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The adipose Nod-like receptor protein 3 (NLRP3) inflammasome senses danger-associated molecular patterns (DAMPs) and initiates insulin resistance, but the mechanisms of adipose inflammasome activation remains elusive. In this study, Homocysteine (Hcy) is revealed to be a DAMP that activates adipocyte NLRP3 inflammasomes, participating in insulin resistance. Hcy-induced activation of NLRP3 inflammasomes were observed in both adipocytes and adipose tissue macrophages (ATMs) and mediated insulin resistance. Lysophosphatidylcholine (lyso-PC) acted as a second signal activator, mediating Hcy-induced adipocyte NLRP3 inflammasome activation. Hcy elevated adipocyte lyso-PC generation in a hypoxia-inducible factor 1 (HIF1)-phospholipase A2 group 16 (PLA2G16) axis-dependent manner. Lyso-PC derived from the Hcy-induced adipocyte also activated ATM NLRP3 inflammasomes in a paracrine manner. This study demonstrated that Hcy activates adipose NLRP3 inflammasomes in an adipocyte lyso-PC-dependent manner and highlights the importance of the adipocyte NLRP3 inflammasome in insulin resistance.
Pubmed ID: 29735414 RIS Download
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An independent, nonprofit organization focused on mammalian genetics research to advance human health. Their mission is to discover the genetic basis for preventing, treating, and curing human disease, and to enable research for the global biomedical community. Jackson Laboratory breeds and manages colonies of mice as resources for other research institutions and laboratories, along with providing software and techniques. Jackson Lab also conducts genetic research and provides educational material for various educational levels.
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View all literature mentionsSoftware for single-cell flow cytometry analysis. Its functions include management, display, manipulation, analysis and publication of the data stream produced by flow and mass cytometers.
View all literature mentionsPrivately held company that develops and produces antibodies, ELISA kits, ChIP kits, proteomic kits, and other related reagents used to study cell signaling pathways that impact human health.
View all literature mentionsProteintech Europe Ltd is an ISO 9001:2008 certified company
View all literature mentionsA software which acquires and processes data sets, primarily through the Xcalibur system.
View all literature mentionsWeb server for statistical, functional and integrative analysis of metabolomics data. Web based tool suite used for metabolomic data processing, normalization, multivariate statistical analysis, and data annotation, biomarker discovery and classification.
View all literature mentionsCell line 3T3-L1 is a Spontaneously immortalized cell line with a species of origin Mus musculus (Mouse)
View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsThis polyclonal targets Mouse IgG
View all literature mentionsThis polyclonal targets donkey anti-goat IgG-HRP
View all literature mentionsThis polyclonal targets goat anti-rabbit IgG-HRP
View all literature mentionsThis monoclonal targets β-Actin
View all literature mentionsThis polyclonal targets HIF1a
View all literature mentionsThis polyclonal targets Mouse IL-1 beta / IL-1F2
View all literature mentionsThis monoclonal targets HRASLS3 (G-12)
View all literature mentionsThis monoclonal targets caspase-1 (14F468)
View all literature mentionsThis unknown targets normal rabbit IgG
View all literature mentionsThis polyclonal targets HIF1A
View all literature mentionsMus musculus with name B6.129-Tg(Adipoq-cre/Esr1*)1Evdr/J from IMSR.
View all literature mentionsAllele Detail: Targeted This is a legacy resource.
View all literature mentionsAllele Detail: Spontaneous, Targeted This is a legacy resource.
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