In vivo transomic analyses of glucose-responsive metabolism in skeletal muscle reveal core differences between the healthy and obese states
Abstract Metabolic regulation in skeletal muscle is essential for blood glucose homeostasis. Obesity causes insulin resistance in skeletal muscle, leading to hyperglycemia and type 2 diabetes. In this study, we performed multiomic analysis of the skeletal muscle of wild-type (WT) and leptin-deficien...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-08-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-17964-9 |
| _version_ | 1811215743981715456 |
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| author | Toshiya Kokaji Miki Eto Atsushi Hatano Katsuyuki Yugi Keigo Morita Satoshi Ohno Masashi Fujii Ken-ichi Hironaka Yuki Ito Riku Egami Saori Uematsu Akira Terakawa Yifei Pan Hideki Maehara Dongzi Li Yunfan Bai Takaho Tsuchiya Haruka Ozaki Hiroshi Inoue Hiroyuki Kubota Yutaka Suzuki Akiyoshi Hirayama Tomoyoshi Soga Shinya Kuroda |
| author_facet | Toshiya Kokaji Miki Eto Atsushi Hatano Katsuyuki Yugi Keigo Morita Satoshi Ohno Masashi Fujii Ken-ichi Hironaka Yuki Ito Riku Egami Saori Uematsu Akira Terakawa Yifei Pan Hideki Maehara Dongzi Li Yunfan Bai Takaho Tsuchiya Haruka Ozaki Hiroshi Inoue Hiroyuki Kubota Yutaka Suzuki Akiyoshi Hirayama Tomoyoshi Soga Shinya Kuroda |
| author_sort | Toshiya Kokaji |
| collection | DOAJ |
| description | Abstract Metabolic regulation in skeletal muscle is essential for blood glucose homeostasis. Obesity causes insulin resistance in skeletal muscle, leading to hyperglycemia and type 2 diabetes. In this study, we performed multiomic analysis of the skeletal muscle of wild-type (WT) and leptin-deficient obese (ob/ob) mice, and constructed regulatory transomic networks for metabolism after oral glucose administration. Our network revealed that metabolic regulation by glucose-responsive metabolites had a major effect on WT mice, especially carbohydrate metabolic pathways. By contrast, in ob/ob mice, much of the metabolic regulation by glucose-responsive metabolites was lost and metabolic regulation by glucose-responsive genes was largely increased, especially in carbohydrate and lipid metabolic pathways. We present some characteristic metabolic regulatory pathways found in central carbon, branched amino acids, and ketone body metabolism. Our transomic analysis will provide insights into how skeletal muscle responds to changes in blood glucose and how it fails to respond in obesity. |
| first_indexed | 2024-04-12T06:27:29Z |
| format | Article |
| id | doaj.art-dd5db8b9f47843dbacf9bbaaf001a016 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-12T06:27:29Z |
| publishDate | 2022-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-dd5db8b9f47843dbacf9bbaaf001a0162022-12-22T03:44:06ZengNature PortfolioScientific Reports2045-23222022-08-0112111910.1038/s41598-022-17964-9In vivo transomic analyses of glucose-responsive metabolism in skeletal muscle reveal core differences between the healthy and obese statesToshiya Kokaji0Miki Eto1Atsushi Hatano2Katsuyuki Yugi3Keigo Morita4Satoshi Ohno5Masashi Fujii6Ken-ichi Hironaka7Yuki Ito8Riku Egami9Saori Uematsu10Akira Terakawa11Yifei Pan12Hideki Maehara13Dongzi Li14Yunfan Bai15Takaho Tsuchiya16Haruka Ozaki17Hiroshi Inoue18Hiroyuki Kubota19Yutaka Suzuki20Akiyoshi Hirayama21Tomoyoshi Soga22Shinya Kuroda23Department of Biological Sciences, Graduate School of Science, University of TokyoDepartment of Biological Sciences, Graduate School of Science, University of TokyoDepartment of Biological Sciences, Graduate School of Science, University of TokyoDepartment of Biological Sciences, Graduate School of Science, University of TokyoDepartment of Biological Sciences, Graduate School of Science, University of TokyoDepartment of Biological Sciences, Graduate School of Science, University of TokyoDepartment of Biological Sciences, Graduate School of Science, University of TokyoDepartment of Biological Sciences, Graduate School of Science, University