AGRIS - 

2016

Sihali-Beloui, Ouahiba | El-Aoufi, Salima | Maouche, Boubekeur | Marco, Sergio

The aim of our transmission electron microscope study was to show, for the first time, the alteration of liver cells involved in the evolution of steatosis to steatohepatitis on a murine model of the diet-induced metabolic syndrome, Psammomys obesus. This pathologic evolution was induced by using the standard laboratory diet during 10 months, and analyzed with metabolic studies and the immunohistochemistry technique. Four months later, hepatocytes charged with lipid vacuoles were involved in autophagy. Furthermore, in the sinusoids, we observed Kupffer cells, neutrophils and macrophages. All those cells were associated with necrotic hepatocytes inducing hepatocellular necrosis. We also noticed a synthesis of extracellular matrix in excess, caused by proliferation and activation of hepatic stellate cells in necrotic areas. We observed as well a fragmentation of the endoplasmic reticulum, which formed isolated membranes (phagophores) surrounding mitochondria. The complex membrane–mitochondria formed like an autophagosome. Thus, a defect in autophagy favored the development and progression of steatohepatitis. In conclusion, our results suggest that P. obesus is very well adapted for experimental research, and could help improve the early therapeutic management of patients and the prevention of autophagic risks in the liver.

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National Agricultural Library - United States of America

2016

Montagner, Alexandra | Polizzi, Arnaud | Fouche, Edwin | Ducheix, Simon | Lippi, Yannick | Lasserre, Frederic | Barquissau, Valentin | Regnier, Marion | Lukowicz, Céline | Benhamed, Fadila | Iroz, Alison | Bertrand-Michel, Justine | Al Saati, Talal | Cano, Patricia | Mselli-Lakhal, Laila | Mithieux, Gilles | Rajas, Fabienne | Lagarrigue, Sandrine | Pineau, Thierry | Loiseau, Nicolas | Postic, Catherine | Langin, Dominique | Wahli, Walter | Guillou, Hervé

Objective:Peroxisome proliferator-activated receptor α (PPARα) is a nuclear receptor expressed in tissues with high oxidative activity that plays a central role in metabolism. In this work, we investigated the effect of hepatocyte PPARα on non-alcoholic fatty liver disease (NAFLD).Design:We constructed a novel hepatocyte-specific PPARα knockout (Pparαhep-/-) mouse model. Using this novel model, we performed transcriptomic analysis following fenofibrate treatment. Next, we investigated which physiological challenges impact on PPARα. Moreover, we measured the contribution of hepatocytic PPARα activity to whole-body metabolism and fibroblast growth factor 21 production during fasting. Finally, we determined the influence of hepatocyte-specific PPARα deficiency in different models of steatosis and during ageing.Results:Hepatocyte PPARα deletion impaired fatty acid catabolism, resulting in hepatic lipid accumulation during fasting and in two preclinical models of steatosis. Fasting mice showed acute PPARα-dependent hepatocyte activity during early night, with correspondingly increased circulating free fatty acids, which could be further stimulated by adipocyte lipolysis. Fasting led to mild hypoglycaemia and hypothermia in Pparαhep-/- mice when compared with Pparα-/- mice implying a role of PPARα activity in non-hepatic tissues. In agreement with this observation, Pparα-/- mice became overweight during ageing while Pparαhep-/- remained lean. However, like Pparα-/- mice, Pparαhep-/- fed a standard diet developed hepatic steatosis in ageing.Conclusions:Altogether, these findings underscore the potential of hepatocyte PPARα as a drug target for NAFLD.

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Institut national de la recherche agronomique - France

2016

Gerunov, V.I. | Teushchakov, D.S. | Goroshenko, Ya.V., Omsk State Agrarian Univ.

