Pathological hypertrophy and cardiac dysfunction are linked to aberrant endogenous unsaturated fatty acid metabolism

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dc.contributor.authorDe Tomasi, Loreta Casquel [UNESP]
dc.contributor.authorSalome Campos, Dijon Henrique [UNESP]
dc.contributor.authorSant'Ana, Paula Grippa [UNESP]
dc.contributor.authorOkoshi, Katashi [UNESP]
dc.contributor.authorPadovani, Carlos Roberto [UNESP]
dc.contributor.authorMurata, Gilson Masahiro
dc.contributor.authorNguyen, Son
dc.contributor.authorKolwicz, Stephen C.
dc.contributor.authorCicogna, Antonio Carlos [UNESP]
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.contributor.institutionUniv Washington
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionUrsinus Coll
dc.date.accessioned2018-11-26T17:48:25Z
dc.date.available2018-11-26T17:48:25Z
dc.date.issued2018-03-01
dc.description.abstractPathological cardiac hypertrophy leads to derangements in lipid metabolism that may contribute to the development of cardiac dysfunction. Since previous studies, using high saturated fat diets, have yielded inconclusive results, we investigated whether provision of a high-unsaturated fatty acid ( HUFA) diet was sufficient to restore impaired lipid metabolism and normalize diastolic dysfunction in the pathologically hypertrophied heart. Male, Wistar rats were subjected to supra-valvar aortic stenosis ( SVAS) or sham surgery. After 6 weeks, diastolic dysfunction and pathological hypertrophy was confirmed and both sham and SVAS rats were treated with either normolipidic or HUFA diet. At 18 weeks post-surgery, the HUFA diet failed to normalize decreased E/A ratios or attenuate measures of cardiac hypertrophy in SVAS animals. Enzymatic activity assays and gene expression analysis showed that both normolipidic and HUFA-fed hypertrophied hearts had similar increases in glycolytic enzyme activity and down-regulation of fatty acid oxidation genes. Mass spectrometry analysis revealed depletion of unsaturated fatty acids, primarily linoleate and oleate, within the endogenous lipid pools of normolipidic SVAS hearts. The HUFA diet did not restore linoleate or oleate in the cardiac lipid pools, but did maintain body weight and adipose mass in SVAS animals. Overall, these results suggest that, in addition to decreased fatty acid oxidation, aberrant unsaturated fatty acid metabolism may be a maladaptive signature of the pathologically hypertrophied heart. The HUFA diet is insufficient to reverse metabolic remodeling, diastolic dysfunction, or pathologically hypertrophy, possibly do to preferentially partitioning of unsaturated fatty acids to adipose tissue.en
dc.description.affiliationSao Paulo State Univ, Dept Internal Med, Botucatu, SP, Brazil
dc.description.affiliationUniv Washington, Dept Anesthesiol & Pain Med, Mitochondria & Metab Ctr, Seattle, WA 98195 USA
dc.description.affiliationSao Paulo State Univ, Dept Biostat, Botucatu, SP, Brazil
dc.description.affiliationUniv Sao Paulo, Dept Biochem, Sao Paulo, SP, Brazil
dc.description.affiliationUrsinus Coll, Hlth & Exercise Physiol Dept, Heart & Muscle Metab Lab, Collegeville, PA 19426 USA
dc.description.affiliationUnespSao Paulo State Univ, Dept Internal Med, Botucatu, SP, Brazil
dc.description.affiliationUnespSao Paulo State Univ, Dept Biostat, Botucatu, SP, Brazil
dc.description.sponsorshipAmerican Heart Association
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipIdAmerican Heart Association: 14SDG18590020
dc.description.sponsorshipIdFAPESP: 2012/19679-0
dc.description.sponsorshipIdFAPESP: 2014/06030-1
dc.format.extent20
dc.identifierhttp://dx.doi.org/10.1371/journal.pone.0193553
dc.identifier.citationPlos One. San Francisco: Public Library Science, v. 13, n. 3, 20 p., 2018.
dc.identifier.doi10.1371/journal.pone.0193553
dc.identifier.fileWOS000426363200066.pdf
dc.identifier.issn1932-6203
dc.identifier.lattes1590971576309420
dc.identifier.urihttp://hdl.handle.net/11449/163920
dc.identifier.wosWOS:000426363200066
dc.language.isoeng
dc.publisherPublic Library Science
dc.relation.ispartofPlos One
dc.relation.ispartofsjr1,164
dc.rights.accessRightsAcesso aberto
dc.sourceWeb of Science
dc.titlePathological hypertrophy and cardiac dysfunction are linked to aberrant endogenous unsaturated fatty acid metabolismen
dc.typeArtigo
dcterms.rightsHolderPublic Library Science
unesp.author.lattes1590971576309420
unesp.author.lattes9418970103564137[9]
unesp.author.lattes8727897080522289[5]
unesp.author.orcid0000-0001-8980-8839[4]
unesp.author.orcid0000-0003-0735-850X[7]
unesp.author.orcid0000-0002-4402-6523[9]
unesp.author.orcid0000-0002-7719-9682[4]

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Artigos - Clínica Médica - FMB
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