NAFPD exacerbation by hyperlipidemia combined with hyperuricemia: a pilot rat experiment in lipidomics

高脂血症合并高尿酸血症加重非酒精性脂肪性腹膜炎:脂质组学大鼠初步实验

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Abstract

BACKGROUND: Hyperuricemia and non-alcoholic fatty pancreas disease (NAFPD) are prevalent metabolic diseases, but the relationship between them remains underexplored. METHODS: Eighteen Sprague-Dawley rats were randomly assigned to three groups: normal (CON), high-fat (PO), and high-fat high-uric acid (PH). After 12 weeks, serum uric acid (SUA) and triacylglycerol levels were measured. Pathological changes in the pancreas were assessed using hematoxylin-eosin (HE) staining. Serum samples were analyzed using lipidomics technology, and multivariate statistical analysis was employed to identify differences in lipid metabolism. RESULTS: SUA levels in the PO group were not significantly different from those in the CON group (p > 0.05). However, from the 4th week onward, SUA levels in the PH group were significantly higher than those in both the PO and CON groups (p < 0.05). HE staining revealed that most rats in the CON group exhibited normal pancreatic islet and acinar cell morphology. The pathological NAFPD score in the PH group was higher than that in the PO group. Lipidomics analysis identified 34 potential serum biomarkers in the CON and PO groups, 38 in the CON and PH groups, and 32 in the PH and PO groups. These metabolites primarily included sphingolipids, cholesterol esters, fatty acids, triacylglycerols, phosphatidylcholines, lysophosphatidylcholine, phosphatidylethanolamine, and lysophosphatidylethanolamine. CONCLUSION: Hyperlipidemia combined with hyperuricemia might exacerbates NAFPD. Glycerophospholipids may serve as key biomarkers in this process, potentially linked to a chronic inflammatory response mediated by glycerophospholipids.

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