Currently, milk coagulation technology with formic acid (FA) for calf rearing is being implemented. However, the information on protective efficacy and safety of this type of milk is extremely contradictive. The purpose of this research is to determine the biochemical indicators of blood and pathomorphological changes of guinea pigs' innards in the course of long-term calf rearing using coagulated milk containing FA. The research was conducted on male guinea pigs at the age of 6 months with the body weight from 580 to 660 g. All animals were divided into 2 groups (control and experimental) of 10 specimens in each. The milk was used, that was coagulated with 8.5% solution of FA in an amount of 20 ml/l at room temperature and repeatedly stirred for 6-12 h. The experimental group was reared daily with coagulated milk with FA in a volume of 40-50 ml per animal for 30 days. Control group was consuming fresh milk. Blood was sampled from heart 30 days after the trial was launched. After the experiment, all the animals were slaughtered and put to pathomorphological examination. Conducted model test demonstrated that the long-term consumption of milk with FA causes a chronic inflammation of gastrointestinal tract with a predominant lesion of the large intestine. Increase in blood serum of alanine aminotransferase, aspartate aminotransferase, gamma glutamyltransferase, creatinine and urea levels by 70.1; 27.5; 55.6; 53.7 and 21.2% (P less than 0.05), respectively, was observed 30 days after the beginning of experiment. The results of biochemical analysis of blood serum and pathological examination indicated hepatic and nephrotoxic effects of FA, which should be considered in the implementation of the described scheme in order to prevent gastrointestinal disorders in calves. | В настоящее время внедряется технология сквашивания молока для выпойки телят раствором муравьиной кислоты (МК). Однако сведения о профилактической эффективности и безопасности такого молока крайне противоречивы. Цель исследования – установить биохимические показатели крови и патоморфологические изменения во внутренних органах у морских свинок при длительном выпаивании молока с добавлением МК. Исследование проводили на 20 морских свинках – самцах в возрасте 6 месяцев с массой тела 580-660 г. Все животные были разделены на 2 группы (контрольную и опытную) по 10 особей в каждой. В эксперименте использовали молоко, которое сквашивали 8,5% раствором МК из расчета 20 мл на 1 л при комнатной температуре и многократно перемешивали в течение 6-12 ч. Животным опытной группы молоко с добавлением МК выпаивали ежедневно в объеме 40-50 мл на голову в течение 30 дней. Контрольные морские свинки получали свежее молоко. Забор крови для проведения исследования осуществляли из сердца через 30 суток после начала опыта. По окончании эксперимента всех животных подвергали убою и патологоанатомическому исследованию. Результаты модельных экспериментов свидетельствуют о том, что длительное выпаивание животным молока с добавлением МК вызывает хроническое воспаление желудочно-кишечного тракта с преимущественным поражением толстой кишки. В сыворотке крови морских свинок через 30 суток после начала опыта наблюдалось повышение содержания аланинаминотрансферазы, аспартатаминотрансферазы, гамма-глутамилтрансферазы, креатинина и мочевины соответственно на 70,1; 27,5; 55,6; 53,7 и 21,2% (P меньше 0,05). Результаты биохимического исследования сыворотки крови и патоморфологическая картина указывают на гепато- и нефротоксическое действие МК, что необходимо учитывать при внедрении в производство описанной схемы профилактики желудочно-кишечных заболеваний у телят.

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Central Scientific Agricultural Library - Russian Federation

