Tokutake Sashima

Anti-obesity and anti-diabetic effects of fucoxanthin on diet-induced obesity conditions in a murine model

Fucoxanthin, a characteristic carotenoid of brown algae, has been reported to exert an anti-diabetic effect in an obese murine model. Wakame (Undaria pinnatifida), an edible seaweed, is rich in fucoxanthin. This study examined the anti-obesity and anti-diabetic effects of fucoxanthin-rich wakame lipids (WLs) on high fat (HF) diet-induced obesity in mice. Mice were fed a high fat control (HFC) or normal fat control (NFC) diet for 10 weeks. The HF diet-fed group was administered a HF diet containing WLs for a further 5 weeks. Parameters related to diabetes and obesity conditions were evaluated and compared. The HF-WL diet, which was rich in fucoxanthin, significantly suppressed body weight and white adipose tissue (WAT) weight gain induced by the HF diet. Dietary administration of the HF diet resulted in hyperglycemia, hyperinsulinemia and hyperleptinemia in the mouse model. These perturbations were completely normalized in the HF-WL diet-fed group. Increased expression of monocyte chemoattractant protein-1 (MCP-1) mRNA expression was observed in HFC mice, but was normalized in the HF-WL groups. Moreover, the HF-WL diet promoted mRNA expression of β3-adrenergic receptor (Adrb3) in WAT and glucose transporter 4 (GLUT4) mRNA in skeletal muscle tissues. These results suggest that dietary WLs may ameliorate alterations in lipid metabolism and insulin resistance induced by a HF diet. There is therefore a biochemical and nutritional basis for the application of fucoxanthin-rich WLs as a functional food to prevent obesity and diabetes-related disorders.

Enhancement of hepatic docosahexaenoic acid and arachidonic acid contents in C57BL/6J mice by dietary fucoxanthin

The n-3 highly unsaturated fatty acids (HUFAs), such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), are known to possess beneficial health properties such as reduction of serum triacylglycerol and cholesterol [1], anti-inflammatory [2], and anticancer effects [3]. In addition, DHA has been reported to be essential for brain function [4] and development, especially in babies and infants [5]. Major source of DHA is fish oil obtained from fishes such as salmon, tuna, and bonito. Dietary intake of fish results in absorption and increases the amount of DHA in body. On the other hand, DHA and EPA are also synthesized from the precursor a-linolenic acid (ALA), while arachidonic acid (AA), an n-6 HUFA, is synthesized from linoleic acid (LA). In these biosynthetic pathways of HUFAs, D6-desaturase, which catalyzes the desaturation of LA, ALA, and 24:5n-3, has been reported to be the ratelimiting enzyme [6]. Fucoxanthin is a major marine carotenoid found in edible seaweeds such as Undaria pinnatifida and Sargassum fulvellum. In a previous study, we reported an increase in the amount of DHA in the livers of 4-week-old, obese/ diabetic KK-A mice due to dietary feeding of fucoxanthin [7]. Because the liver plays an important role in lipid metabolism, an increase in hepatic DHA by fucoxanthin is expected to show beneficial health effects. However, KK-A mouse strain used in our previous study was a genetically modified model for obesity/diabetes syndrome due to its A/? genotype and young, 4-week age. In this study, we therefore examined the effect of fucoxanthin on the level of HUFAs in the liver using normal adult mice, namely C57BL/6J mice (male, 19 weeks old prior to fucoxanthin feeding). Lipids were extracted from commercially available dry wakame (U. pinnatifida) with acetone. Fucoxanthin was purified from the extracted lipids by silica gel column chromatography according to the procedure previously reported [8]. The neutral lipids and chlorophylls were removed with acetone:n-hexane (3:7, v/v), followed by elution of fucoxanthin with acetone:n-hexane (1:1, v/v). Silica gel column chromatography was repeated. Purity of fucoxanthin was 93% by high-performance liquid chromatography (HPLC). C57BL/6J mice (male, 9 weeks old) were purchased from CLEA Japan, Inc. (Tokyo, Japan). The mice were housed at 23 ± 1 C and 50% relative humidity under a 12h light/dark cycle, and had free access to food and drinking water. All procedures for the use and care of animals for this research were approved by the Ethical Committee of Experimental Animal Care at Hokkaido University. Mice were fed with AIN-93G diet containing 7% soybean oil for 10 weeks, and then divided into groups of six each and fed control or experimental diets for the next 5 weeks. Fucoxanthin was added to the basal diet AIN-93G at the rate of 0.025% and 0.05%. Fatty acid composition of lipids contained in 0.025% and 0.05% fucoxanthin diets were the same as that of the control diet with 7% soybean oil. After 5 weeks on the experimental or control diet, animals were T. Tsukui N. Baba M. Hosokawa (&) K. Miyashita Faculty of Fisheries Sciences, Hokkaido University, Hakodate, Hokkaido 041-8611, Japan e-mail: hoso@fish.hokudai.ac.jp