title: Palmitic acid but not palmitoleic acid induces insulin resistance in a human endothelial cell line by decreasing SERCA pump expression.
abstract: Palmitic acid is a negative regulator of insulin activity. At the molecular level, palmitic acid reduces insulin stimulated Akt Ser473 phosphorylation. Interestingly, we have found that incubation with palmitic acid of human umbilical vein endothelial cells induced a biphasic effect, an initial transient elevation followed by a sustained reduction of SERCA pump protein levels. However, palmitic acid produced a sustained inhibition of SERCA pump ATPase activity. Insulin resistance state appeared before there was a significant reduction of SERCA2 expression. The mechanism by which palmitic acid impairs insulin signaling may involve endoplasmic reticulum stress, because this fatty acid induced activation of both PERK, an ER stress marker, and JNK, a kinase associated with insulin resistance. None of these effects were observed by incubating HUVEC-CS cells with palmitoleic acid. Importantly, SERCA2 overexpression decreased the palmitic acid-induced insulin resistance state. All these results suggest that SERCA pump might be the target of palmitic acid to induce the insulin resistance state in a human vascular endothelial cell line. Importantly, these data suggest that HUVEC-CS cells respond to palmitic acid-exposure with a compensatory overexpression of SERCA pump within the first hour, which eventually fades out and insulin resistance prevails.
authors.affiliation: Department of Biochemistry, Center for Research and Advanced Studies of the National Polytechnic Institute, CINVESTAV-IPN, Mexico DF 07360, Mexico.
authors.forename: J
authors.initials: J
authors.lastname: Gustavo Vazquez-Jimenez
authors.affiliation: Department of Biochemistry, Center for Research and Advanced Studies of the National Polytechnic Institute, CINVESTAV-IPN, Mexico DF 07360, Mexico.
authors.forename: Jesus
authors.initials: J
authors.lastname: Chavez-Reyes
authors.affiliation: Department of Biochemistry, Center for Research and Advanced Studies of the National Polytechnic Institute, CINVESTAV-IPN, Mexico DF 07360, Mexico.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Romero-Garcia
authors.affiliation: Department of Biochemistry, School of Medicine, National Autonomous University of Mexico, DF 04510, Mexico.
authors.forename: Angel
authors.initials: A
authors.lastname: Zarain-Herzberg
authors.affiliation: Department of Biochemistry, Center for Research and Advanced Studies of the National Polytechnic Institute, CINVESTAV-IPN, Mexico DF 07360, Mexico.
authors.forename: Jesus
authors.initials: J
authors.lastname: Valdes-Flores
authors.affiliation: Department of Biochemistry, Center for Research and Advanced Studies of the National Polytechnic Institute, CINVESTAV-IPN, Mexico DF 07360, Mexico.
authors.forename: J
authors.initials: J
authors.lastname: Manuel Galindo-Rosales
authors.affiliation: Department of Biochemistry, Center for Research and Advanced Studies of the National Polytechnic Institute, CINVESTAV-IPN, Mexico DF 07360, Mexico.
authors.forename: Angelica
authors.initials: A
authors.lastname: Rueda
authors.affiliation: Department of Biochemistry, Center for Research and Advanced Studies of the National Polytechnic Institute, CINVESTAV-IPN, Mexico DF 07360, Mexico.
authors.forename: Agustin
authors.initials: A
authors.lastname: Guerrero-Hernandez
authors.affiliation: Department of Biochemistry, Center for Research and Advanced Studies of the National Polytechnic Institute, CINVESTAV-IPN, Mexico DF 07360, Mexico. Electronic address: jolivare@cinvestav.mx.
authors.forename: J Alberto
authors.initials: JA
authors.lastname: Olivares-Reyes
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D019308:Palmitic Acid / Q000494:pharmacology*; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism*
chemical_list: D005229:Fatty Acids, Monounsaturated; C008757:palmitoleic acid; D019308:Palmitic Acid; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; C506946:ATP2A2 protein, human
keywords: Endoplasmic reticulum stress; Insulin resistance; Palmitic acid; Palmitoleic acid; SERCA pump