In contrast, protein content of DGAT-2 revealed to be 120% higher (1

In contrast, protein content of DGAT-2 revealed to be 120% higher (1. 290. 2 vs 2 . 850. 6AU; P <0. 02) (Fig. 5) and SREBP1c was 26. 5% greater (0. 870. 07 vs 1 . 090. 07AU; P <0. 05) (Fig. 6) compared SGK to control rats. == Fig. to PCB 126 for 72 h and lipid build up in cells was quantified by Oil-Red-O. Rats were injected with a single dose of PCB126 or vehicle. Seven days later on, 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 raises 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. Keywords: Steatosis, Environmental contaminants, Liver, Rats == Background == Liver plays an essential role in the biogenesis of major metabolites such as lipids. However , an important increased in hepatic fat depot leads to the development of NAFLD. NAFLD is the most prevalent liver disease in North America and reaching approximately 20 % of the populace worldwide, and affecting both adults and children [1, 2]. NAFLD NSC 405020 has become a common cause of chronic metabolic diseases such as steatohepatitis, diabetes [3] and metabolic syndrome [4]. Historically NAFLD was linked to overnutrition, physical inactivity and pharmacology. However , emerging studies have demonstrated that additional contributing factors may play a role in the development of NAFLD, such as prolonged organic pollutants (POPs). Prolonged organic pollutants are chemicals that were mostly used historically because pesticides, solvents, and flame-retardants and have been released in the environment. In North America, POPs have been recognized to be of environmental and potential toxicologic concern, as a result, a variety of POPs have been banned from use since the late 1970s [5]. However , due to their persistence and lipophilicity, these compounds will remain present in the environment for decades and accumulate in living organisms [6]. POPs also accumulate in adipose cells and are constantly released from adipose cells to the blood circulation and to vital organs with lipid content [7]. In humans, a National Health and Nutrition Examination Survey (NHANES) study showed the total participants had detectable circulating POPs levels [8]. POPs regroup polychlorinated biphenyls (PCBs), a family of 209 diverse congeners. A total of 1. three or more million tons of PCBs were manufactured prior 1977 for use in electrical and other industrial applications [9]. PCB126 is the most potent and ubiquitous in the environment amongst congeners [10]. Recent studies possess reported the presence of PCB126 could act as endocrine disruptors at the liver NSC 405020 level NSC 405020 and lead to fatty liver [11]. Hepatic lipid accumulation results from altered intrahepatic TAG elimination and synthesis NSC 405020 mechanisms. Specific key-molecules such as MTP is involved in lipid elimination pathways through VLDL production and secretion, while synthesis pathways regroup DGAT-2 and SREBP1c. Hepatic VLDL production is a complex process involving several enzymes to carry TAG from liver to peripheral tissues [12]. MTP plays a pivotal role in the assembly and secretion of apoB-containing lipoproteins [13]. MTP is a heterodimeric protein expressed around the luminal side of EMERGENY ROOM composed of a catalytic subunit of 97 kDa and a multifunctional protein of 55 kDa, disulfide isomerase [14]. Molecular processes such as fatty acid synthesis and esterification also regulate hepatocytes TAG content. In the liver, DGAT has a role in synthesizing TAG from either fatty acids synthesizedde novoor from fatty acids taken up from the blood circulation. Two DGAT enzymes were identified, DGAT1 and DGAT2. While DGAT1 seems to be associated to TAG synthesis and VLDL secretion stimulation [15], NSC 405020 DGAT2 appears to catalyze the final step in the pathway leading tode novosynthesis and intracellular accumulation of TAG [16]. SREBPs are major transcription factors that regulate the expression of genes involved in lipid synthesis in the liver. Three isoforms exist, SREBP-1a, 1c and 2 [17, 18]. SREBP-2 activates genes involved in cholesterol metabolism, whereas SREBP-1 regulates genes involved in the metabolism of fatty acids [240]. SREBP-1c is the predominant isoform expressed in liver [18] and is mainly responsible for the expression of genes involved in hepatic fatty acid biosynthesis [19]. Over the last decade, interactions of PCB126 with nervous [20] and reproductive [21] metabolic activities for instance, have attracted much interest. However , the effects of PCB126 around the liver, specifically on the underlying molecular mechanisms leading to NAFLD have not yet been defined. Therefore the purpose.