Liu Xinlin, Hu Fenglin, Zhang Yunshu, Ma Shurong, Liu Haihua, Shang Dong, Yin Peiyuan
Clinical Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian 116000, China.
Institute (College) of Integrative Medicine, Dalian Medical University, Dalian 116044, China.
Metabolites. 2025 Mar 3;15(3):173. doi: 10.3390/metabo15030173.
Osteoporosis is frequently observed in patients with chronic pancreatitis, and both conditions are closely associated with systemic metabolic disorders. However, the underlying mechanisms linking chronic pancreatitis and osteoporosis remain unclear. In this study, we utilized high-performance liquid chromatography-mass spectrometry (HPLC-MS) to conduct metabolomics and lipidomics analyses on pancreatic, serum, and other tissues from a mouse model of chronic pancreatitis-induced osteoporosis (CP-OP), with the aim to elucidate the metabolism-related pathogenic mechanisms of CP-OP. We identified over 405 metabolites and 445 lipids, and our findings revealed that several metabolites involving the tricarboxylic acid (TCA) cycle, as well as triacylglycerols and diacylglycerols with higher saturation, were significantly increased in the CP-OP model. In contrast, triglycerides with higher unsaturation were decreased. Differential pathways were enriched in n-3 long-chain polyunsaturated fatty acid metabolism in both pancreatic and bone tissues, and these pathways exhibited positive correlations with bone-related parameters. Furthermore, the modulation of these polyunsaturated fatty acids by Qingyi granules demonstrated significant therapeutic effects on CP-OP, as validated in mouse models. Through the metabolomics approach, we uncovered that disorders in polyunsaturated fatty acids play a critical role in the pathogenesis of CP-OP. This study not only enhances our understanding of the pathogenesis of CP-OP but also highlights the therapeutic potential of targeting polyunsaturated fatty acids as a future intervention strategy for osteoporosis treatment.
骨质疏松症在慢性胰腺炎患者中经常可见，且这两种病症都与全身代谢紊乱密切相关。然而，慢性胰腺炎与骨质疏松症之间的潜在机制仍不清楚。在本研究中，我们利用高效液相色谱-质谱联用技术（HPLC-MS）对慢性胰腺炎诱导的骨质疏松症（CP-OP）小鼠模型的胰腺、血清及其他组织进行代谢组学和脂质组学分析，旨在阐明CP-OP的代谢相关致病机制。我们鉴定出405种以上的代谢物和445种脂质，研究结果显示，在CP-OP模型中，几种参与三羧酸（TCA）循环的代谢物以及饱和度较高的三酰甘油和二酰甘油显著增加。相比之下，不饱和程度较高的甘油三酯减少。胰腺和骨组织中的差异途径在n-3长链多不饱和脂肪酸代谢中富集，且这些途径与骨相关参数呈正相关。此外，在小鼠模型中得到验证，清胰颗粒对这些多不饱和脂肪酸的调节对CP-OP具有显著治疗作用。通过代谢组学方法，我们发现多不饱和脂肪酸紊乱在CP-OP发病机制中起关键作用。本研究不仅增进了我们对CP-OP发病机制的理解，还突出了靶向多不饱和脂肪酸作为未来骨质疏松症治疗干预策略的治疗潜力。
