{"id":28372,"date":"2024-08-23T14:00:20","date_gmt":"2024-08-23T12:00:20","guid":{"rendered":"https:\/\/fgu.antstudio.dev\/vyzkumny-projekt\/metabolomika-lipidomika-a-fluxomika\/"},"modified":"2026-01-16T14:29:08","modified_gmt":"2026-01-16T13:29:08","slug":"metabolomics-lipidomics-and-fluxomics","status":"publish","type":"vyzkumny-projekt","link":"https:\/\/fgu.cas.cz\/en\/research-project\/metabolomics-lipidomics-and-fluxomics\/","title":{"rendered":"Metabolomics, lipidomics and fluxomics"},"content":{"rendered":"<div>\n<table>\n<tbody>\n<tr>\n<td>Software:<\/td>\n<td><a href=\"https:\/\/fgu.cas.cz\/wp-content\/uploads\/2024\/08\/metabologo.svg\"><img decoding=\"async\" class=\"alignnone wp-image-26895\" src=\"https:\/\/fgu.cas.cz\/wp-content\/uploads\/2024\/08\/metabologo.svg\" alt=\"-\" width=\"90\" height=\"90\" title=\"\"><\/a><a href=\"https:\/\/gttatlas.metabolomics.fgu.cas.cz\" target=\"_blank\" rel=\"noopener\">\u00a0GTTAtlas <\/a><\/td>\n<td><a href=\"https:\/\/fgu.cas.cz\/wp-content\/uploads\/2024\/08\/atlas21red.svg\"><img decoding=\"async\" class=\"alignnone wp-image-26897\" src=\"https:\/\/fgu.cas.cz\/wp-content\/uploads\/2024\/08\/atlas21red.svg\" alt=\"-\" width=\"83\" height=\"83\" title=\"\"><\/a><a href=\"https:\/\/metaboatlas21.metabolomics.fgu.cas.cz\" target=\"_blank\" rel=\"noopener\">\u00a0MetaboAtlas21 <\/a><\/td>\n<td><a href=\"https:\/\/fgu.cas.cz\/wp-content\/uploads\/2024\/08\/COMA_moon_anime.svg\"><img decoding=\"async\" class=\"alignnone wp-image-45104 size-medium\" src=\"https:\/\/fgu.cas.cz\/wp-content\/uploads\/2024\/08\/COMA_moon_anime.svg\" alt=\"Circadian ontogenetic metabolomics atlas\" width=\"83\" height=\"83\" title=\"\"><\/a><a href=\"https:\/\/coma.metabolomics.fgu.cas.cz\" target=\"_blank\" rel=\"noopener\">\u00a0COMA <\/a><\/td>\n<td><a href=\"https:\/\/fgu.cas.cz\/wp-content\/uploads\/2024\/08\/mapper_logo.svg\"><img loading=\"lazy\" decoding=\"async\" class=\"alignnone wp-image-26899\" src=\"https:\/\/fgu.cas.cz\/wp-content\/uploads\/2024\/08\/mapper_logo.svg\" alt=\"-\" width=\"76\" height=\"76\" title=\"\"><\/a><a href=\"https:\/\/mapper.metabolomics.fgu.cas.cz\" target=\"_blank\" rel=\"noopener\">\u00a0Mapper <\/a><\/td>\n<td><a href=\"https:\/\/fgu.cas.cz\/wp-content\/uploads\/2024\/08\/mmv_logo.svg\"><img loading=\"lazy\" decoding=\"async\" class=\"alignnone wp-image-26901\" src=\"https:\/\/fgu.cas.cz\/wp-content\/uploads\/2024\/08\/mmv_logo.svg\" alt=\"-\" width=\"75\" height=\"75\" title=\"\"><\/a><a href=\"https:\/\/mmv.metabolomics.fgu.cas.cz\" target=\"_blank\" rel=\"noopener\">\u00a0Reaction network viewer <\/a><\/td>\n<td><a href=\"https:\/\/fgu.cas.cz\/wp-content\/uploads\/2024\/08\/parrot.svg\"><img loading=\"lazy\" decoding=\"async\" class=\"alignnone wp-image-26903\" src=\"https:\/\/fgu.cas.cz\/wp-content\/uploads\/2024\/08\/parrot.svg\" alt=\"-\" width=\"69\" height=\"70\" title=\"\"><\/a><a href=\"https:\/\/lora.metabolomics.fgu.cas.cz\/\" target=\"_blank\" rel=\"noopener\">\u00a0LORA<\/a><\/td>\n<td><img loading=\"lazy\" decoding=\"async\" class=\"alignnone wp-image-26903\" src=\"https:\/\/m3cav.metabolomics.fgu.cas.cz\/assets\/favicons\/caxfavicon.svg\" alt=\"-\" width=\"69\" height=\"70\" title=\"\"><a href=\"https:\/\/lora.metabolomics.fgu.cas.cz\/\" target=\"_blank\" rel=\"noopener\">\u00a0M3CAV<\/a><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<p>Methodological highlighs from publications using small molecule omics techniques.