iTRAQ-Based Quantitative Proteomics Analysis of Sprague-Dawley Rats Liver Reveals Perfluorooctanoic acid-induced Lipid Metabolism and Urea Cycle Dysfunction

Author(s):  
Hui Liu ◽  
Weiqiang Sun ◽  
Yongbing Zhou ◽  
Nathan Griffin ◽  
Sam Faulkner ◽  
...  
2021 ◽  
Author(s):  
Hui Liu ◽  
Fangfang Liu ◽  
Yongbing Zhou ◽  
Nathan Griffin ◽  
Sam Faulkner ◽  
...  

Abstract Perfluorooctanoic acid (PFOA) is a typical C8 representative compound of perfluoroalkyl and polyfluoroalkyl substances (PFAS) widely used in industrial and domestic products. It is a persistent organic pollutant found in the environment as well as in the tissues of humans and wildlife. Despite emerging scientific and public interest, the precise mechanisms of PFOA toxicity remain unclear. In this study, male rats were exposed to 1.25, 5, and 20 mg PFOA/kg body weight/day for 14 days. Urine samples were also collected and monitored by raising rats in metabolic cages. In vivo results demonstrate that PFOA exposure induces significant hepatocellular hypertrophy and reduced urea metabolism. iTRAQ-based quantitative proteomics analysis of Sprague-Dawley (SD) rats livers identified 3,327 non-redundant proteins of which 112 proteins were significantly upregulated and 80 proteins were downregulated. Gene ontology analysis revealed proteins are primarily involved in cellular, metabolic and single − organism processes. Among them, eight proteins (ACOX1, ACOX2, ACOX3, ACSL1, EHHADH, GOT2, MTOR and ACAA1) were related to oxidation of fatty acids and two proteins (ASS1 and CPS1) were found to be associated with urea cycle disorder. The downregulation of urea synthesis proteins ASS1 and CPS1 after exposure to PFOA was then confirmed through qPCR and western blot analysis. Together, these data demonstrate that PFOA exposure directly influences urea metabolism and identify CPS1 as a potential regulatory target.


Nutrients ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 1882 ◽  
Author(s):  
Roy Skinner ◽  
Derek Warren ◽  
Soofia Lateef ◽  
Vagner Benedito ◽  
Janet Tou

Apple pomace, which is a waste byproduct of processing, is rich in several nutrients, particularly dietary fiber, indicating potential benefits for diseases that are attributed to poor diets, such as non-alcoholic fatty liver disease (NAFLD). NAFLD affects over 25% of United States population and is increasing in children. Increasing fruit consumption can influence NAFLD. The study objective was to replace calories in standard or Western diets with apple pomace to determine the effects on genes regulating hepatic lipid metabolism and on risk of NAFLD. Female Sprague-Dawley rats were randomly assigned (n = 8 rats/group) to isocaloric diets of AIN-93G and AIN-93G/10% w/w apple pomace (AIN/AP) or isocaloric diets of Western (45% fat, 33% sucrose) and Western/10% w/w apple pomace (Western/AP) diets for eight weeks. There were no significant effects on hepatic lipid metabolism in rats fed AIN/AP. Western/AP diet containing fiber-rich apple pomace attenuated fat vacuole infiltration, elevated monounsaturated fatty acid content, and triglyceride storage in the liver due to higher circulating bile and upregulated hepatic DGAT2 gene expression induced by feeding a Western diet. The study results showed the replacement of calories in Western diet with apple pomace attenuated NAFLD risk. Therefore, apple pomace has the potential to be developed into a sustainable functional food for human consumption.


Nanoscale ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 5973-5986 ◽  
Author(s):  
Zhangjian Chen ◽  
Shuo Han ◽  
Pai Zheng ◽  
Di Zhou ◽  
Shupei Zhou ◽  
...  

The present study investigated the effect of oral exposure to TiO2 NPs on lipid metabolism by serum lipidomics.


