fucoxanthin and Obesity

Chronic liver disease (CLD) has emerged as a leading cause of human deaths. It caused 1.32 million deaths in 2017, which affected men more than women by a two-to-one ratio. There are various causes of CLD, including obesity, excessive alcohol consumption, and viral infection. Among them, non-alcoholic fatty liver disease (NAFLD), one of obesity-induced liver diseases, is the major cause, representing the cause of more than 50% of cases. Fucoxanthin, a carotenoid mainly found in brown seaweed, exhibits various biological activities against NAFLD. Its role in NAFLD appears in several mechanisms, such as inducing thermogenesis in mitochondrial homeostasis, altering lipid metabolism, and promoting anti-inflammatory and anti-oxidant activities. The corresponding altered signaling pathways are the β3-adorenarine receptor (β3Ad), proliferator-activated receptor gamma coactivator (PGC-1), adenosine monophosphate-activated protein kinase (AMPK), peroxisome proliferator-activated receptor (PPAR), sterol regulatory element binding protein (SREBP), nuclear factor kappa B (NF-κB), mitogen-activated protein kinase (MAPK), protein kinase B (AKT), SMAD2/3, and P13K/Akt pathways. Fucoxanthin also exhibits anti-fibrogenic activity that prevents non-alcoholic steatohepatitis (NASH) development.

Topics: Female; Humans; Lipid Metabolism; Liver; Male; Non-alcoholic Fatty Liver Disease; Obesity; Proto-Oncogene Proteins c-akt; Xanthophylls

Owing to its unique structure and properties, fucoxanthin (FX), a carotenoid, has attracted significant attention. There have been numerous studies that demonstrate FX's anti-inflammatory, antioxidant, antitumor, and anti-obesity properties against inflammation-related diseases. There is no consensus, however, regarding the molecular mechanisms underlying this phenomenon. In this review, we summarize the potential health benefits of FX in inflammatory-related diseases, from the perspective of animal and cellular experiments, to provide insights for future research on FX. Previous work in our lab has demonstrated that FX remarkably decreased LPS-induced inflammation and improved survival in septic mice. Further investigation of the activity of FX against a wide range of diseases will require new approaches to uncover its molecular mechanism. This review will provide an outline of the current state of knowledge regarding FX application in the clinical setting and suggest future directions to implement FX as a therapeutic ingredient in pharmaceutical sciences in order to develop it into a treatment strategy against inflammation-associated disorders.

Topics: Animals; Antioxidants; Inflammation; Mice; Obesity; Xanthophylls

Fucoxanthin is a xanthophyll carotenoid abundant in macroalgae, such as brown seaweeds. When fucoxanthin is consumed, it can be esterified or hydrolyzed to fucoxanthinol in the gastrointestinal tract and further converted into amarouciaxanthin A in the liver. It has a unique chemical structure that confers its biological effects. Fucoxanthin has a strong antioxidant capacity by scavenging singlet molecular oxygen and free radicals. Also, it exerts an anti-inflammatory effect. Studies have demonstrated potential health benefits of fucoxanthin for the prevention of chronic diseases, such as cancer, obesity, diabetes mellitus, and liver disease. Animal studies have shown that fucoxanthin supplementation has no adverse effects. However, investigation of the safety of fucoxanthin consumption in humans is lacking. Clinical trials are required to assess the safety of fucoxanthin in conjunction with the study of mechanisms by which fucoxanthin exhibits its health benefits. This review focuses on current knowledge of metabolism and functions of fucoxanthin with its potential health benefits. This article is part of a Special Issue entitled Carotenoids recent advances in cell and molecular biology edited by Johannes von Lintig and Loredana Quadro.

Topics: Antioxidants; Chronic Disease; Diabetes Mellitus; Gastrointestinal Tract; Humans; Liver; Neoplasms; Obesity; Seaweed; Xanthophylls

Present-day lifestyles associated with high calorie-fat intake and accumulation, as well as energy imbalance, have led to the development of obesity and its comorbidities, which have emerged as some of the major health issues globally. To combat the disease, many studies have reported the anti-obesity effects of natural compounds in foods, with some advantages over chemical treatments. Carotenoids, such as xanthophyll derived from seaweeds, have attracted the attention of researchers due to their notable biological activities, which are associated mainly with their antioxidant properties. Their involvement in oxidative stress modulation, the regulation of major transcription factors and enzymes, and their antagonistic effects on various obesity parameters have been examined in both in vitro and in vivo studies. The present review is a collation of published research over the last decade on the antioxidant properties of seaweed xanthophyll carotenoids, with a focus on fucoxanthin and astaxanthin and their mechanisms of action in obesity prevention and treatment.

