Department of Molecular Biology and Translational Research, Institute of Rural Health, 20-090 Lublin, Poland.
Centre for Radiobiology and Biological Dosimetry, Institute of Nuclear Chemistry and Technology, 03-195 Warsaw, Poland.
Int J Mol Sci. 2023 Nov 7;24(22):16038. doi: 10.3390/ijms242216038.
Organophosphorus pesticides (OPs) are important factors in the etiology of many diseases, including obesity and type 2 diabetes mellitus. The aim of this study was to investigate the effect of a representative of OPs, chlorpyrifos (CPF), on viability, proliferation, differentiation, and fatty acid uptake in 3T3-L1 cells. The effect of CPF exposure on preadipocyte proliferation was examined by the MTT, NR, and BrdU assays. The impact of CPF exposure on the differentiation of preadipocytes into mature adipocytes was evaluated by Oil Red O staining and RT-qPCR. The effect of CPF on free fatty acid uptake in adipocytes was assessed with the fluorescent dye BODIPY. Our experiments demonstrated that exposure to CPF decreased the viability of 3T3-L1 cells; however, it was increased when the cells were exposed to low concentrations of the pesticide. Exposure to CPF inhibited the proliferation and differentiation of 3T3-L1 preadipocytes. CPF exposure resulted in decreased lipid accumulation, accompanied by down-regulation of the two key transcription factors in adipogenesis: C/EBPα and PPARγ. Exposure to CPF increased basal free fatty acid uptake in fully differentiated adipocytes but decreased this uptake when CPF was added during the differentiation process. Increased free fatty acid accumulation in fully differentiated adipocytes may suggest that CPF leads to adipocyte hypertrophy, one of the mechanisms leading to obesity, particularly in adults. It can therefore be concluded that CPF may disturb the activity of preadipocytes and adipocytes, although the role of this pesticide in the development of obesity requires further research.
有机磷农药（OPs）是许多疾病的重要病因，包括肥胖和 2 型糖尿病。本研究旨在研究一种 OPs 的代表物，氯吡硫磷（CPF）对 3T3-L1 细胞活力、增殖、分化和脂肪酸摄取的影响。通过 MTT、NR 和 BrdU 测定法研究 CPF 暴露对前体脂肪细胞增殖的影响。通过油红 O 染色和 RT-qPCR 评估 CPF 暴露对前体脂肪细胞分化为成熟脂肪细胞的影响。用荧光染料 BODIPY 评估 CPF 对脂肪细胞中游离脂肪酸摄取的影响。我们的实验表明，CPF 暴露会降低 3T3-L1 细胞的活力；然而，当细胞暴露于低浓度的农药时，它会增加。CPF 暴露抑制 3T3-L1 前体脂肪细胞的增殖和分化。CPF 暴露导致脂质积累减少，同时脂肪生成的两个关键转录因子 C/EBPα 和 PPARγ 的表达下调。CPF 暴露增加了完全分化的脂肪细胞中基础游离脂肪酸的摄取，但在分化过程中添加 CPF 时会减少这种摄取。完全分化的脂肪细胞中游离脂肪酸积累的增加可能表明 CPF 导致脂肪细胞肥大，这是肥胖的一种机制，尤其是在成年人中。因此，可以得出结论，CPF 可能会干扰前体脂肪细胞和脂肪细胞的活性，尽管这种农药在肥胖发展中的作用需要进一步研究。
