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Environmental Health Risk Assessment of Dynamic Lipid Metabolism in PCB-118-Induced Insulin Resistance Models Using a
Hongshuai Zhang1, Jiayi You1, Jinwei Liu1
1Department of Gastroenterology, Clinical Research Institute, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang 421002, China.
Analytical Chemistry
|October 22, 2025
Summary
Researchers developed a novel fluorescent probe, LD-DCDSB, to track changes in lipid droplets (LDs) and cellular polarity caused by polychlorinated biphenyls (PCBs). This tool aids in understanding PCB-induced insulin resistance and evaluating potential treatments.
Area of Science:
- Environmental Toxicology
- Metabolic Diagnostics
- Chemical Biology
Background:
- Persistent organic pollutants like polychlorinated biphenyls (PCBs) disrupt lipid metabolism and cause insulin resistance (IR).
- Current methods for monitoring the dynamic metabolic effects of PCBs are limited.
- Lipid droplets (LDs) are key organelles involved in cellular lipid metabolism and are affected by PCB exposure.
Purpose of the Study:
- To develop a novel fluorescent probe for real-time monitoring of lipid droplet dynamics and cellular polarity.
- To investigate the metabolic effects of PCB-118 exposure on insulin resistance using the developed probe.
- To elucidate the mechanisms underlying PCB-induced metabolic dysfunction and assess therapeutic interventions.
Main Methods:
- Development of a donor-acceptor-donor (D-A-D) fluorescent probe (LD-DCDSB) with polarity-sensitive emission.
- Application of the probe in various cell types (adipocytes, cancer cells, normal cells) to assess LD characteristics.
- In vitro and in vivo studies using PCB-118 exposure to induce and monitor insulin resistance, with subsequent treatment using metformin or Fsp27 siRNA.
Main Results:
- The LD-DCDSB probe demonstrated high sensitivity to cellular polarity and enabled precise tracking of LDs.
- PCB-118 exposure induced pathological LD hypertrophy, increased LD numbers, and reduced cellular polarity in adipocytes.
- The probe visualized PCB-118-induced IR progression in vivo, with observed changes being reversible by metformin treatment.
- Mechanistic studies revealed ROS-mediated apoptosis contributing to PCB-118's metabolic disruption.
Conclusions:
- The LD-DCDSB probe is a valuable tool for dynamic monitoring of LD dysfunction and cellular polarity changes.
- PCB-118 significantly disrupts lipid metabolism and promotes insulin resistance through mechanisms involving LD dysfunction and ROS-mediated apoptosis.
- This study provides a platform for assessing environmental pollutant risks and evaluating therapeutic strategies for metabolic disorders.
