Huang Zhengqi, Shi Ming, Zhang Chao, Deng Zhihuai, Qin Tianyu, Wu Jiajun, Zhang Xiaohe, Han Weitao, Li Shuangxing, Gao Bo, Xiao Yin, Huang Dongsheng, Ye Wei
Department of Spine Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China; Department of Orthopedics, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, China.
Biochim Biophys Acta Mol Basis Dis. 2025 Mar;1871(3):167635. doi: 10.1016/j.bbadis.2024.167635. Epub 2024 Dec 18.
Disturbances in lipid metabolism are closely related to intervertebral disc degeneration (IDD). However, the lipid metabolism characteristics of nucleus pulposus (NP) cells during IDD are unclear. Exercise protects against IDD and acts as a potent mediator of organ metabolism, in which muscle-secreted myokines actively participate. However, whether exercise-induced myokines alleviate IDD by regulating lipid metabolism in NP cells remains unknown. The present study revealed that lipid accumulation is the metabolic reprogramming phenotype in NP cells during IDD, which was attributed to an imbalance between increased fatty acid/triglyceride synthesis and diminished utilization, and was further associated with extracellular matrix (ECM) degradation and cell senescence. To explore the interaction between exercise and IDD, Sprague-Dawley rats were subjected to five weeks of treadmill running exercise, and rats in the exercise group exhibited less severe IDD than did those in the sedentary group. The expression of meteorin-like protein (Metrnl), a newly-discovered myokine that participates in lipid metabolism regulation, was observed to increase in muscle, serum and NP tissue after exercise. Moreover, Metrnl ameliorated lipid accumulation in NP cells and further alleviated ECM degradation and cell senescence. Mechanistically, Metrnl activated the fatty acid β-oxidation rate-limiting enzyme carnitine palmitoyltransferase 1A (CPT1A) via peroxisome proliferator-activated receptor α (PPARα) to increase lipid utilization in NP cells. This study provides insight into the lipid metabolic features of NP cells in IDD and reveals the intrinsic connections among exercise, metabolism and IDD, with the myokine Metrnl emerging as a pivotal mediator with therapeutic potential.
脂质代谢紊乱与椎间盘退变（IDD）密切相关。然而，IDD过程中髓核（NP）细胞的脂质代谢特征尚不清楚。运动可预防IDD，并作为器官代谢的有力调节因子，肌肉分泌的肌动蛋白在其中发挥积极作用。然而，运动诱导的肌动蛋白是否通过调节NP细胞的脂质代谢来减轻IDD仍不清楚。本研究表明，脂质积累是IDD过程中NP细胞的代谢重编程表型，这归因于脂肪酸/甘油三酯合成增加与利用减少之间的失衡，并进一步与细胞外基质（ECM）降解和细胞衰老相关。为了探讨运动与IDD之间的相互作用，对Sprague-Dawley大鼠进行了为期五周的跑步机跑步运动，运动组大鼠的IDD严重程度低于久坐组。观察到一种新发现的参与脂质代谢调节的肌动蛋白——类陨石蛋白（Metrnl）在运动后的肌肉、血清和NP组织中的表达增加。此外，Metrnl改善了NP细胞中的脂质积累，并进一步减轻了ECM降解和细胞衰老。机制上，Metrnl通过过氧化物酶体增殖物激活受体α（PPARα）激活脂肪酸β-氧化限速酶肉碱棕榈酰转移酶1A（CPT1A），以增加NP细胞中的脂质利用。本研究深入了解了IDD中NP细胞的脂质代谢特征，揭示了运动、代谢和IDD之间的内在联系，肌动蛋白Metrnl成为具有治疗潜力的关键调节因子。
