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The aim of this study was to evaluate the preventive role and underlying mechanisms of fucoxanthin (Fx) on lipopolysaccharide (LPS)-induced intestinal barrier injury in mice. Our results demonstrated that the oral administration of Fx (50 and 200 mg per kg body weight per day) for consecutive 7 days significantly alleviated the severity of LPS-induced intestinal barrier injury in mice, as evidenced by attenuating body weight loss, improving intestinal permeability, and ameliorating intestinal morphological damage such as reduction in the ratio of the villus length to the crypt depth ( V / C ), intestinal epithelium distortion, goblet cell depletion, and low mucin 2 (MUC2) expression. Fx also significantly mitigated LPS-induced excessive apoptosis of intestinal epithelial cells (IECs) and curbed the decrease of tight junction proteins including claudin-1, occludin, and zonula occludens-1 in the ileum and colon. Additionally, Fx effectively alleviated LPS-induced extensive infiltration of macrophages and neutrophils into the intestinal mucosa, the overproduction of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin 1beta (IL-1β) and IL-6, and gasdermin D (GSDMD)-mediated pyroptosis of IECs. The underlying mechanisms might be associated with inhibiting the activation of nuclear factor-kappa B (NF-κB), mitogen-activated protein kinases (MAPKs) and nod-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome signaling pathways. Moreover, Fx also notably restrained intestinal reactive oxygen species (ROS), malondialdehyde and protein carbonylation levels in LPS-treated mice, and it might be mediated by activating the nuclear factor-erythroid 2 related factor 2 (Nrf2) signaling pathway. Overall, these findings indicated that Fx might be developed as a potential effective dietary supplement to prevent intestinal barrier injury.

The purpose of this study was to evaluate the preventive role and underlying mechanisms of fucoxanthin (Fx) on dextran sulfate sodium (DSS)-induced colitis in mice. The present data demonstrated that oral administration of Fx (50 and 200 mg/kg body weight/day) for 36 days significantly alleviated the severity of colitis in DSS-treated mice, as evidenced by attenuating body weight loss, bloody stool, diarrhea, shortened colon length, colonic epithelium distortion, a thin mucus layer, goblet cell depletion, damaged crypts, and extensive infiltration of inflammatory cells in the colonic mucosa. Additionally, Fx notably relieved DSS-induced intestinal epithelial barrier dysfunction via maintaining the tight junction function and preventing excessive apoptosis of colonic epithelial cells. Moreover, Fx effectively diminished colonic inflammation and oxidative stress in DSS-treated mice, and its mechanisms might be due to blunting the activation of NF-κB and NLRP3 inflammasome signaling pathways. Furthermore, Fx also modulates DSS-induced gut microbiota dysbiosis via recovering the richness and diversity of gut microbiota and reshaping the structure of gut microbiota, such as increasing the Firmicutes and Bacteroidota (F/B) ratio and elevating the relative abundance of some potential beneficial bacteria, including Lactobacillaceae and Lachnospiraceae . Overall, Fx might be developed as a promising functional ingredient to prevent colitis and maintain intestinal homeostasis.

Fucoxanthin (Fx) has shown potential cancer chemopreventive functions in a carcinogenic murine azoxymethane/dextran sodium sulfate (AOM/DSS) model. However, the molecular mechanisms based on transcriptome profiles in vivo remain poorly understood. We investigated Fx-dependent alterations of the transcriptome with cancer-associated proteins in colorectal mucosal tissue obtained from AOM/DSS mice with or without Fx treatment. Fx administration (50 mg/kg body weight for 14 weeks) significantly prevented the onset of colorectal adenocarcinoma in AOM/DSS mice. A transcriptome analysis revealed that 11 signals, including adhesion, cell cycle, chemokine receptor, interleukin, MAPK, PI3K/AKT, p53, RAS, STAT, TGF-β, and Wnt were remarkably altered by Fx administration. In particular, chemokine (C-C motif) receptor 1 (Ccr1), which is contained in a gene set related to cytokine-cytokine receptor interactions, was the only significantly down-regulated gene after Fx administration for both 7 and 14 weeks. CCR1, AKT, Cyclin D1, and Smad2 were found to play central roles in the 11 signals shown above. Fx administration significantly down-regulated CCR1 (0.3- and 0.5-fold in mucosal crypts and lamina propria, respectively), pAKT(Ser 473 ) (0.2-fold in mucosal crypts), Cyclin D1 (0.4-fold in mucosal crypts), and pSmad2(Ser 465/467 ) (0.7-fold in mucosal crypts) compared with proteins in these tissues of control mice after Fx administration for 14 weeks. Our findings suggested that Fx exerts a chemopreventive effect in AOM/DSS mice through attenuation of CCR1 expression along with 11 cancer-associated signals., (Copyright © 2021. Published by Elsevier Inc.)

Fucoxanthin (Fx) is a marine carotenoid with anti-inflammatory and anti-cancer properties in various animal models of carcinogenesis. However, there is currently no information on the effects of Fx in animal models of pancreatic cancer. We investigated the chemopreventive effects of Fx in C57BL/6J mice that received allogenic and orthotopic transplantations of cancer cells (KMPC44) derived from a pancreatic cancer murine model ( Ptf1a Cre/+ ; LSL - kras G12D/+ ). Using microarray, immunofluorescence, western blot, and siRNA analyses, alterations in cancer-related genes and protein expression were evaluated in pancreatic tumors of Fx-administered mice. Fx administration prevented the adenocarcinoma (ADC) development of pancreatic and parietal peritoneum tissues in a pancreatic cancer murine model, but not the incidence of ADC. Gene and protein expressions showed that the suppression of chemokine (C-C motif) ligand 21 (CCL21)/chemokine receptor 7 (CCR7) axis, its downstream of Rho A, B- and T-lymphocyte attenuator (BTLA), N-cadherin, αSMA, pFAK(Tyr 397 ), and pPaxillin(Tyr 31 ) were significantly suppressed in the pancreatic tumors of mice treated with Fx. In addition, Ccr7 knockdown significantly attenuated the growth of KMPC44 cells. These results suggest that Fx is a promising candidate for pancreatic cancer chemoprevention that mediates the suppression of the CCL21/CCR7 axis, BTLA, tumor microenvironment, epithelial mesenchymal transition, and adhesion.

