Neuroprotective and Ameliorative Actions of Polyunsaturated Fatty Acids Against Neuronal Diseases: Implication of Fatty Acid–Binding Proteins (FABP) and G Protein–Coupled Receptor 40 (GPR40) in Adult Neurogenesis

Abstract

Abstract. Adult neurogenesis in the mammalian brain is well-known to occur in the subgranular zone of the hippocampus. As the hippocampus is related to learning, memory, and emotions, adult hippocampal neurogenesis possibly contributes to these functions. Adult neurogenesis is modulated by polyunsaturated fatty acids (PUFA) such as docosahexaenoic and arachidonic acids that are essential for normal brain development, maintenance, and function. They are reported to improve spatial learning and memory in rodents and cognitive functions in humans. However, detailed mechanisms of PUFA effects still remain obscure. PUFA are functionally linked with chaperons called fatty acid-binding proteins (FABP). FABP uptake and transport PUFA to different intracellular organelles. Intriguingly, PUFA were determined as ligands for G protein-coupled receptor 40 (GPR40), a cell membrane receptor abundantly expressed in the brain and the pancreas of primates. While the role of GPR40 in pancreatic β-cells is associated with insulin secretion, its role in the brain is not yet clarified presumably because of its absence in the rodent brain. The purpose of this review is to discuss the role of PUFA in adult neurogenesis, considering the role of GPR40 and FABP in the hippocampal neurogenic niche. Here, the authors would like to introduce a PUFA-GPR40 signaling pathway that is specific for the primate brain.

Association of dietary ω-3 and ω-6 fatty acids intake with cognitive performance in older adults: National Health and nutrition examination Survey (NHANES) 2011–2014

“…Second, ω-3 fatty acids increase cell viability through neuroprotective and anti-apoptotic mechanisms [57], and they may reduce neuronal oxidative stress. Third, ω-3 fatty acids can promote neurogenesis and long term potential (LTP) formation in the hippocampus [58], and improve the function of the hippocampus. Calderon et al [59] also found that ω-3 fatty acids could promote the survival of hippocampal neurons, and increase the number and length of neuronal processes significantly.…”

G-Protein Signaling, Lipid Rafts and the Possible Sites of Action for the Antidepressant Effects of n-3 Polyunsaturated Fatty Acids

“…The ability of GPR40 and GPR120 to help mediate taste perception lead some researchers to ponder if these are valuable targets for fighting obesity [38]. It is even possible that these receptors are important in neurogenesis and neurodevelopment [39]. One preliminary line of evidence is that immunostaining of newborn neurons is especially high for GPR40 versus mature neurons [40].…”

Fatty Acid Receptor Gpr40 Mediates Neuromicrovascular Degeneration Induced by Transarachidonic Acids in Rodents

“…46,47 Along these lines, activation of GPR40 by thiazolidinediones 48 but, generally, not by long chain cis-FA, is cytotoxic 49 ; in fact, cytoprotective effects of cis-AA is described. 50,51 On the contrary, TAA have been consistently found to be toxic, [16][17][18]25 and we now found that their effects are mediated via GPR40 (Figures 2-4). This apparent discrepancy between effects of different FAs is most likely attributable to activation of distinct allosteric sites on the receptor by different molecular structures.…”