Journal of gastroenterology and hepatology · 2025
Varespladib Alleviates Colonic Inflammation Induced by High-Fat Diet via Downregulating the TGF-β/Smad Pathway and AA Pathway by Inhibiting sPLA2.
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Shirui Meng, Yuanyuan Li, Linfeng Wang, Jiahao Liu, Daixuan Zhou, Ying Xiong, Chunhong Huang
Аннотация
BACKGROUND AND AIM: High-fat diets (HFD) increase the risk of colonic inflammation. Varespladib, an sPLA2 inhibitor, has shown potential to treat a variety of inflammatory diseases. Its role in colonic inflammation caused by a HFD remains to be studied.
METHODS: C57/BL6 mice were fed a chow diet (NCD), HFD, or HFD with varespladib for 4 weeks. Various parameters were measured to assess the effects of varespladib on HFD-induced metabolic changes. The TGF-β/Smad and the arachidonic acid pathway were analyzed using RT-qPCR and western blotting.
RESULTS: Varespladib supplementation in HFD-fed mice led to reduced body weight and abdominal adiposity, improved intestinal health and blood lipid profiles, mitigated intestinal inflammation and fibrosis, downregulated genes associated with immunity and permeability, and inhibited key inflammatory pathways.
CONCLUSION: Short-term HFD induced intestinal inflammation. These disorders are mainly triggered by sPLA2 upregulation, resulting in activation of the arachidonic acid and TGF-β/smad pathways. Varespladib has significant therapeutic potential for alleviating HFD-induced colonic inflammation in mice.
METHODS: C57/BL6 mice were fed a chow diet (NCD), HFD, or HFD with varespladib for 4 weeks. Various parameters were measured to assess the effects of varespladib on HFD-induced metabolic changes. The TGF-β/Smad and the arachidonic acid pathway were analyzed using RT-qPCR and western blotting.
RESULTS: Varespladib supplementation in HFD-fed mice led to reduced body weight and abdominal adiposity, improved intestinal health and blood lipid profiles, mitigated intestinal inflammation and fibrosis, downregulated genes associated with immunity and permeability, and inhibited key inflammatory pathways.
CONCLUSION: Short-term HFD induced intestinal inflammation. These disorders are mainly triggered by sPLA2 upregulation, resulting in activation of the arachidonic acid and TGF-β/smad pathways. Varespladib has significant therapeutic potential for alleviating HFD-induced colonic inflammation in mice.