Differential susceptibility of BRL cells with/without insulin resistance and the role of endoplasmic reticulum stress signaling pathway in response to acrylamide-exposure toxicity effects in vitro

Toxicology. 2024 Apr 9:153800. doi: 10.1016/j.tox.2024.153800. Online ahead of print.ABSTRACTAcrylamide (ACR) is an endogenous food contaminant, high levels of ACR have been detected in a large number of foods, causing widespread concern. Since different organism states respond differently to the toxic effects of pollutants, this study establishes an insulin-resistant BRL cell model to explore the differential susceptibility of BRL cells with/without insulin resistance in response to acrylamide-exposure (0.0002, 0.02, or 1mM) toxicity effects and its mechanism. The results showed that ACR exposure decreased glucose uptake and increased intracellular lipid levels by promoting the expression of fatty acid synthesis, transport, and gluconeogenesis genes and inhibiting the expression of fatty acid metabolism genes, thereby further exacerbating disorders of gluconeogenesis and lipid metabolism in insulin-resistant BRL cells. Simultaneously, its exposure also exacerbated BRL cells with/without insulin-resistant damage. Meanwhile, insulin resistance significantly raised susceptibility to BRL cell response to ACR-induced toxicity. Furthermore, ACR exposure further activated the endoplasmic reticulum stress (ERS) signaling pathway (promoting phosphorylation of PERK, eIF-2α, and IRE-1α) and the apoptosis signaling pathway (activating Caspase-3 and increasing the Bax/Bcl-2 ratio) in BRL cells with insulin-resistant, which were also attenuated after ROS scavenging or ERS signaling path...

Source: Toxicology - April 11, 2024 Category: Toxicology Authors: Yuchao Guo Houlin Mao Danni Gong Nuo Zhang Dandan Gu Emmanuel Sunday Okeke Weiwei Feng Yao Chen Guanghua Mao Ting Zhao Liuqing Yang Source Type: research