Fucoxanthin (Fx) has preventive effect against muscle atrophy and myotube loss in vitro, but it has not yet been examined in vivo. Therefore, we aimed to investigate the effect of Fx on dexamethasone (Dex)-induced muscle atrophy and fat mass in mice. ICR mice were fed with Fx diets from 2 weeks before Dex treatment to the end of the study. Muscle atrophy was induced in the mice by oral administration of Dex. Body weight was significantly lower by Dex treatment. Visceral fat mass in the Fx-treated group were significantly lower than those in the control group. The Dex-induced decrease in tibialis anterior muscle mass was ameliorated by Fx treatment. Fx treatment significantly attenuated muscle lipid peroxidation compared with the control and Dex-treated groups. The phosphorylation of AMPK was significantly higher in the Dex-treated group than in the control group. The expression of cytochrome c oxidase (COX) IV was significantly higher in the Fx-treated group than in the control group. These results suggest that Fx may be a beneficial material to prevent muscle atrophy in vivo, in addition to the effect of fat loss.

Background/aim: A xanthophyll of fucoxanthin (Fx) is a potential chemopreventive agent. Familial adenomatous polyposis (FAP) is an inherited disease that is associated with a high risk of developing colorectal cancer. However, it remains unclear whether Fx can modify colorectal tumorigenesis in Apc Min/+ mice, a model mouse for human FAP., Materials and Methods: We investigated the chemopreventive effect of Fx in dextran sodium sulfate (DSS)-treated Apc Min/+ mice., Results: Administration of Fx in the diet for 5 weeks significantly suppressed the number of colorectal adenocarcinomas in DSS-treated male Apc Min/+ mice, although the treatment did not affect the occurrence of colorectal dysplastic crypts and adenoma in the mice. In addition, Fx down-regulated cyclin D1 expression (0.6-fold) in colorectal mucosa of Apc Min/+ mice when compared with that of the control mice., Conclusion: Fx possesses chemopreventive potential against progression of colorectal carcinogenesis in Apc Min/+ mice that receive inflammatory stimuli., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Fucoxanthin (Fx), a marine carotenoid found in edible brown algae, is well known for having anticancer properties. The gut microbiota has been demonstrated as a hallmark for colorectal cancer progression in both humans and rodents. However, it remains unclear whether the gut microbiota is associated with the anticancer effect of Fx. We investigated the chemopreventive potency of Fx and its effect on gut microbiota in a mouse model of inflammation-associated colorectal cancer (by azoxymethane/dextran sulfate sodium treatment). Fx administration (30 mg/kg bw) during a 14 week period significantly inhibited the multiplicity of colorectal adenocarcinoma in mice. The number of apoptosis-like cleaved caspase-3high cells increased significantly in both colonic adenocarcinoma and mucosal crypts. Fx administration significantly suppressed Bacteroidlales (f_uc; g_uc) (0.3-fold) and Rikenellaceae (g_uc) (0.6-fold) and increased Lachnospiraceae (g_uc) (2.2-fold), compared with those of control mice. Oral administration of a fecal suspension obtained from Fx-treated mice, aimed to enhance Lachnospiraceae, suppress the number of colorectal adenocarcinomas in azoxymethane/dextran sulfate sodium-treated mice with a successful increase in Lachnospiraceae in the gut. Our findings suggested that an alteration in gut microbiota by dietary Fx might be an essential factor in the cancer chemopreventive effect of Fx in azoxymethane/dextran sulfate sodium-treated mice., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Scope: Fucoxanthin is converted to fucoxanthinol and amarouciaxanthin A in the mouse body. However, further metabolism such as cleavage products (i.e., apocarotenoids) remains unclear. The fucoxanthin-derived apocarotenoid in vivo is investigated and the anti-inflammatory effect of apocarotenoids with fucoxanthin partial structure such as allenic bond and epoxide residue against activated macrophages and adipocytes in vitro is evaluated., Methods and Results: LC-MS analysis indicates the presence of paracentrone, a C 31 -allenic-apocarotenoid, in white adipose tissue of diabetic/obese KK-A y and normal C57BL/6J mice fed 0.2% fucoxanthin diet for 1 week. In lipopolysaccharide-activated RAW264.7 macrophages, paracentrone as well as C 26 - and C 28 -allenic-apocarotenoids suppresses the overexpression of inflammatory factors. Further, apo-10'-fucoxanthinal, a fucoxanthin-derived apocarotenoid which retained epoxide residue, exhibits a most potent anti-inflammatory activity through regulating mitogen-activated protein kinases and nuclear factor-κB inflammatory signal pathways. In contrast, β-apo-8'-carotenal without allenic bond and epoxide residue lacks suppressed inflammation. In 3T3-L1 adipocytes, paracentrone, and apo-10'-fucoxanthinal downregulate the mRNA expression of proinflammatory mediators and chemokines induced by co-culture with RAW264.7 cells., Conclusion: Dietary fucoxanthin accumulates as paracentrone as well as fucoxanthinol and amarouciaxanthin A in the mouse body. Allenic bond and epoxide residue of fucoxanthin-derived apocarotenoids have pivotal roles for anti-inflammatory action against activated macrophages and adipocytes., (© 2020 Wiley-VCH GmbH.)

Nonalcoholic steatohepatitis (NASH) is associated with hepatocyte injury, excessive oxidative stress, and chronic inflammation in fatty liver, and can progress to more severe liver diseases, such as cirrhosis and hepatocellular carcinoma. However, currently there are no effective therapies for NASH. Marine carotenoid, fucoxanthin (Fx), abundant in brown seaweeds, has variable biological properties, such as anti-cancer, anti-inflammatory, anti-oxidative and anti-obesity. However, the effect of Fx on the development of NASH has not been explored. We investigated the protective effects of Fx in diet-induced NASH model mice fed choline-deficient L-amino acid-defined high fat diet (CDAHFD). Fx administration significantly attenuated liver weight gain and hepatic fat accumulation, resulting in the alleviation of hepatic injury. Furthermore, the Fx-fed mice, not only exhibited reduced hepatic lipid oxidation, but also decreased mRNA expression levels of inflammation and infiltration-related genes compared to that of the CDAHFD-fed mice. Moreover, fucoxanthinol and amarouciaxanthin A, two Fx metabolites exerted anti-inflammatory effects in the liver via inhibiting the chemokine production in hepatocytes. In case of fibrosis, one of the features of advanced NASH, the expression of fibrogenic factors including activated-hepatic stellate cell marker was significantly decreased in the liver of Fx-fed mice. Thus, the present study elucidated that dietary Fx not only inhibited hepatic oxidative stress and inflammation but also prevented early phase of fibrosis in the diet-induced NASH model mice., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Fucoxanthin (Fx), a major carotenoid found in brown seaweed, is known to show a unique and wide variety of biological activities. Upon absorption, Fx is metabolized to fucoxanthinol and amarouciaxanthin, and these metabolites mainly accumulate in visceral white adipose tissue (WAT). As seen in other carotenoids, Fx can quench singlet oxygen and scavenge a wide range of free radicals. The antioxidant activity is related to the neuroprotective, photoprotective, and hepatoprotective effects of Fx. Fx is also reported to show anti-cancer activity through the regulation of several biomolecules and signaling pathways that are involved in either cell cycle arrest, apoptosis, or metastasis suppression. Among the biological activities of Fx, anti-obesity is the most well-studied and most promising effect. This effect is primarily based on the upregulation of thermogenesis by uncoupling protein 1 expression and the increase in the metabolic rate induced by mitochondrial activation. In addition, Fx shows anti-diabetic effects by improving insulin resistance and promoting glucose utilization in skeletal muscle., (Copyright © 2020. Published by Elsevier Inc.)

