Temporal Proteomic and Lipidomic Profiles of Cerulein-Induced Acute Pancreatitis Reveal Novel Insights for Metabolic Alterations in the Disease Pathogenesis

Abstract

The pathophysiological mechanisms of acute pancreatitis (AP) are complex and have remained a mystery to date, but metabolism is gradually recognized as an important driver of AP onset and development. We used a cerulein-induced AP mouse model to conduct liquid chromatography–mass spectrometry (LC–MS/MS)-based time-course proteomics and lipidomics in order to better understand the underlying metabolic alterations linked with AP. Results showed that a series of significant changes in proteins over time with a boost in expression were enriched in lipase activity, lipoprotein, and lipids absorption and transport regulation. Furthermore, 16 proteins associated with lipid metabolism and signaling pathways together with the whole lipid species changing profile led to the vital identification of changing law in glycerides, phosphoglycerides, and free fatty acids. In addition to lipid metabolism and regulation-associated proteins, several digestive enzymes and adaptive anti-trypsin, stress response, and energy metabolism-related proteins showed an increment in abundance. Notably, central carbon and branched chain amino acid metabolism were enhanced during 0–24 h from the first cerulein stimulation. Taken together, this integrated proteomics and lipidomics revealed a novel metabolic insight into metabolites transforming rules that might be relevant to their function and drug targets investigation. (Created with .)

Unraveling the Metabolic Changes in Acute Pancreatitis: A Metabolomics-Based Approach for Etiological Differentiation and Acute Biomarker Discovery

“…This research also detected significant alterations in glycerolipids and sterol lipids, aligning with previous research suggesting a disrupted glycerolipid metabolism in pancreatitis [24]. Key glycerolipids such as DG (20:4/20:5/0:0) [iso2] and TG (49:3) are integral to lipid signaling, energy storage, and membrane trafficking, and their aberrations may contribute to pancreatitis progression [25].…”

“…Sphingolipids, such as Cer (d18:0/15:0) and Cer (t18:0/19:0(2OH)), also were found as biomarkers of AP, aligning with increasing evidence of their involvement in inflammatory and apoptotic pathways [24]. In the context of acute pancreatitis, disruptions in sphingolipid metabolism may exacerbate the inflammatory response and tissue damage and potentially lead to organ failure [29].…”

Time-Course Lipidomics of Ornithine-Induced Severe Acute Pancreatitis Model Reveals the Free Fatty Acids Centered Lipids Dysregulation Characteristics

“…The preparation methods for rats' serum and pancreatic tissue are consistent with our report previously [20], using a SCIEX Triple Quad TM 5500+ mass spectrometer equipped with an LC-20AD UPLC system (Shimadzu, Kyoto, Japan) on an HSS T3 column (1.8 µm, 2.1 mm × 100 mm, Waters, Milford, MA, USA), controlled via Analyst software (Version 1.7.2, SCIEX, Framingham, MA, USA). SPLASH™ LIPIDOMIX ® Quantitative Mass Spec Internal Standard (330707-1EA, Avanti ® Polar Lipids, Alabaster, AL, USA.)…”

“…Large autophagic vacuoles containing zymogen particles appeared at 6 h, and lipid droplets persisted in the basal part of the acinar cells during the first 24 h of the disease course. Our previous pancreatic proteomic analysis of the cerulein-induced model [20] suggests that phospholipases appear to be heavily expressed in the early stages of inflammation. In our results, the abundance of PEs and PCs, important components of biofilms, continued to decrease, indicating their degradation likely involved in autophagic processes in acini.…”

“…Lipotoxicity affects not only the multisystem organ failure of AP [17] but also regeneration after AP [18], and lipid saturation is also associated with lipotoxic systemic inflammation [19]; therefore, it is important to identify the lipids involved in the development of AP. We previously reported obviously changed phosphoglycerides and polyunsaturated fatty acyls are probably going to play an important role in the pathogenesis of a cerulein-induced AP mouse model [20]. However, the role of lipids in more severe models is far from clear.…”