scholarly journals Kinetic study of the expression of genes related to hepatic steatosis, global intermediate metabolism and cellular stress during overfeeding in mule ducks

2019 ◽  
Author(s):  
Tracy Pioche ◽  
Fabien Skiba ◽  
Marie-Dominique Bernadet ◽  
Iban Seiliez ◽  
William Massimino ◽  
...  
Keyword(s):  
Hepatic Steatosis ◽  
Plasma Cholesterol ◽  
Cellular Stress ◽  
Cell Signalling ◽  
Liver Weight ◽  
Pathological State ◽  
Cell Protection ◽  
Intermediate Metabolism ◽  
Potential Biomarker ◽  
Cholesterol Biosynthetic Pathway

ABSTRACTInduced by overfeeding, hepatic steatosis is a reversible process exploited for “foie gras” production. To better understand the mechanisms underlying this non-pathological phenomenon, we analysed the physiological responses of the mule duck to cope with 22 carbohydrate meals. A kinetic analysis of intermediate metabolism and cell protection mechanisms was performed during overfeeding. As expected, dietary carbohydrates are up taken mainly by the liver (chrebp, glut1/2/8) and converted into lipids (acox, scd1, acsl1, fas, dgat2). Our study showed an activation of cholesterol biosynthetic pathway with significant correlations between plasma cholesterol, expression of key genes (hmgcr, soat1) and liver weight. Results revealed an activation of insulin and amino acid cell signalling pathway suggesting that ducks boost insulin sensitivity to raise glucose uptake and useviaglycolysis and lipogenesis. Expression ofcpt1a, acad, hadhsuggested an induction of beta-oxidation probably to remove part of newly synthesized lipids and avoid lipotoxicity. Cellular stress analysis revealed an upregulation of autophagy-related gene expression (atg8, atg9, sqstm1) in contrast with an induction ofcyp2e1suggesting that autophagy could be suppressed.Lamp2aandplin2enhanced, conflicting with the idea of an inhibition of lipophagy.Hsbp1overexpression indicated that mechanisms are carried out during overfeeding to limit cellular stress and apoptosis to prevent the switch to pathological state.Atf4andasnsoverexpression reflects the nutritional imbalance during overfeeding. These results permitted to highlight the mechanisms enabling mule ducks to efficiently handle the huge starch overload and reveal potential biomarker candidates of hepatic steatosis as plasma cholesterol for liver weight.

scholarly journals Kinetic study of the expression of genes related to hepatic steatosis, glucose and lipid metabolism, and cellular stress during overfeeding in mule ducks

2020 ◽  
Vol 318 (2) ◽  
pp. R453-R467 ◽  
Author(s):  
Tracy Pioche ◽  
Fabien Skiba ◽  
Marie-Dominique Bernadet ◽  
Iban Seiliez ◽  
William Massimino ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lipid Metabolism ◽  
Hepatic Steatosis ◽  
Plasma Cholesterol ◽  
Cellular Stress ◽  
Liver Weight ◽  
Cell Protection ◽  
Glucose And Lipid Metabolism ◽  
Potential Biomarker ◽  
Cholesterol Biosynthetic Pathway

Induced by overfeeding, hepatic steatosis is a process exploited for the “foie gras” production in mule ducks. To better understand the mechanisms underlying its development, the physiological responses of mule ducks overfed with corn for a duration of 11 days were analyzed. A kinetic analysis of glucose and lipid metabolism and cell protection mechanisms was performed on 96 male mule ducks during overfeeding with three sampling times (after the 4th, the 12th, and the 22nd meal). Gene expression and protein analysis realized on the liver, muscle, and abdominal fat showed an activation of a cholesterol biosynthetic pathway during the complete overfeeding period mainly in livers with significant correlations between its weight and its cholesterolemia ( r = 0.88; P < 0.0001) and between the liver weight and the hmgcr and soat1 expression ( r = 0.4, P < 0.0001 and r = 0.67; P < 0.0001, respectively). Results also revealed an activation of insulin and amino acid cells signaling a pathway suggesting that ducks boost insulin sensitivity to raise glucose uptake and use via glycolysis and lipogenesis. Cellular stress analysis revealed an upregulation of key autophagy-related gene expression atg8 and sqstm1( P < 0.0001) during the complete overfeeding period, mainly in the liver, in contrast to an induction of cyp2e1( P < 0.0001), suggesting that autophagy could be suppressed during steatosis development. This study has highlighted different mechanisms enabling mule ducks to efficiently handle the starch overload by keeping its liver in a nonpathological state. Moreover, it has revealed potential biomarker candidates of hepatic steatosis as plasma cholesterol for the liver weight.

