Trans-omic analysis reveals obesity-associated dysregulation of inter-organ metabolic cycles between the liver and skeletal muscle.
Trans-omic analysis reveals obesity-associated dysregulation of inter-organ metabolic cycles between the liver and skeletal muscle.
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DOI：
10.1016/j.isci.2021.102217
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发表时间：
2021-03-19
期刊：
影响因子：
5.8
通讯作者：
Kuroda S
中科院分区：
文献类型：
--
作者：
Egami R;Kokaji T;Hatano A;Yugi K;Eto M;Morita K;Ohno S;Fujii M;Hironaka KI;Uematsu S;Terakawa A;Bai Y;Pan Y;Tsuchiya T;Ozaki H;Inoue H;Uda S;Kubota H;Suzuki Y;Matsumoto M;Nakayama KI;Hirayama A;Soga T;Kuroda S
全身代谢稳态受涉及多个器官的器官间代谢循环调节。肥胖损害器官间代谢循环，导致代谢性疾病。肥胖症中器官间代谢周期失调的系统性景观尚未被探索。在这里，我们测量了肝脏和骨骼肌中的转录组，蛋白质组和代谢组以及禁食野生型和瘦素缺乏型肥胖（ob/ob）小鼠血液中的代谢组，确定了ob/ob小鼠中具有差异丰度和差异调节的组分。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trans-omic网络，我们提供了与肥胖相关的肝脏和骨骼肌之间代谢周期功能障碍的潜在机制，包括葡萄糖-丙氨酸，葡萄糖-乳酸和酮体。我们的研究揭示了肥胖相关的器官间代谢循环功能障碍的全身病理机制。测量WT和ob/ob小鼠肝脏和骨骼肌中的多组学数据我们开发了差异调节的代谢反应的跨组学网络揭示了与肥胖相关的器官间代谢周期的失调生物科学;内分泌学;系统生物学;组学;蛋白质组学;代谢组学;转录组学
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. Multi-omic data in liver and skeletal muscle of WT and ob/ob mice were measured We developed the trans-omic network of differentially regulated metabolic reactions Dysregulation of inter-organ metabolic cycles associated with obesity was revealed Biological Sciences ; Endocrinology ; Systems Biology ; Omics ; Proteomics ; Metabolomics ; Transcriptomic
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影响因子：
14.9
作者：
Flicek P;Amode MR;Barrell D;Beal K;Billis K;Brent S;Carvalho-Silva D;Clapham P;Coates G;Fitzgerald S;Gil L;Girón CG;Gordon L;Hourlier T;Hunt S;Johnson N;Juettemann T;Kähäri AK;Keenan S;Kulesha E;Martin FJ;Maurel T;McLaren WM;Murphy DN;Nag R;Overduin B;Pignatelli M;Pritchard B;Pritchard E;Riat HS;Ruffier M;Sheppard D;Taylor K;Thormann A;Trevanion SJ;Vullo A;Wilder SP;Wilson M;Zadissa A;Aken BL;Birney E;Cunningham F;Harrow J;Herrero J;Hubbard TJ;Kinsella R;Muffato M;Parker A;Spudich G;Yates A;Zerbino DR;Searle SM
通讯作者：
Searle SM
影响因子：
14.9
作者：
Jeske L;Placzek S;Schomburg I;Chang A;Schomburg D
通讯作者：
Schomburg D
影响因子：
4.4
作者：
Freidman, Natasha;Chen, Ichia;Ryan, Renae
通讯作者：
Ryan, Renae
影响因子：
64.8
作者：
Kahn, Steven E.;Hull, Rebecca L.;Utzschneider, Kristina M.
通讯作者：
Utzschneider, Kristina M.
人类脂肪肝病：旧问题和新见解。
DOI：
10.1126/science.1204265
发表时间：
2011-06-24
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Cohen JC;Horton JD;Hobbs HH
通讯作者：
Hobbs HH