Background/ Aim: A high polar xanthophyll of Fucoxanthin (Fx) is abundantly contained in edible brown algae, and it has chemopreventive effects in mouse cancer models, however, the underlying mechanisms of these effects are not well understood. Thus, we aimed to investigate the effects of Fx on the tumor microenvironment in cancer model mice., Materials and Methods: We investigated the effect of Fx (30 mg/kg body weight) in a variety of cell types within the tumor microenvironment of α mouse preclinical colorectal cancer model and analyzed the mouse saliva in search of predictors for cancer chemopreventive effects., Results: Fx administration significantly decreased the number of colorectal polyps and tended to decrease colonic lesions compared to untreated control mice. In addition, Fx administration showed significantly lower numbers of colorectal cancer stem cells-like CD44 high /EpCAM high cells, cancer-associated fibroblasts-like αSMA high cells, tumor-associated macrophages-like and dendritic cells-like CD206 high cells by 0.6-, 0.5- and 0.6-fold, respectively, compared to untreated control mice. Moreover, the treatment also showed significantly lower levels of salivary glycine by 0.5-fold., Conclusion: Our results suggest that salivary glycine may be a predictor representing the chemopreventive effect of Fx in mice., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Fucoxanthin (Fx) and its biotransformed fucoxanthinol (FxOH) present strong anti-cancer effects in vitro and in vivo, however, the underlying mechanisms are not well known. We recently demonstrated that FxOH could induce anoikis-like cells in human colorectal cancer (CRC) cells. Thus, we developed molecular hallmarks for anoikis in vitro, and to confirm induction of such molecular hallmarks in an azoxymethane/ dextran sodium sulfate carcinogenic model by Fx ingestion. During the process of anoikis by FxOH (2.5 μmol/l) in DLD-1 cells, the cells show the characteristics of integrin β1 low/- , p-FAK(Tyr 397 ) low/- or p-Paxillin(Tyr 31 ) low/- cells with cleaved caspase-3 high , which may be useful as molecular hallmarks. Fx administration (30 mg/kg body weight) significantly suppressed the number and size of polyps compared with untreated control mice. In addition, the incidence and multiplicity of colonic lesions tended to reduce. Moreover, cells showing integrin β1 low/- , p-FAK(Tyr 397 ) low/- and p-Paxillin(Tyr 31 ) low/- with cleaved caspase-3 high in colonic crypts were significantly increased 2.2-, 4.8- and 5.2-fold by Fx administration compared with untreated control mice, respectively. Our results suggest that Fx showed a chemopreventive effect in the carcinogenic models through anoikis-like cells induction., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Microencapsulation is a promising approach in drug delivery to protect the drug from degradation and allow controlled release of the drug in the body. Fucoxanthin-loaded microsphere (F-LM) was fabricated by two step w/o/w double emulsion solvent evaporation method with poly (L-lactic-coglycolic acid) (PLGA) as carrier. The effect of four types of surfactants (PVA, Tween-20, Span-20 and SDS), homogenization speed, and concentration of PLGA polymer and surfactant (PVA), respectively, on particle size and morphology of F-LM were investigated. Among the surfactants tested, PVA showed the best results with smallest particle size (9.18 µm) and a smooth spherical surface. Increasing the homogenization speed resulted in a smaller mean F-LM particle size [d(0.50)] from 17.12 to 9.18 µm. Best particle size results and good morphology were attained at homogenization speed of 20 500 rpm. Meanwhile, increased PLGA concentration from 1.5 to 11.0 (% w/v) resulted in increased F-LM particle size. The mean particle size [d(0.5)] of F-LM increased from 3.93 to 11.88 µm. At 6.0 (% w/v) PLGA, F-LM showed the best structure and external morphology. Finally, increasing PVA concentration from 0.5 to 3.5 (% w/v) resulted in decreased particle size from 9.18 to 4.86 µm. Fucoxanthin characterization before and after microencapsulation was carried out to assess the success of the microencapsulation procedure. Thermo gravimetry analysis (TGA), glass transition (Tg) temperature of F-LM and fucoxanthin measured using DSC, ATR-FTIR and XRD indicated that fucoxanthin was successfully encapsulated into the PLGA matrix, while maintaining the structural and chemical integrity of fucoxanthin.

Fucoxanthin (Fx) is a marine carotenoid found in edible brown seaweeds. We previously reported that dietary Fx metabolite into fucoxanthinol (FxOH), attenuates the weight gain of white adipose tissue of diabetic/obese KK-Ay mice. In this study, to evaluate anti-diabetic effects of Fx, we investigated improving the effect of insulin resistance on the diabetic model of KK-Ay mice. Furthermore, preventing the effect of FxOH on low-grade chronic inflammation related to oxidative stress was evaluated on 3T3-L1 adipocyte cells and a RAW264.7 macrophage cell co-culture system. A diet containing 0.1% Fx was fed to diabetic model KK-Ay mice for three weeks, then glucose tolerance was observed. Fx diet significantly improved glucose tolerance compared with the control diet group.  In in vitro studies, FxOH showed suppressed tumor necrosis factor-α (TNF-α), and monocyte chemotactic protein-1 (MCP-1) mRNA expression and protein levels in a co-culture of adipocyte and macrophage cells. These findings suggest that Fx ameliorates glucose tolerance in the diabetic model mice. Furthermore, FxOH, a metabolite of Fx, suppresses low-grade chronic inflammation in adipocyte cells.

