Polychlorinated biphenyl 126 exposure in L6 myotubes alters glucose metabolism: a pilot study

Abstract

Polychlorinated biphenyls (PCBs) are increasingly recognized as metabolic disruptors. Due to its mass, skeletal muscle is the major site of glucose disposal. While muscle mitochondrial dysfunction and oxidative stress have been shown to play a central role in metabolic disease development, no studies to date have investigated the effect of PCB exposure on muscle energy metabolism and oxidative stress. In this pilot study, we tested the effect of exposure to PCB126 in L6 myotubes (from 1 to 2500 nM for 24 h) on mitochondrial function, glucose metabolism, and oxidative stress. Exposure to PCB126 had no apparent effect on resting, maximal, and proton leak-dependent oxygen consumption rate in intact L6 myotubes. However, basal glucose uptake and glycolysis were inhibited by 20-30 % in L6 myotubes exposed to PCB126. Exposure to PCB126 did not appear to alter skeletal muscle anti-oxidant defense or oxidative stress. In conclusion, our study shows for the first time that exposure to a dioxin-like PCB adversely affects skeletal muscle glucose metabolism. Given the importance of skeletal muscle in the maintenance of glucose homeostasis, PCB126 could play an important role in the development of metabolic disorders.

PCB126-mediated effects on adipocyte energy metabolism and adipokine secretion may result in abnormal glucose uptake in muscle cells

“…Despite the growing body of evidence supporting the role of coplanar PCBs in the development of insulin resistance and type 2 diabetes, the effects of PCB exposure on the insulin sensitivity and energy metabolism of skeletal muscle has not been thoroughly investigated. Our group demonstrated that a 24hr-exposure of L6 skeletal muscle cells to PCB126 induced a 20% decrease in glucose uptake and glycolysis (Mauger, Nadeau, Caron, Chapados, & Aguer, 2016). This altered glucose metabolism in PCB126-treated L6 myotubes was consistent with another study showing decreased GLUT4 translocation and glucose uptake in muscle of rats exposed to a mixture of PCBs (Williams et al, 2013).…”

“…Exposure to PCB126 has been associated with the development of insulin resistance and mitochondrial dysfunction (Connell, Singh, & Chu, 1999;Kim et al, 2017;Mauger et al, 2016;Tremblay-Laganière et al, 2019;Wakabayashi & Karbowski, 2001). PCB126 is a lipophilic compound that increases inflammation in adipose tissue (Gadupudi, Gourronc, Ludewig, Robertson, & Klingelhutz, 2015;Gourronc, Robertson, & Klingelhutz, 2017), and increased adipose tissue inflammation is one potential cause of insulin resistance and mitochondrial dysfunction development in skeletal muscle (Bhatnagar et al, 2010;Hwang et al, 2016).…”

“…However, no mitochondrial dysfunction was detected in vitro in L6 muscle cells exposed directly to PCB126 (Mauger et al, 2016). Skeletal muscle response to PCB126 is therefore different in vivo (whole organism) and in vitro (direct exposure of muscle cells 5 to PCB126).…”

“…High circulating levels of pollutants have been associated with decreased mitochondrial enzyme activity in human skeletal muscle (Imbeault et al, 2002). Furthermore, our team showed that PCB126 exposure in rats was associated with decreased mitochondrial function in muscle (Tremblay-Laganière et al, 2019), which was not reproduced when muscle cells were directly exposed to the pollutant (Mauger et al, 2016). Here, we tested whether the adipose-to-muscle communication in the context of PCB126 exposure could induce mitochondrial dysfunction in skeletal muscle.…”

“…PCB126 exposure has been associated with reduced glucose uptake in L6 myotubes (Mauger et al, 2016) and inhibition of the insulin signaling pathway in the muscle of rats (Wang et al, 2010). Moreover, adipose tissue inflammation is associated with decreased insulin sensitivity in skeletal muscle (Matsuda & Shimomura, 2013;Rains & Jain, 2011;Steinberg, 2007).…”