Baicalin ameliorates renal fibrosis by upregulating CPT1α-mediated fatty acid oxidation in diabetic kidney disease

BACKGROUND: Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease (ESRD). The progression of DKD is often marked by heightened renal fibrosis due to hindered fatty acid oxidation within renal tubules. Baicalin (BA), a naturally derived compound, has exhibited the potential to mitigate the advancement of DKD. Delving deeper into the precise targets and mechanisms of BA's effect on DKD is crucial. PURPOSE: This study sought to elucidate the specific mechanism through which BA moderates the progression of DKD. METHODS: Renal tubular tissues from diabetic (db/db) and control (db/m) mice were subjected to mRNA sequencing to discern BA's influence on DKD. Immunohistochemical staining and Western blot were employed to assess the expression of CPT1α in DKD patients and db/db and db/m mice administered with either BA (50 mg/kg/day) or a vehicle for 12 weeks. In vitro, human proximal renal tubule cells (HK-2) were treated with 40 mM high glucose or 50 μM BA. The potential inhibitory mechanism of BA on renal fibrosis in DKD was evaluated using Oil Red O staining and oxygen consumption rate (OCR) measurements. RESULTS: The results demonstrated that BA notably reduced lipid accumulation and renal fibrosis in db/db mice. Moreover, mRNA sequencing pinpointed a significant downregulation of CPT1α in DKD. In vitro assays revealed that both the overexpression of CPT1α and treatment with BA exerted similar influences on mitochondrial respiration, fatty acid oxidation, and renal fibrosis levels. Given the pronounced downregulation of CPT1α in DKD patients and its substantial correlation with clinical indicators, it was evident that CPT1α could serve as a therapeutic target for BA in addressing DKD. CONCLUSION: Our findings demonstrated that BA potentially enhances FAO by augmenting the expression of CPT1α, subsequently diminishing renal fibrosis in DKD. As such, CPT1α emerges as a promising therapeutic target for DKD intervention.