Targeting the FABP4-PPARγ axis with IPA improves obesity-related glomerulopathy

Obesity-related glomerulopathy (ORG) is a significant renal complication associated with obesity, characterized by glomerular fibrosis and lipid accumulation. The underlying molecular mechanisms remain poorly understood, necessitating the exploration of potential therapeutic targets. This study aimed to investigate the effects of indole-3-propionic acid (IPA) on the modulation of key proteins involved in ORG. Utilizing virtual screening, we identified fatty acid-binding protein 4 (FABP4) as a target protein for IPA. Our findings revealed that IPA did not alter the expression of FABP4, but it significantly increased protein abundance of peroxisome proliferator-activated receptor γ (PPARγ). Mechanistically, IPA competitively binds to FABP4, thereby disrupting the FABP4-PPARγ interaction. This reduction in binding led to decreased degradation of PPARγ, ultimately resulting in attenuated renal fibrosis and reduced lipid deposition in a PPARγ-dependent manner. These results suggest that IPA may serve as a potential therapeutic agent for the treatment of ORG by modulating the FABP4-PPARγ axis.