2016

Tkachenko, E.A., South-Ural State Agrarian Univ., Chelyabinsk

Исследования проводили с целью оценки способности наночастиц серебра влиять на уровень аккумуляции и выраженность токсических эффектов кадмия в организме курнесушек кросса "Ломан белый". Объектом исследования служили 22-недельные куры-несушки, материалом – печень и кровь птицы. Для проведения опыта сформировали 4 группы. Первая – контрольная (кур содержали на стандартном пищевом и водном рационе кормления). Вторая опытная группа служила фоном токсического действия кадмия (CdSO4*8H2O), который задавали в хлебных болюсах в дозе 1/10 ЛД50 (52,5 мг/кг) в течение 15 сут., на организм птиц. В третьей и четвертой группах пероральное введение сульфата кадмия сочетали с добавлением в воду наночастиц серебра из расчета соответственно 14,0 и 7,0 мг/кг. Сульфат кадмия в организме кур II опытной группы активно депонировался в печени (через 15 сут. токсикоза ИЗВ= 962,44±22,57 усл. ед), что сопровождалось снижением в крови уровня эритроцитов на 27,74%, увеличением содержания гемоглобина на 11,55% и насыщенности эритроцитов гемоглобином – на 81,59%. Однако гемоглобин крови на 49,27% был представлен метгемоглобином. Наночастицы серебра в суточной дозе 14 мг/кг на фоне кадмиевой интоксикацией к концу эксперимента снижали степень аккумуляции кадмия в печени кур на 29,13%, увеличивали количество эритроцитов на 32,30%, гемоглобина, который на 16,58% был представлен метгемоглобином, – на 29,49%, сохраняли насыщенность эритроцитов гемоглобином. Комбинирование воздействия сульфата кадмия на организм птиц с наночастицами серебра в суточной дозе 7 мг/кг характеризовалось более выраженным антитоксическим действием: в печени кур депонировалось на 48,41% меньше кадмия, количество эритроцитов увеличивалось на 34,02%, гемоглобина, в котором метгемоглобин составлял только 5,70%, – на 20,89%. | The aim of the research was to evaluate the ability of silver nanoparticles to affect the level of accumulation and intensity of toxic effects of cadmium in organisms of laying hens of the Lohmann White cross. Twenty two-week-old laying hens were the object of the research, their liver and blood was the material. Four groups were formed for the experiment. The first one was the control (chickens were kept on standard food and water diet). The second experimental group served as the background of the toxic effect of cadmium (CdSO4 x 8H2O) in bodies of birds, which was fed in bread boluses at a dose of 1/10 LD50 (52.5 mg/kg) during 15 days. In the third and fourth groups the oral administration of cadmium sulfate was combined with addition of silver nanoparticles in water in the doses of 14.0 and 7.0 mg/kg, respectively. Cadmium sulfate accumulated actively in the liver of hens from the second group (in 15 days of toxicosis IWP was 962.44 ± 22.57 standard units), which was accompanied by a decrease in red blood cells level in blood by 27.74%, the increase in hemoglobin content at 11.55 % and in saturation of erythrocytes by hemoglobin on 81.59%. However, the hemoglobin of blood was represented by methemoglobin on 49.27%. By the end of the experiment silver nanoparticles at the daily dose of 14 mg/kg against the background of cadmium intoxication reduced the degree of cadmium accumulation in chicken liver by 29.13%, increased the number of red blood cells on 32.30%, hemoglobin , which was represented by methemoglobin by 16.58%–on 29.49%, maintained a saturation of erythrocytes by hemoglobin. The combined effect of cadmium sulfate with silver nanoparticles on poultry organisms at the daily dose of 7 mg/kg was characterized by more pronounced anti-toxic effect. So in chicken liver it was accumulated less cadmium by 48.41%, the number of erythrocytes increased on 34.02%, hemoglobin content grew on 20.89%, and methemoglobin consisted only 5.70% in it.

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Central Scientific Agricultural Library - Russian Federation

2016

Kurlykova, Yu.A. | Savinkov, A.V., Samara State Agricultural Academy

Цель исследования – повышение продуктивных качеств поросят за счет улучшения морфофункциональных показателей системы пищеварения. Для проведения опыта было сформировано две группы клинически здоровых поросят сразу после отъема в возрасте 35 дней. Каждая группа состояла из 10 голов, подбор осуществлялся по принципу аналогов. Животные опытной группы ежедневно в течение 2 мес. получали с кормом сыворотку молочную гидролизованную из расчета 2 мл/кг живой массы. По завершении опыта средний показатель живой массы поросят контрольной группы имел значение 26,1±1,2 кг, а опытной группы – 32,3±0,8 кг, разница составила 23% (р меньше 0,05). В результате гистоморфологического исследования выявлено увеличение размера крипт и каемчатых эпителиоцитов в слизистой оболочке тощей кишки поросят опытной группы. Это свидетельствует об усилении пищеварительной активности органа. Появление светлоклеточных зон в печени и уменьшение долек свидетельствует об усилении регенераторной способности и повышении детоксикационной функции. В лимфатических узлах появление фолликулов малого размера с выраженными светлыми центрами, как и в печени, свидетельствует об усилении потенциала регенерации и активизации иммунной функции. Сделан вывод, что применение сыворотки положительно влияет на состояние пищеварительной системы поросят и их организма в целом. | The object of research is increasing of productive qualities of pigs due to improvement the morphofunctional indicators of the digestion system. To carry out an experiment, two groups of clinically healthy pigs right after depriving at the age of 35 days were formed. Each group consisted of 10 heads; the selection was carried out by the principle of analogs. The experimental animals annually for 2 months received with feed hydrolyzed whey ob the basis of 2 ml/kg of body weight. After completion of the experiment an average value of the body weight of the control group pigs was 26.1±1.2 kg, and in the experimental group - 32.3±0.8 kg, the difference was 23% (рles than 0.05). A histomorphologic study has found increasing the size of crypts and limbic epithelial cells in the mucous membrane of empty intestine of pigs in the experimental group, this testifies to strengthening of body digestive activity. Emergence of light-cellular zones in liver and reduction of segments testifies to strengthening the regeneration ability and activation of detoxication function. In lymph nodes the emergence of follicles of the small size with pronounced light centers as well as in liver, testifies to enhancing the potential regeneration and activity of the immune function. It has been concluded that the use of whey positively influences the state of the digestive system of young pigs and their body in general.

