ArticleDigestive diseases and sciences2025
NXT629 Ameliorates Cholesterol Gallstones in Mice Model by Improving Lipid Metabolism Disorder and Cholesterol Homeostasis Through Inhibiting the GPAM Pathway.
Article in Digestive diseases and sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Biological relationship between Parkinson's disease and gallstone disease.Neuroprotection (Chichester, England) · 2025Review
- The Role and Function of Non-Coding RNAs in Cholangiocarcinoma Invasiveness.Biomedicines · 2025Review
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6 authors.
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Abstract
backgroundNXT629, a PPAR-alpha antagonist, exerts widespread effects in many diseases; however, its function and relevant mechanism in cholesterol gallstones (CG) remain largely unknown.
methodsMale C57BL/6 J mice were fed a regular diet or lithogenic diet (LD), followed by treatment with intraperitoneal injection of NXT629. H&E staining was performed to analyze hepatic pathological changes, and Oil red O staining was conducted to detect lipid accumulation. Concentrations of total cholesterol (TC), triglyceride (TG), phospholipids (PL), total bile acids (TBA), and cholesterol saturation index (CSI) in both bile and serum were analyzed using commercially available kits. The mRNA expressions of ABCG5/8, CYP7A1, CYP7B1, PPAR-α, and ABCB11 in mouse liver tissues were measured by qRT-PCR assay. Overexpression of glycerol-3-phosphate acyltransferase mitochondrial (GPAM) was constructed to investigate the molecular mechanism of NXT629 in CG.
resultsNXT629 could prevent the formation of cholesterol gallstones (CG) and improve lipid metabolic disorders in mice fed a lithogenic diet (LD). Treatment with NXT629 significantly reduced the levels of ABCG5, ABCG8, and ABCB11, while increasing the levels of CYP7A1 and CYP7B1 in the LD group. Additionally, NXT629 treatment downregulated GPAM expression in hepatic tissue from LD-fed mice. Overexpression of GPAM partially counteracted the beneficial effects of NXT629 on CG formation, lipid metabolic disorders, and lipid-related gene expressions.
conclusionNXT629 can inhibit CG formation, improve lipid metabolism disorders and cholesterol homeostasis by inhibiting GPAM expression, suggesting that NXT629 may serve as a potential therapeutic strategy for cholesterol stones prevention and treatment.
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