Regulating metabolic disorders has become a promising focus in treating intervertebral disc degeneration (IDD). A few drugs regulating metabolism, such as atorvastatin, metformin, and melatonin, show positive effects in treating IDD. Glutamine participates in multiple metabolic processes, including glutaminolysis and glycolysis; however, its impact on IDD is unclear. The current study reveals that glutamine levels are decreased in severely degenerated human nucleus pulposus (NP) tissues and aging Sprague-Dawley (SD) rat nucleus pulposus tissues, while lactate accumulation and lactylation are increased. Supplementary glutamine suppresses glycolysis and reduces lactate production, which downregulates adenosine-5’-monophosphate-activated protein kinase α (AMPKα) lactylation and upregulates AMPKα phosphorylation. Moreover, glutamine treatment reduces NP cell senescence and enhances autophagy and matrix synthesis via inhibition of glycolysis and AMPK lactylation, and glycolysis inhibition suppresses lactylation. Our results indicate that glutamine could prevent IDD by glycolysis inhibition-decreased AMPKα lactylation, which promotes autophagy and suppresses NP cell senescence.

调节代谢紊乱已成为治疗椎间盘退变（IDD）的一个有前景的焦点。一些调节代谢的药物，如阿托伐他汀、二甲双胍和褪黑激素，在治疗 IDD 方面显示出积极的效果。谷氨酰胺参与多种代谢过程，包括谷氨酰胺分解和糖酵解；然而，它对 IDD 的影响尚不清楚。目前的研究表明，严重退化的人类髓核（NP）组织和衰老的SD大鼠髓核组织中谷氨酰胺水平降低，而乳​​酸积累和乳酸化增加。补充谷氨酰胺可抑制糖酵解并减少乳酸产生，从而下调 5'-单磷酸腺苷激活蛋白激酶 α (AMPKα) 乳酰化并上调 AMPKα 磷酸化。此外，谷氨酰胺处理可通过抑制糖酵解和 AMPK 乳酰化来减少 NP 细胞衰老并增强自噬和基质合成，而糖酵解抑制又会抑制乳酰化。我们的结果表明，谷氨酰胺可以通过糖酵解抑制-减少 AMPKα 乳酰化来预防 IDD，从而促进自噬并抑制 NP 细胞衰老。