Hypoxia Induces Saturated Fatty Acids Accumulation and Reduces Unsaturated Fatty Acids Independently of Reverse Tricarboxylic Acid Cycle in L6 Myotubes
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 tricarboxyl...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-03-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2022.663625/full |
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| author | Lukas Vacek Ales Dvorak Kamila Bechynska Vit Kosek Moustafa Elkalaf Moustafa Elkalaf Minh Duc Trinh Ivana Fiserova Katerina Pospisilova Lucie Slovakova Libor Vitek Libor Vitek Jana Hajslova Jan Polak |
| author_facet | Lukas Vacek Ales Dvorak Kamila Bechynska Vit Kosek Moustafa Elkalaf Moustafa Elkalaf Minh Duc Trinh Ivana Fiserova Katerina Pospisilova Lucie Slovakova Libor Vitek Libor Vitek Jana Hajslova Jan Polak |
| author_sort | Lukas Vacek |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-17T20:27:04Z |
| format | Article |
| id | doaj.art-0f3252c7e9e442509bbef5ffbe6ca6e2 |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-12-17T20:27:04Z |
| publishDate | 2022-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-0f3252c7e9e442509bbef5ffbe6ca6e22022-12-21T21:33:44ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922022-03-011310.3389/fendo.2022.663625663625Hypoxia Induces Saturated Fatty Acids Accumulation and Reduces Unsaturated Fatty Acids Independently of Reverse Tricarboxylic Acid Cycle in L6 MyotubesLukas Vacek0Ales Dvorak1Kamila Bechynska2Vit Kosek3Moustafa Elkalaf4Moustafa Elkalaf5Minh Duc Trinh6Ivana Fiserova7Katerina Pospisilova8Lucie Slovakova9Libor Vitek10Libor Vitek11Jana Hajslova12Jan Polak13Department of Pathophysiology, Third Faculty of Medicine, Charles University, Prague, CzechiaInstitute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University, Prague, CzechiaInstitute of Food and Nutrition Analysis, Faculty of Food and Biochemical Technology, University of Chemistry and Technology in Prague, Prague, CzechiaInstitute of Food and Nutrition Analysis, Faculty of Food and Biochemical Technology, University of Chemistry and Technology in Prague, Prague, CzechiaDepartment of Pathophysiology, Third Faculty of Medicine, Charles University, Prague, CzechiaDepartment of Physiology, Faculty of Medicine in Hradec Králové, Charles University, Hradec Králové, CzechiaDepartment of Pathophysiology, Third Faculty of Medicine, Charles University, Prague, CzechiaDepartment of Pathophysiology, Third Faculty of Medicine, Charles University, Prague, CzechiaInstitute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University, Prague, CzechiaDepartment of Pathophysiology, Third Faculty of Medicine, Charles University, Prague, CzechiaInstitute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University, Prague, Czechia4th Department of Internal Medicine, Faculty General Hospital and 1stFaculty of Medicine, Charles University, Prague, CzechiaInstitute of Food and Nutrition Analysis, Faculty of Food and Biochemical Technology, University of Chemistry and Technology in Prague, Prague, CzechiaDepartment of Pathophysiology, Third Faculty of Medicine, Charles University, Prague, CzechiaObstructive 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.https://www.frontiersin.org/articles/10.3389/fendo.2022.663625/fullhypoxiareverse TCAL6 myotubesglutaminlipidsobstructive sleep apnea |
| spellingShingle | Lukas Vacek Ales Dvorak Kamila Bechynska Vit Kosek Moustafa Elkalaf Moustafa Elkalaf Minh Duc Trinh Ivana Fiserova Katerina Pospisilova Lucie Slovakova Libor Vitek Libor Vitek Jana Hajslova Jan Polak Hypoxia Induces Saturated Fatty Acids Accumulation and Reduces Unsaturated Fatty Acids Independently of Reverse Tricarboxylic Acid Cycle in L6 Myotubes Frontiers in Endocrinology hypoxia reverse TCA L6 myotubes glutamin lipids obstructive sleep apnea |
| title | Hypoxia Induces Saturated Fatty Acids Accumulation and Reduces Unsaturated Fatty Acids Independently of Reverse Tricarboxylic Acid Cycle in L6 Myotubes |
| title_full | Hypoxia Induces Saturated Fatty Acids Accumulation and Reduces Unsaturated Fatty Acids Independently of Reverse Tricarboxylic Acid Cycle in L6 Myotubes |
| title_fullStr | Hypoxia Induces Saturated Fatty Acids Accumulation and Reduces Unsaturated Fatty Acids Independently of Reverse Tricarboxylic Acid Cycle in L6 Myotubes |
| title_full_unstemmed | Hypoxia Induces Saturated Fatty Acids Accumulation and Reduces Unsaturated Fatty Acids Independently of Reverse Tricarboxylic Acid Cycle in L6 Myotubes |
| title_short | Hypoxia Induces Saturated Fatty Acids Accumulation and Reduces Unsaturated Fatty Acids Independently of Reverse Tricarboxylic Acid Cycle in L6 Myotubes |
| title_sort | hypoxia induces saturated fatty acids accumulation and reduces unsaturated fatty acids independently of reverse tricarboxylic acid cycle in l6 myotubes |
| topic | hypoxia reverse TCA L6 myotubes glutamin lipids obstructive sleep apnea |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2022.663625/full |
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