<\/p>\n<hr \/>\n<p>\u25ba Pauline Morigny, Michaela Vondrackova, Honglei Ji, Kristyna Brejchova, Monika Krakovkova, Konstantinos Makris, Radka Trubacova, Tuna F. Samanci, Doris Kaltenecker, Su-Ping Ng, Vignesh Karthikaisamy, Sophia E. Chrysostomou, Anna Bidovec, Mariana Ponce-de-Leon, Tanja Krauss, Claudine Seeliger, Olga Prokopchuk, Marc E. Martignoni, Melina Claussnitzer, Hans Hauner, Martina Schweiger, Laure B. Bindels, Mauricio Berriel Diaz, Stephan Herzig, Dominik Lutter, Ondrej Kuda<sup>\u2709<\/sup> &amp; Maria Rohm<sup>\u2709<\/sup><\/p>\n<p><strong>Multi-omics profiling of cachexia-targeted tissues reveals a spatio-temporally coordinated response to cancer.<\/strong><br \/>\nNat Metab (2026) DOI: <a href=\"https:\/\/doi.org\/10.1038\/s42255-025-01434-3\" target=\"_blank\" rel=\"noopener\">https:\/\/doi.org\/10.1038\/s42255-025-01434-3<\/a><\/p>\n<p><a href=\"https:\/\/doi.org\/10.1038\/s42255-025-01434-3\" target=\"_blank\" rel=\"noopener\">Cachexia is a wasting disorder associated with high morbidity and mortality&#8230;.<\/a><\/p>\n<ul>\n<li>Associated atlas: Mouse Multiorgan Metabolomics Cancer Cachexia Viewer <a href=\"https:\/\/m3cav.metabolomics.fgu.cas.cz\/\" target=\"_blank\" rel=\"noopener\">\u00a0M3CAV<\/a><\/li>\n<\/ul>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignnone wp-image-53345 size-large\" src=\"https:\/\/fgu.cas.cz\/wp-content\/uploads\/2024\/08\/morigny-web-abstract-1024x402.jpg\" alt=\"Multi-omics profiling of cachexia-targeted tissues reveals a spatio-temporally coordinated response to cancer\" width=\"800\" height=\"314\" title=\"\" srcset=\"https:\/\/fgu.cas.cz\/wp-content\/uploads\/2024\/08\/morigny-web-abstract-1024x402.jpg 1024w, https:\/\/fgu.cas.cz\/wp-content\/uploads\/2024\/08\/morigny-web-abstract-300x118.jpg 300w, https:\/\/fgu.cas.cz\/wp-content\/uploads\/2024\/08\/morigny-web-abstract-768x301.jpg 768w, https:\/\/fgu.cas.cz\/wp-content\/uploads\/2024\/08\/morigny-web-abstract-1536x602.jpg 1536w, https:\/\/fgu.cas.cz\/wp-content\/uploads\/2024\/08\/morigny-web-abstract-2048x803.jpg 2048w\" sizes=\"(max-width: 800px) 100vw, 800px\" \/><\/p>\n<hr \/>\n<p>\u25ba Riecan M, Kasperova BJ, Vondrackova M, Janovska P, Haasova E, Adamcova K, Ivak P, Hlavacek D, Kroupova K, Cajka T, Kopecky J, Hub\u00e1\u010dkov\u00e1 S\u0160, Mraz M, Netuka I, Melenovsky V, Haluzik M, Kuda O. <sup>\u2709<\/sup><br \/>\n<strong>Epicardial adipose tissue produces L-3-hydroxybutyrate in advanced heart failure: direct analysis of fat metabolic remodeling.<\/strong><br \/>\nMetabolism. 2025 Dec 3:156465. DOI: <a href=\"https:\/\/doi.org\/10.1016\/j.metabol.2025.156465\" target=\"_blank\" rel=\"noopener\">https:\/\/doi.org\/10.1016\/j.metabol.2025.156465<\/a><\/p>\n<p><a href=\"https:\/\/doi.org\/10.1016\/j.metabol.2025.156465\" target=\"_blank\" rel=\"noopener\">Heart failure (HF) progression involves complex metabolic&#8230;.<\/a><\/p>\n<ul>\n<li>Heart failure triggers distinct metabolic shifts in epicardial and subcutaneous fat.<\/li>\n<li>Advanced heart failure impairs fatty acid oxidation in epicardial adipose tissue.<\/li>\n<li>Production of L-3-hydroxybutyrate is markedly upregulated especially in EAT.<\/li>\n<li>Metabolomics reveals depot-specific adaptations in lipid and energy metabolism.