title: Lipid droplet formation in response to oleic acid in Huh-7 cells is mediated by the fatty acid receptor FFAR4.
abstract: It is unclear how changes in lipid droplet size and number are regulated - for example, it is not known whether this involves a signalling pathway or is directed by cellular lipid uptake. Here, we show that oleic acid stimulates lipid droplet formation by activating the long-chain fatty acid receptor FFAR4, which signals through a pertussis-toxin-sensitive G-protein signalling pathway involving phosphoinositide 3-kinase (PI3-kinase), AKT (also known as protein kinase B) and phospholipase D (PLD) activities. This initial lipid droplet formation is not dependent upon exogenous lipid, whereas the subsequent more sustained increase in the number of lipid droplets is dependent upon lipid uptake. These two mechanisms of lipid droplet formation point to distinct potential intervention points.
authors.affiliation: Signalling Programme, Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK.
authors.forename: Arndt
authors.initials: A
authors.lastname: Rohwedder
authors.affiliation: Signalling Programme, Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK.
authors.forename: Qifeng
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Signalling Programme, Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK.
authors.forename: Simon A
authors.initials: SA
authors.lastname: Rudge
authors.affiliation: Signalling Programme, Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK Michael.wakelam@babraham.ac.uk.
authors.forename: Michael J O
authors.initials: MJ
authors.lastname: Wakelam
mesh_terms: D045744:Cell Line, Tumor; D006801:Humans; D066292:Lipid Droplets / Q000378:metabolism*; D009829:Oleic Acids / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010739:Phospholipase D / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C519853:FFAR4 protein, human; D009829:Oleic Acids; D043562:Receptors, G-Protein-Coupled; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D010739:Phospholipase D
keywords: FFAR4; Fatty acid receptor; Lipid droplets; Oleic acid; PI3-kinase; Phospholipase D