Topics: Animals; Gene Expression Regulation; Humans; Obesity; Obesity Management; Oxidative Stress; Seaweed; Signal Transduction; Xanthophylls

Cell, animal and human studies dealing with carotenoids and carotenoid derivatives as nutritional regulators of adipose tissue biology with implications for the etiology and management of obesity and obesity-related metabolic diseases are reviewed. Most studied carotenoids in this context are β-carotene, cryptoxanthin, astaxanthin and fucoxanthin, together with β-carotene-derived retinoids and some other apocarotenoids. Studies indicate an impact of these compounds on essential aspects of adipose tissue biology including the control of adipocyte differentiation (adipogenesis), adipocyte metabolism, oxidative stress and the production of adipose tissue-derived regulatory signals and inflammatory mediators. Specific carotenoids and carotenoid derivatives restrain adipogenesis and adipocyte hypertrophy while enhancing fat oxidation and energy dissipation in brown and white adipocytes, and counteract obesity in animal models. Intake, blood levels and adipocyte content of carotenoids are reduced in human obesity. Specifically designed human intervention studies in the field, though still sparse, indicate a beneficial effect of carotenoid supplementation in the accrual of abdominal adiposity. In summary, studies support a role of specific carotenoids and carotenoid derivatives in the prevention of excess adiposity, and suggest that carotenoid requirements may be dependent on body composition.

Topics: Adipocytes; Adipose Tissue; Animals; beta Carotene; Carotenoids; Cryptoxanthins; Humans; Obesity; Xanthophylls

Obesity is a major epidemic that poses a worldwide threat to human health, as it is also associated with metabolic syndrome, type 2 diabetes and cardiovascular disease. Therapeutic intervention through weight loss drugs, accompanied by diet and exercise, is one of the options for the treatment and management of obesity. However, the only approved anti-obesity drug currently available in the market is orlistat, a synthetic inhibitor of pancreatic lipase. Other anti-obesity drugs are still being evaluated at different stages of clinical trials, while some have been withdrawn due to their severe adverse effects. Thus, there is a need to look for new anti-obesity agents, especially from biological sources. Marine algae, especially seaweeds are a promising source of anti-obesity agents. Four major bioactive compounds from seaweeds which have the potential as anti-obesity agents are fucoxanthin, alginates, fucoidans and phlorotannins. The anti-obesity effects of such compounds are due to several mechanisms, which include the inhibition of lipid absorption and metabolism (e.g., fucoxanthin and fucoidans), effect on satiety feeling (e.g., alginates), and inhibition of adipocyte differentiation (e.g., fucoxanthin). Further studies, especially testing bioactive compounds in long-term human trials are required before any new anti-obesity drugs based on algal products can be developed.

Topics: Alginates; Animals; Anti-Obesity Agents; Aquatic Organisms; Humans; Obesity; Polysaccharides; Seaweed; Xanthophylls

Obesity, which results from an imbalance between energy intake and energy expenditure, has become a major health risk factor worldwide, causing numerous and various diseases such as diabetes, hypertension, and cardiovascular diseases. Fucoxanthin, a specific carotenoid in brown algae, has garnered much attention for its anti-obesity and anti-diabetic effects attributable to a unique mechanism. Fucoxanthin induces uncoupling protein 1 (UCP1) expression in white adipose tissue (WAT). That inner membrane mitochondrial protein, UCP1, can dissipate energy through oxidation of fatty acids and heat production. Furthermore, fucoxanthin improves insulin resistance and ameliorates blood glucose levels through down-regulation of adipocytokines related to insulin resistance in WAT and up-regulation of glucose transporter 4 (GLUT4) in skeletal muscle. Algae fucoxanthin is a beneficial compound for the prevention of the metabolic syndrome.

