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Increased glycolysis in skeletal muscle coordinates with adipose tissue in systemic metabolic homeostasis |
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| Authors: | Cong Xiang Yannan Zhang Qiaoli Chen Aina Sun Yamei Peng Guoxin Zhang Danxia Zhou Yinyin Xie Xiaoshuang Hou Fangfang Zheng Fan Wang Zhenji Gan Shuai Chen Geng Liu |
| Institution: | 1. State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Center, School of Medicine, Nanjing University, Nanjing, China
Contribution: Conceptualization (lead), Data curation (lead), Formal analysis (lead), ?Investigation (lead), Software (lead), Validation (equal), Writing - original draft (lead), Writing - review & editing (lead);2. State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Center, School of Medicine, Nanjing University, Nanjing, China Contribution: Data curation (equal), Formal analysis (supporting), ?Investigation (equal), Software (supporting), Writing - review & editing (supporting);3. State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Center, School of Medicine, Nanjing University, Nanjing, China Contribution: Data curation (supporting), ?Investigation (supporting), Methodology (supporting), Writing - review & editing (supporting);4. State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Center, School of Medicine, Nanjing University, Nanjing, China Contribution: Data curation (supporting), Methodology (supporting), Writing - review & editing (supporting);5. State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Center, School of Medicine, Nanjing University, Nanjing, China Contribution: Data curation (supporting), Formal analysis (supporting), Writing - review & editing (supporting);6. State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Center, School of Medicine, Nanjing University, Nanjing, China Contribution: Data curation (supporting), Validation (supporting), Writing - review & editing (supporting);7. State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Center, School of Medicine, Nanjing University, Nanjing, China Contribution: Data curation (supporting), Writing - review & editing (supporting);8. State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Center, School of Medicine, Nanjing University, Nanjing, China Contribution: Data curation (supporting), ?Investigation (supporting), Writing - review & editing (supporting);9. State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Center, School of Medicine, Nanjing University, Nanjing, China Contribution: Formal analysis (supporting), Writing - review & editing (supporting);10. State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Center, School of Medicine, Nanjing University, Nanjing, China Contribution: ?Investigation (supporting), Writing - review & editing (supporting);11. State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Center, School of Medicine, Nanjing University, Nanjing, China |
| Abstract: | Insulin-independent glucose metabolism, including anaerobic glycolysis that is promoted in resistance training, plays critical roles in glucose disposal and systemic metabolic regulation. However, the underlying mechanisms are not completely understood. In this study, through genetically manipulating the glycolytic process by overexpressing human glucose transporter 1 (GLUT1), hexokinase 2 (HK2) and 6-phosphofructo-2-kinase-fructose-2,6-biphosphatase 3 (PFKFB3) in mouse skeletal muscle, we examined the impact of enhanced glycolysis in metabolic homeostasis. Enhanced glycolysis in skeletal muscle promoted accelerated glucose disposal, a lean phenotype and a high metabolic rate in mice despite attenuated lipid metabolism in muscle, even under High-Fat diet (HFD). Further study revealed that the glucose metabolite sensor carbohydrate-response element-binding protein (ChREBP) was activated in the highly glycolytic muscle and stimulated the elevation of plasma fibroblast growth factor 21 (FGF21), possibly mediating enhanced lipid oxidation in adipose tissue and contributing to a systemic effect. PFKFB3 was critically involved in promoting the glucose-sensing mechanism in myocytes. Thus, a high level of glycolysis in skeletal muscle may be intrinsically coupled to distal lipid metabolism through intracellular glucose sensing. This study provides novel insights for the benefit of resistance training and for manipulating insulin-independent glucose metabolism. |
| Keywords: | adipose tissue FGF21 glucose sensing glycolysis obesity skeletal muscle |