Egami Riku, Kokaji Toshiya, Hatano Atsushi, Yugi Katsuyuki, Eto Miki, Morita Keigo, Ohno Satoshi, Fujii Masashi, Hironaka Ken-Ichi, Uematsu Saori, Terakawa Akira, Bai Yunfan, Pan Yifei, Tsuchiya Takaho, Ozaki Haruka, Inoue Hiroshi, Uda Shinsuke, Kubota Hiroyuki, Suzuki Yutaka, Matsumoto Masaki, Nakayama Keiichi I, Hirayama Akiyoshi, Soga Tomoyoshi, Kuroda Shinya
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.
iScience. 2021 Feb 20;24(3):102217. doi: 10.1016/j.isci.2021.102217. eCollection 2021 Mar 19.
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 (/) mice, identifying components with differential abundance and differential regulation in / mice. By constructing and evaluating the trans-omic network controlling the differences in metabolic reactions between fasted wild-type and / 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.
全身代谢稳态由涉及多个器官的器官间代谢循环调节。肥胖会损害器官间代谢循环，导致代谢疾病。肥胖中失调的器官间代谢循环的全身情况尚未得到探索。在此，我们测量了禁食的野生型和瘦素缺乏型肥胖（ob/ob）小鼠肝脏和骨骼肌中的转录组、蛋白质组和代谢组以及血液中的代谢组，鉴定出ob/ob小鼠中丰度和调节存在差异的成分。通过构建和评估控制禁食野生型和ob/ob小鼠之间代谢反应差异的跨组学网络，我们提供了涉及葡萄糖-丙氨酸、葡萄糖-乳酸和酮体的肝脏与骨骼肌之间代谢循环肥胖相关功能障碍的潜在机制。我们的研究揭示了器官间代谢循环功能障碍的肥胖相关全身病理机制。