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Central Scientific Agricultural Library - Russian Federation

2016

Chun, S.K., University of Florida, Gainesville, USA | Go, K., University of Florida, Gainesville, USA | Yang, M.J., University of Florida, Gainesville, USA | Zendejas, I., University of Florida, Gainesville, USA | Behrns, K.E., University of Florida, Gainesville, USA | Kim, J.S., University of Florida, Gainesville, USA

No-flow ischemia occurs during cardiac arrest, hemorrhagic shock, liver resection and transplantation. Recovery of blood flow and normal physiological pH, however, irreversibly injures the liver and other tissues. Although the liver has the powerful machinery for mitochondrial quality control, a process called mitophagy, mitochondrial dysfunction and subsequent cell death occur after reperfusion. Growing evidence indicates that reperfusion impairs mitophagy, leading to mitochondrial dysfunction, defective oxidative phosphorylation, accumulation of toxic metabolites, energy loss and ultimately cell death. The importance of acetylation/deacetylation cycle in the mitochondria and mitophagy has recently gained attention. Emerging data suggest that sirtuins, enzymes deacetylating a variety of target proteins in cellular metabolism, survival and longevity, may also act as an autophagy modulator. This review highlights recent advances of our understanding of a mechanistic correlation between sirtuin 1, mitophagy and ischemic liver injury.

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Korea Agricultural Science Digital Library - Republic of Korea

2016

Vial, Guillaume | Le Guen, Marie | Lamarche, Frédéric | Detaille, Dominique | Cottet‐Rousselle, Cécile | Demaison, Luc | Hininger-Favier, Isabelle | Theurey, Pierre | Crouzier, David | Debouzy, Jean‐Claude | Dubouchaud, Hervé | Fontaine, Éric

Fundamental Library of Latvia University of Life Sciences and Technologies - Latvia

2016

Roux, Pierre-François | Frésard, Laure | Boutin, Morgane | Leroux, Sophie | Klopp, Christophe | Djari, Anis | Esquerre, Diane | Martin, Pascal | Zerjal, Tatiana | Gourichon, David | Pitel, Frederique | Lagarrigue, Sandrine

RNA editing is a post-transcriptional process leading to differences between genomic DNA and transcript sequences, potentially enhancing transcriptome diversity. With recent advances in high-throughput sequencing, many efforts have been made to describe mRNA editing at the transcriptome scale, especially in mammals, raising contradictory conclusions regarding the extent of this phenomenon. We show by a detailed description of the 25 studies focusing so far on mRNA editing at the whole-transcriptome scale that systematic sequencing artifacts are somehow considered in most studies, whereas biological replication is often neglected and multi-alignment not properly evaluated, which ultimately impairs the legitimacy of results. We recently developed a rigorous strategy to identify mRNA editing using mRNA and genomic DNA sequencings, taking into account sequencing and mapping artifacts, and biological replicates. We applied this method to screen for mRNA editing in liver and white adipose tissue from 8 chickens and confirm the small extent of mRNA recoding in this species. Among the 25 unique edited sites identified, 3 events were previously described in mammals, attesting this phenomenon is conserved through evolution. Deeper investigations on 5 sites revealed the impact of tissular context, genotype, age, feeding condition and sex on mRNA editing levels. More specifically, this analysis highlighted that the editing level at the site located on COG3 was strongly regulated by 4 out of these factors. By comprehensively characterizing the mRNA editing landscape in chicken, our results highlight how this phenomenon is limited, and suggest a regulation of editing levels by various genetic and environmental factors.

