Mokpo National University

Epidemiological studies have revealed a correlation between a long-term exposure to organochlorine pesticides (OCPs) and type 2 diabetes mellitus (T2DM). However, supportive evidence from pathological studies in rodent models remains limited. In this study, we addressed this gap by investigating the metabolic effects of a defined OCP mixture (OCPM)-hexachlorobenzene, β-hexachlorocyclohexane, p,p՛-DDT, heptachlor, and chlordane (1:1:1:1:1) was administered orally to C57BL/6J mice at doses of 0.5 mg/kg and 2.0 mg/kg of body weight (BW) for 90 days. This OCPM reflects environmentally relevant co-exposure patterns that have rarely been examined in animal studies to date. Unlike prior studies, this study investigates the chronic effects of a low-dose, mixture toxicity of OCPs in a controlled in vivo model, providing novel insights into the metabolic disruption caused by chemical mixtures. Chronic low-dose exposure to OCPM significantly impaired glucose homeostasis, evidenced by elevated fasting blood glucose, plasma glucose, insulin and free fatty acid, along with increased HOMA-IR and oral glucose intolerance, which are associated with insulin resistance. At molecular level, OCPM significantly altered multiple metabolic pathways, including insulin signaling, mitochondrial function, oxidative stress response, gluconeogenesis, and lipid metabolism, in both skeletal muscle and liver tissues. These changes are all associated with the development of T2DM. Notably, the effects were more pronounced at lower dose of 0.5 mg/kg-BW than the higher dose, suggesting possible non-linear response. Collectively, these findings underscore the diabetogenic potential of chronic low-dose exposure of OCPM and provide a novel insight into how persistent environmental mixtures may contribute to the onset and progression of insulin resistance and T2DM.

The innate immune system of teleost fish depends on antimicrobial peptides (AMPs) to combat diverse pathogens. Pleurocidins, cationic α-helical AMPs of the piscidin family, are conserved in flatfish and other teleosts, with amphipathic structures evolved for antimicrobial defense. These peptides exhibit potent activity against bacteria, viruses, and fungi, making them promising candidates for aquaculture disease control and therapeutic applications. Their structural conservation reflects adaptations to diverse aquatic environments, enhancing host defense against microbial threats. The starry flounder (Platichthys stellatus), a commercially valuable demersal species resilient to low temperatures and salinity, relies on AMPs to maintain robust disease resistance, supporting its growing role in aquaculture. In this study, we identified a novel pleurocidin gene (SF1) in starry flounder using liver transcriptome data. The SF1 gene encodes a 68-amino-acid prepro-pleurocidin, yielding a 22-amino-acid mature peptide. Phylogenetic analysis confirmed the SF1 mature peptide's close relation to flatfish pleurocidins. Moreover, quantitative RT-PCR revealed elevated SF1 mRNA expression in immune organs, significantly upregulated by lipopolysaccharide (LPS) stimulation, indicating a key role in innate immune responses. Structural modeling demonstrated an amphipathic α-helical conformation in the SF1 mature peptide, with optimized hydrophobicity and charge driving its potent antimicrobial activity against Gram-positive and -negative bacteria. Finally, scanning electron microscopy evidenced marked membrane disruption, corroborating its mechanism of action. These findings establish SF1 as a critical component of starry flounder's innate immunity, suggesting the potential of the SF1 mature peptide as a sustainable antibiotic alternative for aquaculture and therapeutic applications.