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

## TL;DR

Cadmium exposure disrupts liver lipid balance through multiple mechanisms and raises unresolved questions about its effects and potential treatments.

## Contribution

This review clarifies molecular pathways of cadmium-induced hepatic lipid dysregulation and highlights unresolved controversies and therapeutic strategies.

## Key findings

- Cadmium causes mitochondrial dysfunction and promotes de novo lipogenesis via nuclear receptor activation.
- Cadmium exposure increases oxidative stress and inflammation while disrupting the gut-liver axis.
- Sexual dimorphism and co-exposure with microplastics may influence cadmium's hepatotoxic effects.

## Abstract

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 de novo 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.

Biological sciences