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Fundamental Library of Latvia University of Life Sciences and Technologies - Latvia

2016

Panchenko, Polina | Voisin, Sarah | Jouin, Melanie | Jouneau, Luc | Prézelin, Audrey | Lecoutre, Simon | Breton, Christophe | Jammes, Hélène | Junien, Claudine

Maternal obesity impacts fetal growth and pregnancy outcomes. To counteract the deleterious effects of obesity on fertility and pregnancy issue, preconceptional weight loss is recommended to obese women. Whether this weight loss is beneficial/detrimental for offspring remains poorly explored. Epigenetic mechanisms could be affected by maternal weight changes, perturbing expression of key developmental genes in the placenta or fetus. Our aim was to investigate the effects of chronic maternal obesity on feto-placental growth along with the underlying epigenetic mechanisms. We also tested whether preconceptional weight loss could alleviate these effects.Female mice were fed either a control diet (CTRL group), a high-fat diet (obese (OB) group), or a high-fat diet switched to a control diet 2 months before conception (weight loss (WL) group). At mating, OB females presented an obese phenotype while WL females normalized metabolic parameters. At embryonic day 18.5 (E18.5), fetuses from OB females presented fetal growth restriction (FGR; −13 %) and 28 % of the fetuses were small for gestational age (SGA). Fetuses from WL females normalized this phenotype. The expression of 60 epigenetic machinery genes and 32 metabolic genes was measured in the fetal liver, placental labyrinth, and junctional zone. We revealed 23 genes altered by maternal weight trajectories in at least one of three tissues. The fetal liver and placental labyrinth were more responsive to maternal obesity than junctional zone. One third (18/60) of the epigenetic machinery genes were differentially expressed between at least two maternal groups. Interestingly, genes involved in the histone acetylation pathway were particularly altered (13/18). In OB group, lysine acetyltransferases and Bromodomain-containing protein 2 were upregulated, while most histone deacetylases were downregulated. In WL group, the expression of only a subset of these genes was normalized.This study highlights the high sensitivity of the epigenetic machinery gene expression, and particularly the histone acetylation pathway, to maternal obesity. These obesity-induced transcriptional changes could alter the placental and the hepatic epigenome, leading to FGR. Preconceptional weight loss appears beneficial to fetal growth, but some effects of previous obesity were retained in offspring phenotype.

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Fundamental Library of Latvia University of Life Sciences and Technologies - Latvia

2016

DANCER, Marine | CAUSSY, Cyrielle | Di Filippo, Mathilde | Moulin, Philippe | Marcais, Christophe | CHARRIERE, Sybil

Background and aims: APOC3 is a major regulator of triglycerides metabolism. Several APOC3 variants are associated with hypertriglyceridemia (HTG). Our aim was to establish the potential regulation of APOC3 3'UTR variants associated with HTG by liver or intestinal miRNAs.Methods: We sequenced APOC3 3'UTR in 100 type 2 diabetic (TD2) patients with severe HTG (TG > 15 mmol/L) (HTG group) compared to 100 normotriglyceridemic patients (NTG group). We performed in silico studies to identify potential loss of miRNA binding induced by APOC3 3'UTR variants. We also performed in vitro studies to test the functionality of miRNA/APOC3 variants interactions: APOC3 3'UTR plasmids coupled with a firefly luciferase reporter were transfected in HepG2, HuH-7 and Caco-2 cells.Results: We identified only two variants: SstI (rs5128) and BbvI (rs5225) in APOC3 3'UTR in the 2 groups of patients. Only the SstI-S2 rare allele was significantly associated with HTG (allele frequency 19,5% in HTG group vs. 9,5% in NTG group, p = 0.0045). In silico studies predicted a potential loss in the binding of 5 miRNAs induced by the S2 variant. These 5 miRNAs are all endogenously expressed in human liver and intestine, as well as in the cell models studied. However, in vitro, the S2 variant did not modulate APOC3 3'UTR reporter gene expression in HepG2, HuH-7 and Caco-2 cells.Conclusions: Our results do not confirm the hypothesis of a direct regulation of the APOC3 SstI variant by hepatic or intestinal miRNAs.

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Institut national de la recherche agronomique - France