Chemokines are members of the chemoattractant cytokine family. They play key roles in the trafficking of leukocytes and in the induction of chemotaxis through the activation of G protein-coupled receptor. Considerable interest has been paid to these molecules to elucidate their roles in the unique inflammatory responses elicited in the central nervous system (CNS). Chemokine CCL2 (also known as monocyte chemoattractant protein-1, MCP-1) is one of the vital chemokines that control the migration and infiltration of monocytes/macrophages. CCL2 and its receptor CCR2 have been shown to be induced and involved in various neurodegenerative disorders including Alzheimer's disease, multiple sclerosis, and ischemic brain injury. The present review will focus on the biological and pathophysiological aspects of CCL2 and CCR2 in the CNS and the possible therapeutic approaches for targeting these two proteins to combat neurodegenerative diseases.

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Plantaricin A (plA) is a 26-residue bacteria-produced peptide pheromone with membrane-permeabilizing antimicrobial activity. In this study the interaction of plA with membranes is shown to be highly dependent on the membrane lipid composition. PlA bound readily to zwitterionic 1-stearoyl-2-oleoyl-sn-glycero-3-phosphocholine (SOPC) monolayers and liposomes, yet without significantly penetrating into these membranes. The presence of cholesterol attenuated the intercalation of plA into SOPC monolayers. The association of plA to phosphatidylcholine was, however, sufficient to induce membrane permeabilization, with nanomolar concentrations of the peptide triggering dye leakage from SOPC liposomes. The addition of the negatively charged phospholipid, 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-rac-glycerol POPG (SOPC/POPG; molar ratio 8:2) enhanced the membrane penetration of the peptide, as revealed by (i) peptide-induced increment in the surface pressure of lipid monolayers, (ii) increase in diphenylhexatriene (DPH) emission anisotropy measured for bilayers, and (iii) fluorescence characteristics of the two Trps of plA in the presence of liposomes, measured as such as well as in the presence of different quenchers. Despite deeper intercalation of plA into the SOPC/POPG lipid bilayer, much less peptide-induced dye leakage was observed for these liposomes than for the SOPC liposomes. Further changes in the mode of interaction of plA with lipids were evident when also the zwitterionic phospholipid, 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphoethanolaminne (POPE) was present (SOPC/POPG/POPE, molar ratio 3:2:5), thus suggesting increase in membrane spontaneous negative curvature to affect the mode of association of this peptide with lipid bilayer. PlA induced more efficient aggregation of the SOPC/POPG and SOPC/POPG/POPE liposomes than of the SOPC liposomes, which could explain the attenuated peptide-induced dye leakage from the former liposomes. At micromolar concentrations, plA killed human leukemic T-cells by both necrosis and apoptosis. Interestingly, plA formed supramolecular protein-lipid amyloid-like fibers upon binding to negatively charged phospholipid-containing membranes, suggesting a possible mechanistic connection between fibril formation and the cytotoxicity of plA.

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Accumulating evidence suggests relationship of compositional changes of gut microbiota with onset of metabolic disorders and obesity. Kimchi, a traditional Korean side dish, is known for its beneficial impact on metabolic parameters and anti-obesity effects. The current study was designed to evaluate the association between gut microbiota and human genome after kimchi intervention in an effort to understand the molecular mechanism(s) underlying the antiobesity impact of kimchi. Twenty-four obese women were randomly assigned to either fresh or fermented kimchi group for eight weeks of kimchi intervention. Pyrosequencing of fecal microbiota and microarray analyses of blood samples revealed that fresh and fermented kimchi interventions exerted differential effects on the obesity-related clinical parameters. Correlations of these effects with changes in blood gene expression and gut microbial population were more evident in the fermented kimchi group than the fresh kimchi group.

