iScience (Mar 2021)
Trans-omic analysis reveals obesity-associated dysregulation of inter-organ metabolic cycles between the liver and skeletal muscle
- Riku Egami,
- Toshiya Kokaji,
- Atsushi Hatano,
- Katsuyuki Yugi,
- Miki Eto,
- Keigo Morita,
- Satoshi Ohno,
- Masashi Fujii,
- Ken-ichi Hironaka,
- Saori Uematsu,
- Akira Terakawa,
- Yunfan Bai,
- Yifei Pan,
- Takaho Tsuchiya,
- Haruka Ozaki,
- Hiroshi Inoue,
- Shinsuke Uda,
- Hiroyuki Kubota,
- Yutaka Suzuki,
- Masaki Matsumoto,
- Keiichi I. Nakayama,
- Akiyoshi Hirayama,
- Tomoyoshi Soga,
- Shinya Kuroda
Affiliations
- Riku Egami
- Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8562, Japan
- Toshiya Kokaji
- Department of Biological Sciences, Graduate School of Science, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
- Atsushi Hatano
- Department of Biological Sciences, Graduate School of Science, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan; Laboratory for Integrated Cellular Systems, RIKEN Center for Integrative Medical Sciences, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan; Department of Omics and Systems Biology, Graduate School of Medical and Dental Sciences, Niigata University, 757 Ichibancho, Asahimachi-dori, Chuo-ku, Niigata City, Niigata 951-8510, Japan
- Katsuyuki Yugi
- Department of Biological Sciences, Graduate School of Science, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan; Laboratory for Integrated Cellular Systems, RIKEN Center for Integrative Medical Sciences, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan; Institute for Advanced Biosciences, Keio University, Fujisawa, 252-8520, Japan; PRESTO, Japan Science and Technology Agency, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan
- Miki Eto
- Department of Biological Sciences, Graduate School of Science, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
- Keigo Morita
- Department of Biological Sciences, Graduate School of Science, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
- Satoshi Ohno
- Department of Biological Sciences, Graduate School of Science, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan; Molecular Genetics Research Laboratory, Graduate School of Science, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
- Masashi Fujii
- Department of Biological Sciences, Graduate School of Science, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan; Molecular Genetics Research Laboratory, Graduate School of Science, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan; Department of Mathematical and Life Sciences, Graduate School of Integrated Sciences for Life, Hiroshima University, 1-3-1 Kagamiyama, Higashi-hiroshima City, Hiroshima, 739-8526, Japan
- Ken-ichi Hironaka
- Department of Biological Sciences, Graduate School of Science, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
- Saori Uematsu
- Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8562, Japan
- Akira Terakawa
- Department of Biological Sciences, Graduate School of Science, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
- Yunfan Bai
- Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8562, Japan
- Yifei Pan
- Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8562, Japan
- Takaho Tsuchiya
- Bioinformatics Laboratory, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan; Center for Artificial Intelligence Research, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8577, Japan
- Haruka Ozaki
- Bioinformatics Laboratory, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan; Center for Artificial Intelligence Research, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8577, Japan
- Hiroshi Inoue
- Metabolism and Nutrition Research Unit, Institute for Frontier Science Initiative, Kanazawa University, 13-1 Takaramachi, Kanazawa, Ishikawa, 920-8641, Japan
- Shinsuke Uda
- Division of Integrated Omics, Research Center for Transomics Medicine, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
- Hiroyuki Kubota
- Division of Integrated Omics, Research Center for Transomics Medicine, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
- Yutaka Suzuki
- Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8562, Japan
- Masaki Matsumoto
- Department of Omics and Systems Biology, Graduate School of Medical and Dental Sciences, Niigata University, 757 Ichibancho, Asahimachi-dori, Chuo-ku, Niigata City, Niigata 951-8510, Japan
- Keiichi I. Nakayama
- Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
- Akiyoshi Hirayama
- Institute for Advanced Biosciences, Keio University, 246-2 Mizukami, Kakuganji, Tsuruoka, Yamagata, 997-0052, Japan
- Tomoyoshi Soga
- Institute for Advanced Biosciences, Keio University, 246-2 Mizukami, Kakuganji, Tsuruoka, Yamagata, 997-0052, Japan
- Shinya Kuroda
- Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8562, Japan; Department of Biological Sciences, Graduate School of Science, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan; Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency, Bunkyo-ku, Tokyo 113-0033, Japan; Corresponding author
- Journal volume & issue
-
Vol. 24,
no. 3
p. 102217
Abstract
Summary: Systemic metabolic homeostasis is regulated by inter-organ metabolic cycles involving multiple organs. Obesity impairs inter-organ metabolic cycles, resulting in metabolic diseases. The systemic landscape of dysregulated inter-organ metabolic cycles in obesity has yet to be explored. Here, we measured the transcriptome, proteome, and metabolome in the liver and skeletal muscle and the metabolome in blood of fasted wild-type and leptin-deficient obese (ob/ob) mice, identifying components with differential abundance and differential regulation in ob/ob mice. By constructing and evaluating the trans-omic network controlling the differences in metabolic reactions between fasted wild-type and ob/ob mice, we provided potential mechanisms of the obesity-associated dysfunctions of metabolic cycles between liver and skeletal muscle involving glucose-alanine, glucose-lactate, and ketone bodies. Our study revealed obesity-associated systemic pathological mechanisms of dysfunction of inter-organ metabolic cycles.