The effects of a seaweed carotenoid, fucoxanthin, and its physiological metabolite, fucoxanthinol, on the biosynthesis of polyunsaturated fatty acids (PUFA) were investigated using cultured rat hepatoma BRL-3A. The metabolism of α-linolenic acid (18:3n-3) was suppressed by the addition of these carotenoids, resulting in a decrease in the content of eicosapentaenoic acid (20:5n-3), which suggested a down-regulation of metabolic enzymes such as fatty acid desaturase and elongase. An increase in the content of docosahexaenoic acid (22:6n-3), as observed in previous studies in vivo, might be a buffering action to maintain the membrane fluidity. The suppressive effect of fucoxanthinol on ∆6 fatty acid desaturase was not at the level of gene expression but due to specific modifications of the protein via a ubiquitin-proteasome system. A proteomic analysis revealed several factors such as phosphatidylethanolamine-binding protein that might be involved in the observed action of fucoxanthin. These findings will contribute to studies on the elucidation of the precise molecular mechanisms underlying the regulation of PUFA biosynthesis by fucoxanthin.

Fucoxanthin is a marine carotenoid exhibiting several health benefits. The anti-cancer effect of fucoxanthin and its deacetylated metabolite, fucoxanthinol, is well documented. In view of its potent anti-carcinogenic activity, the need to understand the underlying mechanisms has gained prominence. Towards achieving this goal, several researchers have carried out studies in various cell lines and in vivo and have deciphered that fucoxanthin exerts its anti-proliferative and cancer preventing influence via different molecules and pathways including the Bcl-2 proteins, MAPK, NFκB, Caspases, GADD45, and several other molecules that are involved in either cell cycle arrest, apoptosis, or metastasis. Thus, in addition to decreasing the frequency of occurrence and growth of tumours, fucoxanthin has a cytotoxic effect on cancer cells. Some studies show that this effect is selective, i.e., fucoxanthin has the capability to target cancer cells only, leaving normal physiological cells unaffected/less affected. Hence, fucoxanthin and its metabolites show great promise as chemotherapeutic agents in cancer.

Stearoyl-coenzyme A desaturase-1 (SCD1) is a rate-limiting enzyme that catalyzes the biosynthesis of monounsaturated fatty acids from saturated fatty acids. Recently, SCD1 down-regulation has been implicated in the prevention of obesity, and the improvement of insulin and leptin sensitivity. In this study, we examined the effect of fucoxanthin, a marine carotenoid, on hepatic SCD1 in obese mouse models of hyperleptinemia KK-A(y) and leptin-deficiency ob/ob. In KK-A(y) mice, providing a diet containing 0.2 % fucoxanthin for 2 weeks markedly suppressed SCD1 mRNA and protein expressions in the liver. The fatty acid composition of liver lipids was also affected by an observed decrease in the ratio of oleic acid to stearic acid. Furthermore, serum leptin levels were significantly decreased in hyperleptinemia KK-A(y) mice after 2 weeks of fucoxanthin feeding. However, the suppressive effects of fucoxanthin on hepatic SCD1 and body weight gain were not observed in ob/ob mice. These results show that fucoxanthin down-regulates SCD1 expression and alters fatty acid composition of the liver via regulation of leptin signaling in hyperleptinemia KK-A(y) mice but not in leptin-deficient ob/ob mice.

Background: Fucoxanthin is a xanthophyll present in brown seaweeds and has several beneficial effects, including anti-obesity and anti-diabetic effects. However, we and another group previously observed that fucoxanthin increases serum cholesterol levels in rodents. Cholesterol is an important component of cell membranes and biosynthesis of bile acids. Serum cholesterol levels are also closely associated with atherosclerosis. Therefore, we sought to identify the mechanism underlying the increase in serum cholesterol levels by fucoxanthin., Methods: Diabetic/obese KK-A(y) mice were fed a diet containing 0.2% fucoxanthin for 4 weeks. The mice were sacrificed, and total blood samples were collected for the measurement of serum total cholesterol, HDL-cholesterol and non-HDL-cholesterol levels. Cholesterol content in tissues was also analyzed. Real-time PCR and Western blotting were performed to determine hepatic mRNA and protein expression of genes involved in cholesterol metabolism, respectively., Results: Dietary fucoxanthin significantly increased serum HDL and non-HDL cholesterol levels, and reduced hepatic cholesterol content. In liver, the expression of SREBP1, SREBP2 and their target genes involved in cholesterol biosynthesis significantly increased and tended to increase in the fucoxanthin-fed mice, respectively. In contrast, hepatic levels of LDLR and SR-B1 proteins which is important factors for LDL-cholesterol and HDL-cholesterol uptake in the liver from serum, decreased to 60% and 80% in the fucoxanthin-fed mice, respectively, compared with the control mice. Further, we found that dietary fucoxanthin significantly increased the mRNA expression of proprotein convertase subtilisin/kexin type 9 (PCSK9), which enhances intracellular degradation of LDLR in lysosomes., Conclusions: Fucoxanthin increased HDL-cholesterol and non-HDL-cholesterol levels in KK-A(y) mice by inducing SREBP expression and reduced cholesterol uptake in the liver via down-regulation of LDLR and SR-B1, resulted in increased serum cholesterol in the mice.

Fucoxanthin (Fx) isolated from Undaria pinnatifida suppresses the development of hyperglycemia and hyperinsulinemia of diabetic/obese KK-A(y) mice after 2 weeks of feeding 0.2% Fx-containing diet. In the soleus muscle of KK-A(y) mice that were fed Fx, glucose transporter 4 (GLUT4) translocation to plasma membranes from cytosol was promoted. On the other hand, Fx increased GLUT4 expression levels in the extensor digitorum longus (EDL) muscle, although GLUT4 translocation tended to increase. The expression levels of insulin receptor (IR) mRNA and phosphorylation of Akt, which are in upstream of the insulin signaling pathway regulating GLUT4 translocation, were also enhanced in the soleus and EDL muscles of the mice fed Fx. Furthermore, Fx induced peroxisome proliferator activated receptor γ coactivator-1α (PGC-1α), which has been reported to increase GLUT4 expression, in both soleus and EDL muscles. These results suggest that in diabetic/obese KK-A(y) mice, Fx improves hyperglycemia by activating the insulin signaling pathway, including GLUT4 translocation, and inducing GLUT4 expression in the soleus and EDL muscles, respectively, of diabetic/obese KK-A(y) mice., (Copyright © 2011 Elsevier GmbH. All rights reserved.)

