Atraric acid alleviates high-fat diet-induced renal injury, lipid accumulation, and fibrosis in mice by regulating oxidative stress and inflammation through AMPK-dependent Nrf2 and NF-κB signaling pathways.

Abstract

This study explores the protective effects of Atraric Acid (AA) against chronic kidney disease (CKD) induced by a high-fat diet (HFD) and its underlying mechanisms. In vivo HFD-induced CKD mouse models and in vitro OA/PA-stimulated HK2 cells were treated with AA. AA improved kidney morphology, reduced fibrosis, lipid accumulation, and body weight. It also decreased serum TC, TG, HDL-C, Scr, BUN, and Cys-C levels, indicating improved renal function. AA alleviated oxidative stress, ROS accumulation, and inflammation, as confirmed by DHE staining, oxidative stress markers, and pro-inflammatory cytokine levels. Western blotting showed that AA activated Nrf2 and suppressed NF-κB signaling. AMPK inhibition experiments demonstrated that AA regulated Nrf2 and NF-κB via AMPKα phosphorylation. In conclusion, AA mitigates HFD-induced CKD by targeting AMPKα to regulate oxidative stress and inflammation.