Under insulin-stimulated conditions, skeletal muscle is the largest glucose consumer in the body. Mitochondrial dysfunction and damage to this tissue from oxidative stress are linked to the ...pathogenesis of type 2 diabetes. Environmental exposure to dichlorodiphenyltrichloroethane (DDT) and its metabolite, 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE), has been associated with the incidence of type 2 diabetes as well as altered oxidative stress and mitochondrial dysfunction in non-muscle tissues. We hypothesized that energy metabolism and insulin sensitivity in skeletal muscle will be altered with exposure to DDT and DDE. In this pilot study, mitochondrial function was measured in permeabilized muscle fibers from Sprague-Dawley rats after one week of exposure to a single injection of DDT (40 μg/kg), a dose comparable to DDT levels in the diets of the Inuit of Northern Canada. The levels of oxidative phosphorylation chain complexes and ROS detoxification enzymes were measured in muscle tissue from these specimens. This acute in vivo exposure to DDT decreased muscle mitochondrial function by 45% without affecting the levels of mitochondrial oxidative phosphorylation chain complexes nor levels of ROS detoxification enzymes. To isolate the effects of DDT and DDE exposure on muscle, L6 myotubes were exposed to DDT or DDE (0, 10, 100, 1000, 10 000 nM) for 24 h. Only very high concentrations of DDT and DDE (1 000 – 10 000 nM) altered maximal respiration with only DDT altering basal glucose uptake in L6 myotubes. This did not alter levels of ROS detoxification enzymes or malondialdehyde (MDA) in L6 myotubes. Altogether, acute exposure to environmentally relevant doses of DDT resulted in muscle mitochondrial dysfunction in vivo in rats, but not when muscle cells were directly exposed to the pollutant or its metabolite.
Display omitted
•A single exposure to DDT in rats alters skeletal muscle mitochondrial function.•A single exposure to DDT in rats does not alter circulating glucose and insulin.•Exposure of L6 myotubes to low levels of DTT does not alter insulin sensitivity.•Exposure of L6 myotubes to low levels of DTT does not alter mitochondrial function.•DTT exposure in rats or myotubes does not alter muscle oxidative stress markers.
Hepatic endoplasmic reticulum (ER) stress has recently been associated with several health complications such as obesity, type 2 diabetes, and hepatic steatosis. Exercise training has been recognized ...for many years to have important beneficial effects in these metabolic complications, however much remains unknown regarding the effects of exercise training on ER stress in the liver. A better understanding of the effects of exercise training on hepatic ER stress response requires studies in which the exercise training protocol is well assessed. Therefore, the purpose of this chapter is to provide detailed description of an endurance-training program and suggest a dietary approach in order to help induce and study changes in ER stress molecular markers expression levels in the liver of rats in response to exercise training.
Background
Non alcoholic fatty liver disease (NAFLD) results from alteration in lipid synthesis and elimination mechanisms such as very-low density lipoprotein (VLDL) production and
de novo
...lipogenesis. Persistent organic pollutants (POPs) are chemicals that were mostly used historically as pesticides, solvents, flame retardant, and other applications. Among POPs, polychlorinated biphenyls (PCB) have been recognized to be of environmental and potential toxicologic concerns. Specifically, PCB126 could act as endocrine disruptors and has recently been associated with hepatic fat accumulation. The purpose of the study was to investigate the effects of PCB126 on the molecular development of NAFLD using hepatocyte and rat models.
Methods
Hepatocytes were exposed to PCB 126 for 72 h and lipid accumulation in cells was quantified by Oil-Red-O. Rats were injected with a single dose of PCB126 or vehicle. Seven days later, liver triglycerides (TAG) content was measured along with protein quantification of hepatic microsomal triglyceride transfer protein (MTP), sterol regulatory element-binding protein 1c (SREBP1c) and diacylglycerol O-acyltransferase 2 (DGAT-2).
Results
Exposure to PCB126 resulted in significant increases of lipid accumulation in hepatocytes (38 %,
P
<0.05) and hepatic TAG concentrations (64 %,
P
<0.001) in rats compared to respective control groups. Rats with fatty livers depicted lower MTP (40 %,
P
<0.02), higher SREBP1c (27 %,
P
< 0.05) and DGAT-2 (120 %,
P
< 0.02) protein content levels compared to Placebo group in rats.
Conclusions
It seems that exposure to PCB126 has an important emerging role in the pathophysiology of NAFLD by 1) altering elimination mechanisms such as VLDL synthesis and secretion, through MTP; and 2) increasing hepatic TAG synthesis mechanisms through DGAT 2 and SREBP1c.
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.
In the past few years, polychlorinated biphenyls (PCBs), a class of environmental pollutants, have been associated with metabolism dysregulation. Muscle is one of the key regulators of metabolism ...because of its mass and its important role in terms of glucose consumption and glucose storage. It has been shown that muscle alterations, such as oxidative stress and mitochondrial dysfunction, contribute significantly to the development of metabolic diseases. No study has yet investigated the toxicological effect of PCBs on muscle mitochondrial function and oxidative stress in vivo. The aim of this study was to assess the effect of PCB126 in vivo exposure (single dose of 1.05 μmol/kg) on muscle mitochondrial function and oxidative stress in rats. PCB126-treated rats showed a marked increase in
Cyp1a1
mRNA levels in skeletal muscles in association with a 40% reduction in state 3 oxygen consumption rate measured with complex I substrates in permeabilized muscle fibers. Furthermore, PCB126 exposure altered the expression of some enzymes involved in ROS detoxification such as catalase and glutaredoxin 2. Our results highlight for the first time a toxic effect of coplanar PCBs on skeletal muscle mitochondrial function and oxidative stress. This suggests that acute PCB exposure, by affecting muscle metabolism, could contribute to the development of metabolic disorders. Studies are needed to determine if lower-level but longer-term PCB exposure exhibits the same effect.
Abstract Objective The aim of the present study was to investigate the effects of maintaining only one of the two components of a food restriction (FR) + resistance training (RT) regimen on the ...regain of body weight and fat mass (liver and adipocytes) in ovariectomized (Ovx) rats. Methods Five week Ovx rats were submitted to a weight loss program consisting of a 26% FR combined with RT (OvxFR + RT) for 8 weeks. RT consisted of climbing a 1.5 m vertical grid with a load attached to the tail, 20–40 times with progressively increasing loads 4 times/week. Following this weight loss intervention, OvxFR + RT rats were sub-divided into 3 groups for an additional 5 weeks: 2 groups went back to a normal ad libitum feeding with or without RT and the other group kept only FR. Results Combined FR + RT program in Ovx rats led to lower body mass gain, liver triacylglycerol (TAG) levels, and fat mass gain compared to sedentary normally fed Ovx rats ( P < 0.01). Stopping both FR and RT over a 5 week period resulted in the regain of body weight, intra-abdominal fat pad weight and liver TAG ( P < 0.01). When only FR was maintained, the regain of body and fat pad weight as well as liver and plasma TAG concentrations was completely prevented. However, when only RT was maintained, regain in the aforementioned parameters was attenuated but not prevented ( P < 0.05). Conclusion It is concluded that following a FR + RT weight loss program, continuation of only RT constitutes an asset to attenuate body weight and fat mass regain in Ovx rats; although the impact is less than the maintaining FR alone. These results suggest that, in post-menopausal women, RT is a positive strategy to reduce body weight and fat mass relapse.
PDF