The in vitro reactivity of capsanthin (1) and fucoxanthin (2) with peroxynitrite was investigated, and the reaction products produced by scavenging with peroxynitrite were analyzed. (14'Z)-Nitrocapsanthin (3) and 12-nitrocapsanthin (4) were isolated from the products of the reaction of capsanthin with peroxynitrite. Similarly, (14Z)-15-nitrofucoxanthin (5), (11Z)-11-nitrofucoxanthin (6), and (14Z,9'Z)-15-nitrofucoxanthin (7) were obtained from the reaction of peroxynitrite reaction with fucoxanthin. Capsanthin and fucoxanthin inhibited the nitration of tyrosine by peroxynitrite. Furthermore, nitrocapsanthins (3 and 4) and nitrofucoxanthins (5 and 6) exhibited an inhibitory effect on Epstein-Barr virus early antigen activation in Raji cells and an antiproliferative effect on human pancreatic carcinoma. Moreover, nitrocapsanthins (3 and 4) inhibited carcinogensis of mouse skin tumors initiated by 7,12-dimethylbenz[a]anthracene (DMBN).

Obesity and type 2 diabetes are pathologies with rapidly growing prevalence throughout the world. A few molecular targets offer the most hope for anti-obesity and anti-diabetic therapeutics. One of the keys to success will be the induction of uncoupling protein 1 (UCP1) in abdominal white adipose tissue (WAT) and the regulation of cytokine secretions from both abdominal adipose cells and macrophage cells infiltrated into adipose tissue. Anti-obesity and anti-diabetic effects of fucoxanthin, a characteristic carotenoid found in brown seaweeds, have been reported. Nutrigenomic studies reveal that fucoxanthin induces UCP1 in abdominal WAT mitochondria, leading to the oxidation of fatty acids and heat production in WAT. Fucoxanthin improves insulin resistance and decreases blood glucose levels through the regulation of cytokine secretions from WAT. The key structure of carotenoids for the expression of anti-obesity effect is suggested to be the carotenoid end of the polyene chromophore, which contains an allenic bond and two hydroxyl groups., (Copyright © 2011 Society of Chemical Industry.)

Fucoxanthin is converted to fucoxanthinol and amarouciaxanthin A in mice. It was previously reported that fucoxanthinol attenuated the adipogenesis of 3T3-L1 cells. However, the effects of amarouciaxanthin A on adipocyte differentiation have not been clarified. This study examined the effects of amarouciaxanthin A on 3T3-L1 adipogenesis by comparing the effects of fucoxanthinol, isofucoxanthinol, and amarouciaxanthin B. Amarouciaxanthin A significantly decreased glycerol-3-phosphate dehydrogenase (GPDH) activity, which was measured as an indicator of adipocyte differentiation. The suppressive effect of amarouciaxanthin A was stronger than that of fucoxanthinol, amarouciaxanthin B, and isofucoxanthinol. The mRNA expressions of adipocyte fatty acid-binding protein (aP2), lipoprotein lipase (LPL), and glucose-transporter 4 (Glut4) in 3T3-L1 cells were markedly down-regulated by amarouciaxanthin A compared to fucoxanthinol. Furthermore, the expression levels of peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT-enhancer-binding protein α (C/EBPα),, which are the key adipogenic transcriptional factors, were also decreased by amarouciaxanthin A during adipocyte differentiation. These results show that amarouciaxanthin A, which is a dominant metabolite of fucoxanthin in white adipose tissue, suppressed 3T3-L1 adipocyte differentiation.

Based on previous research findings, a capsule was developed containing n-3 polyunsaturated fatty acid rich scallop phospholipids (PLs) with an incorporation of brown seaweed (Undaria pinnatifida) lipids (ULs) containing fucoxanthin. The antiobesity effects of the capsules were evaluated with an animal model using 3-wk-old male KK-A(y) mice. Each group received different combinations of lipid (UL, PL, UL + PL, or UL + PL capsule) either incorporated into the diet or into drinking water. Animals were sacrificed after a 4-wk experimental feeding period, and adipose tissues and organs were dissected and weighed. Blood samples were obtained to determine plasma lipid profiles. Uncoupling protein 1 (UCP1) mRNA expression levels were determined by real-time polymerase chain reaction analysis, and UCP1 expression was determined by western blotting analysis. Treatment with either UL alone or UL + PL (capsule) through drinking water resulted in a significant reduction in body weight, compared to the control group. The total white adipose tissue weight of mice fed the UL + PL capsule in drinking water was significantly reduced. Both UCP1 and UCP1 mRNA expression in epididymal fat from mice fed the capsule were significantly higher than in the control group. These results suggest that incorporation of UL into scallop-derived PL by means of capsulation may lead to an additive increase in the antiobesity properties of these bioactive lipids.

Fucoxanthin, a marine carotenoid found in edible brown seaweeds, attenuates white adipose tissue (WAT) weight gain and hyperglycemia in diabetic/obese KK-A(y) mice, although it does not affect these parameters in lean C57BL/6J mice. In perigonadal and mesenteric WATs of KK-A(y) mice fed fucoxanthin, mRNA expression levels of monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-α (TNF-α), which are considered to induce insulin resistance, were markedly reduced compared to control mice. In contrast to KK-A(y) mice, fucoxanthin did not alter MCP-1 and TNF-α mRNA expression levels in the WAT of lean C57BL/6J mice. Interleukin-6 (IL-6) and plasminogen activator inhibitor-1 mRNA expression levels in WAT were also decreased by fucoxanthin in KK-A(y) mice. In differentiating 3T3-F442A adipocytes, fucoxanthinol, which is a fucoxanthin metabolite found in WAT, attenuated TNF-α-induced MCP-1 and IL-6 mRNA overexpression and protein secretion into the culture medium. In addition, fucoxanthinol decreased TNF-α, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) mRNA expression in RAW264.7 macrophage-like cells stimulated by palmitic acid. These findings indicate that fucoxanthin regulates mRNA expression of inflammatory adipocytokines involved in insulin resistance, iNOS, and COX-2 in WAT and has specific effects on diabetic/obese KK-A(y) mice, but not on lean C57BL/6J mice., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Background: Fucoxanthin isolated from edible seaweeds and its metabolite fucoxanthinol have been recently found to have anti-obesity effects, but the mechanism is not fully understood., Aim of Study: We investigated the effects of these carotenoids on the absorption of triglycerides in conscious rats implanted with cannulae into a lymph duct and the portal or jugular vein., Methods: A duodenal infusion of 1 ml of test oil emulsion with or without 2 mg of fucoxanthin or fucoxanthinol was administered in the lymph duct and the portal (Experiment 1) or the jugular vein (Experiment 2) cannulated rats. The test oil contained 10% soybean oil (Experiment 1) and pre-digested 10% soybean oil (Experiment 2). The inhibitory activities of these carotenoids on pancreatic lipase activity were measured in vitro., Results: Increases in lymphatic and blood triglyceride levels were much lower in the two carotenoid-treated groups than in the carotenoid-free group, indicating that these carotenoids inhibit triglyceride absorption. The total amounts of triglycerides released into the lymph after 4 h in the carotenoid-free, fucoxanthin and fucoxanthinol groups were 113.5, 59.4 and 53.1 micromol, respectively. The inhibitory effects of carotenoids were completely abolished after an infusion of pre-digested soybean oil containing carotenoids. Furthermore, these carotenoids inhibited pancreatic lipase activity in vitro. Regarding absorptive route, we found that fucoxanthinol, but not fucoxanthin, appeared in lymph fluid, whereas neither carotenoid was detected in portal blood., Conclusion: These results show that these two marine carotenoids inhibit lipase activity in the gastrointestinal lumen and suppress triglyceride absorption, and fucoxanthin was converted to fucoxanthinol in the intestine and released into the lymph.

