Broccoli Sprout Extract Restores Renal Lipid Metabolism in High-Fat Diet-Fed Mice Involving Modulation of AMPK/Nrf2 Signaling and the NLRP3 Inflammasome.

Broccoli sprout extract (BSE) has shown promise in metabolic disorders, but its effect on renal lipid metabolism and injury in high-fat diet (HFD)-fed mice remains unclear. This study demonstrated that 12-week BSE supplementation (600 mg/kg diet) significantly ameliorated HFD-induced renal dysfunction, reducing blood urea nitrogen (BUN) from 6.29 to 3.02 mmol/L (by 52.0%), uric acid (UA) from 56.38 to 17.25 μmol/L (by 69.4%), and serum creatinine (SCr) from 19.21 to 11.54 μmol/L (by 39.9%), while decreasing renal triglycerides (TG) from 3.86 to 2.43 mmol/g (by 37.1%) and total cholesterol (TC) from 19.47 to 14.43 mmol/g (by 25.9%). BSE also restored oxidative balance, increasing superoxide dismutase (SOD) activity from 4.37 to 6.54 U/mg protein (by 49.7%) and total antioxidant capacity (T-AOC) from 1.78 to 2.97 μmol/mg protein (by 66.9%), with a reduction in malonaldehyde (MDA) from 1.68 to 1.19 nmol/mg protein (by 29.2%). Untargeted lipidomics revealed that BSE normalized four lipid mediators linked to lipotoxicity, including CAR 22:1, LPC 16:0, PI-Cer 38:1; O3, and NAE 26:5. Mechanistically, BSE activated AMPK signaling (increasing p-AMPKα2 protein and AMPKα2 mRNA expression by 1.72-fold and 2.13-fold, respectively) to inhibit lipogenesis (downregulating SREBP1 and SCD by 21.4% and 37.3%, respectively) and promote fatty acid oxidation (upregulating SIRT1, PPARα, CPT1A, and PGC1α by 1.3-, 2.1-, 4.6-, and 1.3-fold, respectively), enhanced Nrf2-driven antioxidant defense (upregulating Nrf2, HO-1, and NQO1 mRNA expression by 1.2-, 3.3-, and 1.9-fold, respectively), and suppressed the NLRP3 inflammasome cascade (reducing NLRP3 by 29.0%, cleaved caspase-1 by 13.8%, and IL-1β by 39.5%, respectively). These findings establish that BSE protects against HFD-induced renal injury involving modulation of AMPK/Nrf2 signaling and the NLRP3 inflammasome, supporting its potential as a dietary strategy for metabolic kidney disease.