1999 ◽  
Vol 46 (10) ◽  
pp. 638-644 ◽  
Author(s):  
Michiko NONAKA ◽  
Yoichi NAGAMORI ◽  
Koji YAMADA ◽  
Michihiro SUGANO

1999 ◽  
Vol 63 (12) ◽  
pp. 2163-2167 ◽  
Author(s):  
Koji YAMADA ◽  
Yoko TOKUNAGA ◽  
Atsushi IKEDA ◽  
Ken-ichi OHKURA ◽  
Soichi MAMIYA ◽  
...  

Author(s):  
Sara J Lupton ◽  
Heldur Hakk

Perfluorooctanoic acid (PFOA) is a perfluorinated alkyl substance (PFAS) used as surfactant in a wide variety of industrial and consumer products. Over the past decade, concern has increased over the presence of PFOA in biosolids from wastewater treatment plants used as fertilizer on agricultural lands having the potential to enter the food chain. In this study, the uptake of 14C-PFOA from soil by alfalfa was determined, as was the bioavailability of 14C-PFOA-incurred into alfalfa in Sprague-Dawley rats. Alfalfa leaves accumulated PFOA to as high as 4-5 µg/g of dry leaf, approximately 10 times higher than accumulation in the stem. Alfalfa was ground for feeding to 15 female Sprague-Dawley rats (175-200 g). Animals within metabolism cages were fed 10 g of feed (6 g alfalfa + 4 g ground rat chow) twice a day for 14 days (equivalent to 50 ug-PFOA/kg/day). At the end of the feeding period, rats (n=3) were sacrificed at withdrawal days of 0, 3, 7, 11, and 14 days. During the feeding and withdrawal phases, urine and feces were collected daily. At sacrifice, blood, liver, kidney, adipose, muscle, skin, brain, heart, adrenals, spleen, lungs, and thymus were removed and assayed for 14C-PFOA by combustion and LSC analysis. Rats eliminated 72.8 ± 3.4% of the total dose via urine at 14-days, but urinary radioactivity fell below the LOD by day 3 of the withdrawal period. Fecal elimination was 6.5 ± 1.2 % of the dose and fell below the LOD by 2 days of withdrawal. The rapid and high elimination via urine indicates that a majority of the dose was absorbed. The uptake of PFOA into alfalfa was low from a high organic content soil, however, PFOA was highly bioavailable from the alfalfa when used as a feed component for rats. This study provides data for regulators investigating PFOA bioavailability and disposition in animals or animal products exposed to contaminated feed.


Marine Drugs ◽  
2020 ◽  
Vol 18 (8) ◽  
pp. 408 ◽  
Author(s):  
Shing-Hwa Liu ◽  
Rui-Yi Chen ◽  
Meng-Tsan Chiang

Chitosan oligosaccharide is known to ameliorate hypercholesterolemia and diabetes. However, some studies found that chitosan oligosaccharide might induce mild to moderate hepatic damage in high-fat (HF) diet-induced obese rats or diabetic rats. Chitosan oligosaccharide can be as a dietary supplement, functional food, or drug. Its possible toxic effects to normal subjects need to be clarified. This study is designed to investigate the effects of chitosan oligosaccharide on plasma and hepatic lipid metabolism and liver histomorphology in normal Sprague-Dawley rats. Diets supplemented with 5% chitosan oligosaccharide have been found to induce liver damage in HF diet-fed rats. We therefore selected 5% chitosan oligosaccharide as an experimental object. Rats were divided into: a normal control diet group and a normal control diet +5% chitosan oligosaccharide group. The experimental period was 12 weeks. The results showed that supplementation of 5% chitosan oligosaccharide did not significantly change the body weight, food intake, liver/adipose tissue weights, plasma lipids, hepatic lipids, plasma levels of AST, ALT, and TNF-α/IL-6, hepatic lipid peroxidation and anti-oxidative enzyme activities, fecal lipids, and liver histomorphology in normal rats. These findings suggest that supplementation of 5% chitosan oligosaccharide for 12 weeks may not induce lipid metabolism disorder and liver toxicity in normal rats.


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