chondroitin-sulfates and Obesity

There is growing recognition of the importance of nutritional factors in the maintenance of bone and joint health, and that nutritional imbalance combined with endocrine abnormalities may be involved in the pathogenesis of osteoarthritis (OA) and osteochondritis dissecans (OCD). Despite this, dietary programs have played a secondary role in the management of these connective tissue disorders. Articular cartilage is critically dependent upon the regular provision of nutrients (glucose and amino acids), vitamins (particularly vitamin C), and essential trace elements (zinc, magnesium, and copper). Therefore, dietary supplementation programs and nutraceuticals used in conjunction with non-steroidal, anti-inflammatory drugs (NSAIDs) may offer significant benefits to patients with joint disorders, such as OA and OCD. This article examines the available clinical evidence for the efficacy of nutraceuticals, antioxidant vitamin C, polyphenols, essential fatty acids, and mineral cofactors in the treatment of OA and related joint disorders in humans and veterinary species. This article also attempts to clarify the current state of knowledge. It also highlights the need for additional targeted research to elucidate the changes in nutritional status and potential alterations to the expression of plasma membrane transport systems in synovial structures in pathophysiological states, so that current therapy and future treatments may be better focused.

Topics: Amino Acids; Animals; Anti-Inflammatory Agents, Non-Steroidal; Bivalvia; Camellia sinensis; Cartilage; Chondroitin Sulfates; Fatty Acids, Essential; Flavonoids; Glucosamine; Glucose; Humans; Nutritional Status; Obesity; Osteoarthritis; Osteochondritis Dissecans; Phenols; Polyphenols; Trace Elements; Vitamins

Chondroitin sulfate (CS) is a special bioactive substance with lipid metabolism regulation functions; its molecular mechanisms, however, need further study. This study aimed to study the role of gut microbiota and liver metabolome in the anti-obesity effects of CS. The results demonstrated that CS significantly reduced body weight gain and alleviated insulin resistance and dyslipidemia induced by high-fat diet treatment. Moreover, CS interestingly increased the content of Firmicutes in intestinal microbiota. Further studies showed that there were 11 different metabolites involved in metabolic pathways, including the unsaturated fatty acid biosynthesis pathway, primary bile acid biosynthesis, and taurine and hypotaurine metabolism. In addition, Spearman's correlation analysis indicated that the anti-obesity effect of CS is closely related to liver metabolic regulation. Overall, these results provide a possible molecular mechanism by which CS reduces body weight and lipid accumulation.

Topics: Animals; Body Weight; Chondroitin Sulfates; Diet, High-Fat; Gastrointestinal Microbiome; Liver; Metabolome; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity

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

This study evaluated the possible prebiotic effects of dietary fucosylated chondroitin sulfate from Acaudina molpadioides (Am-CHS) on the modulation of the gut microbiota and the improvement in the risk factors for chronic inflammation in high fat diet-fed mice. The results showed that the Am-CHS treatment greatly modified the gut microbiota, including the decrease in Bacteroidetes, increase in Firmicutes, elevation in Lactobacillus (intestinal barrier protector) and short chain fatty acid (SCFA)-producing bacteria (Lactobacillus, Bifidobacterium, and Lachnospiraceae NK4A136 group), and reduction in the lipopolysaccharide (LPS) producer (Escherichia coli). This modulation inhibited inflammatory response, manifesting the decreases in circulating proinflammatory cytokines and their mRNA expression, and the increases in interleukin-10. Dietary Am-CHS caused reductions in serum and fecal LPS concentrations and inhibition of transcription of toll-like receptor 4 (TLR4) and its downstream proteins. In addition, there were increases in the portal levels of fecal SCFAs, which probably contributed to an increase in the adenosine monophosphate-activated protein kinase (AMPK) protein in Am-CHS-treated mice. These results suggest that modulation of gut microbiota by Am-CHS can improve chronic inflammation by reducing LPS levels and TLR4 signaling. Modulation also appears to increase the levels of fecal SCFAs, which activates AMPK and finally leads to inflammation resistance.

Topics: Animals; Chondroitin Sulfates; Cytokines; DNA, Bacterial; Escherichia coli Proteins; Fatty Acids, Volatile; Gastrointestinal Microbiome; Gene Expression Regulation; Inflammation; Intestinal Mucosa; Intestines; Lipopolysaccharides; Male; Membrane Proteins; Mice; Mice, Inbred C57BL; Obesity; Phosphotransferases; RNA, Messenger; Sea Cucumbers

We aimed to investigate the anti-obesity effects of chondroitin sulfate (CS) oligosaccharides obtained from cartilage of the skate Raja pulchra and to compare them with those of CSs of other molecular weights (MWts) (skate CS polysaccharides) and origins (shark CS, bovine CS). CSs suppressed pancreatic lipase activity as well as proliferation and lipid accumulation in mature adipocytes. Higher MWt CS had a greater lipase inhibitory activity than lower MWt CS. CSs of different origin show differing potencies for lipase inhibition and effects on adipocytes. Also, dietary intake of skate CS oligosaccharides could ameliorate obesity in high-fat diet mice model: it prevented gaining in body weight, liver weight and adipose tissue weight, maintained lower food consumption, inhibited intestinal absorption of triglyceride, and adjusted the serum endotoxin level. In conclusion, skate CS oligosaccharides have an anti-obesity activity, and the MWt and origin of the CSs may affect this activity.