<\/li>\n<\/ul>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignnone wp-image-51761 size-medium\" src=\"https:\/\/fgu.cas.cz\/wp-content\/uploads\/2024\/08\/fgu019-riecan-2025-300x115.png\" alt=\"-\" width=\"300\" height=\"115\" title=\"\" srcset=\"https:\/\/fgu.cas.cz\/wp-content\/uploads\/2024\/08\/fgu019-riecan-2025-300x115.png 300w, https:\/\/fgu.cas.cz\/wp-content\/uploads\/2024\/08\/fgu019-riecan-2025-1024x394.png 1024w, https:\/\/fgu.cas.cz\/wp-content\/uploads\/2024\/08\/fgu019-riecan-2025-768x295.png 768w, https:\/\/fgu.cas.cz\/wp-content\/uploads\/2024\/08\/fgu019-riecan-2025-1536x591.png 1536w, https:\/\/fgu.cas.cz\/wp-content\/uploads\/2024\/08\/fgu019-riecan-2025-2048x788.png 2048w\" sizes=\"(max-width: 300px) 100vw, 300px\" \/><\/p>\n<hr \/>\n<\/div>\n<p>\u25ba Lucie Rudl Kulhava, Pavel Houdek, Michaela Novakova, Jiri Hricko, Michaela Paucova, Ondrej Kuda, Martin Sladek, Oliver Fiehn, Alena Sumova &amp; Tomas Cajka <sup>\u2709<\/sup><br \/>\n<strong>Circadian ontogenetic metabolomics atlas: an interactive resource with insights from rat plasma, tissues, and feces<\/strong><br \/>\nCellular and Molecular Life Sciences, 2025, Volume 82, article number 264. DOI <a href=\"https:\/\/doi.org\/10.1007\/s00018-025-05783-w\" target=\"_blank\" rel=\"noopener\">https:\/\/doi.org\/10.1007\/s00018-025-05783-w<\/a><\/p>\n<h2><a href=\"https:\/\/coma.metabolomics.fgu.cas.cz\" target=\"_blank\" rel=\"noopener\"><img loading=\"lazy\" decoding=\"async\" class=\"alignnone wp-image-45104 size-medium\" src=\"https:\/\/fgu.cas.cz\/wp-content\/uploads\/2024\/08\/COMA_moon_anime.svg\" alt=\"-\" width=\"83\" height=\"83\" title=\"\"><\/a> COMA &#8211; Circadian ontogenetic metabolomics atlas<\/h2>\n<h4 class=\"c-article-title\" data-test=\"article-title\">An interactive resource with insights from rat plasma, tissues, and feces<\/h4>\n<ul>\n<li>Interactive metabolomic, lipidomic, and RNA atlas of polar and nonpolar metabolites.<\/li>\n<li>Web app: <a href=\"https:\/\/coma.metabolomics.fgu.cas.cz\/\" target=\"_blank\" rel=\"noopener\">COMA<\/a><\/li>\n<\/ul>\n<hr \/>\n<p>\u25ba Kristyna Brejchova, Michal Rahm, Andrea Benova, Veronika Domanska, Paul Reyes-Gutierez, Martina Dzubanova, Radka Trubacova, Michaela Vondrackova, Tomas Cajka, Michaela Tencerova, Milan Vrabel, Ondrej Kuda <sup>\u2709<\/sup><br \/>\n<strong>Uncovering mechanisms of thiazolidinediones on osteogenesis and adipogenesis using spatial fluxomics<\/strong><br \/>\nMetabolism. 2025 May:166:156157. DOI: <a href=\"https:\/\/doi.org\/10.1016\/j.metabol.2025.156157\" target=\"_blank\" rel=\"noopener\">https:\/\/doi.org\/10.1016\/j.metabol.2025.156157<\/a><\/p>\n<p><a href=\"https:\/\/doi.org\/10.1016\/j.metabol.2025.156157\" target=\"_blank\" rel=\"noopener\">Insulin-sensitizing drugs, despite their broad use against type 2 diabetes&#8230;<\/a><\/p>\n<ul>\n<li>MSDC-0602K differentially affects BM-MSCs and AT-MSCs.<\/li>\n<li>Bioorthogonal click chemistry allowed measurement of pyruvate pools.<\/li>\n<li>Subcellular metabolic flux analysis revealed rewiring of pyruvate pathways.<\/li>\n<li>Metabolic flux analysis of TG synthesis showed distinct adipogenic strategies.