# Oral cadmium exposure to environmental doses induces visceral adiposopathy in Wistar rats

## TL;DR

This study shows that low levels of cadmium exposure in drinking water can cause inflammation and dysfunction in fat tissue in rats, potentially leading to metabolic diseases.

## Contribution

The study is the first to demonstrate that environmental doses of cadmium induce visceral adiposopathy in rats.

## Key findings

- Cadmium exposure increases proinflammatory cytokines and activates NF-κB in adipose tissue.
- Cadmium exposure shifts macrophage phenotype and disrupts the adiponectin/leptin axis.
- Fibrosis in adipose tissue develops in later stages of cadmium exposure.

## Abstract

Chronic cadmium exposure, even in environmental doses, has been linked to multiple metabolic disturbances, including white adipose tissue (WAT) dysfunction. WAT dysfunction is defined as a loss of endocrine, immunologic, and metabolic homeostasis, characterized by a low-grade, progressive, and non-resolving inflammation development, namely adiposopathy. This study evaluated the immunometabolic effects of Cd exposure in drinking water on WAT of male Wistar rats, using concentrations of 15 and 32 ppm (environmental doses) over periods of up to 5 months. Inflammatory markers in serum and tissue were analyzed, along with macrophage phenotype, NF-κB pathway activation, leptin and adiponectin expression, correlations with the adiponectin/leptin (A/L) index, and the development of fibrosis. The results showed a progressive increase in proinflammatory cytokines (IL-6, TNF-α, IL-1β), sustained NF-κB activation, and a shift from anti-inflammatory (CD206⁺) to proinflammatory (CD16⁺) macrophages. These changes were accompanied by dysregulation of the adiponectin/leptin axis and a decrease in the A/L ratio, with dynamic correlations to immune markers. Fibrosis was detected in late stages. In conclusion, our results demonstrated for the first time that Cd exposure in environmental doses induces adiposopathy; thereby, findings indicate that Cd can progressively disrupt the immunometabolic homeostasis of adipose tissue, promoting an inflammatory and profibrotic environment with potential implications for the development of metabolic diseases.

The online version contains supplementary material available at 10.1007/s00204-025-04228-4.