Fucoxanthin is one of the most abundant carotenoids found in Undaria pinnatifida and has been shown to inhibit tumor proliferation in vitro. However, the mechanisms underlying the anti-cancer effects of fucoxanthin are unclear. In this study, we hypothesized that fucoxanthin may cause cell cycle arrest and enhance gap junctional intercellular communication (GJIC) in SK-Hep-1 human hepatoma cells. Data revealed that fucoxanthin (1-20microM) strongly and concentration-dependently inhibited the proliferation of SK-Hep-1 cells at 24h of incubation, whereas fucoxanthin facilitated the growth of a murine embryonic hepatic (BNL CL.2) cells at 24h of incubation and only slightly slowed the cell proliferation at 48h. In SK-Hep-1 cells, fucoxanthin caused cell cycle arrest at G0/G1 phase and induced cell apoptosis, as evidenced by increased subG1 cells and induction of DNA strand breaks. Using scrape loading-dye-transfer assay, fucoxanthin was found to significantly enhance GJIC of SK-Hep-1 cells without affecting that of BNL CL.2 cells. In addition, fucoxanthin significantly increased protein and mRNA expressions of connexin 43 (Cx43) and connexin 32 (Cx32) in SK-Hep-1 cells. Moreover, fucoxanthin markedly increased the concentration of intracellular calcium levels in SK-Hep-1 cells. Thus, fucoxanthin is specifically antiproliferative against SK-Hep-1 cells, and the effect is associated with upregulation of Cx32 and Cx43, which enhances GJIC of SK-Hep-1 cells. The enhanced GJIC may be responsible for the increase of the intracellular calcium level, which then causes cell cycle arrest and apoptosis.

Fucoxanthin (FX), a xanthophyll derivative, is an orange-colored pigment present in edible brown algae. As a part of safety evaluation, single and repeated oral dose toxicity study of FX was conducted. In a single dose study, FX purified from seaweed was orally administered to male and female ICR mice at doses of 1,000 and 2,000 mg/kg. In a repeated doses study, FX at doses of 500 and 1,000 mg/kg was orally administered for 30 days. In both studies, no mortality and no abnormalities in gross appearance were observed. In the repeated doses study, histological observation revealed no abnormal changes in liver, kidney, spleen and gonadal tissues of any of the FX-treated groups. However, significantly increased total cholesterol concentrations were shown by plasma biochemical analyses in all FX-treated groups. Although total bilirubin concentrations were increased by FX, it was established that presence of fucoxanthinol, a major metabolite of FX, interfered with bilirubin determination in plasma. To further ascertain the safety of FX, the mechanism by which FX induces hypercholesterolemia in mice and species differences in the induction of hypercholesterolemia should be elucidated.

To investigate anti-inflammatory effects of carotenoids from Halocynthia roretzi, gene expression levels were measured for pro-inflammatory cytokines and enzymes in the murine macrophage-like cell line, RAW264.7, stimulated with lipopolysaccharide (LPS). All-trans alloxanthin, all-trans diatoxanthin, and their 9-cis isomers isolated from H. roretzi significantly suppressed expression of IL-1beta and IL-6 mRNA in cells induced by LPS without cytotoxicity. The expression level of IL-1beta mRNA in cells treated with 25 microM all-trans alloxanthin for 24 h, followed by stimulation with 0.1 microg/mL LPS for 24 h in the presence of carotenoid decreased to 33.7+/-3.0% from that of control cells stimulated with LPS alone. All-trans diatoxanthin, 9-cis alloxanthin and 9-cis diatoxanthin also decreased expression of IL-1beta mRNA to 25.1+/-2.1, 28.2+/-0.9 and 32.9+/-3.3%, respectively, from that of control cells stimulated with LPS. IL-1beta production in culture medium was also suppressed by all-trans alloxanthin and all-trans diatoxanthin. Furthermore, all-trans alloxanthin, all-trans diatoxanthin and their 9-cis isomers suppressed the over-expression of cyclooxygenase-2 and nitric oxide synthase mRNA in RAW264.7 cells induced by LPS. The suppressive effects of these carotenoids were remarkable compared to those of beta-carotene and zeaxanthin.

Fucoxanthin has a unique structure including an unusual allenic bond and 5, 6-monoepoxide in its molecule. We found that abdominal white adipose tissue (WAT) weights of rats and mice fed fucoxanthin were significantly lower than those fed a control diet. The daily intake of fucoxanthin in mice also caused a significant reductions of body weight. Clear signals of uncoupling protein 1 (UCP1) and its mRNA were detected by Western and Northern blot analyses in abdominal WAT in mice fed fucoxanthin, although there is little expression of UCP1 in WAT in mice fed a control diet. UCP1 expression in WAT by fucoxanthin intake leads to oxidation of fatty acids and heat production in WAT mitochondria. Substrate oxidation can directly reduce WAT in animals. Fucoxanthin intake also significantly reduced blood glucose and plasma insulin. Furthermore, feeding fucoxanthin significantly increased the level of hepatic docosahexaenoic acid (DHA), a most important n-3 functional polyunsaturated fatty acid in biological systems. These multi-functionalities of fucoxanthin indicate that it is an important bioactive carotenoid that is beneficial for the prevention of the metabolicsyndrome.

