Authors
Hala A Addassi, Irena Krga, Karen Matsukuma, Gerardo G Mackenzie
Published in
Archives of biochemistry and biophysics. Pages 111012. Sep 29, 2026. Epub Sep 29, 2026.
Abstract
Acute pancreatitis (AP) is a multifactorial inflammatory disease driven by premature activation of pancreatic digestive enzymes, with obesity representing a major risk factor for increased disease severity and systemic complications. Phospholipase D (PLD) regulates inflammatory signaling, and expression of its classical isoform, PLD1, is upregulated during AP; however, its role in obesity-associated AP remains poorly defined. In this study, we investigated the contribution of PLD1 to high-fat diet (HFD)-exacerbated AP in vivo. Male and female wild-type (WT) and PLD1-deficient (Pld1-/-) mice were fed a control diet (CD) or HFD for 18 weeks, followed by cerulein-induced AP. HFD feeding increased body weight, fat mass, and serum leptin levels in both WT and Pld1-/- mice, while serum adiponectin was significantly reduced in WT-HFD mice. Importantly, HFD significantly exacerbated pancreatic edema and increased pancreatic weight in WT mice; these effects were attenuated by PLD1 ablation. Exploratory transcriptomic and targeted gene expression analyses revealed that PLD1 deficiency promoted survival and regenerative gene expression programs while suppressing HFD-induced pancreatic Il-1β expression. Together, these findings identify PLD1 as a modulator of obesity-associated pancreatic injury and inflammation and suggest that targeting PLD1 may represent a promising therapeutic strategy to mitigate HFD-driven exacerbation of AP.
PMID:
42810488
Bibliographic data and abstract were imported from PubMed on 30 Sep 2026.
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