title: Fabrication of size-controlled linoleic acid particles and evaluation of their in-vitro lipotoxicity.
abstract: The biological activities of fatty acids (FAs) can differ with size even for lipids of similar compositions. The aim of this study was to develop size-controlled FA particles and to evaluate their toxicity as a function of size. Well-stabilized nano- and microscale linoleic acid (LA) were fabricated based on specific physical factors. Then, resulting LAs were characterized by size distribution, surface charge, assembly structure, composition, and serum effects. The sizes of the nano- (LAnano) and microscale (LAmicro) LAs, determined by electron microscopy, were 109 nm and 12 μm, respectively. LAnano, a multilamellar structure as determined by cryo-electron microscopy, was rapidly internalized into cells via free fatty acid receptor 3. After internalization, LAnano, but not LAmicro, induced nuclear translocation of fatty acid binding protein 4 (FABP4). Translocation of FABP4 into the nucleus then induced expression of the FA metabolism-related genes InsR and AdipoR1. Their expression was significantly increased in the presence of only LAnano. Cytotoxicity was also significantly increased in cells treated with LAnano, but not LAmicro, as indicated by the endoplasmic reticulum stress markers CHOP and GRP78. Therefore, our results demonstrated that FAs with the same composition but varying in size can cause different cellular responses.
authors.affiliation: Center for Nano-Bio Measurement, Korea Research Institute of Standards and Science, 267 Gajeong-Ro, Yuseong-Gu, Daejeon 305-340, Republic of Korea.
authors.forename: Eun-Soo
authors.initials: ES
authors.lastname: Lee
authors.affiliation: Center for Nano-Bio Measurement, Korea Research Institute of Standards and Science, 267 Gajeong-Ro, Yuseong-Gu, Daejeon 305-340, Republic of Korea; Center for Nanosafety Metrology, Korea Research Institute of Standards and Science, 267 Gajeong-Ro, Yuseong-Gu, Daejeon 305-340, Republic of Korea; Department of Bio-Analytical Science, Korea University of Science and Technology, 217 Gajeong-Ro, Yuseong-Gu, Daejeon 341-113, Republic of Korea. Electronic address: shkim@kriss.re.kr.
authors.forename: Se-Hwa
authors.initials: SH
authors.lastname: Kim
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects*; D002478:Cells, Cultured; D020285:Cryoelectron Microscopy; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005434:Flow Cytometry; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D007124:Immunoenzyme Techniques; D066298:In Vitro Techniques; D019787:Linoleic Acid / Q000737:chemistry* / Q000633:toxicity*; D008055:Lipids / Q000032:analysis*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D010316:Particle Size; D060888:Real-Time Polymerase Chain Reaction; D051742:Transcription Factor CHOP / Q000235:genetics / Q000378:metabolism
chemical_list: C497249:DDIT3 protein, human; D000091342:Endoplasmic Reticulum Chaperone BiP; C493410:FABP4 protein, human; D050556:Fatty Acid-Binding Proteins; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; C000717248:Hspa5 protein, mouse; D008055:Lipids; D051742:Transcription Factor CHOP; D019787:Linoleic Acid
keywords: Fatty acids; Lipid metabolism; Lipotoxicity; Size