Activating PPARβ/δ-Mediated Fatty Acid β-Oxidation Mitigates Mitochondrial Dysfunction Co-induced by Environmentally Relevant Levels of Molybdenum and Cadmium in Duck Kidneys.

Abstract

Cadmium (Cd) and high molybdenum (Mo) pose deleterious effects on health. Prior studies have indicated that exposure to Mo and Cd leads to damage in duck kidneys, but limited studies have explored this damage from the perspective of fatty acid metabolism. In this study, 40 healthy 8-day-old ducks were randomly assigned to four groups and fed a basic diet containing Cd (4 mg/kg Cd) or Mo (100 mg/kg Mo) or both. Kidney tissues were harvested on the 16th week. Results demonstrated that Cd and/or Mo inhibited mitochondrial fatty acid β-oxidation and disrupted mitochondrial dynamics, along with significant suppression of peroxisome proliferator-activated receptor β/δ (PPARβ/δ) protein in duck kidneys. In vitro study, duck renal tubular epithelial cells were exposed for 12 h to either Mo (480 μM Mo), Cd (2.5 μM Cd), and GW0742 (0.3 μM, a potent agonist of PPARβ/δ) alone or in combination. The results demonstrated that Cd and/or Mo led to marked fatty acid oxidation deficiency and mitochondrial dysfunction and that PPARβ/δ protein was involved in the process. Altogether, this study found that activating PPARβ/δ-mediated fatty acid β-oxidation mitigates mitochondrial dysfunction co-induced by Mo and Cd in duck kidneys.