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Hypoxia Induces Saturated Fatty Acids Accumulation and Reduces Unsaturated Fatty Acids Independently of Reverse Tricarboxylic Acid Cycle in L6 Myotubes

The result's identifiers

  • Result code in IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11120%2F22%3A43923014" target="_blank" >RIV/00216208:11120/22:43923014 - isvavai.cz</a>

  • Alternative codes found

    RIV/60461373:22330/22:43925108 RIV/00064165:_____/22:10441849 RIV/00216208:11110/22:10441849 RIV/00216208:11150/22:10441849

  • Result on the web

    <a href="https://doi.org/10.3389/fendo.2022.663625" target="_blank" >https://doi.org/10.3389/fendo.2022.663625</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.3389/fendo.2022.663625" target="_blank" >10.3389/fendo.2022.663625</a>

Alternative languages

  • Result language

    angličtina

  • Original language name

    Hypoxia Induces Saturated Fatty Acids Accumulation and Reduces Unsaturated Fatty Acids Independently of Reverse Tricarboxylic Acid Cycle in L6 Myotubes

  • Original language description

    Obstructive sleep apnea syndrome, characterized by repetitive episodes of tissue hypoxia, is associated with several metabolic impairments. Role of fatty acids and lipids attracts attention in its pathogenesis for their metabolic effects. Parallelly, hypoxia-induced activation of reverse tricarboxylic acid cycle (rTCA) with reductive glutamine metabolism provides precursor molecules for de novo lipogenesis. Gas-permeable cultureware was used to culture L6-myotubes in chronic hypoxia (12%, 4% and 1% O2) with 13C labelled glutamine and inhibitors of glutamine uptake or rTCA-mediated lipogenesis. We investigated changes in lipidomic profile, 13C appearance in rTCA-related metabolites, gene and protein expression of rTCA-related proteins and glutamine transporters, glucose uptake and lactate production. Lipid content increased by 308% at 1% O2, predominantly composed of saturated fatty acids, while triacylglyceroles containing unsaturated fatty acids and membrane lipids (phosphatidylcholines, phosphatidylethanolamines, phosphatidylinositol) decreased by 20-70%. rTCA labelling of malate, citrate and 2-hydroxyglutarate increased by 4.7-fold, 2.2-fold and 1.9-fold in 1% O2, respectively. ATP-dependent citrate lyase inhibition in 1% O2 decreased lipid amount by 23% and increased intensity of triacylglyceroles containing unsaturated fatty acids by 56-80%. Lactate production increased with hypoxia. Glucose uptake dropped by 75% with progression of hypoxia from 4% to 1% O2. Protein expression remained unchanged. Altogether, hypoxia modified cell metabolism leading to lipid composition alteration and rTCA activation.

  • Czech name

  • Czech description

Classification

  • Type

    J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database

  • CEP classification

  • OECD FORD branch

    30202 - Endocrinology and metabolism (including diabetes, hormones)

Result continuities

  • Project

    Result was created during the realization of more than one project. More information in the Projects tab.

  • Continuities

    P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Others

  • Publication year

    2022

  • Confidentiality

    S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Data specific for result type

  • Name of the periodical

    Frontiers in Endocrinology

  • ISSN

    1664-2392

  • e-ISSN

    1664-2392

  • Volume of the periodical

    13

  • Issue of the periodical within the volume

    March

  • Country of publishing house

    CH - SWITZERLAND

  • Number of pages

    12

  • Pages from-to

    663625

  • UT code for WoS article

    000777104900001

  • EID of the result in the Scopus database

    2-s2.0-85127753843