The objective of this study was to assess the suppressive effects of 13 naturally occurring carotenoids on the adipocyte differentiation of 3T3-L1. The relationship between carotenoid structure and suppressive effects was also examined. Treatment with neoxanthin significantly reduced lipid accumulation, as well as glycerol-3-phosphate dehydrogenase activity. This suppressive effect on adipose cell differentiation was not observed in the other 12 carotenoids used in this study. Neoxanthin treatment also decreased expression of CCAAT/enhancer binding protein alpha (C/EBPalpha) and peroxisome proliferator-activated receptor gamma (PPARgamma) mRNAs. An examination of structure and function suggested that carotenoids containing an allene bond and an additional hydroxyl substituent on the side group may show suppressive effects on adipocyte differentiation in 3T3-L1 cells.

Antioxidant activity of carotenoids is suggested to be one of the factors for their disease preventing effects. Marine carotenoids fucoxanthin and its two metabolites, fucoxanthinol and halocynthiaxanthin, have been shown to exhibit several biological effects. The antioxidant activities of these three carotenoids were assessed in vitro with respect to radical scavenging and singlet oxygen quenching abilities. The 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity of fucoxanthin and fucoxanthinol was higher than that of halocynthiaxanthin, with the effective concentration for 50% scavenging (EC 50) being 164.60, 153.78, and 826.39 microM, respectively. 2,2'-Azinobis-3-ethylbenzo thizoline-6-sulphonate radical scavenging activity of fucoxanthinol (EC 50, 2.49 microM) was stronger than that of fucoxanthin (EC 50, 8.94 microM). Hydroxyl radical scavenging activity as measured by the chemiluminescence technique showed that the scavenging activity of fucoxanthin was 7.9 times higher than that by fucoxanthinol, 16.3 times higher than that by halocynthiaxanthin, and 13.5 times higher than that by alpha-tocopherol. A similar trend was observed when the hydroxyl radical scavenging was assessed by the electron spin resonance (ESR) technique. ESR analysis of the superoxide radical scavenging activity also showed the superiority of fucoxanthin over the other two carotenoids tested. Singlet oxygen quenching ability of the three carotenoids was lower than that of beta-carotene, with quenching rate constants ( k Q, x10 (10) M (-1) s (-1)) being 1.19, 1.81, 0.80, and 12.78 for fucoxanthin, fucoxanthinol, halocynthiaxanthin, and beta-carotene, respectively. The higher radical scavenging activity of fucoxanthin and fucoxanthinol compared with halocynthiaxanthin is assumed to be due to presence of the allenic bond.

Fucoxanthin is a marine carotenoid found in edible brown seaweeds. We previously reported that dietary fucoxanthin attenuates the weight gain of white adipose tissue (WAT) of diabetic/obese KK- A(y) mice. In this study, to evaluate the antiobesity and antidiabetic effects of fucoxanthin and fish oil, we investigated the effect on the WAT weight, blood glucose, and insulin levels of KK- A(y) mice. Furthermore, the expression level of uncoupling protein 1 (UCP1) and adipokine mRNA in WAT were measured. After 4 weeks of feeding, 0.2% fucoxanthin in the diet markedly attenuated the gain of WAT weight in KK- A(y) mice with increasing UCP1 expression compared with the control mice. The WAT weight of the mice fed 0.1% fucoxanthin and 6.9% fish oil was also significantly lower than that of the mice fed fucoxanthin alone. In addition, 0.2% fucoxanthin markedly decreased the blood glucose and plasma insulin concentrations in KK- A(y) mice. The mice fed with the combination diet of 0.1% fucoxanthin and fish oil also showed improvements similar to that of 0.2% fucoxanthin. Leptin and tumor necrosis factor (TNFalpha) mRNA expression in WAT were significantly down-regulated by 0.2% fucoxanthin. These results suggest that dietary fucoxanthin decreases the blood glucose and plasma insulin concentration of KK- A(y) along with down-regulating TNFalpha mRNA. In addition, the combination of fucoxanthin and fish oil is more effective for attenuating the weight gain of WAT than feeding with fucoxanthin alone.

This study examined the effect of dietary fucoxanthin or fucoxanthinol on the amount of docosahexaenoic acid (DHA) in the liver of KKAy mice, a model for obese/type II diabetes. In the first experiment, mice were fed diets containing crude fucoxanthin or glyceroglycolipid for 4 weeks. Results showed a significant increase in the level of DHA in mice fed 0.53% crude fucoxanthin, from 2.3% in control mice to 5.1% of fatty acid composition of total liver lipids. On the other hand, in mice fed crude glyceroglycolipid, the level of DHA as a proportion of total liver fatty acids remained unchanged. To clarify the enhancement of hepatic DHA, in the second experiment, KKAy mice were fed a diet containing purified fucoxanthin or its deacetylated derivative, fucoxanthinol. Results from a quantitative analysis using an internal standard showed that in mice fed 0.2% fucoxanthin, the amount of hepatic DHA was 2-fold higher than in control mice, whereas DHA levels in the small intestine remained unchanged. Furthermore, 0.2% fucoxanthinol led to 1.8- and 1.2-fold increases in the amount of hepatic DHA and arachidonic acid compared to control mice, respectively. These results indicate for the first time that dietary fucoxanthin and fucoxanthinol enhance the amount of DHA in the liver of KKAy mice.

Dietary effects of medium-chain triacylglycerols (MCT) and fucoxanthin (Fc) on abdominal fat weight were determined using KK-Ay obese mouse. Experimental diet contained MCT(0.9%), Fc (0.1%), or MCT (0.9%) +Fc (0.1%). The abdominal fat weight of mice fed with Fc was significantly lower than that of mice fed with MCT. Uncoupling protein 1 (UCP1), a key molecule for metabolic thermogenesis, was clearly expressed in the white adipose tissue (WAT) of mice fed Fc, but little expression in that of the mice fed MCT. The anti-obesity effect of Fc was increased by mixing Fc with MCT. This increase would be due to the increase in the absorption rate of Fc by MCT.

