chondroitin-sulfates and Hyperlipidemias

Fucosylated chondroitin sulfate from Isostichopus badionotus (fCS-Ib) is a kind of sulfated polysaccharides with well-repeated structure. In our former publications, fCS-Ib has been reported to be a functional food ingredient with hypoglycemic and antilipemic activities. However, there is no systematic study to investigate the effects of fCS-Ib on metabolic syndromes. In the present study, C57BL/6 mice fed on a high-fat and high sucrose diet (HFSD) for 6 weeks was used to cause metabolic syndromes. The final results showed that fCS-Ib alleviated obesity, hyperlipidemia, hyperglycemia, inflammation, liver steatosis, and adipocyte hypertrophy caused by HFSD. Meanwhile, fCS-Ib showed powerful effects on moderating gut microbiota dysbiosis in the HFSD-fed mice. Supplement of fCS-Ib could reduce ratio of Firmicutes to Bacteroidetes by decreasing abundance of Lachnospiraceae and Allobaculum while increasing abundance of Porphyromonadaceae, Barnesiella, and Bacteroides. Our results showed that fCS-Ib could be further developed as a potential pharmaceutical agent to prevent metabolic syndromes and gut microbiota dysbiosis.

Topics: Adipocytes; Animals; Chondroitin Sulfates; Diet, High-Fat; Dysbiosis; Fatty Liver; Fructose; Gastrointestinal Microbiome; Humans; Hyperglycemia; Hyperlipidemias; Hypertrophy; Inflammation; Metabolic Syndrome; Mice; Obesity; Sea Cucumbers

Fucosylated chondroitin sulfate (fCS) and its depolymerized derivative (DfCS), prepared from sea cucumbers, are well-known for their anticoagulant activity. However, their other functional activities are poorly understood. Recently, we obtained fCS oligosaccharides from Isostichopus Badionotus by a modified controllable Fenton-system, named as DfCS-Ib. The functional activities of these oligosaccharides are still unclear. The present study investigated anti-hyperlipidemic activity of DfCS-Ib using a high-fat diet (HFD)-fed mice model. The results indicated that DfCS-Ib reduced obesity, hyperlipidemia, and inflammation caused by HFD. Meanwhile, DfCS-Ib increased the mRNA expression of PPARγ and decreased the mRNA expression of leptin, aP2, and F4/80 in fat tissue. Transcriptome analysis indicated that DfCS-Ib normalized the expressions of genes regulating lipid metabolism. Our results suggested that DfCS-Ib can alleviated lipid disorder by reducing lipid synthesis and promoting lipid lipidolysis. DfCS-Ib can act as a functional agent to regulate lipid disorder.

Topics: Animals; Chondroitin Sulfates; Dietary Fats; Disease Models, Animal; Hyperlipidemias; Male; Mice; Obesity; Oligosaccharides; Sea Cucumbers

The specific interaction of lipoproteins with arterial wall constituents, particularly proteoglycans (APG), is believed to play an important role in the development of atherosclerosis. The objective of this study was to examine the interaction of apolipoprotein B (apoB) containing lipoprotein subfractions (VLDL1, Sf 60 to 400; VLDL2, Sf 20 to 60; IDL1, Sf 16 to 20; IDL2, Sf 12 to 16; LDLA, Sf 8 to 12; and LDLB, Sf 0 to 8) prepared by cumulative density gradient centrifugation with chondroitin sulfate-rich APG. Eighteen subjects were studied, and a similar pattern of interaction between the lipoprotein species and APG was found in all. The order of reactivity (as measured by increased turbidity due to insoluble complex formation) was IDL Sf 12 to 16 > or = LDL Sf 8 to 12 > LDL Sf 0 to 8 > IDL Sf 16 to 20 >> VLDL Sf 20 to 60 > VLDL Sf 60 to 400. When the subjects were divided on the basis of their LDL subfraction profile, the extent of insoluble complex formation was highest in the group in which small, dense LDLIII was predominant; intermediate in the group whose LDL was mainly LDLII; and lowest in the group with a high proportion of LDLI (the mean reactivity, AU at 600 nm. of APG with IDL Sf 12 to 16 and LDL Sf 8 to 12 was 0.66; 0.62 and 0.46, 0.43 and 0.20, and 0.21 for the three groups, respectively). Fibrate lipid-lowering treatment decreased the percentage of LDLIII and increased the percentage of LDLI within total LDL and reduced the reactivity of all apoB-containing lipoprotein fractions toward APG. Sialic acid content varied in different lipoprotein subfractions, being the highest in VLDL and lowest in LDL. However, across lipoprotein species, it did not significantly correlate with APG-binding reactivity, suggesting that other factors are important in determining the interaction of lipoproteins with APG. Modification of LDL arginine and lysine residues abolished the ability of the lipoprotein to interact with APG, a finding that supports the hypothesis that the interaction is dependent on key positively charged amino acids on apoB. These findings demonstrate that (1) the overall reactivity of apoB-containing lipoproteins is greatest in individuals with small, dense LDL and (2) within an individual, IDL of Sf 12 to 16 is the most reactive species, and this may in part explain the positive correlation between IDL and risk of coronary heart disease.

