Open AccessIncreased glycolysis in skeletal muscle coordinates with adipose tissue in systemic metabolic homeostasis
Author(s) -
Xiang Cong,
Zhang Yannan,
Chen Qiaoli,
Sun Aina,
Peng Yamei,
Zhang Guoxin,
Zhou Danxia,
Xie Yinyin,
Hou Xiaoshuang,
Zheng Fangfang,
Wang Fan,
Gan Zhenji,
Chen Shuai,
Liu Geng
Publication year - 2021
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.16698
Subject(s) - glycolysis , skeletal muscle , carbohydrate metabolism , glucose uptake , glucose transporter , medicine , adipose tissue , endocrinology , insulin resistance , glucose homeostasis , fgf21 , biology , anaerobic glycolysis , lipid metabolism , fructose , insulin , metabolism , biochemistry , fibroblast growth factor , receptor
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.