Topics: Adipokines; Adipose Tissue, White; Animals; Blood Glucose; Diabetes Mellitus; Disease Models, Animal; Energy Metabolism; Fatty Acids; Gene Expression; Gene Expression Regulation, Plant; Glucose Transporter Type 4; Humans; Insulin Resistance; Ion Channels; Metabolic Syndrome; Mice; Mitochondrial Proteins; Muscle, Skeletal; Obesity; Oxidation-Reduction; Phaeophyceae; Phytotherapy; Uncoupling Protein 1; Xanthophylls

Nowadays the global tendency towards physical activity reduction and an augmented dietary intake of fats, sugars and calories is leading to a growing propagation of overweight, obesity and lifestyle-related diseases, such diabetes, hypertension, dyslipidemia and metabolic syndrome. In particular, obesity, characterized as a state of low-level inflammation, is a powerful determinant both in the development of insulin resistance and in the progression to type 2 diabetes. A few molecular targets offer hope for anti-obesity therapeutics. One of the keys to success could 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 effects of fucoxanthin, a characteristic carotenoid, exactly belonging to xanthophylls, 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 anti-obesity effect is suggested to be the carotenoid end of the polyene chromophore, which contains an allenic bond and two hydroxyl groups. Fucoxanthin, which can be isolated from edible brown seaweeds, recently displayed its many physiological functions and biological properties. We reviewed recent studies and this article aims to explain essential background of fucoxanthin, focusing on its promising potential anti-obesity effects. In this respect, fucoxanthin can be developed into promising marine drugs and nutritional products, in order to become a helpful functional food.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Anti-Obesity Agents; Antioxidants; Diatoms; Dietary Supplements; Humans; Laminaria; Non-alcoholic Fatty Liver Disease; Obesity; Oxidative Stress; Seaweed; Stramenopiles; Undaria; Xanthophylls

To investigate the effects of Xanthigen (brown marine algae fucoxanthin + pomegranate seed oil (PSO)) on body weight, body fat, liver lipids, and blood biochemistry; and Xanthigen and its individual components on resting energy expenditure (REE) in obese, non-diabetic female volunteers with non-alcoholic fatty liver disease (NAFLD) and normal liver fat (NLF) content.. Sixteen-week, double-blind, randomized, placebo-controlled study. Food record data, body composition, REE (only 41 volunteers with NAFLD) and blood sample analysis were assessed weekly for 16 weeks in 151 non-diabetic, obese premenopausal women with liver fat content above 11% (NAFLD) n = 113, and below 6.5% (NLF) n = 38.. Xanthigen-600/2.4 mg (300 mg PSO + 300 mg brown seaweed extract containing 2.4 mg fucoxanthin) resulted in statistically significant reduction of body weight (5.5 +/- 1.4 kg NAFLD group and 4.9 +/- 1.2 kg NLF group, p < 0.05), waist circumference (NAFLD group only), body (3.5 +/- 1.9 kg NAFLD group, p < 0.001; 3.6 +/- 0.7 kg NLF group, p < 0.05) and liver fat content, liver enzymes (NAFLD group only), serum triglycerides and C-reactive protein. Weight loss and reduction in body and liver fat content occurred earlier in patients with NLF than in patients with NAFLD. Fucoxanthin (> 2.4 mg) and Xanthigen-400/1.6 mg (200 mg PSO + 200 mg brown seaweed extract containing 1.6 mg fucoxanthin) significantly increased REE in NAFLD subjects compared to placebo.. Xanthigen promoted weight loss, reduced body and liver fat content, and improved liver function tests in obese non-diabetic women. Xanthigen and Fucoxanthin also increased REE. This product may be considered a promising food supplement in the management of obesity.

Topics: Adult; Anti-Obesity Agents; Body Mass Index; Body Weight; Double-Blind Method; Drug Combinations; Energy Metabolism; Fatty Liver; Female; Humans; Obesity; Plant Oils; Premenopause; Treatment Outcome; Weight Loss; Xanthophylls

The anti-obesity activity of encapsulated fucoxanthin in fucoidan-based nanoemulsion was investigated. Then, high-fat diet (HFD) induced-obese rats were fed along with different treatments including administration of encapsulated fucoxanthin (10 mg/kg and 50 mg/kg/day), fucoidan (70 mg/kg), Nigella sativa oil (250 mg/kg), metformin (200 mg/kg), and free form of fucoxanthin (50 mg/kg) by oral gavage daily for 7 weeks. The study discovered that fucoidan-based nanoemulsions with a low and high dose of fucoxanthin had droplet size in the range of 181.70-184.87 nm and encapsulation efficacy of 89.94-91.68 %, respectively. Also exhibited 75.86 % and 83.76 % fucoxanthin in vitro release. The TEM images and FTIR spectera confirmed the particle size and encapsulation of fucoxanthin, respectively. Moreover, in vivo results revealed that encapsulated fucoxanthin reduced body and liver weight compared with a HFD group (p < 0.05). Biochemical parameters (FBS, TG, TC, HDL, LDL) and liver enzymes (ALP, AST, and ALT) were decreased after fucoxanthin and fucoidan administration. According to the histopathological analysis, fucoxanthin and fucoidan attenuated lipid accumulation in the liver.

