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.

Cartilage is a nonedible byproduct with little saleable value. However, previous studies have proposed the possibility of producing peptides from cartilage with immune function modulation potential. The current study aimed to investigate the potential anti-inflammatory activity of peptides derived from sturgeon (Acipenser schrenckii) cartilage in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Five peptide sequences, including four novel peptides, were identified from ethanol-soluble cartilage hydrolysates. Among these five peptides, LTGP, LLLE, LLEL and VGPAGPAGP reduced the production of nitric oxide (NO) and interleukin-6 (IL-6) while increasing interleukin-10 (IL-10) excretion. Transcriptome analysis suggested the inhibition of activated mitogen-activated protein kinase (MAPK) and interleukin-17 (IL-17) signaling pathways after LLEL intervention. MAPK, which is involved in the IL-17 signaling pathway, was further proved to be blocked by downregulating the phosphorylation of p38, extracellular-signal regulated protein kinase (ERK), and c-jun N-terminal kinase (JNK). This novel peptide offers an attractive approach to develop functional foods.