<\/li>\n<\/ul>\n<figure id=\"attachment_42944\" aria-describedby=\"caption-attachment-42944\" style=\"width: 300px\" class=\"wp-caption alignnone\"><img loading=\"lazy\" decoding=\"async\" class=\"wp-image-42944 size-medium\" src=\"https:\/\/fgu.cas.cz\/wp-content\/uploads\/2024\/08\/brejchova-msdc-300x297.jpg\" alt=\"Uncovering mechanisms of thiazolidinediones on osteogenesis and adipogenesis using spatial fluxomics\" width=\"300\" height=\"297\" title=\"\" srcset=\"https:\/\/fgu.cas.cz\/wp-content\/uploads\/2024\/08\/brejchova-msdc-300x297.jpg 300w, https:\/\/fgu.cas.cz\/wp-content\/uploads\/2024\/08\/brejchova-msdc-1024x1014.jpg 1024w, https:\/\/fgu.cas.cz\/wp-content\/uploads\/2024\/08\/brejchova-msdc-150x150.jpg 150w, https:\/\/fgu.cas.cz\/wp-content\/uploads\/2024\/08\/brejchova-msdc-768x760.jpg 768w, https:\/\/fgu.cas.cz\/wp-content\/uploads\/2024\/08\/brejchova-msdc.jpg 1096w\" sizes=\"(max-width: 300px) 100vw, 300px\" \/><figcaption id=\"caption-attachment-42944\" class=\"wp-caption-text\">Subcellular 13C fluxomics<\/figcaption><\/figure>\n<hr \/>\n<p>\u25ba Magno Lopes, Kristyna Brejchova, Martin Riecan, Michaela Novakova, Martin Rossmeisl, Tomas Cajka, Ondrej Kuda<sup>\u2709<\/sup><br \/>\n<strong>Metabolomics atlas of oral 13C-glucose tolerance test in mice<\/strong><br \/>\nCell Reports, 2021, 27 (2), 109833 DOI <a href=\"https:\/\/doi.org\/10.1016\/j.celrep.2021.109833\" target=\"_blank\" rel=\"noopener\">https:\/\/doi.org\/10.1016\/j.celrep.2021.109833<\/a><\/p>\n<p><a href=\"https:\/\/doi.org\/10.1016\/j.celrep.2021.109833\" target=\"_blank\" rel=\"noopener\">Glucose tolerance represents a complex phenotype in which &#8230;<\/a><\/p>\n<ul>\n<li>A systems-level organ-specific metabolomics atlas of mouse tissues<\/li>\n<li><sup>13<\/sup>C<sub>6<\/sub>-glucose tracer tissue distribution during glucose tolerance test<\/li>\n<li>Interactive online application for metabolic pathway exploration<\/li>\n<li>LC-MS data resource covering polar metabolites and complex lipids<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignnone wp-image-26908\" src=\"https:\/\/fgu.cas.cz\/wp-content\/uploads\/2024\/08\/gttatlas-web-banner-01-1024x134.jpg\" alt=\"-\" width=\"1029\" height=\"135\" title=\"\" srcset=\"https:\/\/fgu.cas.cz\/wp-content\/uploads\/2024\/08\/gttatlas-web-banner-01-1024x134.jpg 1024w, https:\/\/fgu.cas.cz\/wp-content\/uploads\/2024\/08\/gttatlas-web-banner-01-300x39.jpg 300w, https:\/\/fgu.cas.cz\/wp-content\/uploads\/2024\/08\/gttatlas-web-banner-01-768x100.jpg 768w, https:\/\/fgu.cas.cz\/wp-content\/uploads\/2024\/08\/gttatlas-web-banner-01-1536x201.jpg 1536w, https:\/\/fgu.cas.cz\/wp-content\/uploads\/2024\/08\/gttatlas-web-banner-01-2048x268.jpg 2048w\" sizes=\"(max-width: 1029px) 100vw, 1029px\" \/><\/p>\n<h2><a href=\"https:\/\/gttatlas.metabolomics.fgu.cas.cz\" target=\"_blank\" rel=\"noopener\"><img loading=\"lazy\" decoding=\"async\" class=\"alignnone wp-image-26895\" src=\"https:\/\/fgu.cas.cz\/wp-content\/uploads\/2024\/08\/metabologo.svg\" alt=\"-\" width=\"80\" height=\"80\" title=\"\"> GTTAtlas <\/a><\/h2>\n<h4>Metabolomics atlas of mouse tissue during oral glucose tolerance test using [<sup>13<\/sup>C<sub>6<\/sub>]-glucose as a tracer.<\/h4>\n<ul>\n<li>Interactive metabolomics and lipidomics atlas of polar and non-polar metabolites.<\/li>\n<li>Standard oral glucose tolerance test (OGTT) with [<sup>13<\/sup>C<sub>6<\/sub>]-glucose was performed.<\/li>\n<li>Twelve metabolically-relevant mouse organs and plasma were collected at specific time points during the OGTT.<\/li>\n<li>Six-dimensional metabolipidomic LC-MS platform was used to analyze samples.<\/li>\n<li>High resolution accurate mass spectrometry was used to detect metabolite isotopologues labeled with <sup>13<\/sup>C.<\/li>\n<li>Metabolic pathways were used to explore the fate of <sup>13<\/sup>C-labeled glucose.