Phytanic acid and pristanic acid, branched-chain fatty acids associated with Refsum disease and other inherited peroxisomal disorders, mediate intracellular Ca2+ signaling through activation of free fatty acid receptor GPR40.

摘要: The accumulation of the two branched-chain fatty acids phytanic acid and pristanic is known to play an important role in several diseases with peroxisomal impairment, like Refsum disease, Zellweger syndrome α-methylacyl-CoA racemase deficiency. Recent studies elucidated that toxic activity mediated by multiple mitochondrial dysfunctions, generation reactive oxygen species Ca2+ deregulation via InsP3-Ca2+ signaling pathway glial cells. However, exact mechanism through which both mediate toxicity still under debate. Here, we studied ability activate free receptor GPR40, a G-protein-coupled receptor, was described be involved acids. We treated HEK 293 cells expressing GPR40 or acid. This resulted significant increase intracellular level, similar effect seen after treatment synthetic agonist GW9508. Furthermore, demonstrate activation might due interaction carboxylate moiety receptor. Our findings indicate acid- acid-mediated can involve GPR40. Therefore, suppose part cascade