Do DDT and DDE persist in adipose tissue and drive long-term metabolic, endocrine, and oxidative stress?

Dichlorodiphenyltrichloroethane (DDT) and its primary metabolite, dichlorodiphenyldichloroethylene (DDE), are persistent organic pollutants that continue to pose chronic health risks decades after exposure due to their unique accumulation profiles and systemic toxicity.

Adipose Sequestration and Kinetics

• Extreme Lipophilicity: DDT and DDE exhibit high octanol-water partition coefficients ($\log K_{\text{ow}} \sim 6.5 \text{ to } 7.5$), causing them to partition heavily into neutral lipids. This results in adipose tissue concentrations that are 280- to 450-fold higher than in circulating blood.
• Persistent Internal Reservoir: Once stored, mobilization is extremely slow. The biological half-life is 3 to 6 years for DDT and over 8 to 10 years for DDE, creating a permanent internal source of low-dose exposure that persists long after environmental exposure ceases.

Mechanistic Pathways of Cellular and Endocrine Stress

• Mitochondrial Decay and Oxidative Stress: Stored DDE directly impairs mitochondrial complexes II and V of the electron transport chain in adipocytes. This disruption causes chronic reactive oxygen species (ROS) production, lipid peroxidation, and systemic oxidative stress.
• Endocrine and Metabolic Disruption: These compounds interfere with thyroid hormone pathways, sex steroid receptors, and peroxisome proliferator-activated receptor-gamma (PPAR$\gamma$) signaling. This alters adipogenesis, leading to dysfunctional, hypertrophic adipocytes.
• Adipose Inflammation: Sequestration in adipose depots promotes macrophage recruitment, pro-inflammatory polarization, and altered adipokine secretion (e.g., elevated leptin and resistin). This localized tissue inflammation ultimately drives systemic insulin resistance, metabolic syndrome, and type 2 diabetes.

Bottom line

• DDT and DDE bioaccumulate extensively in adipose tissue, forming a highly persistent internal reservoir. The slow, continuous release of these lipophilic compounds drives long-term endocrine disruption, mitochondrial decay, and tissue inflammation, leading to sustained metabolic and oxidative stress.