<\/li>\n<li>Inter-organ metabolism of glucose and its metabolites was evaluated.<\/li>\n<li>Software for metabolic pathway mapping: <a href=\"https:\/\/mapper.metabolomics.fgu.cas.cz\/\" target=\"_blank\" rel=\"noopener\">Mapper &#8211; a pathway mapping tool<\/a>.<\/li>\n<\/ul>\n<hr \/>\n<h2><a href=\"https:\/\/metaboatlas21.metabolomics.fgu.cas.cz\" target=\"_blank\" rel=\"noopener\"><img loading=\"lazy\" decoding=\"async\" class=\"alignnone wp-image-26897\" src=\"https:\/\/fgu.cas.cz\/wp-content\/uploads\/2024\/08\/atlas21red.svg\" alt=\"-\" width=\"92\" height=\"92\" title=\"\">\u00a0MetaboAtlas21 <\/a><\/h2>\n<h4>MetaboAtlas21 is a comprehensive atlas of the mouse metabolome and lipidome.<\/h4>\n<ul>\n<li>In collaboration with Laboratory of Metabolomics.<\/li>\n<li>Interactive metabolomics and lipidomics atlas of polar and non-polar metabolites.<\/li>\n<li>Twenty one mouse organs and biofluids &amp; two diets &amp; three reference serum\/plasma samples were analyzed.<\/li>\n<li>Seven\/eight-dimensional metabolipidomic LC-MS platform was used to analyze samples.<\/li>\n<li>Computational resources were supplied by the project &#8220;e-Infrastruktura CZ&#8221; (e-INFRA LM2018140) provided within the program Projects of Large Research, Development and Innovations Infrastructures.<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n<hr \/>\n<h2><a href=\"https:\/\/mapper.metabolomics.fgu.cas.cz\" target=\"_blank\" rel=\"noopener\"><img loading=\"lazy\" decoding=\"async\" class=\"alignnone wp-image-26899\" src=\"https:\/\/fgu.cas.cz\/wp-content\/uploads\/2024\/08\/mapper_logo.svg\" alt=\"-\" width=\"102\" height=\"102\" title=\"\">\u00a0Mapper &#8211; a pathway mapping tool <\/a><\/h2>\n<ul>\n<li>Online metabolite mapping tool.<\/li>\n<li>Use an excel file to map metabolite concentration on a metabolic pathway map.<\/li>\n<li>Supports simple bar graphs and stacked bar graphs for isotopologues.<\/li>\n<\/ul>\n<hr \/>\n<h2><a href=\"https:\/\/mmv.metabolomics.fgu.cas.cz\" target=\"_blank\" rel=\"noopener\"><img loading=\"lazy\" decoding=\"async\" class=\"alignnone wp-image-26901\" src=\"https:\/\/fgu.cas.cz\/wp-content\/uploads\/2024\/08\/mmv_logo.svg\" alt=\"-\" width=\"90\" height=\"90\" title=\"\">\u00a0Metabolic model viewer <\/a><\/h2>\n<ul>\n<li>Online metabolic network (biochemical reaction network) visualization tool.<\/li>\n<li>Supports <sup>13<\/sup>C-based models and elementary metabolite unit (EMU) notation &#8216;A (abc) -&gt; B (ab) + C (c)&#8217;.<\/li>\n<li>Compatible with models for the MFA Suite\u2122 (Metabolic Flux Analysis Suite) <a href=\"https:\/\/mfa.vueinnovations.com\/\" target=\"_blank\" rel=\"noopener\">https:\/\/mfa.vueinnovations.com\/<\/a>.<\/li>\n<\/ul>\n<hr \/>\n<p>\u25ba Michaela Vondrackova, Dominik Kopczynski, Nils Hoffmann, Ondrej Kuda<sup>\u2709<\/sup><br \/>\n<strong>LORA, Lipid Over-Representation Analysis Based on Structural Information<\/strong><br \/>\nAnalytical Chemistry, 2023 DOI <a href=\"https:\/\/doi.org\/10.1021\/acs.analchem.3c02039\" target=\"_blank\" rel=\"noopener\">https:\/\/doi.org\/10.1021\/acs.analchem.3c02039<\/a><\/p>\n<p><a href=\"https:\/\/doi.org\/10.1021\/acs.analchem.3c02039\" target=\"_blank\" rel=\"noopener\">With the increasing number of lipidomic studies, there is a need for an efficient&#8230;&#8230;<\/a><\/p>\n<ul>\n<li>Web application <a href=\"https:\/\/lora.metabolomics.fgu.cas.cz\" target=\"_blank\" rel=\"noopener\">LORA.metabolomics.fgu.cas.cz<\/a><\/li>\n<li>GIT <a href=\"https:\/\/github.com\/IPHYS-Bioinformatics\/LORA\" target=\"_blank\" rel=\"noopener\">https:\/\/github.com\/IPHYS-Bioinformatics\/LORA<\/a><\/li>\n<\/ul>\n<h2><a href=\"https:\/\/lora.metabolomics.fgu.cas.cz\/\" target=\"_blank\" rel=\"noopener\"><img loading=\"lazy\" decoding=\"async\" class=\"alignnone wp-image-26903\" src=\"https:\/\/fgu.cas.cz\/wp-content\/uploads\/2024\/08\/parrot.svg\" alt=\"-\" width=\"88\" height=\"89\" title=\"\">\u00a0LORA<\/a><\/h2>\n<ul>\n<li>Online Lipid Over-Representation Analysis tool.<\/li>\n<li>Built on Goslin grammars, supports multiple lipid annotation dialects.<\/li>\n<li>Uses UpSet plot, circular hierarchical tree and Cytoscape network to describe lipidome data enrichment.<\/li>\n<\/ul>\n<hr \/>\n<h3>Dynamic metabolomics &#8211; tracing <sup>13<\/sup>C glucose<\/h3>\n<p>5-PAHSA primes adipocytes for glucose metabolism in a different way from insulin. 5-PAHSA partially re-wires glucose metabolism pathways in favor of Krebs cycle, NADPH synthesis and <em>de novo<\/em> lipogenesis. Simplified metabolic situation is animated through the pathway within 15 minutes of glucose uptake into adipocytes. Details and conditions in Paluchova et al. <a href=\"https:\/\/doi.org\/10.2337\/db19-0494\" target=\"_blank\" rel=\"noopener\">DOI<\/a> and <a href=\"https:\/\/www.fgu.cas.cz\/en\/articles\/781-branched-fatty-acid-esters-of-hydroxy-fatty-acids-fahfa\" target=\"_blank\" rel=\"noopener\">FAHFA page<\/a><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter wp-image-26918 size-large\" src=\"https:\/\/fgu.cas.cz\/wp-content\/uploads\/2024\/08\/glucose-uptake-5-pahsa-1-1024x787.gif\" alt=\"-\" width=\"800\" height=\"615\" title=\"\" srcset=\"https:\/\/fgu.cas.cz\/wp-content\/uploads\/2024\/08\/glucose-uptake-5-pahsa-1-1024x787.gif 1024w, https:\/\/fgu.cas.cz\/wp-content\/uploads\/2024\/08\/glucose-uptake-5-pahsa-1-300x230.gif 300w, https:\/\/fgu.cas.cz\/wp-content\/uploads\/2024\/08\/glucose-uptake-5-pahsa-1-768x590.gif 768w\" sizes=\"(max-width: 800px) 100vw, 800px\" \/><\/p>\n<hr \/>\n<h3>Use of [4-<sup>2<\/sup>H]-glucose for metabolic labeling of NADPH.<\/h3>\n<p>[4-<sup>2<\/sup>H]-glucose can be used as a malic enzyme tracer, which specifically labels NADPH\u2019s redox active hydrogen. The deuteron from [4-<sup>2<\/sup>H]-glucose is passed to NAD<sup>2<\/sup>H by glyceraldehyde 3-phosphate dehydrogenase (<em>GAPDH<\/em>) during glycolysis. This cytosolic NAD<sup>2<\/sup>H can be used by cytosolic malate dehydrogenase 1 (<em>MDH<\/em>) to convert cytosolic oxaloacetate (coming from citrate cleavage by ATP citrate lyase) to cytosolic [2-<sup>2<\/sup>H]-malate. This deuterated malate can be either transported to mitochondria or converted by malic enzyme 1 (<em>ME1<\/em>) to cytosolic pyruvate and cytosolic NADP<sup>2<\/sup>H. This NADP<sup>2<\/sup>H represents the energy for DNL. During the synthesis of a fatty acid from acetyl-CoA units (via malonyl-CoA), two NADPH molecules are used per one C<sub>2<\/sub> unit. The fatty acid labeling is the result of two stochastic hydrogen selection processes, with 1\/3 of hydrogens coming from water and 2\/3 coming from NADPH. If cytosolic NADP<sup>2<\/sup>H is present, contribution of malic enzyme 1 NADPH to fatty acid synthesis can be measured.