Increased secretory sphingomyelinase activity in the first trimester of pregnancy in women later developing preeclampsia: a nested case-control study

2016 ◽  
Vol 397 (3) ◽  
pp. 269-279 ◽  
Author(s):  
Víctor Rodríguez-Sureda ◽  
Francesca Crovetto ◽  
Stefania Triunfo ◽  
Olga Sánchez ◽  
Fátima Crispi ◽  
...  
Keyword(s):  
Plasma Cholesterol ◽  
First Trimester ◽  
Endothelial Damage ◽  
Biologically Active ◽  
Control Groups ◽  
Potential Biomarker ◽  
Circulating Markers ◽  
First Trimester Of Pregnancy ◽  
Nested Case Control ◽  
Control Study

Abstract The pathogenic basis of abnormal placentation and dysfunction in preeclampsia (PE) is highly complex and incompletely understood. Secretory sphyngomyelinase activity (S-ASM) was analyzed in plasma samples from 158 pregnant women developing PE and 112 healthy pregnant controls. Serum PlGF, sFlt-1, s-Endoglin and sVCAM were measured. Results showed S-ASM activity to be higher in women who later developed PE than in those with uncomplicated pregnancies (40.6% and 28.8% higher in the late- and early-onset groups, respectively). Plasma S-ASM activity correlated significantly with circulating markers of endothelial damage in the late-PE group (endoglin and sVCAM-1), with plasma cholesterol and total lipid levels. However, these significant associations were not observed in the early-PE or control groups. This work provides the first evidence of significantly elevated circulating S-ASM activity in the first trimester of pregnancy in women who go on to develop PE; thus, it may be deduced that the circulating form of ASM is biologically active in PE and could contribute to promoting endothelial dysfunction and cardiovascular programming. Plasma S-ASM measurement may have clinical relevance as a further potential biomarker contributing to the earliest identification of women at risk of developing preeclampsia.

scholarly journals Treatment with Lobeglitazone Attenuates Hepatic Steatosis in Diet-Induced Obese Mice

PPAR Research ◽  
2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Sorim Choung ◽  
Kyong Hye Joung ◽  
Bo Ram You ◽  
Sang Ki Park ◽  
Hyun Jin Kim ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Hepatic Steatosis ◽  
Plasma Cholesterol ◽  
Cholesterol Biosynthesis ◽  
Peroxisome Proliferator ◽  
Obese Mice ◽  
Nonalcoholic Fatty Liver ◽  
Hepatic Lipid ◽  
Hepatic Expression ◽  
Expression Of Genes

Nonalcoholic fatty liver disease (NAFLD) is strongly associated with insulin resistance. The peroxisome proliferator-activated receptor (PPAR) activators, thiazolidinediones, (TZDs), are insulin sensitizers used as a treatment for NAFLD. However, TZDs are a controversial treatment for NAFLD because of conflicting results regarding hepatic steatosis and fibrosis. To evaluate a possible effective drug for treatment of NAFLD, we investigated the effects of a newly developed TZD, lobeglitazone, with an emphasis on hepatic lipid metabolism. Lobeglitazone treatment for 4 weeks in high fat diet- (HFD-) induced obese mice (HL group) improved insulin resistance and glucose intolerance compared to HFD-induced obese mice (HU group). The gene levels related to hepatic gluconeogenesis also decreased after treatment by lobeglitazone. The livers of mice in the HL group showed histologically reduced lipid accumulation, with lowered total plasma cholesterol and triglyceride levels. In addition, the HL group significantly decreased the hepatic expression of genes associated with lipid synthesis, cholesterol biosynthesis, and lipid droplet development and increased the hepatic expression of genes associated with fatty acid β-oxidation, thus suggesting that lobeglitazone decreased hepatic steatosis and reversed hepatic lipid dysregulation. Livers with steatohepatitis contained increased levels of PPARγ and phosphorylated PPARγ at serine 273, leading to downregulation of expression of genes associated with insulin sensitivity. Notably, the treatment of lobeglitazone increased the protein levels of PPARα and diminished levels of PPARγ phosphorylated at serine 273, which were increased by a HFD, suggesting that induction of PPARα and posttranslational modification of PPARγ in livers by lobeglitazone might be an underlying mechanism of the improvement seen in NAFLD. Taken together, our data showed that lobeglitazone might be an effective treatment for NAFLD.

