Background
Obesity-related glomerulopathy (ORG) is a kidney disorder associated with obesity, where dysbiosis of the gut microbiota and disturbances in lipid metabolism play crucial roles in its development. However, the exact mechanisms by which imbalances in gut microbiota influence lipid metabolism and contribute to the pathogenesis of ORG are still not fully understood.
Methods
A high-fat diet (HFD)-induced ORG model was established using 6-week-old male C57BL/6 J mice to investigate the role of gut microbiota and gut-derived metabolites in ORG progression. 16S rRNA sequencing was employed to profile the gut microbiota, while liquid chromatography-tandem mass spectrometry (LC-MS/MS) was applied for metabolite analysis in fecal, serum, and kidney samples.
Results
Compared to age-matched normal diet (ND) mice, ORG mice exhibited significant increases in triglycerides (TG), cholesterol (CHO), and urinary albumin-to-creatinine ratio (UACR), alongside enhanced lipid droplet accumulation in renal tubules and glomerular hypertrophy. Metabolomic analysis revealed altered metabolic profiles in ORG mice, particularly the reprogramming of glycerophospholipid metabolism. Additionally, 16S rRNA sequencing demonstrated reduced gut microbiota diversity in ORG mice relative to the ND group. Further investigation revealed that the shift in renal glycerophospholipid metabolism and elevated blood lipid levels in ORG mice were closely linked to gut microbiota dysbiosis, specifically increased abundance of Lachnospiraceae and decreased abundance of Muribaculaceae.
Conclusion
The dysbiosis of gut microbiota induced by a HFD leads to glycerophospholipid metabolic reprogramming, promoting lipid droplet deposition in the kidneys and contributing to ORG progression. Our study highlights the contribution of gut microbial metabolism to the development of ORG, offering new perspectives for potential therapeutic strategies targeting the gut in ORG treatment.
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