AI Article Synopsis
- Defective fatty acid oxidation (FAO) is linked to diabetic kidney disease (DKD), with carnitine palmitoyltransferase-1A (CPT1A) as a key enzyme whose role in DKD progression remains unclear.
- Research shows that CPT1A levels are lower in diabetic patients' glomeruli, but increasing CPT1A expression in diabetic mouse models improved kidney function and reduced damage.
- The study reveals that CPT1A helps reduce harmful lipids and prevents cell death by stabilizing important proteins in mitochondria, suggesting targeting CPT1A could be a viable treatment strategy for DKD.
Article Abstract
Defective fatty acid oxidation (FAO) has been implicated in diabetic kidney disease (DKD), yet little is known about the role of carnitine palmitoyltransferase-1A (CPT1A), a pivotal rate-limiting enzyme of FAO, in the progression of DKD. Here, we investigate whether CPT1A is a reliable therapeutic target for DKD. We first confirmed the downregulation expression of CPT1A in glomeruli from patients with diabetes. We further evaluated the function of CPT1A in diabetic models. Overexpression of CPT1A exhibited protective effects in diabetic conditions, improving albuminuria and glomerular sclerosis as well as mitigating glomerular lipid deposits and podocyte injury in streptozotocin-induced diabetic mice. Mechanistically, CPT1A not only fostered lipid consumption via fatty acid metabolism pathways, thereby reducing lipotoxicity, but also anchored Bcl2 to the mitochondrial membrane, thence preventing cytochrome C release and inhibiting the mitochondrial apoptotic process. Furthermore, a novel transcription factor of CPT1A, FOXA1, was identified. We elucidate the crucial role of CPT1A in mitigating podocyte injury and the progression of DKD, indicating that targeting CPT1A may be a promising avenue for DKD treatment.
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| http://dx.doi.org/10.2337/db23-0811 | DOI Listing |
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