Sulfated Polysaccharides from Enteromorpha prolifera Attenuate Lipid Metabolism Disorders in Mice with Obesity Induced by a High-Fat Diet via a Pathway Dependent on AMP-Activated Protein Kinase.

BACKGROUND: Obesity-related metabolic diseases have recently evoked worldwide attention. Studies have demonstrated that Enteromorpha polysaccharide (EP) exerts lipid-lowering effects, but the underlying mechanism remains unclear. OBJECTIVES: We investigated whether EP regulates lipid metabolism disorders in mice with high-fat diet (HFD)-induced obesity via an AMP-activated protein kinase (AMPK)-dependent pathway. METHODS: Six-week-old male C57BL/6J mice (18 ± 2 g) were fed a normal diet (ND; 10% energy from fats) or an HFD (60% energy from fats) for 6 weeks to induce obesity and treated intragastrically with EP (200 mg/kg body weight) or distilled water (10 mL/kg body weight) for 8 weeks. Biochemical indicators, AMPK-dependent pathways, and lipid metabolism-related genes were evaluated to assess the effects of EP on HFD-induced lipid metabolism disorders. The essential role of AMPK in the EP-mediated regulation of lipid metabolism was confirmed using HFD-fed male Ampka2-knockout mice (aged 6 weeks; 17 ± 2 g) treated or not treated with the above-mentioned dose of EP. The data were analyzed by t-tests, 2-factor and 1-way ANOVAs. RESULTS: Compared to the ND, the HFD resulted in a greater body weight (24.3%), perirenal fat index (2.2-fold), and serum total cholesterol (24.66%) and LDL cholesterol (1.25-fold) concentrations (P < 0.05) and dysregulated the AMPK-dependent pathway and the expression of most lipid metabolism-related genes (P < 0.05). Compared to the HFD, EP treatment resulted in a lower perirenal fat index (31.22%) and LDL cholesterol concentration (23.98%) and partly reversed the dysregulation of the AMPK-dependent pathway and the altered expression of lipid metabolism-related genes (P < 0.05). Ampka2 knockout abolished the above-mentioned effects of EP in obese mice and the EP-mediated effects on the expression of lipid metabolism-related genes (P > 0.05). CONCLUSIONS: These findings suggest that EP can ameliorate lipid metabolism disorders in mice with HFD-induced obesity via an AMPK-dependent pathway.

Sulfated Polysaccharides from Enteromorpha prolifera Attenuate Lipid Metabolism Disorders in Mice with Obesity Induced by a High-Fat Diet via a Pathway Dependent on AMP-Activated Protein Kinase.

BACKGROUND: Obesity-related metabolic diseases have recently evoked worldwide attention. Studies have demonstrated that Enteromorpha polysaccharide (EP) exerts lipid-lowering effects, but the underlying mechanism remains unclear. OBJECTIVES: We investigated whether EP regulates lipid metabolism disorders in mice with high-fat diet (HFD)-induced obesity via an AMP-activated protein kinase (AMPK)-dependent pathway. METHODS: Six-week-old male C57BL/6J mice (18 ± 2 g) were fed a normal diet (ND; 10% energy from fats) or an HFD (60% energy from fats) for 6 weeks to induce obesity and treated intragastrically with EP (200 mg/kg body weight) or distilled water (10 mL/kg body weight) for 8 weeks. Biochemical indicators, AMPK-dependent pathways, and lipid metabolism-related genes were evaluated to assess the effects of EP on HFD-induced lipid metabolism disorders. The essential role of AMPK in the EP-mediated regulation of lipid metabolism was confirmed using HFD-fed male Ampka2-knockout mice (aged 6 weeks; 17 ± 2 g) treated or not treated with the above-mentioned dose of EP. The data were analyzed by t-tests, 2-factor and 1-way ANOVAs. RESULTS: Compared to the ND, the HFD resulted in a greater body weight (24.3%), perirenal fat index (2.2-fold), and serum total cholesterol (24.66%) and LDL cholesterol (1.25-fold) concentrations (P < 0.05) and dysregulated the AMPK-dependent pathway and the expression of most lipid metabolism-related genes (P < 0.05). Compared to the HFD, EP treatment resulted in a lower perirenal fat index (31.22%) and LDL cholesterol concentration (23.98%) and partly reversed the dysregulation of the AMPK-dependent pathway and the altered expression of lipid metabolism-related genes (P < 0.05). Ampka2 knockout abolished the above-mentioned effects of EP in obese mice and the EP-mediated effects on the expression of lipid metabolism-related genes (P > 0.05). CONCLUSIONS: These findings suggest that EP can ameliorate lipid metabolism disorders in mice with HFD-induced obesity via an AMPK-dependent pathway.

