title: Sequestration of fatty acids in triglycerides prevents endoplasmic reticulum stress in an in vitro model of cardiomyocyte lipotoxicity.
abstract: We used human cardiomyocyte-derived cells to create an in vitro model to study lipid metabolism and explored the effects of PPARγ; ACSL1 and ATGL on fatty acid-induced ER stress. Compared to oleate, palmitate treatment resulted in less intracellular accumulation of lipid droplets and more ER stress, as measured by upregulation of CHOP, ATF6 and GRP78 gene expression and phosphorylation of eukaryotic initiation factor 2a (EIF2a). Both ACSL1 and PPARγ adenovirus-mediated expression augmented neutral lipid accumulation and reduced palmitate-induced upregulation of ER stress markers to levels similar to those in the oleate and control treatment groups. This suggests that increased channeling of non-esterified free fatty acids (NEFA) towards storage in the form of neutral lipids in lipid droplets protects against palmitate-induced ER stress. Overexpression of ATGL in cells incubated with oleate-containing medium increased NEFA release and stimulated expression of ER stress markers. Thus, inefficient creation of lipid droplets as well greater release of stored lipids induces ER stress.
authors.forename: Madeleen
authors.initials: M
authors.lastname: Bosma
authors.forename: Dianne H
authors.initials: DH
authors.lastname: Dapito
authors.forename: Zoi
authors.initials: Z
authors.lastname: Drosatos-Tampakaki
authors.forename: Ni
authors.initials: N
authors.lastname: Huiping-Son
authors.forename: Li-Shin
authors.initials: LS
authors.lastname: Huang
authors.forename: Sander
authors.initials: S
authors.lastname: Kersten
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Drosatos
authors.forename: Ira J
authors.initials: IJ
authors.lastname: Goldberg
mesh_terms: D000106:Acetate-CoA Ligase / Q000378:metabolism; D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D005227:Fatty Acids / Q000633:toxicity*; D057809:HEK293 Cells; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D008049:Lipase / Q000378:metabolism; D008954:Models, Biological; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D047495:PPAR gamma / Q000378:metabolism; D010168:Palmitates / Q000633:toxicity; D014280:Triglycerides / Q000633:toxicity*; D000217:Acyltransferases
chemical_list: D000106:Acetate-CoA Ligase; D015415:Biomarkers; D000091342:Endoplasmic Reticulum Chaperone BiP; D005227:Fatty Acids; D008049:Lipase; D047495:PPAR gamma; D010168:Palmitates; D014280:Triglycerides; C000717247:HSPA5 protein, human; C494794:PNPLA2 protein, human; D000217:Acyltransferases