Fucoxanthin is a major carotenoid found in edible seaweed such as Undaria pinnatifida and Hijikia fusiformis. We investigated the suppressive effects of fucoxanthin and its metabolite, fucoxanthinol, on the differentiation of 3T3-L1 preadipocytes to adipocytes. Fucoxanthin inhibited intercellular lipid accumulation during adipocyte differentiation of 3T3-L1 cells. Furthermore, fucoxanthin was converted to fucoxanthinol in 3T3-L1 cells. Fucoxanthinol also exhibited suppressive effects on lipid accumulation and decreased glycerol-3-phosphate dehydrogenase activity, an indicator of adipocyte differentiation. The suppressive effect of fucoxanthinol was stronger than that of fucoxanthin. In addition, in 3T3-L1 cells treated with fucoxanthin and fucoxanthinol, peroxisome proliferator-activated receptor gamma (PPARgamma), which regulates adipogenic gene expression, was down-regulated in a dose-dependent manner. These results suggest that fucoxanthin and fucoxanthinol inhibit the adipocyte differentiation of 3T3-L1 cells through down-regulation of PPARgamma. Fucoxanthinol had stronger suppressive effects than fucoxanthin on adipocyte differentiation in 3T3-L1 cells.

The sea squirt Halocynthia roretzi metabolizes fucoxanthin, and subsequently accumulates its derived carotenoids with characteristic structures. In the present study, we isolated halocynthiaxanthin and fucoxanthinol as carotenoids having antiproliferative activity from H. roretzi. Halocynthiaxanthin and fucoxanthinol inhibited the growth of HL-60 human leukemia cells in a dose- and time-dependent manner. Viability of HL-60 treated with 12.5 microM halocynthiaxanthin and fucoxanthinol was decreased by 12.1% and 5.7% of control after 48 h incubation, respectively. Furthermore, halocynthiaxanthin and fucoxanthinol induced apoptosis in HL-60 cells, MCF-7 human breast cancer cells, and Caco-2 human colon cancer cells. When HL-60 cells were incubated with 12.5 microM halocynthiaxanthin and fucoxanthinol for 48 h, relative DNA fragmentations were enhanced to 5- and 7-fold compared to that in control cells, respectively. The activities of apoptosis induction by halocynthiaxanthin and fucoxanthinol were higher than that of fucoxanthin which we have previously reported as a carotenoid possessing the ability to induce apoptosis. Fucoxanthinol exhibited the highest apoptosis-inducing activity among the three carotenoids. Furthermore, the expression levels of apoptosis-suppressing protein Bcl-2 were decreased in HL-60 cells treated with halocynthiaxanthin and fucoxanthinol. These results suggest that halocynthiaxanthin and fucoxanthinol exhibited potential antiproliferative effects via apoptosis induction in several cancer cell lines.

The aim of the present study was to investigate the efficacy of fucoxanthin on endotoxin-induced uveitis (EIU) in rats. The effects of fucoxanthin on endotoxin-induced leucocyte and protein infiltration, nitric oxide (NO), prostaglandin (PG)-E2 and tumour necrosis factor (TNF)-alpha concentrations in rat aqueous humour, as well as on the cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) protein expression in a mouse macrophage cell line (RAW 264.7 cells) were studied. EIU was induced in male Lewis rats by a footpad injection of lipopolysaccharide (LPS). Immediately after the LPS injection, either 0.1, 1 or 10mgkg(-1) of fucoxanthin was injected intravenously. The aqueous humour was collected 24hr later from both eyes, and both the number of cells infiltrating into the aqueous humour and the aqueous humour protein concentration were measured. The levels of PGE2, NO and TNF-alpha were determined by enzyme-linked immunosorbent assay. The RAW 264.7 cells were pretreated with various concentrations of fucoxanthin for 24hr and subsequently incubated with LPS for 24hr. COX-2 and iNOS protein expression was analysed by the Western blotting method. Levels of PGE2, NO and TNF-alpha production were determined. Fucoxanthin suppressed the development of EIU in a dose-dependent fashion. Treatment with fucoxanthin resulted in a reduction in PGE2, NO and TNF-alpha concentrations in the aqueous humour. The expression of COX and iNOS protein in the fucoxanthin treated RAW264.7 cells decreased significantly compared to that the LPS group. It also significantly reduced the concentration of PGE2, NO and TNF-alpha production in the medium of cells. The present result indicate fucoxanthin suppresses the inflammation of EIU by blocking the iNOS and COX-2 protein expression and its anti-inflammatory effect on eye is comparable with the effect of predinisolone used in similar doses.

Mitochondrial uncoupling protein 1 (UCP1) is usually expressed only in brown adipose tissue (BAT) and a key molecule for metabolic thermogenesis to avoid an excess of fat accumulation. However, there is little BAT in adult humans. Therefore, UCP1 expression in tissues other than BAT is expected to reduce abdominal fat. Here, we show reduction of abdominal white adipose tissue (WAT) weights in rats and mice by feeding lipids from edible seaweed, Undaria pinnatifida. Clear signals of UCP1 protein and mRNA were detected in WAT of mice fed the Undaria lipids, although there is little expression of UCP1 in WAT of mice fed control diet. The Undaria lipids mainly consisted of glycolipids and seaweed carotenoid, fucoxanthin. In the fucoxanthin-fed mice, WAT weight significantly decreased and UCP1 was clearly expressed in the WAT, while there was no difference in WAT weight and little expression of UCP1 in the glycolipids-fed mice. This result indicates that fucoxanthin upregulates the expression of UCP1 in WAT, which may contribute to reducing WAT weight.

The effect of fucoxanthin, from the edible seaweed Undaria pinnatifida on viability of colon cancer cells and induction of apoptosis was investigated. Fucoxanthin remarkably reduced the viability of human colon cancer cell lines, Caco-2, HT-29 and DLD-1. Furthermore, treatment with fucoxanthin induced DNA fragmentation, indicating apoptosis. The DNA fragmentation in Caco-2 cells treated with 22.6 microM fucoxanthin for 24 h was 10-fold higher than in the control. Fucoxanthin suppressed the level of Bcl-2 protein. Also, DNA fragmentation induced by fucoxanthin was partially inhibited by a caspase inhibitor Z-VAD-fmk. Moreover, combined treatment with 3.8 microM fucoxanthin and 10 microM troglitazone, which is a specific ligand for peroxisome proliferator-activated receptor (PPAR) gamma, effectively decreased the viability of Caco-2 cells. However, separate treatments with these same concentrations of fucoxanthin nor troglitazone did not affect cell viability. These findings indicate that fucoxanthin may act as a chemopreventive and/or chemotherapeutic carotenoid in colon cancer cells by modulating cell viability in combination with troglitazone.