PFOS induces adipogenesis and glucose uptake in association with activation of Nrf2 signaling pathway

Abstract

PFOS is a chemical of nearly ubiquitous exposure in humans. Recent studies have associated PFOS exposure to adipose tissue-related effects. The present study was to determine whether PFOS alters the process of adipogenesis and regulates insulin-stimulated glucose uptake in mouse and human preadipocytes. In murine-derived 3T3-L1 preadipocytes, PFOS enhanced hormone-induced differentiation to adipocytes and adipogenic gene expression, increased insulin-stimulated glucose uptake at concentrations ranging from 10 to 100 µM, and enhanced Glucose transporter type 4 and Insulin receptor substrate-1 expression. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), NAD(P)H dehydrogenase, quinone 1 and Glutamate-cysteine ligase, catalytic subunit were significantly induced in 3T3-L1 cells treated with PFOS, along with a robust induction of Antioxidant Response Element (ARE) reporter in mouse embryonic fibroblasts isolated from ARE-hPAP transgenic mice by PFOS treatment. Chromatin immunoprecipitation assays further illustrated that PFOS increased Nrf2 binding to ARE sites in mouse Nqo1 promoter, suggesting that PFOS activated Nrf2 signaling in murine-derived preadipocytes. Additionally, PFOS administration in mice (100 µg/kg/day) induced adipogenic gene expression and activated Nrf2 signaling in epididymal white adipose tissue. Moreover, the treatment on human visceral preadipocytes illustrated that PFOS (5 and 50 µM) promoted adipogenesis and increased cellular lipid accumulation. It was observed that PFOS increased Nrf2 binding to ARE sites in association with Nrf2 signaling activation, induction of Peroxisome proliferator-activated receptor γ and CCAAT/enhancer-binding protein α expression, and increased adipogenesis. This study points to a potential role PFOS in dysregulation of adipose tissue expandability, and warrants further investigations on the adverse effects of persistent pollutants on human health.

Perfluorobutanesulfonic Acid Disrupts Pancreatic Organogenesis and Regulation of Lipid Metabolism in the Zebrafish, Danio rerio

“…All concentrations were selected based on previous studies conducted with the C8 perfluorinated compound (PFOS), which was found to produce pancreas phenotypes investigated in this study. These PFOS concentrations were initially selected based on other zebrafish and cell culture studies (Chen et al, 2014;Wang et al, 2011;Xu et al, 2016;Zheng et al, 2012).…”

The Role of MicroRNAs in Environmental Risk Factors, Noise-Induced Hearing Loss, and Mental Stress

“…Perfluorooctanesulfonate. PFOS has been shown to induce adipogenesis and glucose uptake in preadipocytes and this was associated with activation of the oxidative stress responsive transcription factor Nrf2, which is important for upregulating antioxidant genes and metabolic reprogramming (219). In addition, it has been shown in rats that PFOS tends to accumulate in the liver, resulting in hepatomegaly, actin filament remodeling, endothelial permeability changes, and ROS production.…”

Chemical Characterization of a Legacy Aqueous Film-Forming Foam Sample and Developmental Toxicity in Zebrafish ( Danio rerio )

“…PFOS is one of the most widely studied PFAS and has been associated with adverse outcomes in humans (Fleisch et al 2017;Halldorsson et al 2012;Høyer et al 2015) and toxicity in animal models, including zebrafish (Menger et al 2020;Sharpe et al 2010;Xu et al 2016). These outcomes include liver toxicity, thyroid disruption, neurotoxicity, immunotoxicity, cardiovascular toxicity, renal toxicity, and effects on the reproductive system (reviewed in Saikat et al 2013;Zeng et al 2019).…”