Translational research : the journal of laboratory and clinical medicine
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Diabetic lipo-toxicity is a fundamental pathophysiologic mechanism in DM and is now increasingly recognized a key determinant of DKD. Targeting lipid metabolic disorders is an important therapeutic strategy for the treatment of DM and its complications, including DKD. This study aimed to explore the molecular mechanism of lipid metabolic regulation in kidney, especially renal PTECs, and elucidate the role of lipid metabolic related molecule lipin-1 in diabetic lipid-related kidney damage. ⋯ Interestingly, lipin-1 deficiency might be a pathogenic driver of DKD-to-CKD transition, which could further accelerate the imbalance of renal lipid homeostasis, the dysfunction of mitochondrial and energy metabolism in PTECs. Mechanistically, lipin-1 deficiency resulted in aggravated PTECs injury to tubulointerstitial fibrosis in DKD by downregulating FAO via inhibiting PGC-1α/PPARα mediated Cpt1α/HNF4α signaling and upregulating SREBPs to promote fat synthesis. This study provided new insights into the role of lipin-1 as a regulator for maintaining lipid homeostasis in the kidney, especially PTECs, and its deficiency led to the progression of DKD.