ABSTRACT
Aim Excessive cerebral inflammation caused by chronic alcohol intake is an important risk factor for central nervous system injury. The purpose of this study was to explore the protective effect of konjac mannan oligosaccharide (KMOS) on central nervous system inflammation in alcohol-fed mice and its mechanism. Methods The chronic alcohol fed model of C57BL/6J mice was established using Gao-binge method. And the different doses of KMOS were gavaged every day for 6 weeks. The neuronal damage and microglia activation were evaluated in cerebral cortex and hippocampus. The damage of colon tissue was assessed and serum LPS concentrations were measured. In vitro, Caco-2 cells were stimulated with LPS to establish intestinal mucosal injury model. Results Chronic alcohol intake can cause brain neuron damage in mice, and different doses of KMOS effectively reduced the activation state of microglia, decreased the expression of inflammatory factors caused by the activation of the NLRP3 inflammasome and alleviated neuronal damage in the brain tissue of alcohol-fed mice. The results of colon tissue analysis showed that the use of KMOS effectively reduced the concentration of endotoxin LPS in serum of alcohol-fed mice, alleviated the pathological injury and inflammatory response of colon tissue, and enhanced the expression of Occludin in intestinal tissue. In vitro experiments also showed that KMOS significantly inhibited the inflammatory reaction of Caco-2 cells exposed to alcohol and increased the expression of Occludin protein. Conclusions KMOS treatment effectively inhibited intestinal inflammation caused by alcohol intake, repaired intestinal barrier to prevent the entry of intestinal LPS into brain tissue, decreased the activation of microglia, and then improved brain neuron damage. KMOS had the potential to prevent alcoholic nerve injury.
ABSTRACT
Functional oligosaccharides, particularly konjac mannan oligosaccharides (KMOS), can regulate glucose metabolism. However, the molecular mechanisms involved in the hypoglycemic effect of KMOS remain largely unknown. Here, the effect of KMOS supplementation on glucose homeostasis was evaluated in both high-fat diet (HFD)-fed C57BL/6J mice and high-glucosamine-induced HepG2 cells. KMOS supplementation remarkably ameliorated the fasting blood glucose, glucose tolerance, and insulin tolerance of HFD-fed mice. Abnormalities of triglyceride and glycogen metabolism in the liver induced by the HFD were reversed by KMOS supplementation. The insulin signaling pathway was activated by KMOS, with stimulation of GLUT2 membrane translocation and glucose uptake in HepG2 cells via the AMPK pathway. Moreover, KMOS suppressed p-mTOR expression and stimulated the GSK-3ß/CREB pathway via the AMPK pathway. KMOS significantly upregulated leptin receptor expression and downregulated PTP1B and SOCS3 levels in the liver and brain, with a decreased serum leptin concentration. Phosphorylation of JAK2 and STAT3 in the liver was activated by KMOS supplementation, while the expressions of Sirt1, Tfam, and Pgc1-α in the brain were elevated. Conclusively, KMOS attenuated HFD-induced glucose metabolism dysfunction through the regulation of insulin resistance and leptin resistance. This finding indicates that KMOS have potential value as an anti-hyperglycemic dietary supplement.
Subject(s)
Blood Glucose/drug effects , Dietary Supplements , Glucose Metabolism Disorders/drug therapy , Hepatocytes/drug effects , Hypoglycemic Agents/pharmacology , Insulin Resistance , Insulin/blood , Leptin/metabolism , Liver/drug effects , Mannans/pharmacology , Animals , Biomarkers/blood , Blood Glucose/metabolism , Diet, High-Fat , Disease Models, Animal , Glucose Metabolism Disorders/blood , Glucose Metabolism Disorders/etiology , Hep G2 Cells , Hepatocytes/metabolism , Homeostasis , Humans , Liver/metabolism , Male , Mice, Inbred C57BL , Signal TransductionABSTRACT
Type 2 diabetes (T2D) induced by obesity and high-fat diet is significantly associated with gut microbiota dysbacteriosis. Because the first line clinical medicine of metformin has several intestinal drawbacks, combination usage of metformin with a prebiotic of konjac mannan-oligosaccharides (MOS) was conceived and implemented aiming to investigate whether there were some intestinal synergetic effects and how MOS would function. Composite treatment of metformin and MOS demonstrated synergistic effects on ameliorating insulin resistance and glucose tolerance, also on repairing islet and hepatic histology. In addition, MF+MOS altered the gut community composition and structure by decreasing the relative abundances of family Rikenellaceae and order Clostridiales while increasing an unnamed OTU05945 of family S24-7, Akkermansia muciniphila, and Bifidobacterium pseudolongum. The present study suggested that usage of MOS could augment the hypoglycemic effects of metformin in association with gut microbiota modulation, which could provide references for further medication.
