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Multi-omics-based label-free metabolic flux inference reveals obesity-associated dysregulatory mechanisms in liver glucose metabolism
Glucose homeostasis is maintained by modulation of metabolic flux. Enzymes and metabolites regulate the involved metabolic pathways. Dysregulation of glucose homeostasis is a pathological event in obesity. Analyzing metabolic pathways and the mechanisms contributing to obesity-associated dysregulati...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8859528/ https://www.ncbi.nlm.nih.gov/pubmed/35243212 http://dx.doi.org/10.1016/j.isci.2022.103787 |
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author | Uematsu, Saori Ohno, Satoshi Tanaka, Kaori Y. Hatano, Atsushi Kokaji, Toshiya Ito, Yuki Kubota, Hiroyuki Hironaka, Ken-ichi Suzuki, Yutaka Matsumoto, Masaki Nakayama, Keiichi I. Hirayama, Akiyoshi Soga, Tomoyoshi Kuroda, Shinya |
author_facet | Uematsu, Saori Ohno, Satoshi Tanaka, Kaori Y. Hatano, Atsushi Kokaji, Toshiya Ito, Yuki Kubota, Hiroyuki Hironaka, Ken-ichi Suzuki, Yutaka Matsumoto, Masaki Nakayama, Keiichi I. Hirayama, Akiyoshi Soga, Tomoyoshi Kuroda, Shinya |
author_sort | Uematsu, Saori |
collection | PubMed |
description | Glucose homeostasis is maintained by modulation of metabolic flux. Enzymes and metabolites regulate the involved metabolic pathways. Dysregulation of glucose homeostasis is a pathological event in obesity. Analyzing metabolic pathways and the mechanisms contributing to obesity-associated dysregulation in vivo is challenging. Here, we introduce OMELET: Omics-Based Metabolic Flux Estimation without Labeling for Extended Trans-omic Analysis. OMELET uses metabolomic, proteomic, and transcriptomic data to identify relative changes in metabolic flux, and to calculate contributions of metabolites, enzymes, and transcripts to the changes in metabolic flux. By evaluating the livers of fasting ob/ob mice, we found that increased metabolic flux through gluconeogenesis resulted primarily from increased transcripts, whereas that through the pyruvate cycle resulted from both increased transcripts and changes in substrates of metabolic enzymes. With OMELET, we identified mechanisms underlying the obesity-associated dysregulation of metabolic flux in the liver. |
format | Online Article Text |
id | pubmed-8859528 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-88595282022-03-02 Multi-omics-based label-free metabolic flux inference reveals obesity-associated dysregulatory mechanisms in liver glucose metabolism Uematsu, Saori Ohno, Satoshi Tanaka, Kaori Y. Hatano, Atsushi Kokaji, Toshiya Ito, Yuki Kubota, Hiroyuki Hironaka, Ken-ichi Suzuki, Yutaka Matsumoto, Masaki Nakayama, Keiichi I. Hirayama, Akiyoshi Soga, Tomoyoshi Kuroda, Shinya iScience Article Glucose homeostasis is maintained by modulation of metabolic flux. Enzymes and metabolites regulate the involved metabolic pathways. Dysregulation of glucose homeostasis is a pathological event in obesity. Analyzing metabolic pathways and the mechanisms contributing to obesity-associated dysregulation in vivo is challenging. Here, we introduce OMELET: Omics-Based Metabolic Flux Estimation without Labeling for Extended Trans-omic Analysis. OMELET uses metabolomic, proteomic, and transcriptomic data to identify relative changes in metabolic flux, and to calculate contributions of metabolites, enzymes, and transcripts to the changes in metabolic flux. By evaluating the livers of fasting ob/ob mice, we found that increased metabolic flux through gluconeogenesis resulted primarily from increased transcripts, whereas that through the pyruvate cycle resulted from both increased transcripts and changes in substrates of metabolic enzymes. With OMELET, we identified mechanisms underlying the obesity-associated dysregulation of metabolic flux in the liver. Elsevier 2022-02-04 /pmc/articles/PMC8859528/ /pubmed/35243212 http://dx.doi.org/10.1016/j.isci.2022.103787 Text en © 2022 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Uematsu, Saori Ohno, Satoshi Tanaka, Kaori Y. Hatano, Atsushi Kokaji, Toshiya Ito, Yuki Kubota, Hiroyuki Hironaka, Ken-ichi Suzuki, Yutaka Matsumoto, Masaki Nakayama, Keiichi I. Hirayama, Akiyoshi Soga, Tomoyoshi Kuroda, Shinya Multi-omics-based label-free metabolic flux inference reveals obesity-associated dysregulatory mechanisms in liver glucose metabolism |
title | Multi-omics-based label-free metabolic flux inference reveals obesity-associated dysregulatory mechanisms in liver glucose metabolism |
title_full | Multi-omics-based label-free metabolic flux inference reveals obesity-associated dysregulatory mechanisms in liver glucose metabolism |
title_fullStr | Multi-omics-based label-free metabolic flux inference reveals obesity-associated dysregulatory mechanisms in liver glucose metabolism |
title_full_unstemmed | Multi-omics-based label-free metabolic flux inference reveals obesity-associated dysregulatory mechanisms in liver glucose metabolism |
title_short | Multi-omics-based label-free metabolic flux inference reveals obesity-associated dysregulatory mechanisms in liver glucose metabolism |
title_sort | multi-omics-based label-free metabolic flux inference reveals obesity-associated dysregulatory mechanisms in liver glucose metabolism |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8859528/ https://www.ncbi.nlm.nih.gov/pubmed/35243212 http://dx.doi.org/10.1016/j.isci.2022.103787 |
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