributed to the reduction in cellular lipid peroxidation. Our findings suggest that ZEA has the potential for NAFLD intervention.

Topics: Fatty Acids, Nonesterified; Ferroptosis; Hep G2 Cells; Humans; Lipid Metabolism; Mitochondria; Non-alcoholic Fatty Liver Disease; Obesity; Tumor Suppressor Protein p53; Zeaxanthins

Previous studies showed lutein and zeaxanthin (L and Z) may influence cognitive function by different mechanisms. Our study aimed to be the first to examine whether the risk of non-alcoholic fatty liver disease (NAFLD) mediated the possible association between the dietary intake of L and Z and cognitive function.. We conducted a cross-sectional analysis of participants aged 60 years or over in the National Health and Nutrition Examination Survey (NHANES) 2011-2014. Multivariable linear regression was used to investigate the association between the dietary intake of L and Z and cognitive function, and structural equation modeling tested the mediation effect.. The fatty liver index for the United States population (US FLI) acted as a mediator in the association between the higher intake of L and Z and the Animal Fluency Test, the Digit Symbol Substitution Test (DSST), and composite score and mediated 13.89%, 17.87%, and 13.79% of the total association in dietary L and Z intake (14.29%, 13.68%, and 10.34% of the total association in total L and Z intake), respectively.. Our study indicated the potential role of the risk of NAFLD as a mediator of associations between the dietary intake of L and Z and cognitive function in the geriatric American population.

Topics: Aged; Cognition; Cross-Sectional Studies; Humans; Lutein; Non-alcoholic Fatty Liver Disease; Nutrition Surveys; United States; Zeaxanthins