trans-Chalcone inhibits high-fat diet-induced disturbances in FXR/SREBP-1c/FAS and FXR/Smad-3 pathways in the kidney of rats

High-fat diet (HFD) intake is linked to chronic kidney disease. Farnesoid X receptor (FXR) controls the renal lipid metabolism and fibrosis. The purpose of the current study was to evaluate the possible impacts of trans-chalcone on HFD-induced changes in renal lipid metabolism and Smad-3 expression through the regulation of FXR expression. To this aim, 28 rats were randomly divided into control, chalcone, HFD, and HFD + chalcone groups. At the end of treatments, renal FXR, sterol regulatory element-binding protein (SREBP)-1c, fatty acid synthase (FAS), Smad-3, and neutrophil gelatinase-associated lipocalin (NGAL) expression levels were assayed. Moreover, insulin sensitivity check index (QUICKI) was calculated. trans-Chalcone significantly inhibited HFD-induced reduction of insulin sensitivity. Moreover, HFD decreased the FXR expression, and trans-chalcone reversed this change. trans-Chalcone also inhibited HFD-induced increases in expression levels of SREBP-1c, FAS, Smad-3, and NGAL. Therefore, trans-chalcone, as a renoprotective agent, inhibits HFD-induced disturbances in FXR/SREBP-1c/FAS and FXR/Smad-3 pathways. PRACTICAL APPLICATIONS: Non-alcoholic fatty liver disease and metabolic syndrome, two health concerns with increasing prevalence, are known as important risk factors for chronic kidney disease. The current study indicated the preventive effect of trans-chalcone administration on HFD-induced disturbances in renal FXR/SREBP-1c/FAS and FXR/Smad-3 pathways. According to these results, trans-chalcone can be regarded as a renoprotective functional food component that can protect individuals with metabolic syndrome against chronic renal disease.

Keywords: FXR; SREBP-1c; Smad-3; high-fat diet; kidney; trans-chalcone.