siphonaxanthin and Obesity

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

Marine carotenoids have been reported to prevent and alleviate lifestyle-related diseases including diabetes and obesity. We previously reported that siphonaxanthin, a green algal carotenoid, effectively suppresses adipogenesis in 3T3-L1 cells and prevents lipid accumulation in mesenteric adipose tissue of KK-Ay mice. Thus, we expect that dietary siphonaxanthin-rich marine green algae may effectively prevent obesity. Here, we assessed the effect of dietary siphonaxanthin-rich green algae (Codium cylindricum) on the development of diet-induced obesity in C57BL/6J mice. The mice were fed a low-fat diet (LF; 7% fat, w/w), a high-fat diet (HF; 35% fat, w/w), or a high-fat diet supplemented with 1% or 5% green algal powder (1GA or 5GA) for 78 d. Our results showed that weights of body and perirenal white adipose tissue (WAT) in the 5GA group were significantly lower than that in the HF group. The mesenteric and total WAT, as well as plasma and hepatic cholesterol concentrations tended to be lower in both the 1GA and 5GA groups compared to the HF group. Dietary green algal powder reduced the expression of lipogenesis-related genes and enhanced the expression of energy expenditure-related genes in the mesenteric WAT. Siphonaxanthin accumulated in the mesenteric WAT may contribute to the prevention of adiposity in mesenteric WAT. Furthermore, the reduction in the weight of WAT was attributed to the inhibitory effect on fat absorption of dietary fiber contained in the green algae. Overall, these results indicated that siphonaxanthin-rich green algae may be beneficial for the prevention of obesity and regulation of lipid metabolism.

Topics: Adipose Tissue, White; Adiposity; Animals; Anti-Obesity Agents; Body Weight; Chlorophyta; Cholesterol; Diet, High-Fat; Dietary Fiber; Dietary Supplements; Energy Metabolism; Gene Expression; Intestinal Absorption; Intra-Abdominal Fat; Lipid Metabolism; Liver; Male; Mesentery; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity; Xanthophylls