Topics: Animals; Diet, High-Fat; Liver; Obesity; Plant Oils; Rats

Obesity, a chronic disease characterized by excessive body fat accumulation, is associated with significant health risks. The state of being overweight or obese leads to a number of chronic diseases, including cardiovascular disease, type 2 diabetes, cancer, and osteoarthritis. Accordingly, the regulation of adipocyte proliferation and differentiation has been the focus of many studies. The goal of the present study was to investigate the function of fucoxanthin, extracted from Sargassum horneri, in adipocyte (3T3-L1 cells) differentiation. A quantitative real-time polymerase chain reaction was conducted to investigate the mRNA expression levels of adipocyte differentiation-related genes under fucoxanthin stimulation. All adipocyte-related genes responded to PIC stimuli. Additionally, using western blotting, we confirmed that fucoxanthin reduced adipocyte differentiation. These results indicate that fucoxanthin extracted from Sargassum horneri can regulate adipogenesis. Further studies are needed to reveal the signaling pathways that lead to reduced adipocyte differentiation induced by fucoxanthin.

Topics: 3T3-L1 Cells; Adipocytes; Animals; Cell Differentiation; Diabetes Mellitus, Type 2; Mice; Obesity; Sargassum

Fucoxanthin (Fx) has poor water solubility and bioavailability, which limits its application in the food industry. To improve the physicochemical properties of Fx, hydroxypropyl-β-cyclodextrin (HP-β-CD) encapsulated Fx nanofibers (Fx/HP-β-CD nanofibers) were fabricated via electrospinning without using polymer. Molecular docking analysis showed the Fx/HP-β-CD nanofibers contained Fx and HP-β-CD at 1:2. Morphological analysis revealed the nanofibers were homogeneous without beads, having a diameter around 499 nm. The thermostability of Fx was significantly improved after encapsulationg by HP-β-CD. Animal studies showed that there was a 14% decrease of body weight, 11% white adipose tissue reduction and 9% lower of liver triglyceride for the mice treated with Fx/HP-β-CD nanofibers as compared with that of Fx treated mice. The total cholesterol was reduced by 23% in mice serum after treatment with Fx/HP-β-CD as compared with that of Fx. Interestingly, the Fx/HP-β-CD in this study could attenuate the testicular histopathology in obese mice.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Animals; Diet, High-Fat; Mice; Mice, Obese; Molecular Docking Simulation; Nanofibers; Obesity; Solubility

Fucoxanthin is a marine carotenoid found in brown seaweeds and several microalgae. It has been reported that fucoxanthin has health benefits such as anti-obesity and anti-diabetic effects. To facilitate fucoxanthin applications in the food industry, it is important to improve its low bioavailability. We attempted the combined feeding of fucoxanthin-containing seaweed oil (SO) and monocaprin in a powder diet and analyzed the fucoxanthin metabolite contents in the liver, small intestine and serum of diabetic/obese KK-

Topics: Animals; Biological Availability; Diabetes Mellitus; Glycerides; Mice; Mice, Obese; Obesity; Seaweed; Xanthophylls

Phycobiliproteins, fucoxanthin, and krill oil are natural marine products with excellent activities. In the study, we prepared the complex of phycobiliproteins, fucoxanthin, and krill oil (PFK) and assessed the anti-obesity, lipid-lowering, and antioxidant activities in high-fat diet rats. The results showed that the rats significantly and safely reduced body weight gain and regulated serum biochemical parameters at 50 mg/kg phycobiliproteins, 10 mg/kg fucoxanthin, and 100 mg/kg krill oil. Furthermore, the molecular mechanism study suggested that the complex of PFK confined the enzyme activities of lipid synthesis and enhanced antioxidant activity to improve obesity indirectly. The conclusions demonstrated that the complex of PFK has potent anti-obesity and hypolipidemic effects which have potential use as a natural and healthy food and medicine for anti-obesity and lowering blood lipids in the future.

