Tributyltin Enhances Macrophage Inflammation and Lipolysis, Contributing to Adipose Tissue Dysfunction

Area of Science:

• Environmental Toxicology
• Endocrinology
• Immunology

Background:

• Tributyltin (TBT) is an industrial chemical with known obesogenic effects.
• TBT exposure during gestation causes transgenerational obesity, affecting white adipose tissue in subsequent generations.
• The impact of TBT on adipose tissue macrophages and their role in obesity remained unclear.

Purpose of the Study:

• To investigate the effects of TBT on macrophages.
• To determine the impact of TBT-modified macrophages on adipocyte function.
• To explore the transgenerational effects of TBT on adipose tissue macrophages and inflammation.

Main Methods:

• Primary mouse bone marrow derived macrophages were treated with TBT and exposed to palmitate.
• Gene expression of inflammatory markers was analyzed, with and without PPARγ activation.
• White adipocytes differentiated from mesenchymal stromal stem cells were co-cultured with TBT-treated macrophages.
• Adipose tissue resident macrophages from TBT-exposed and unexposed generations were analyzed for inflammatory markers.

Main Results:

• TBT significantly enhanced palmitate-induced inflammatory gene expression in macrophages, an effect mitigated by PPARγ activation.
• TBT-exposed macrophages reduced lipid accumulation in adipocytes and increased lipolysis gene expression.
• Ancestral TBT exposure led to increased TNF expression in adipose tissue macrophages of both exposed (F2) and unexposed (F3) generations.

Conclusions:

• TBT exposure promotes inflammation in adipose tissue macrophages.
• TBT-induced macrophage dysfunction impairs adipocyte function, contributing to obesity.
• TBT exposure establishes an inherited predisposition to inflammatory adipose tissue macrophages, influencing metabolic health across generations.