Modulation of platelet aggregation-related eicosanoid production by dietary F-fucoidan from brown alga Laminaria japonica in human subjects.

Laminaria japonica is traditionally eaten in Japan as a beneficial food for thrombosis. The alga contains two specific ingredients, a xanthophyll fucoxanthin (FX) and a polysaccharide, F-fucoidan (FD). The aim of the present study was to investigate whether FX or FD exhibited anti-thrombotic effects. For this purpose, three types of capsules, containing 1 mg FX, 400 mg fucoidan, and both, were prepared from the alga and administered to volunteers for 5 weeks. The dose of FD or FD+FX significantly shortened lysis time (LT) of the thrombus measured by a global thrombosis test in the blood, but FX did not. Examining the mechanism, dietary FD increased H2O2 and the secretion of prostacyclin (PGI2), a potent inhibitor of platelet aggregation, in the blood, although FD was under the detection limit in the blood, determining with its monoclonal antibody. Furthermore, in mouse experiments, dietary FD was totally excreted into the faeces and was not incorporated into the blood. We then employed a co-culture system of a Caco-2 cell monolayer with fresh human blood. The addition of FD to Caco-2 cells stimulated the expression of NADPH oxidase 1 (NOX1) and dual oxidase 2 (DUOX2) mRNA and secreted H2O2 onto the blood side accompanied by a significant increase in serum PGI2 production. These effects were invalidated by the combined addition of FD with its monoclonal antibody. The results suggested that dietary FD stimulated the expression of H2O2-producing enzymes in intestinal epithelial cells and released H2O2 into the blood, which played a signalling role to increase PGI2 production and then shortened LT for thrombi.

A lipid peroxidation product 9-oxononanoic acid induces phospholipase A2 activity and thromboxane A2 production in human blood.

Lipid peroxidation products are known to cause toxicity by reacting with biologically significant proteins, but the inducing role of peroxidation products has been not noted to produce degenerative disease-related eicosanoids. Here, 9-oxononanoic acid (9-ONA), one of the major products of peroxidized fatty acids, was found to stimulate the activity of phospholipase A2 (PLA2), the key enzyme to initiate arachidonate cascade and eicosanoid production. An exposure of fresh human blood to the atmosphere at 37°C accumulated 9-ONA, increasing peroxide value and thiobarbituric acid reactive substances in the blood. The lipid peroxidation was accompanied by significant increases of PLA2 activity and thromboxane B2 (TxB2) production, which is a stable metabolite of thromboxane A2 (TxA2) and a potent agonist of platelet aggregation. These events were abolished by standing the blood under nitrogen. The addition of organically synthesized 9-ONA resumed the activity of PLA2 and the production of TxB2. Also, 9-ONA induced platelet aggregation dose-dependently. These results indicated that 9-ONA is the primary inducer of PLA2 activity and TxA2 production, and is probably followed by the development of diseases such as thrombus formation. This is the first report to find that a lipid peroxidation product, 9-ONA, stimulates the activity of PLA2.

Polysaccharides derived from natural sources regulate triglyceride and cholesterol metabolism: a review of the mechanisms.

