Validation experiment designed to validate causal mechanisms targeting CPT1A in conditional CPT1A knockout mice. Primary outcome: proximal tubule injury and metabolic gene expression
This study examined the effects of aging combined with high fat diet (HFD) on kidney proximal tubules, specifically investigating the role of carnitine palmitoyltransferase 1A (CPT1A) in fatty acid oxidation. The experiment compared young and aged mice fed HFD, analyzing transcriptional changes in metabolism-related pathways in proximal tubules versus distal convoluted tubules (DCT). The study used conditional CPT1A knockout mice to examine the specific role of this enzyme in proximal tubule metabolism and kidney injury. Researchers measured fibrosis, inflammation, and proximal tubule cell injury, along with gene expression changes in metabolic pathways. The proximal tubules showed suppressed expression of genes related to metabolism and fatty acid oxidation with aging and HFD, while DCT showed more inflammation-related changes.
HFD feeding in young vs aged mice with conditional CPT1A knockout, transcriptional analysis of kidney segments
HFD-aged mice would show increased fibrosis, inflammation, and PT injury with altered metabolism gene expression
significant transcriptional changes in metabolism-related pathways in PT segments
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