Chlorantraniliprole exposure aggravates high-fat diet-induced metabolic disorders in mice by regulating gut microbiota and its metabolites

Food contaminants, particularly insecticides, are important factors contributing to obesity and other adverse effects. As the most widely used diamide insecticide worldwide, chlorantraniliprole (CP) is ubiquitous in food and the environment. However, the influence of CP on obesity and the gut microbiota remains unknown. In this study, we administered CP/carboxymethyl cellulose sodium to C57BL/6J mice with a high-fat diet (HFD) via gavage for 13 weeks. The CP exposure induced significant increases in body weight gain, fat mass, serum total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C). Moreover, CP aggravated the imbalance in the gut microbiota by increasing the relative abundance of obesity-associated bacteria and reducing the relative abundance of beneficial bacteria. Based on untargeted metabolomics analysis, CP was found to be involved in the regulation of pathways including Alanine, aspartate and glutamate metabolism and Arginine and proline metabolism. Notably, CP exposure primarily induced alterations in microbial metabolites within these pathways, such as L-(+)-aspartic acid and L-glutamic acid. Additionally, individual metabolites, such as the lipid mediator (oleoyl ethanolamide), also demonstrated alterations upon CP exposure. Furthermore, Spearman correlation analysis revealed several noteworthy associations between microbial alterations, metabolite changes, and phenotypes. The results of the study demonstrate a connection between microbiota, metabolites, and the effects of CP exposure on HFD-induced obesity, elucidating the critical role of the gut microbiota and its metabolites in the toxic effects of CP.