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"size-large wp-image-26912 aligncenter\" src=\"https:\/\/fgu.cas.cz\/wp-content\/uploads\/2024\/08\/nadph-deuterium-labeling-01-1024x720.jpg\" alt=\"-\" width=\"800\" height=\"563\" title=\"\" srcset=\"https:\/\/fgu.cas.cz\/wp-content\/uploads\/2024\/08\/nadph-deuterium-labeling-01-1024x720.jpg 1024w, https:\/\/fgu.cas.cz\/wp-content\/uploads\/2024\/08\/nadph-deuterium-labeling-01-300x211.jpg 300w, https:\/\/fgu.cas.cz\/wp-content\/uploads\/2024\/08\/nadph-deuterium-labeling-01-768x540.jpg 768w, https:\/\/fgu.cas.cz\/wp-content\/uploads\/2024\/08\/nadph-deuterium-labeling-01-1536x1080.jpg 1536w, https:\/\/fgu.cas.cz\/wp-content\/uploads\/2024\/08\/nadph-deuterium-labeling-01.jpg 1801w\" sizes=\"(max-width: 800px) 100vw, 800px\" \/><\/p>\n<p>3T3-L1 differentiated adipocytes were incubated with or without 40 \u00b5M 5-PAHSA in medium with [4-<sup>2<\/sup>H]-glucose for 24 hours without insulin, metabolism quenched on liquid nitrogen, cells extracted to preserve NADPH and NADP+ ratio, and raw extracts immediately measured by LC-MS\/MS according to a published protocol.<br \/>\nMalate labeling M+1 documents that the deuteron was introduced by labeled NADH. For further details regarding malate labeling and its alternative fate see ref. Lewis et al. NADPH M+1 over NAPD+ M+1 labeling represent the redox-active deuteron on NADP<sup>2<\/sup>H. 5-PAHSA treatment resulted in significantly higher labeling of cytosolic NADPH. For more details see ref. Lie et al. Scheme adapted from Lewis et al.. Data from this labeling experiments were adjusted for C, H, O, N, P natural abundance and tracer purity using IsoCor-2.0.5. Details and conditions in Paluchova et al. <a href=\"https:\/\/doi.org\/10.2337\/db19-0494\" target=\"_blank\" rel=\"noopener\">DOI<\/a> and <a href=\"https:\/\/www.fgu.cas.cz\/en\/articles\/781-branched-fatty-acid-esters-of-hydroxy-fatty-acids-fahfa\" target=\"_blank\" rel=\"noopener\">FAHFA page<\/a><\/p>\n<p>&nbsp;<\/p>\n<hr \/>\n<h3>Lipid labeling using <sup>2<\/sup>H<sub>2<\/sub>O &#8211; labeling of neutral lipids<\/h3>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"size-large wp-image-26914 aligncenter\" src=\"https:\/\/fgu.cas.cz\/wp-content\/uploads\/2024\/08\/d2o-labeling-verze-text-01-1024x464.jpg\" alt=\"-\" width=\"800\" height=\"363\" title=\"\" srcset=\"https:\/\/fgu.cas.cz\/wp-content\/uploads\/2024\/08\/d2o-labeling-verze-text-01-1024x464.jpg 1024w, https:\/\/fgu.cas.cz\/wp-content\/uploads\/2024\/08\/d2o-labeling-verze-text-01-300x136.jpg 300w, https:\/\/fgu.cas.cz\/wp-content\/uploads\/2024\/08\/d2o-labeling-verze-text-01-768x348.jpg 768w, https:\/\/fgu.cas.cz\/wp-content\/uploads\/2024\/08\/d2o-labeling-verze-text-01-1536x696.jpg 1536w, https:\/\/fgu.cas.cz\/wp-content\/uploads\/2024\/08\/d2o-labeling-verze-text-01-2048x929.jpg 2048w\" sizes=\"(max-width: 800px) 100vw, 800px\" \/><\/p>\n<p>For the simple synthesis of TAGs, glycerol phosphate and acyl-CoAs are needed. WAT is virtually lacking glycerol kinase, thus all glycerol phosphate has to be synthesized either via glycolysis (green path) or glyceroneogenesis (pink path). During glycolysis, deuteria (up to 3, M+3) could be incorporated from water within the equilibrium between Glyceraldehyde-\u24c5, Dihydroxyacetone-\u24c5, and Glycerol-3-\u24c5. The alternative glyceroneogenic pathway precursors are deuterium-labeled within the Krebs cycle and further during conversion of Phosphoenolpyruvate to Glyceraldehyde-\u24c5. This path may incorporate up to 5 deuteria per glycerol after several turns of the Krebs