Cadmium disrupts hepatic lipid homeostasis: molecular mechanisms, unresolved controversies, and therapeutic strategies

Cadmium, a pervasive environmental toxicant with profound bioaccumulation potential, poses a significant threat to hepatic lipid homeostasis. This review systematically delineates the intricate molecular mechanisms underlying the cadmium-induced dysregulation of hepatic lipid metabolism. We highlight that cadmium accumulation in the liver triggers a cascade of pathological events, including mitochondrial dysfunction, aberrant activation of nuclear receptors driving lipogenesis, and epigenetic reprogramming. Concurrently, cadmium exacerbates oxidative stress, amplifies inflammatory cascades, and disrupts the gut-liver axis. Critically, unresolved controversies such as the dual effects on liver lipid homeostasis under chronic environmental cadmium exposure, sexual dimorphism in susceptibility (potentially estrogen-mediated), and synergistic hepatotoxicity from co-exposure with microplastics are discussed. We further explore emerging therapeutic strategies targeting these pathways, including antioxidant therapy, epigenetic modulation, and microbiota-based interventions. This synthesis clarifies the mechanistic pathways linking cadmium exposure to hepatic lipid accumulation and identifies critical research gaps for future investigation.