DOI: 10.1097/imna-d-25-00059 ISSN: 2773-0395

Tangshen Formula Ameliorates Diabetic Kidney Disease by Regulating Renal Lipid Accumulation

Zhengri Shen, Junwei Gao, Hailing Zhao, Peng Liu
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Background:

Abnormal renal lipid deposition is recognized as a central mechanism driving diabetic kidney disease (DKD). This study investigated the efficacy of Tangshen Formula (TSF), a clinically validated Chinese herbal preparation, in attenuating DKD by concurrently suppressing de novo lipogenesis (DNL) and enhancing both fatty acid oxidation and cholesterol efflux, thereby minimizing renal lipid burden.

Methods:

Male db/db mice and sodium palmitate (PA)-induced mouse tubular epithelial cells served as the in vivo and in vitro models, respectively. Systemic metabolic parameters, renal function, histological changes, and renal lipid accumulation were assessed in vivo . Cellular lipid content, fatty acid oxidation, and cholesterol efflux were measured in vitro . The expression levels of key regulators involved in fatty acid oxidation, cholesterol efflux, and the DNL pathway were analyzed using Western blot, real-time quantitative polymerase chain reaction, and immunofluorescence. In addition, siRNA-mediated knockdown was performed to verify target specificity.

Results:

TSF treatment significantly improved renal function and attenuated renal lipid accumulation in db/db mice, accompanied by reduced urinary albumin-to-creatinine ratio, serum creatinine (Scr), blood urea nitrogen (BUN), and serum lipid levels, as well as improved glomerular and tubular pathology. Mechanistically, TSF enhanced fatty acid oxidation and cholesterol efflux through upregulation of the peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) signaling axis, while simultaneously suppressing DNL via farnesoid X receptor (FXR)-mediated inhibition of the sterol regulatory element-binding protein-1c pathway. Genetic silencing of either PGC-1α or FXR specifically abolished the corresponding lipid-modulating effects of TSF.

Conclusion:

TSF ameliorated renal lipid accumulation and renal injury in DKD through the coordinated regulation of lipid metabolic pathways, promoting lipid catabolism and efflux via PGC-1α while inhibiting DNL through FXR activation. This multitargeting capability positions TSF as a promising therapeutic candidate for combating lipotoxicity in DKD.

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