Minimal Risk Doses of Cadmium Exposure Induce Histological and Functional Alterations in the Brown Adipose Tissue of...

Cadmium exposure, even at doses currently regarded as minimal risk, has been associated with significant metabolic alterations. While its effects on organs such as the liver, kidney, and pancreas have been widely studied, its impact on brown adipose tissue (BAT) remains poorly understood. In this study, we evaluated the effects of oral Cd exposure (15 and 32 ppm) over subacute, subchronic, and chronic periods on BAT functionality and structure in Wistar rats (n = 90). A metabolic, toxicological, and hormonal profile, as well as histology, expression of leptin, PPARγ, PPARα, and UCP-1, and mitochondrial complexes activity, were assessed and analyzed using one-way ANOVA and the Kruskal-Wallis test for quantitative and semiquantitative data. The results revealed progressive metabolic dysfunction, liver and renal impairment, increased free T3, and BAT dysfunction characterized by hypertrophy, downregulation of UCP-1 and PPARα, and disorganization of mitochondrial complexes and supercomplexes. These findings suggest a defect in BAT function and loss of its thermogenic capacity. In conclusion, results demonstrate that chronic Cd exposure induces mitochondrial toxic effects by impairing the function of brown adipose tissue and promoting the development of metabolic diseases, even under exposure levels considered to be of minimal risk.