of TokyoDepartment of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, University of TokyoDepartment of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, University of TokyoDepartment of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, University of TokyoDepartment of Biological Sciences, Graduate School of Science, University of TokyoDepartment of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, University of TokyoDepartment of Biological Sciences, Graduate School of Science, University of TokyoDepartment of Biological Sciences, Graduate School of Science, University of TokyoDepartment of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, University of TokyoBioinformatics Laboratory, Faculty of Medicine, University of TsukubaBioinformatics Laboratory, Faculty of Medicine, University of TsukubaMetabolism and Nutrition Research Unit, Institute for Frontier Science Initiative, Kanazawa UniversityDivision of Integrated Omics, Medical Research Center for High Depth Omics, Medical Institute of Bioregulation, Kyushu UniversityDepartment of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, University of TokyoInstitute for Advanced Biosciences, Keio UniversityInstitute for Advanced Biosciences, Keio UniversityDepartment of Biological Sciences, Graduate School of Science, University of TokyoAbstract Metabolic regulation in skeletal muscle is essential for blood glucose homeostasis. Obesity causes insulin resistance in skeletal muscle, leading to hyperglycemia and type 2 diabetes. In this study, we performed multiomic analysis of the skeletal muscle of wild-type (WT) and leptin-deficient obese (ob/ob) mice, and constructed regulatory transomic networks for metabolism after oral glucose administration. Our network revealed that metabolic regulation by glucose-responsive metabolites had a major effect on WT mice, especially carbohydrate metabolic pathways. By contrast, in ob/ob mice, much of the metabolic regulation by glucose-responsive metabolites was lost and metabolic regulation by glucose-responsive genes was largely increased, especially in carbohydrate and lipid metabolic pathways. We present some characteristic metabolic regulatory pathways found in central carbon, branched amino acids, and ketone body metabolism. Our transomic analysis will provide insights into how skeletal muscle responds to changes in blood glucose and how it fails to respond in obesity.https://doi.org/10.1038/s41598-022-17964-9 |
| spellingShingle | Toshiya Kokaji Miki Eto Atsushi Hatano Katsuyuki Yugi Keigo Morita Satoshi Ohno Masashi Fujii Ken-ichi Hironaka Yuki Ito Riku Egami Saori Uematsu Akira Terakawa Yifei Pan Hideki Maehara Dongzi Li Yunfan Bai Takaho Tsuchiya Haruka Ozaki Hiroshi Inoue Hiroyuki Kubota Yutaka Suzuki Akiyoshi Hirayama Tomoyoshi Soga Shinya Kuroda In vivo transomic analyses of glucose-responsive metabolism in skeletal muscle reveal core differences between the healthy and obese states Scientific Reports |
| title | In vivo transomic analyses of glucose-responsive metabolism in skeletal muscle reveal core differences between the healthy and obese states |
| title_full | In vivo transomic analyses of glucose-responsive metabolism in skeletal muscle reveal core differences between the healthy and obese states |
| title_fullStr | In vivo transomic analyses of glucose-responsive metabolism in skeletal muscle reveal core differences between the healthy and obese states |
| title_full_unstemmed | In vivo transomic analyses of glucose-responsive metabolism in skeletal muscle reveal core differences between the healthy and obese states |
| title_short | In vivo transomic analyses of glucose-responsive metabolism in skeletal muscle reveal core differences between the healthy and obese states |
| title_sort | in vivo transomic analyses of glucose responsive metabolism in skeletal muscle reveal core differences between the healthy and obese states |
| url | https://doi.org/10.1038/s41598-022-17964-9 |
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