Tangerine Peel Polysaccharide Alleviates High-Fat Diet-Induced Renal Lipotoxicity in Association with Gut Microbiota Remodeling in Mice

Abstract

Chronic kidney disease (CKD) may result from ectopic fat accumulation induced by a high-fat diet (HFD), which has been closely linked to dysbiosis of the gut microbiota. In this study, we investigated the effects of a polysaccharide fraction derived from tangerine peel, Pericarpium Citri Reticulatae “Chachiensis” (PCRCPI), on renal fat accumulation and lipotoxicity in mouse models. Oral administration of PCRCPI markedly reduced renal fat deposition, inflammation, fibrogenesis and dysfunction in HFD-fed mice. PCRCPI treatment notably upregulated the mRNA expression of growth differentiation factor 15 (GDF-15), a stress-response molecule, and downregulated lipid synthesis in the kidney. PCRCPI reshaped the HFD-induced intestinal microbial composition and structure by enriching beneficial bacteria, including Ligilactobacillus and Lactobacillus. Transplantation with gut microbiota from PCRCPI-treated mice effectively upregulated GDF15 mRNA expression and alleviated renal dysfunction and lipotoxicity in HFD-fed mice, indicating that the effects of PCRCPI in maintaining GDF-15 expression and preventing renal lipotoxicity may be dependent on the gut microbiota. This study introduces a potential prophylactic treatment that may act through gut microibota-associated pathways and offers valuable insights into the mechanisms of CKD prevention.