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Exposure to 2,4-dichlorophenoxyacetic Acid Induced PPARβ-dependent Disruption of Glucose Metabolism in HepG2 Cells

Haidong Sun, Wentao Shao, Hui Liu, Zhaoyan Jiang

Environ Sci Pollut Res Int. 2018 Jun;25(17):17050-17057.

PMID: 29633193

Abstract:

2,4-Dichlorophenoxyacetic acid is one of the most widely used herbicides. Its impact on health is increasingly attracting great attentions. This study aimed to investigate the effect of 2,4-dichlorophenoxyacetic acid on glucose metabolism in HepG2 cells and the underlying mechanism. After 24 h exposure to 2,4-dichlorophenoxyacetic acid, glycogen was measured by PAS staining and glucose by ELISA in HepG2 cells. The expression of genes involved in glucose metabolism was measured by real-time PCR, Western blotting, and immunofluorescence. HepG2 cells presented more extracellular glucose consumption and glycogen content after exposed to 2,4-dichlorophenoxyacetic acid. Expression of gluconeogenesis-related genes, FoxO1, and CREB is significantly elevated. Moreover, PPARβ was up-regulated dose-dependently. SiRNA knockdown of PPARβ completely rescued the increase of glycogen accumulation and glucose uptake, and the up-regulation of FOXO1 and CREB expression. Our findings propose novel mechanisms that 2,4-dichlorophenoxyacetic acid causes glucose metabolism dysfunction through PPARβ in HepG2 cells.

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AP5980972 2,4,6-Trimethylphenylboronic acid 2,4,6-Trimethylphenylboronic acid 5980-97-2 Price
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