Siphonaxanthin, a carotenoid from green algae Codium cylindricum, protects Ob/Ob mice fed on a high-fat diet against lipotoxicity by ameliorating somatic stresses and restoring anti-oxidative capacity

• Published in: Nutrition research (New York, N.Y.) Vol. 77; pp. 29 - 42
• Main Authors: Zheng, Jiawen, Manabe, Yuki, Sugawara, Tatsuya
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.05.2020
• Subjects: adiposity; alanine transaminase; animal disease models; antioxidant activity; antioxidant genes; antioxidants; beta oxidation; blood glucose; Carotenoid; carotenoids; Codium; diabetes mellitus; Endothelium reticulum stress; fatty liver; gene expression; high fat diet; human cell lines; kidneys; lipid peroxidation; lipids; lipogenesis; lipotoxicity; liver; mice; Non-alcoholic fatty liver diseases; Obesity; Oxidative stress; pathogenesis; protein degradation; Oxidative stress; NAFLD; DMSO; ALT; PDA; HDL; TBA; NEFA; UPR; GSH; HPLC; Obesity; GSSG; Endothelium reticulum stress; AST; H&E; qRT-PCR; TBARS; NASH; ER; ERAD; SDS-PAGE; TCA; ROS; Non-alcoholic fatty liver diseases; Carotenoid
• ISSN: 0271-5317; 1879-0739; 1879-0739
• DOI: 10.1016/j.nutres.2020.02.001

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.