The skeletal muscle-adipose creatine metabolic axis: A novel paradigm for lipid metabolism reprogramming and obesity management.

IF 2.8 4区医学 Q2 PHYSIOLOGY

Experimental Physiology Pub Date : 2025-10-10 DOI:10.1113/EP093049

Yuhui Su, Na Liu, Yang Liu, Yiqun Sun, Yike Jiao

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Abstract

The global prevalence of obesity and related metabolic disorders has spurred interdisciplinary research to develop new intervention strategies. Current research is increasingly focusing on the exercise-induced browning of white adipose tissue and the mechanisms by which it improves energy metabolism. Creatine, as the primary carrier of high-energy phosphate bonds within cells, is gaining attention for its role in the metabolic reprogramming of adipose tissue. This review aims to clarify the synergistic regulatory mechanisms between exercise and creatine metabolism, and introduces an innovative 'skeletal muscle-adipose creatine metabolic axis' model. Exercise may upregulate the expression of the creatine transporter in skeletal muscle by activating the AMP-activated protein kinase/peroxisome proliferator-activated receptor γ coactivator 1-α signalling pathway, enhancing phosphocreatine shuttle kinetics, and thereby increasing energy metabolism efficiency. Concurrently, exercise-induced exosomes or miRNAs from skeletal muscle may regulate the futile creatine cycle in adipose tissue and activate non-uncoupling protein 1-dependent thermogenic pathways, thus alleviating obesity conditions. This model not only reveals the multi-organ cross-talk mechanism mediated by exercise in lipid metabolism regulation but also provides a theoretical basis for creatine metabolism-targeted obesity interventions.

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骨骼肌-脂肪肌酸代谢轴：脂质代谢重编程和肥胖管理的新范式。

肥胖症及相关代谢紊乱的全球流行已促使跨学科研究开发新的干预策略。目前的研究越来越关注运动诱导的白色脂肪组织褐变及其改善能量代谢的机制。肌酸作为细胞内高能磷酸键的主要载体，因其在脂肪组织代谢重编程中的作用而受到关注。本文旨在阐明运动与肌酸代谢之间的协同调节机制，并介绍一种创新的“骨骼肌-脂肪肌酸代谢轴”模型。运动可能通过激活amp激活的蛋白激酶/过氧化物酶体增殖体激活受体γ共激活因子1-α信号通路，提高磷酸肌酸穿梭动力学，从而提高能量代谢效率，从而上调骨骼肌肌酸转运蛋白的表达。同时，来自骨骼肌的运动诱导外泌体或mirna可能调节脂肪组织中的无用肌酸循环，激活非解偶联蛋白1依赖性产热途径，从而减轻肥胖状况。该模型不仅揭示了运动在脂质代谢调节中的多器官串扰机制，也为以肌酸代谢为目标的肥胖干预提供了理论依据。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Experimental Physiology 医学-生理学

CiteScore

5.10

自引率

3.70%

发文量

262

审稿时长

1 months

期刊介绍： Experimental Physiology publishes research papers that report novel insights into homeostatic and adaptive responses in health, as well as those that further our understanding of pathophysiological mechanisms in disease. We encourage papers that embrace the journal’s orientation of translation and integration, including studies of the adaptive responses to exercise, acute and chronic environmental stressors, growth and aging, and diseases where integrative homeostatic mechanisms play a key role in the response to and evolution of the disease process. Examples of such diseases include hypertension, heart failure, hypoxic lung disease, endocrine and neurological disorders. We are also keen to publish research that has a translational aspect or clinical application. Comparative physiology work that can be applied to aid the understanding human physiology is also encouraged. Manuscripts that report the use of bioinformatic, genomic, molecular, proteomic and cellular techniques to provide novel insights into integrative physiological and pathophysiological mechanisms are welcomed.