Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8358975 | Progress in Lipid Research | 2015 | 42 Pages |
Abstract
G protein-coupled receptor 40 (GPR40), a receptor for diverse non-esterified fatty acids, is expressed predominantly in the wide variety of neurons of the central nervous system and β-cells in the pancreatic islets. Since deorphanization of GPR40 in 2003, the past decade has seen major advances in our understanding of its role in the insulin secretion. However, there is still a great deal to be elucidated about the role of GPR40 in the brain, because the latter shows the most abundant GPR40 mRNA expression among the human tissues. Since a substantial expression of GPR40 is also seen in the hypothalamus, 'brain-lipid sensing' might be involved in the control of insulin secretion and energy balance. The preceding experiments using monkeys after transient global brain ischemia, have highlighted implication of GPR40 for amplifying adult hippocampal neurogenesis. Although GPR40-mediated intracellular signaling was recently found to result in phosphorylation of cAMP response element-binding protein (CREB) necessary for the neuronal differentiation and synaptic plasticity, the signaling cascade is still incompletely understood. Furthermore, in response to conjugated linoleic acids or trans isomers of arachidonic acid, GPR40 was recently demonstrated in rodents to mediate lipotoxicity to β-cells, neurons, or microvessels, which result in diabetes, retinopathy, stroke, etc. However, it still remains undetermined in humans whether and how oxidized, conjugated, or excessive fatty acids evoke lipotoxicity. Although literature about GPR40 is limited especially about the brain or the brain-pancreas interaction, this review aims at summarizing beneficial as well as detrimental effects of this receptor in the brain and pancreas in response to diverse fatty acids.
Keywords
pCREBERKCLACOANGFDcxIP3PSA-NCAMPLCPKCSGZVGCCGPCRGPR40NEFAGαqTSP-1PIP2G protein-coupled receptor 40PKD1Protein kinase D1phosphorylated cAMP response element-binding proteinPolysialylated-neural cell adhesion moleculeHeme oxygenasesCREBEPAPPAR-γTAAcyclic AMPBDNFcAMPinositol 1,4,5-trisphosphateMAPKNFκBABCDHydrogen peroxideEicosapentaenoic aciddocosahexaenoic acidPolyunsaturated fatty acidsPUFAArachidonic acidsconjugated linoleic acidsnon-esterified fatty acidsinsulinThrombospondin-1ABC transportersCNSdoublecortinDHAdiacylglycerolDAGcentral nervous systemendoplasmic reticulumnerve growth factorBrain-derived neurotrophic factornuclear factor κBphosphatidylinositol 4,5-bisphosphatephospholipase Csubgranular zonecarbon monoxideadult neurogenesisH2O2PancreascAMP response element-binding proteinProtein kinase Cmitogen-activated protein kinaseVoltage-gated Ca2+ channelBKCa channelsCa2+-activated K+ channelscoenzyme Aextracellular signal-regulated kinasePeroxisome proliferator-activated receptor-γG protein-coupled receptor
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Authors
Tetsumori Yamashima,