Dual effects of the fatty acid receptor ‘GPR40’ for human health

Publication date: Available online 20 January 2015 Source:Progress in Lipid Research Author(s): Tetsumori Yamashima Free fatty acid receptor ‘GPR40’ is expressed predominantly in the wide variety of neurons of the central nervous system and ß-cells in the pancreatic islets. Since its deorphanization in 2003, the past decade has seen major advances in our understanding of its role in insulin secretion. In contrast, there is still a great deal to be learned about the relationship between GPR40 and brain, despite the most abundant mRNA expression. Since GPR40 is expressed also in the hypothalamus, ‘brain-lipid sensing’ might be involved in the control of insulin secretion and energy balance. Furthermore, the monkey experimental paradigm has highlighted implication of GPR40 for amplifying adult hippocampal neurogenesis. Although GPR40-mediated intracellular signaling was recently found to be related to the phosphorylation of cAMP response element-binding protein necessary for the neuronal differentiation and synaptic plasticity, the signaling cascade is still incompletely understood. Furthermore, in response to conjugated linoleic acids or trans-arachidonic acids in rodents, GPR40 opposingly mediates lipotoxicity to ß-cells, neurons, or microvessels, which result in diabetes, retinopathy, stroke etc. However, it still remains undetermined in humans how oxidized or excessive FFA evoke lipotoxicity. Overcoming paucity of knowledge about GPR40, this review aims at sum...

Source: Progress in Lipid Research - January 26, 2015 Category: Lipidology Source Type: research