Topics: Animals; Antioxidants; Euphausiacea; Lipid Metabolism; Lipids; Obesity; Oils; Phycobiliproteins; Rats

Fucoxanthin (Fx) is a marine carotenoid found in brown seaweeds and several marine microalgae. Recent studies have reported that dietary Fx exhibits many health-promoting functions such as anti-obesity and anti-diabetic effects in animal experiments. A human clinical trial of Fx showed high potential on reduction of body weight and fat content. The anti-obesity effect of Fx is due to several mechanisms, which include the suppression of adipocyte differentiation, anti-inflammation, and uncouple protein 1 induction in white adipose tissue. Furthermore, Fx reduced blood glucose level and improved insulin resistance through the regulation of adipokine mRNA expressions. In this chapter, we reviewed health beneficial effects and safety of Fx and discussed their molecular mechanisms.

Topics: Adipose Tissue, White; Animals; Anti-Obesity Agents; Humans; Obesity; Xanthophylls

Obesity is a major health concern worldwide and is considered to be associated with disruption of host-microbial homeostasis, especially microbiota composition in the gastrointestinal tract. Use of microbiota-directed foods or nutraceuticals therefore represents a promising approach for the control of obesity. Fucoxanthin, a marine carotenoid, has been proven to be one of the most effective anti-obesity natural products. However, its action mechanism is yet to be unraveled, especially with respect to its role in the modulation of gut microbiota composition. In the present study, profiles of microbiota in both the cecal and fecal samples from BALB/c mice given respectively the following treatments were examined: normal chow diet (NCD), NCD + fucoxanthin (NCDF), high-fat-diet (HFD), and HFD + fucoxanthin (HFDF). The results showed that fucoxanthin supplementation for 4 weeks significantly changed the composition of both cecal and fecal microbiota. In addition, a differential effect was observed between the supplementation to NCD and to HFD. The changes in the Firmicutes/Bacteroidetes ratio and the abundance of S24-7 and Akkermansia were identified to be among the major gut microbiota modulating events associated with the anti-obesity bioactivity of fucoxanthin. Hence, our results suggested that fucoxanthin could be a promising microbiota-targeted functional-food ingredient.

Topics: Animals; Bacteria; Cecum; Feces; Gastrointestinal Microbiome; Humans; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Obesity; Xanthophylls

Brown algae and its carotenoids have been shown to have a positive influence on obesity and its comorbidities. This study evaluated the effect of Undaria pinnatifida and fucoxanthin on biochemical, physiological and inflammation markers related to obesity and on the expression of genes engaged on white adipose tissue lipid metabolism in a murine model of diet-induced obesity. The treatments improved energy expenditure, β-oxidation and adipogenesis by upregulating PPARα, PGC1α, PPARγ and UCP-1. Adipogenesis was also confirmed by image analysis of the retroperitoneal adipose tissue, by measuring cell area, perimeter and cellular density. Additionally, the treatments, ameliorated adipose tissue accumulation, insulin resistance, blood pressure, cholesterol and triglycerides concentration in serum, and reduced lipogenesis and inflammation by downregulating acetyl-CoA carboxylase (ACC) gene expression, increasing serum concentration and expression of adiponectin as well as downregulating IL-6 expression. Both fucoxanthin and Undaria pinnatifida may be considered for treating obesity and other diseases related.

Topics: Acetyl-CoA Carboxylase; Adiponectin; Adipose Tissue, White; Animals; Biomarkers; Diet, High-Fat; Diet, Vegetarian; Disease Models, Animal; Humans; Inflammation; Interleukin-6; Lipogenesis; Male; Metabolic Syndrome; Obesity; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Phaeophyceae; PPAR alpha; PPAR gamma; Rats; Rats, Wistar; Uncoupling Protein 1; Undaria; Xanthophylls

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.