cycle. The intermediates labeled with deuteria within the Krebs cycle may also enter the de novo lipogenic pathway (blue path) as labeled Acetyl-CoA. The first (and future terminal methyl group) Acetyl-CoA keeps the deuteria, while the later Acetyl-CoAs are converted to Malonyl-CoAs and lose one deuteria from the Krebs cycle. During the elongation process of the acyl-intermediate, NADPH+H+ provides additional deuteria equilibrated from body water, thus potentially increasing the enrichment (red path). Finally, both glycerol phosphate and newly synthesized palmitate can form TAG. The degree of enrichment of the final TAG might be diluted by the contribution of FA re-esterification \/ lipolysis or import of external fatty acids. There are up to 6 metabolically different hydrogens, which could be exchanged for deuterium in a simple TAG.<\/p>\n<h3>Literature:<\/h3>\n<ol>\n<li>Liu et al. <a href=\"https:\/\/doi.org\/10.1038\/nchembio.2047\" target=\"_blank\" rel=\"noopener\">DOI<\/a><\/li>\n<li>Lewis et al. <a href=\"https:\/\/doi.org\/10.1016\/j.molcel.2014.05.008\" target=\"_blank\" rel=\"noopener\">DOI<\/a><\/li>\n<li>Zhang et al. <a href=\"https:\/\/doi.org\/10.1021\/jacs.7b08012\" target=\"_blank\" rel=\"noopener\">DOI<\/a><\/li>\n<li>Krycer et al. <a href=\"https:\/\/doi.org\/10.1016\/j.celrep.2017.11.085\" target=\"_blank\" rel=\"noopener\">DOI<\/a><\/li>\n<li>Paluchova et al. <a href=\"https:\/\/doi.org\/10.2337\/db19-0494\" target=\"_blank\" rel=\"noopener\">DOI<\/a><\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"<p>Software: \u00a0GTTAtlas \u00a0MetaboAtlas21 \u00a0COMA \u00a0Mapper \u00a0Reaction network viewer \u00a0LORA \u00a0M3CAV Methodological highlighs from publications using small molecule omics techniques. \u25ba Pauline Morigny, Michaela Vondrackova, Honglei Ji, Kristyna Brejchova, Monika Krakovkova, Konstantinos Makris, Radka Trubacova, Tuna F. Samanci, Doris Kaltenecker, Su-Ping Ng, Vignesh Karthikaisamy, Sophia E. Chrysostomou, Anna Bidovec, Mariana Ponce-de-Leon, Tanja Krauss, Claudine Seeliger, Olga [&hellip;]<\/p>\n","protected":false},"author":1,"template":"","meta":{"_acf_changed":false,"inline_featured_image":false,"footnotes":""},"oddeleni":[161],"poskytovatel":[],"stav-projektu":[209],"class_list":["post-28372","vyzkumny-projekt","type-vyzkumny-projekt","status-publish","hentry","oddeleni-metabolism-of-bioactive-lipids","stav-projektu-current-projects"],"acf":[],"_links":{"self":[{"href":"https:\/\/fgu.cas.cz\/en\/wp-json\/wp\/v2\/vyzkumny-projekt\/28372","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/fgu.cas.cz\/en\/wp-json\/wp\/v2\/vyzkumny-projekt"}],"about":[{"href":"https:\/\/fgu.cas.cz\/en\/wp-json\/wp\/v2\/types\/vyzkumny-projekt"}],"author":[{"embeddable":true,"href":"https:\/\/fgu.cas.cz\/en\/wp-json\/wp\/v2\/users\/1"}],"version-history":[{"count":0,"href":"https:\/\/fgu.cas.cz\/en\/wp-json\/wp\/v2\/vyzkumny-projekt\/28372\/revisions"}],"wp:attachment":[{"href":"https:\/\/fgu.cas.cz\/en\/wp-json\/wp\/v2\/media?parent=28372"}],"wp:term":[{"taxonomy":"oddeleni","embeddable":true,"href":"https:\/\/fgu.cas.cz\/en\/wp-json\/wp\/v2\/oddeleni?post=28372"},{"taxonomy":"poskytovatel","embeddable":true,"href":"https:\/\/fgu.cas.cz\/en\/wp-json\/wp\/v2\/poskytovatel?post=28372"},{"taxonomy":"stav-projektu","embeddable":true,"href":"https:\/\/fgu.cas.cz\/en\/wp-json\/wp\/v2\/stav-projektu?post=28372"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}