Organotins in obesity and associated metabolic disturbances

Area of Science:

• Environmental Toxicology
• Metabolic Endocrinology
• Molecular Biology

Background:

• Organotin compounds (OTCs) are environmental contaminants with known toxicological effects.
• Adipogenesis, obesity, and metabolic disturbances are significant public health concerns.
• Understanding the molecular mechanisms linking environmental exposures to metabolic diseases is crucial.

Purpose of the Study:

• To review the mechanisms by which organotins induce adipogenesis, obesity, and metabolic dysfunction.
• To synthesize current knowledge on the molecular pathways involved in organotin-induced metabolic changes.
• To identify gaps in the research, particularly regarding human epidemiological data.

Main Methods:

• Literature review of existing studies on organotin compounds and their effects on adipogenesis and metabolism.
• Analysis of cell and animal models investigating organotin exposure.
• Examination of molecular mechanisms including receptor activation, gene expression, and signaling pathways.

Main Results:

• Organotin exposure activates peroxisome proliferator-activated receptor gamma (PPARγ) and retinoid X receptor alpha (RXRα), driving adipogenesis.
• OTCs alter the expression of PPARγ-targeted genes, affecting adipokines, glucose transporters, and lipid/carbohydrate metabolism, leading to hyperglycemia and insulin resistance.
• Organotins disrupt neural appetite regulation by altering neuropeptide Y (NPY), pro-opiomelanocortin (POMC), Agouti-related protein (AgRP), and cocaine- and amphetamine-regulated transcript (CART) levels.
• Transgenerational inheritance of obesity has been observed in animal models.
• Potential alternative mechanisms include estrogen receptor and corticosteroid signaling, altered DNA methylation, and gut dysfunction.

Conclusions:

• Organotins are potent inducers of adipogenesis and obesity through multiple molecular pathways, including key nuclear receptor activation and neuroendocrine disruption.
• While strong evidence exists in experimental models, direct epidemiological evidence linking organotin exposure to human obesity is lacking and existing indirect data are contradictory.
• Further research, especially human studies, is needed to confirm the association between organotin exposure and obesity in populations.