Topics: Adult; Aged; Aorta; Apolipoproteins B; Arginine; Chondroitin Sulfates; Clofibric Acid; Coronary Artery Disease; Fibric Acids; Humans; Hyperlipidemias; Hypolipidemic Agents; Lipoproteins; Lipoproteins, IDL; Lipoproteins, LDL; Lipoproteins, VLDL; Lysine; Male; Middle Aged; N-Acetylneuraminic Acid; Neuraminidase; Protein Binding; Proteoglycans

The binding of intact, high molecular weight, aortic proteoglycan (PG) isolated from grossly normal appearing aortas of atherosclerosis-susceptible White Carneau pigeons (WC-2) and -resistant Show Racer pigeons (SR) to homologous and heterologous serum lipoproteins from both normolipemic and hyperlipemic pigeons was examined. In vitro binding studies were done using a mixture of purified chondroitin sulfate PG and dermatan sulfate PG monomers to simulate an in situ composition. For each animal, a binding potential or reactivity number was calculated and corresponded to the shape and slope of the PG-LDL binding curve, where higher values indicated greater reactivity. For WC-2 normal sera, mean values were 0.97 and 0.95 using WC-2 and SR PG respectively, compared to SR normal sera (equivalent total plasma cholesterol) where values were 0.80 and 0.82. Corresponding mean reactivity values for hyperlipemic sera (diluted to a cholesterol concentration of 300 mg/dl) were 0.95, 1.00, 0.73, and 0.79. The results suggest that LDL from both normolipemic and hyperlipemic atherosclerosis-susceptible WC-2 pigeons is more reactive in complexing to artery wall derived PG than LDL from SR pigeons, regardless of PG source.

Topics: Animals; Aorta, Thoracic; Arteriosclerosis; Chondroitin Sulfates; Columbidae; Disease Susceptibility; Electrophoresis, Agar Gel; Hyperlipidemias; Immunity, Innate; Lipoproteins; Lipoproteins, LDL; Protein Binding; Protein Conformation; Proteoglycans

The examination was conducted in 1048 patients with the ischaemic heart disease. Both males, and females displayed most frequently Type II hyperlipidemia. Type IV was more frequent in males, than in females. The incidence of Types IIa and IIb depended on the stage of coronary atherosclerosis, the age and sex of the patients. The concomitant diseases were found to influence the incidence of hyperlipidemia. Among the tested drugs administered in a course of therapy of 4 weeks atromidine proved to be most effective for the examined types of hyperlipidemia (IIa, IIb, IV). Hyperlipidemia relapsed in 1/3 of the patients within 1 year.

Topics: Adult; Age Factors; Aged; Cholesterol; Chondroitin Sulfates; Coronary Disease; Drug Evaluation; Female; Humans; Hyperlipidemias; Hypolipidemic Agents; Lipoproteins, LDL; Male; Middle Aged; Saponins; Thioctic Acid; Triglycerides