Imidacloprid exposure is associated with brown adipose tissue impairment in high-fat diet-fed C57BL/6 mice.

Imidacloprid, a broad-spectrum neonicotinoid insecticide widely used in agriculture, may impair mitochondria-rich brown adipose tissue (BAT), increase the risk of obesity, and alter systemic metabolic homeostasis. This study investigated the obesogenic effects of imidacloprid in a mouse model. The results revealed that imidacloprid intervention resulted in increased body weight, impaired glucose tolerance, altered lipid profiles, and a reduced mitochondrial membrane potential in brown adipocytes, particularly upon high-fat diet. Additionally, analysis using the Seahorse XF24 Analyzer also indicated a decrease in the maximum respiratory activity of BAT following imidacloprid treatment. Furthermore, integrative transcriptome analysis identified robust differentially expressed genes (DEGs) in BAT under imidacloprid treatment combined with a high-fat diet, with pathway and Gene Set Enrichment analyses revealing that metabolism-related signaling pathways (such as the thyroid hormone signaling and tricarboxylic acid cycle) were significantly affected. While future studies with expanded sample sizes and female cohorts are warranted to generalize these translational outcomes, our findings collectively demonstrate that low-dose imidacloprid exposure compromises BAT metabolic bioenergetics, highlighting its potential link to obesity as an overlooked factor.