Background and AimIncreasing evidence has indicated a close association of host-gut flora metabolic interaction with obesity. Flos Lonicera, a traditional herbal medicine, is used widely in eastern Asia for the treatment of various disorders. The aim of this study was to evaluate whether unfermented or fermented formulations of Flos Lonicera could exert a beneficial impact to combat obesity and related metabolic endotoxemia.MethodsObesity and metabolic endotoxemia were induced separately or together in rats through feeding a eight-week high fat diet either alone (HFD control group) or in combination with a single LPS stimulation (intraperitoneal injection, 0.75 mg/kg) (LPS control group). While, the mechanism of action of the Lonicera formulations was explored in vitro using RAW 264.7 and HCT 116 cell lines as models.ResultsIn cell-based studies, treatment with both unfermented Flos Lonicera (UFL) and fermented Flos Lonicera (FFL) formulations resulted in suppression of LPS-induced NO production and gene expression of vital proinflammatory cytokines (TNF-α, COX-2, and IL-6) in RAW 264.7 cells, reduced the gene expression of zonula occludens (ZO)-1 and claudin-1, and normalized trans epithelial electric resistance (TEER) and horseradish peroxidase (HRP) flux in LPS-treated HCT-116 cells. In an animal study, treatment of HFD as well as HFD+LPS groups with UFL or FFL resulted in a notable decrease in body and adipose tissue weights, ameliorated total cholesterol, HDL, triglyceride, aspartate transaminase and endotoxin levels in serum, reduced the urinary lactulose/mannitol ratio, and markedly alleviated lipid accumulation in liver. In addition, exposure of HFD as well as HFD+LPS groups with UFL or FFL resulted in significant alteration of the distribution of intestinal flora, especially affecting the population of Akkermansia spp. and ratio of Bacteroidetes and Firmicutes.ConclusionThis evidence collectively demonstrates that Flos Lonicera ameliorates obesity and related metabolic endotoxemia via regulating distribution of gut flora and gut permeability.

The identification of new probiotics with anti-obesity properties has attracted considerable interest. In the present study, the anti-obesity activities of Akkermansia muciniphila (A. muciniphila) strains isolated from human stool samples and their relationship with the gut microbiota were evaluated using a high fat-diet (HFD)-fed mice model. Three strains of A. muciniphila were chosen from 27 isolates selected based on their anti-lipogenic activity in 3T3-L1 cells. The anti-lipogenic, anti-adipogenic and anti-obesity properties of these three strains were evaluated further in HFD-induced obese mice. The animals were administered these strains six times per week for 12 weeks. The treatment improved the HFD-induced metabolic disorders in mice in terms of the prevention of body weight gain, caloric intake and reduction in the weights of the major adipose tissues and total fat. In addition, it improved glucose homeostasis and insulin sensitivity. These effects were also associated with the inhibition of low-grade intestinal inflammation and restoration of damaged gut integrity, prevention of liver steatosis and improvement of hepatic function. These results revealed a difference in the distribution pattern of the gut microbial communities between groups. Therefore, the gut microbial population modulation, at least in part, might contribute to the beneficial impact of the selected A. muciniphila strains against metabolic disorders.

Accumulating evidence suggests the anti-inflammatory and anti-obesity activities of Rhizoma Atractylodis Macrocephalae (RAM). Here, we evaluated the anti-obesity impact of unfermented (URAM) versus fermented RAM (FRAM) using both in vitro and in vivo models. Both URAM and FRAM exhibited marked anti-inflammatory, anti-adipogenic, and anti-obesity activities, and modulation of the gut microbial distribution. However, FRAM, compared to URAM, resulted in more efficient suppression of NO production and normalization of transepithelial electrical resistance in LPS-treated RAW 264.7 and HCT 116 cells, respectively. Compared to URAM, FRAM more effectively reduced the adipose tissue weight; ameliorated the serum triglyceride and aspartate transaminase levels; restored the serum HDL level and intestinal epithelial barrier function in the LPS control group. The relative abundance of Bifidobacterium and Akkermansia as well as Bacteriodetes/Firmicutes ratio in the gut of the LPS control group was significantly enhanced by both URAM and FRAM. However, FRAM, but not URAM, resulted in a significant increase in the distribution of Bacteriodetes and Lactobacillus in the gut of the HFD + LPS group. Our results suggest that FRAM with probiotics can exert a greater anti-obesity effect than URAM, which is probably mediated at least in part via regulation of the intestinal microbiota and gut permeability.