Topics: 3T3-L1 Cells; Adipocytes; Adipose Tissue, White; Animals; beta Carotene; Blood Glucose; Cell Line; Chemokine CCL2; Diabetes Mellitus, Experimental; Diet; Disease Models, Animal; Inflammation; Insulin Resistance; Macrophages; Mice; Obesity; RNA, Messenger; Tumor Necrosis Factor-alpha; Weight Gain; Xanthophylls

Obesity, characterized as a state of low-level inflammation, is a powerful determinant influencing the development of insulin resistance and progression to type 2 diabetes. The purpose of the present study was to investigate the anti-inflammatory activity of fucoxanthin in experimental high-fat-diet-induced obesity in mice and antioxidant activity in PC12 cells under oxidative stress situation. The anti-inflammatory potential of fucoxanthin in the regulation of maleic dialdehyde (MDA), polymorphonuclear cells (PMNs), interleukin-1β (IL-1β), inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-α), and cyclooxygenase-2 (COX-2) was determined by ELISA. Fucoxanthin significantly inhibited obesity-induced upregulation of the production of IL-1β, TNF-α, iNOS, and COX-2. Moreover, fucoxanthin suppressed MDA and infiltration of PMNs. The protective effects were associated with lack of hypertrophy and crown-like structures in mammary gland. At the same time, fucoxanthin showed an advantage of antioxidant activity in PC12 cells under oxidative stress situation. These results suggest that supplementation of fucoxanthin is a promising strategy for blocking macrophage-mediated inflammation and inflammation-induced obesity and its associated complications.

Topics: Adipose Tissue; Animals; Anti-Inflammatory Agents; Antioxidants; Cyclooxygenase 2; Dietary Fats; Disease Models, Animal; Inflammation; Inflammation Mediators; Interleukin-1beta; Macrophages; Malondialdehyde; Mice; Nitric Oxide Synthase Type II; Obesity; Oxidative Stress; PC12 Cells; Rats; Time Factors; Tumor Necrosis Factor-alpha; Xanthophylls

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.

Topics: Animals; Blood Glucose; Down-Regulation; Fatty Acids; Female; Leptin; Liver; Mice; Mice, Obese; Obesity; RNA, Messenger; Seaweed; Signal Transduction; Stearoyl-CoA Desaturase; Weight Gain; Xanthophylls

The present study investigated the effects of combined fucoxanthin (Fc) and conjugated linoleic acid (CLA) on high-fat diet-induced obese rats. Thirty five rats were divided into four groups, fed a high-fat diet (Control, 15% fat, wt/wt), supplemented with low Fc (FCL, 0.083 mg/kg/bw), high Fc (FCH, 0.167 mg/kg/bw) and FCL (0.083 mg/kg/bw) plus CLA (0.15 g/kg/bw) (FCL+CLA) for 52 d. Body weight and white adipose tissue (WAT) weight were significantly suppressed in FCL+CLA group than those in control group. WAT weight was also markedly attenuated in FCL and FCH groups. Accumulation of hepatic lipid droplets and the perirenal adipocyte size of FCL, FCH and FCL+CLA groups were diminished compared to control group. Serum total cholesterol level in FCH group, triacylglycerol and leptin levels in FCL, FCH and FCL+CLA groups, and glucose concentration in FCH and FCL+CLA groups were significantly decreased than those in control group. The mRNA expression of adiponectin, adipose triacylglycerol lipase, carnitine palmitoyltransferase 1A was remarkably up-regulated in FCL, FCH and FCL+CLA groups. These results suggest that Fc and FCL+CLA could reduce serum levels of triacylglycerol, glucose and leptin, and FCL+CLA could exert anti-obesity effects by regulating mRNA expression of enzymes related to lipid metabolism in WAT of diet-induced obesity rats.

Topics: Adipocytes; Adiponectin; Adipose Tissue, White; Animals; Blood Glucose; Body Weight; Carnitine O-Palmitoyltransferase; Cholesterol; Diet, High-Fat; Dietary Fats; Gene Expression; Leptin; Linoleic Acids, Conjugated; Lipase; Lipid Metabolism; Liver; Male; Obesity; Rats; Rats, Sprague-Dawley; Triglycerides; Xanthophylls

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.

Topics: Animals; Biological Transport; Blood Glucose; Cell Membrane; Diabetes Mellitus; Female; Glucose Transporter Type 4; Insulin; Mice; Mice, Obese; Mice, Transgenic; Muscle, Skeletal; Obesity; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Receptor, Insulin; RNA, Messenger; Transcription Factors; Undaria; Xanthophylls