With great changes in people's lifestyles, the incidence of hyperlipidaemia has dramatically increased in recent years. Numerous studies have demonstrated that natural polysaccharides have lipid lowering effects. In this review, the causes and mechanisms of hyperlipidaemia are discussed in order to better understand how polysaccharides alleviate hyperlipidaemia. Natural polysaccharides reduce triglyceride levels through ATGL-(PPAR-α)/(PGC-1α), (SREBP-1c)-ACC/FAS and ACC-CPT1 signal pathways, and exert cholesterol lowering effects via (SREBP-2)-HMGCR and bile acid biosynthesis pathways. Activation of adenosine monophosphate-activated protein kinase (AMPK) is the key factor that mediated the simultaneous regulation of both glucose and lipid metabolism by polysaccharides. The new discovery of polysaccharides increasing the production of endogenous H2S, an important physiological gaseous signaling molecule, is also discussed. Collectively, the current available data suggest that natural polysaccharides could be potentially developed as new and safe lipid-lowering drugs; yet further mechanistic and clinical studies are required during this long-term process.

Sulfated polysaccharide from Enteromorpha prolifera increases hydrogen sulfide production and attenuates non-alcoholic fatty liver disease in high-fat diet rats.

Enteromorpha prolifera is an edible alga and previous studies have indicated that E. prolifera polysaccharide (EP) attenuates non-alcoholic fatty liver disease (NAFLD) in high-fat diet rats. Hydrogen sulfide (H2S) has recently been found to exert many physiological effects. The purpose of this study was to evaluate whether EP prevents NAFLD via regulation of H2S production. EP was orally administered to high-fat diet rats for 5 weeks. Treatment with EP (200 mg per kg body weight per d) significantly increased the serum H2S level and reduced the serum triglyceride level (p < 0.05) in rats fed a high-fat diet. These effects were similar to those observed with NaHS, a H2S donor. Real-time PCR and western blotting analysis revealed that EP significantly upregulated hepatic mRNA and protein expression of cystathionine-ß-synthase, which is the enzyme responsible for H2S production. These results indicate that EP decreases the serum TG level by increasing H2S production, suggesting that EP may be beneficial for the treatment of NAFLD and may reduce the risk of cardiovascular disease.

Sulfated polysaccharides from Enteromorpha prolifera suppress SREBP-2 and HMG-CoA reductase expression and attenuate non-alcoholic fatty liver disease induced by a high-fat diet.

Non-alcoholic fatty liver disease (NAFLD) is caused by fat accumulation and is associated with abnormal cholesterol metabolism. Previous work indicates that polysaccharides from alga Enteromorpha prolifera improve glucose metabolism and lower cholesterol in diabetic rats. Thus, we studied the possible protective effects of E. prolifera polysaccharides (EP) in the development of NAFLD and underlying mechanisms. EP (200 mg kg-1) significantly reduced the liver weight and significantly lowered hepatic HMG-CoA reductase (HMGCR) mRNA protein expression. EP suppressed sterol regulatory element binding protein-2, which is a key transcription factor in cholesterol metabolism and regulates the expression of HMGCR. Therefore, EP may be a functional food that can prevent NAFLD.

Fucoxanthin induces apoptosis in osteoclast-like cells differentiated from RAW264.7 cells.

Fucoxanthin is an oxygenated carotenoid present in edible brown sea algae, and dietary fucoxanthin is recognized to exhibit various beneficial effects. In the present study, the effects of fucoxanthin on osteoclastogenesis were investigated using cells from the macrophage cell line RAW264.7, which have the capacity to differentiate into osteoclast-like cells when stimulated by receptor activator of nuclear factor kappaB ligand. Fucoxanthin significantly suppressed the differentiation of RAW264.7 cells at 2.5 microM, which was not toxic to RAW264.7 cells. Treatment with 2.5 microM fucoxanthin also induced apoptosis accompanied by activation of caspase-3 in osteoclast-like cells. On the other hand, 2.5 microM fucoxanthin did not decrease cell viability in cells of the osteoblast-like cell line MC3T3-E1, indicating that the apoptosis-inducing activity of fucoxanthin in osteoclasts is stronger than that in osteoblasts. The present in vitro study suggests that fucoxanthin suppresses osteoclastogenesis via the inhibition of osteoclast differentiation and the induction of apoptosis in osteoclasts, but not bone formation.