There has been an explosion of interest in the signaling capacity of energy metabolites. A prime example is the Krebs cycle substrate succinate, an archetypal respiratory substrate with functions beyond energy production as an intracellular and extracellular signaling molecule. Long associated with inflammation, emerging evidence supports a key role for succinate in metabolic processes relating to energy management. As the natural ligand for SUCNR1, a G protein–coupled receptor, succinate is akin to hormones and likely functions as a reporter of metabolism and stress. In this review, we reconcile new and old observations to outline a regulatory role for succinate in metabolic homeostasis. We highlight the importance of the succinate–SUCNR1 axis in metabolic diseases as an integrator of macrophage immune response, and we discuss new metabolic functions recently ascribed to succinate in specific tissues. Because circulating succinate has emerged as a promising biomarker in chronic metabolic diseases, a better understanding of the physiopathological role of the succinate–SUCNR1 axis in metabolism might open new avenues for clinical use in patients with obesity or diabetes.

人们对能量代谢物的信号传递能力产生了浓厚的兴趣。一个典型的例子是克雷布斯循环底物琥珀酸盐，这是一种典型的呼吸底物，其功能超越了作为细胞内和细胞外信号分子的能量产生。长期与炎症相关，新出现的证据支持琥珀酸在与能量管理相关的代谢过程中的关键作用。作为 SUCNR1（一种 G 蛋白偶联受体）的天然配体，琥珀酸盐类似于激素，可能充当新陈代谢和压力的报告者。在这篇综述中，我们调和了新旧观察结果，概述了琥珀酸在代谢稳态中的调节作用。我们强调了琥珀酸-SUCNR1 轴在代谢疾病中作为巨噬细胞免疫反应整合者的重要性，我们讨论了最近归因于特定组织中琥珀酸的新代谢功能。由于循环琥珀酸已成为慢性代谢疾病的一种有前途的生物标志物，因此更好地了解琥珀酸-SUCNR1 轴在代谢中的生理病理学作用可能为肥胖或糖尿病患者的临床应用开辟新途径。