Topics: 3T3-L1 Cells; Adipocytes; Animals; Anti-Obesity Agents; Cattle; Cell Proliferation; Chondroitin Sulfates; Endotoxins; Enzyme Inhibitors; Lipase; Lipid Droplets; Male; Mice; Mice, Inbred Strains; Obesity; Oligosaccharides; Sharks; Skates, Fish; Swine

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

Osteoarthritic patients treated with high doses of chondroitin sulfate (CS) have a lower incidence of coronary heart disease--but the mechanistic aspects of these beneficial effects of CS remain undefined. We examined how CS treatment affects the formation of atheroma via interaction with endothelial cells and monocytes.. We characterized arterial atheromatous plaques by multiphoton microscopy and serum pro-inflammatory cytokines by immunoenzymatic techniques in obese mice receiving CS (1 g/kg/day, i.p.) or vehicle for 6 days. Effects of CS on signaling pathways, cytokine secretion and macrophage migration were evaluated in cultures of human coronary endothelial cells and in a monocyte cell line stimulated with TNF-α by Western blot, immunoenzymatic techniques and transwell migration assays.. Treatment of obese mice with CS reduced the extension of foam cell coverage in atheromatous plaques of arterial bifurcations by 62.5%, the serum concentration of IL1β by 70%, TNF-α by 82% and selected chemokines by 25-35%. Cultures of coronary endothelial cells and monocytes stimulated with TNF-α secreted less pro-inflammatory cytokines in the presence of CS (P < 0.01). CS reduced the activation of the TNF-α signaling pathway in endothelial cells (pErk 36% of reduction, and NFκB 33% of reduction), and the migration of activated monocytes to inflamed endothelial cells in transwells (81 ± 6 vs. 13 ± 2, P < 0.001).. CS interferes with the pro-inflammatory activation of monocytes and endothelial cells driven by TNF-α thus reducing the propagation of inflammation and preventing the formation of atherosclerotic plaques.

Topics: Animals; Atherosclerosis; Cell Line; Chondroitin Sulfates; Disease Models, Animal; Endothelium, Vascular; Inflammation; Male; Mice; Mice, Obese; Obesity

Chondroitin sulfate is an acidic polymer consisting of repeating D-glucuronic acid and D-N-acetylgalactosamine units, and the N-acetylgalactosamine is substituted with the sulfate at either the 4' or 6' position, with approximately one sulfate being present per disaccharide unit. The present study assessed the effects of chondroitin sulfate on the activity of pancreatic lipase and lipid uptake into brush border membrane vesicles of the rat small intestine in vitro, and on the degree of fat storage induced in mice by the oral administration of a high-fat diet for 8 weeks.. Experiments were carried out to clarify whether or not chondroitin sulfate inhibited pancreatic lipase activity in assay systems using triolein emulsified with phosphatidylcholine or gum arabic. In addition, the effects of chondroitin sulfate on lipid absorption by brush border membrane vesicles were examined. Moreover, mice were fed a high-fat diet and treated with chondroitin sulfate for 8 weeks.. Chondroitin sulfate dose-dependently inhibited the pancreatic lipase activity in an assay system using triolein emulsified with phosphatidylcholine. In addition, chondroitin sulfate inhibited the palmitic acid uptake into the brush border membrane vesicles of the rat jejunum. Chondroitin sulfate caused the reduction of body weight and parametrial adipose tissue weight, and prevention of fatty liver and hyperlipidemia in mice fed a high-fat diet.. The reduction of fat storage and the antihyperlipidemic action of chondroitin sulfate might be due to the inhibition of small intestinal absorption of dietary fat through the inhibition of pancreatic lipase activity and fatty acid uptake through brush border membrane.

Topics: Adipose Tissue; Administration, Oral; Animals; Cartilage; Chondroitin Sulfates; Dietary Fats; Dose-Response Relationship, Drug; Female; Hypolipidemic Agents; Intestinal Absorption; Lipase; Lipid Metabolism; Liver; Male; Mice; Mice, Inbred ICR; Obesity; Pancreas; Rats; Rats, Wistar; Salmon

Heparin was found to inhibit the Ca2+ release induced by inositol 1,4,5-trisphosphate (IP3) in permeabilized pancreatic beta-cells obtained from obese hyperglycemic mice. The effect of heparin was dose-dependent and not due to inhibition of Ca2+ uptake into the IP3-sensitive pool. The effect appeared specific for heparin and was not reproduced by other polysaccharides such as chondroitin sulfates. Heparin might consequently be a useful tool when investigating the molecular mechanism whereby IP3 mobilizes Ca2+.

Topics: Animals; Calcium; Cell Membrane Permeability; Chondroitin Sulfates; Dose-Response Relationship, Drug; Heparin; Hyperglycemia; Inositol 1,4,5-Trisphosphate; Inositol Phosphates; Islets of Langerhans; Mice; Mice, Obese; Obesity; Sugar Phosphates