In this study, we investigated the antiobesity properties of Petalonia binghamiae extract (PBE) in mice in which obesity was induced with a high-fat diet (HFD). PBE administration (150 mg/kg/day) for 70 days decreased body weight gain, adipose tissue weight, and the serum triglyceride level in mice fed a HFD. PBE reduced serum levels of glutamic pyruvic transaminase and glutamic oxaloacetic transaminase as well as the accumulation of lipid droplets in the liver. PBE restored the HFD-induced decrease in phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) in epididymal adipose tissue. PBE increased the phosphorylation of AMPK and ACC and decreased the expression of SREBP1c in mature 3T3-L1 adipocytes. In addition, we further explored the active compound responsible for AMPK activation by PBE in 3T3-L1 adipocytes. Fucoxanthin isolated from PBE increased the phosphorylation of AMPK and ACC with increasing LKB1 phosphorylation in mature 3T3-L1 adipocytes. Taken together, these data suggest that PBE (or fucoxanthin) exert improving effects on HFD-induced obesity by promoting β-oxidation and reducing lipogenesis.

Topics: 3T3 Cells; Adipose Tissue; AMP-Activated Protein Kinases; Animals; Anti-Obesity Agents; Biological Factors; Body Weight; Diet, High-Fat; Eating; Humans; Male; Mice; Mice, Inbred C57BL; Obesity; Phaeophyceae; Triglycerides; Xanthophylls

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.. 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.. 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.. 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.

Topics: Adipose Tissue, White; Administration, Oral; Animals; Anti-Obesity Agents; Cholesterol; Epididymis; Gene Expression; Hydroxymethylglutaryl CoA Reductases; Liver; Male; Mice; Mice, Obese; Muscle, Skeletal; Obesity; Organ Size; Proprotein Convertase 9; Proprotein Convertases; Serine Endopeptidases; Xanthophylls

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.

Topics: Adipokines; Adipose Tissue, White; Animals; Anti-Obesity Agents; Blood Glucose; Cell Line; Diabetes Complications; Female; Gene Expression Regulation; Hypoglycemic Agents; Macrophages; Mice; Obesity; RNA, Messenger; Xanthophylls

This study investigated the effects of fucoxanthin isolated from marine plant extracts on lipid metabolism and blood glucose concentration in high-fat diet fed C57BL/6N mice. The mice were divided into high-fat control (HFC; 20% fat, w/w), low-fucoxanthin (low-Fxn; HFC+0.05% Fxn, w/w) and high-fucoxanthin (high-Fxn; HFC+0.2% Fxn, w/w) groups. Fxn supplementation significantly lowered the concentration of plasma triglyceride with a concomitant increase of fecal lipids in comparison to the HFC group. Also, the hepatic lipid contents were significantly lowered in the Fxn supplemented groups which seemed to be due to the reduced activity of the hepatic lipogenic enzymes, glucose-6-phosphate dehydrogenase, malic enzyme, fatty acid synthase and phosphatidate phosphohydrolase and the enhanced activity of beta-oxidation. Plasma high-density lipoprotein cholesterol concentrations and its percentage were markedly elevated by Fxn supplementation. Activities of two key cholesterol regulating enzymes: 3-hydroxy-3-methylglutaryl coenzyme A reductase and acyl coenzyme A: cholesterol acyltransferase, were significantly suppressed by Fxn regardless of the dosage. Relative mRNA expressions of acyl-coA oxidase 1, palmitoyl (ACOX1) and peroxisome proliferators activated receptor alpha (PPARalpha) and gamma (PPARgamma) were significantly altered by Fxn supplementation in the liver. Fxn also lowered blood glucose and HbA(1c) levels along with plasma resistin and insulin concentrations. These results suggest that Fxn supplementation plays a beneficial role in not only regulating the plasma and hepatic lipids metabolism but also for blood glucose-lowering action in high-fat fed mice.

Topics: Animals; Blood Glucose; Dietary Fats; Dietary Supplements; Eating; Glucagon; Hemoglobin A; Insulin; Lipid Metabolism; Liver; Male; Mice; Mice, Inbred C57BL; Obesity; Phaeophyceae; Plant Extracts; RNA, Messenger; Weight Gain; Xanthophylls

