In vivo transomic analyses of glucose-responsive metabolism in skeletal muscle reveal core differences between the healthy and obese states.
In vivo transomic analyses of glucose-responsive metabolism in skeletal muscle reveal core differences between the healthy and obese states.
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DOI：
10.1038/s41598-022-17964-9
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发表时间：
2022-08-12
影响因子：
4.6
通讯作者：
Kuroda, Shinya
中科院分区：
文献类型：
--
作者：
Kokaji, Toshiya;Eto, Miki;Hatano, Atsushi;Yugi, Katsuyuki;Morita, Keigo;Ohno, Satoshi;Fujii, Masashi;Hironaka, Ken-ichi;Ito, Yuki;Egami, Riku;Uematsu, Saori;Terakawa, Akira;Pan, Yifei;Maehara, Hideki;Li, Dongzi;Bai, Yunfan;Tsuchiya, Takaho;Ozaki, Haruka;Inoue, Hiroshi;Kubota, Hiroyuki;Suzuki, Yutaka;Hirayama, Akiyoshi;Soga, Tomoyoshi;Kuroda, Shinya
骨骼肌的代谢调节是维持血糖动态平衡的关键。肥胖导致骨骼肌中的胰岛素抵抗，导致高血糖和2型糖尿病。在这项研究中，我们对野生型(WT)和瘦素缺乏性肥胖(ob/ob)小鼠的骨骼肌进行了多组学分析，并构建了口服葡萄糖后代谢的调节跨体网络。我们的网络显示，葡萄糖反应性代谢物对WT小鼠的代谢调节有重要影响，特别是碳水化合物代谢途径。相比之下，在ob/ob小鼠中，葡萄糖反应代谢物的代谢调节大部分丢失，而葡萄糖反应基因的代谢调节大大增加，特别是在碳水化合物和脂肪代谢途径中。我们介绍了在中心碳、分支氨基酸和酮体代谢中发现的一些特有的代谢调节途径。我们的转体分析将提供有关骨骼肌如何对血糖变化做出反应以及它如何对肥胖做出反应的见解。
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.
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影响因子：
56.9
作者：
Ishii, Nobuyoshi;Nakahigashi, Kenji;Tomita, Masaru
通讯作者：
Tomita, Masaru
影响因子：
14.9
作者：
Kanehisa M;Goto S;Sato Y;Furumichi M;Tanabe M
通讯作者：
Tanabe M
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：
5.8
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
通讯作者：
Kuroda S
影响因子：
5.8
作者：
Kawata K;Hatano A;Yugi K;Kubota H;Sano T;Fujii M;Tomizawa Y;Kokaji T;Tanaka KY;Uda S;Suzuki Y;Matsumoto M;Nakayama KI;Saitoh K;Kato K;Ueno A;Ohishi M;Hirayama A;Soga T;Kuroda S
通讯作者：
Kuroda S