title: A potential role of IL-6 in the chito-oligosaccharide-mediated inhibition of adipogenesis.
abstract: Recent studies have suggested that chito-oligosaccharides can have anti-adipogenic properties. The objectives of the present study were to evaluate the anti-adipogenic potential of four different chito-oligosaccharides (molecular weight (MW) < 1000, 1000-3000, 3000-5000 and 5000-10,000 Da) and to identify molecular mechanisms underlying the chito-oligosaccharide-mediated inhibition of adipogenesis. Mouse 3T3-L1 cells were allowed to differentiate in the presence of chito-oligosaccharide. At day 8 post-induction of differentiation, lipid accumulation, free glycerol release and the quantitative expression of adipogenic marker genes were evaluated. Chito-oligosaccharides had concentration- and MW-dependent inhibitory effects on lipid accumulation (P < 0·001 and < 0·05, respectively), as well as a concentration-dependent effect (P < 0·001) on free glycerol release and the expression of adipogenic marker genes. The 5000-10,000 Da chito-oligosaccharide was selected for subsequent molecular studies. A panel of forty-four lipid metabolic pathway-specific genes was analysed by quantitative real-time PCR. Chito-oligosaccharide-mediated inhibition of adipogenesis was associated with the up-regulation of the IL-6 gene at all concentrations of chito-oligosaccharide examined and the PG-endoperoxide synthase 2 (PTGS2) gene at higher concentrations of chito-oligosaccharide. The effect of chito-oligosaccharide on gene expression was validated by measuring IL-6 protein concentrations in the media. Finally, an IL-6 promoter assay was developed to characterise the effect of chito-oligosaccharide on the transcriptional activity of the IL-6 promoter, which was increased in a concentration-dependent manner (P < 0·001). We conclude that IL-6 is a candidate signalling molecule in the chito-oligosaccharide-mediated inhibition of adipogenesis in 3T3-L1 cells.
authors: Institute of Food and Health, School of Agriculture, Food Science and Veterinary Medicine, University College Dublin, Belfield, Dublin 4, Republic of Ireland.
authors: Bojlul
authors: B
authors: Bahar
authors: John V
authors: JV
authors: O'Doherty
authors: Torres
authors: T
authors: Sweeney
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D050156:Adipogenesis / Q000187:drug effects* / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D015850:Interleukin-6 / Q000235:genetics / Q000502:physiology*; D050356:Lipid Metabolism / Q000187:drug effects / Q000235:genetics; D053858:Metabolic Networks and Pathways / Q000187:drug effects / Q000235:genetics; D051379:Mice; D008970:Molecular Weight; D009844:Oligosaccharides / Q000737:chemistry / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D060888:Real-Time Polymerase Chain Reaction; D059467:Transcriptome / Q000187:drug effects
chemical_list: D017931:DNA Primers; D015850:Interleukin-6; D009844:Oligosaccharides