An ethanol extract of fucoxanthin-rich seaweed was examined for its effectiveness as a nutraceutical for body fat-lowering agent and for an antiobese effect based on mode of actions in C57BL/6J mice. Animals were randomized to receive a semi-purified high-fat diet (20% dietary fat, 10% corn oil and 10% lard) supplemented with 0.2% conjugated linoleic acid (CLA) as the positive control, 1.43% or 5.72% fucoxanthin-rich seaweed ethanol extract (Fx-SEE), equivalent to 0.05% or 0.2% dietary fucoxanthin for six weeks. Results showed that supplementation with both doses of Fx-SEE significantly reduced body and abdominal white adipose tissue (WAT) weights, plasma and hepatic triglyceride (TG), and/or cholesterol concentrations compared to the high-fat control group. Activities of adipocytic fatty acid (FA) synthesis, hepatic FA and TG synthesis, and cholesterol-regulating enzyme were also lowered by Fx-SEE supplement. Concentrations of plasma high-density lipoprotein-cholesterol, fecal TG and cholesterol, as well as FA oxidation enzyme activity and UCP1 mRNA expression in epididymal WAT were significantly higher in the Fx-SEE groups than in the high-fat control group. CLA treatment reduced the body weight gain and plasma TG concentration. Overall, these results indicate that Fx-SEE affects the plasma and hepatic lipid profile, fecal lipids and body fat mass, and alters hepatic cholesterol metabolism, FA synthesis and lipid absorption.

Topics: Animals; Anti-Obesity Agents; Body Weight; Cholesterol; Dietary Fats; Dietary Supplements; Lipid Metabolism; Lipids; Male; Mice; Mice, Inbred C57BL; Obesity; Plant Extracts; Seaweed; Weight Gain; Xanthophylls

This study investigated the anti-obesity effects of fucoxanthin in diet-induced obesity mice fed a high-fat diet (20% fat, wt/wt). The mice were supplemented with two doses of fucoxanthin (0.05 and 0.2%, wt/wt) for 6 wk. Fucoxanthin significantly lowered body weight and visceral fat-pads weights compared with the control group without altering food intake. In epididymal adipose tissue of fucoxanthin-fed mice, adipocyte sizes and mRNA expression of lipogenic and fatty acid beta-oxidation enzymes were significantly altered in a dose-dependent manner. Plasma leptin level was significantly lower in the fucoxanthin groups than in the control group, while the adiponectin level was elevated. Fucoxanthin significantly down-regulated various lipogenic enzyme activities in epididymal adipose tissue with a simultaneous decrease in fatty acid beta-oxidation activity. The 0.2% fucoxanthin supplement led to increase mRNA expression of uncoupling protein-1 (UCP-1) and UCP-3 in brown adipose tissue and that of UCP-2 in the epididymal white adipose tissue. However, the 0.05% fucoxanthin only elevated UCP-1 mRNA expression in epididymal white adipose tissue. These results suggest that the anti-obesity effect of fucoxanthin could be mediated by altering lipid-regulating enzymes and UCPs in the visceral fat tissues and plasma adipokine levels.

Topics: Adipokines; Adipose Tissue, Brown; Animals; Anti-Obesity Agents; Cell Size; Dietary Fats; Intra-Abdominal Fat; Ion Channels; Lipid Metabolism; Male; Mice; Mice, Inbred C57BL; Mitochondrial Proteins; Obesity; Random Allocation; Time Factors; Uncoupling Agents; Uncoupling Protein 1; Uncoupling Protein 2; Uncoupling Protein 3; Undaria; Weight Gain; Xanthophylls

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.

Topics: Adipose Tissue; Animals; Blood Glucose; Carotenoids; Female; Humans; Insulin; Ion Channels; Male; Metabolic Syndrome; Mice; Mice, Inbred Strains; Mitochondrial Proteins; Obesity; Random Allocation; Rats; Rats, Wistar; RNA, Messenger; Seaweed; Uncoupling Protein 1; Xanthophylls

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.

Topics: Animals; beta Carotene; Diabetes Mellitus, Type 2; Diet; Docosahexaenoic Acids; Female; Liver; Mice; Obesity; Xanthophylls

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.

Topics: Adipose Tissue; Animals; Blood Glucose; Diabetes Mellitus; Diet; Female; Fish Oils; Mice; Mice, Obese; Obesity; Weight Gain; Xanthophylls

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.

Topics: Abdominal Fat; Adipose Tissue; Animals; Dietary Fats; Female; Intestinal Absorption; Leptin; Mice; Obesity; Triglycerides; Xanthophylls

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.

Topics: Adipose Tissue; Administration, Oral; Animals; Carrier Proteins; Dose-Response Relationship, Drug; Female; Ion Channels; Male; Membrane Proteins; Mice; Mitochondrial Proteins; Obesity; Organ Size; Plant Extracts; Rats; Rats, Wistar; Seaweed; Treatment Outcome; Uncoupling Protein 1; Xanthophylls