siphonaxanthin and Non-alcoholic-Fatty-Liver-Disease

Oxidative stress is implicated in the pathogenesis of many diseases including obesity, non-alcoholic fatty liver disease, and diabetes mellitus. Previously, we reported that siphonaxanthin, a carotenoid from green algae, elicited a potent inhibitory effect on hepatic de novo lipogenesis, and an anti-obesity effect in both 3T3L1 cells and KKAy mice. Thus, we hypothesized that consumption of siphonaxanthin could improve metabolic disorders including hepatic steatosis and systemic adiposity, as well as ameliorate somatic stress under obese conditions. Both the hepatocyte cell line HepG2 and a mouse model of severe obesity, produced by feeding Ob/Ob mice on a high-fat diet (HFD), were used to test this hypothesis. In obese mice, siphonaxanthin intake did not improve liver steatosis or systemic adiposity. However, intake did lower plasma glucose and alanine aminotransferase (ALT) levels and diminished hepatic lipid peroxidation products and antioxidant gene expression, which increased significantly in control group obese mice. Renal protein carbonyl content decreased significantly in the siphonaxanthin group, which might also indicate an ameliorated oxidative stress. Siphonaxanthin restored gene expression related to antioxidant signaling, lipid β-oxidation, and endoplasmic-reticulum-associated protein degradation in the kidney, which decreased significantly in obese mice. Liver and kidney responded to obesity-induced somatic stress in a divergent pattern. In addition, we confirmed that siphonaxanthin potently induced Nrf2-regulated antioxidant signaling in HepG2 cells. In conclusion, our results indicated that siphonaxanthin might protect obesity-leading somatic stress through restoration of Nrf2-regulated antioxidant signaling, and might be a promising nutritional supplement.

Topics: Animals; Antioxidants; Chlorophyta; Diet, High-Fat; Dietary Supplements; Endoplasmic Reticulum Stress; Gene Expression Regulation; Heme Oxygenase-1; Hep G2 Cells; Humans; Kidney; Lipid Metabolism; Liver; Male; Membrane Proteins; Mice, Obese; NF-E2-Related Factor 2; Non-alcoholic Fatty Liver Disease; Obesity; Oxidation-Reduction; Oxidative Stress; Signal Transduction; Thiobarbituric Acid Reactive Substances; Xanthophylls

Nonalcoholic fatty liver disease (NAFLD) has shown an increasing morbidity in recent years. Here, we demonstrated that siphonaxanthin (SPX), a rare marine carotenoid, exhibits a strong inhibitory effect on aggravated hepatic lipogenesis in vitro and would be a promising candidate in the prevention and alleviation of NAFLD in the future. In this study, we conducted a preliminary assessment of the effect of SPX on hepatic lipogenesis by using the HepG2 cell line, derived from human liver cancer, as a model of the liver. SPX significantly suppressed the excess accumulation of triacylglycerol induced by liver X receptor α (LXRα) agonist by downregulating a nuclear transcription factor named sterol regulatory element-binding protein-1c and a set of related genes. Moreover, fatty acid translocase (CD36) and fatty acid-binding protein-1, which regulates fatty acid uptake, also exhibited significant decrease in transcriptional levels. Furthermore, we found that SPX blocked LXRα activation and would be a promising candidate for antagonist of LXRα.

Topics: Carotenoids; CD36 Antigens; Chlorophyta; Fatty Acids; Hep G2 Cells; Hepatocytes; Humans; Lipogenesis; Liver X Receptors; Non-alcoholic Fatty Liver Disease; Sterol Regulatory Element Binding Protein 1; Xanthophylls