Cafeteria diet from birth to adulthood promotes hepatic steatosis and redox imbalance in Wistar rats

2020 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Letícia Fernandes Gomes ◽  
Sibelle Aparecida Madureira Costa ◽  
Arthur Rocha-Gomes ◽  
Amanda Escobar Teixeira ◽  
Alexandre Alves da Silva ◽  
...  
Keyword(s):  
Hepatic Steatosis ◽  
Liver Tissue ◽  
Design Methodology ◽  
Wistar Rats ◽  
Redox State ◽  
Liver Weight ◽  
Cafeteria Diet ◽  
Control Group ◽  
Content Type ◽  
Markers Of Oxidative Stress

Purpose The purpose of this paper is to evaluate the pathological, biochemical and redox state parameters of liver tissue in Wistar rats treated from birth to adulthood (119 days) with cafeteria diet. Design/methodology/approach During the lactation, 6 liters of Wistar rats (dam + 8 pups each) were fed one of two diets: control (CTRL; n = 3) or cafeteria (CAF; n = 3) diets and water ad libitum. After weaning, the males were placed in individual cages, receiving the same diet offered to their respective dams (CTRL or CAF; n = 18) until adulthood. The following parameters were evaluated: absolute and relative liver weight; blood, liver and feces biochemistry; liver histology; and redox state of the liver. Findings When assessing the relative and absolute organ weight, no significant differences were found between the groups. The Cafeteria group exhibited higher values of serum LDL-c (p = 0.008), VLDL-c (p = 0.03) and triglycerides (p = 0.01), as well as several micro and macrovacuoles of fat accumulation, higher hepatic lipid (p = 0.03) and cholesterol (p = 0.0001) levels regarding Control group. Cafeteria group showed greater expression of glutathione-s-transferase (p = 0.03) and superoxide dismutase (p = 0.005) enzymes compared to the control group. In the case of the markers of oxidative stress, there was no difference between the groups. Originality/value A simple and standardized cafeteria diet caused an accumulation of fatty acids in liver tissue, inducing a state of hepatic steatosis besides an increased expression of antioxidant enzymes.

Consumption of sucrose, but not high fructose corn syrup, leads to increased adiposity and dyslipidaemia in the pregnant and lactating rat

2014 ◽  
Vol 6 (1) ◽  
pp. 38-46 ◽  
Author(s):  
C. R. Toop ◽  
B. S. Muhlhausler ◽  
K. O’Dea ◽  
S. Gentili
Keyword(s):  
Plasma Cholesterol ◽  
Liver Weight ◽  
Metabolic Health ◽  
High Fructose Corn Syrup ◽  
Sucrose Consumption ◽  
Corn Syrup ◽  
Added Sugars ◽  
High Fructose ◽  
Pregnancy And Lactation ◽  
The Impact

Excess consumption of added sugars, including sucrose and high fructose corn syrup (HFCS-55), have been implicated in the global epidemics of obesity and type 2 diabetes. This study aimed to investigate and compare the impact of maternal consumption of sucrose or HFCS-55 during pregnancy and lactation on the metabolic health of the dam and her offspring at birth. Female Albino Wistar rats were given access to chow and water, in addition to a sucrose or HFCS-55 beverage (10% w/v) before, and during pregnancy and lactation. Maternal glucose tolerance was determined throughout the study, and a postmortem was conducted on dams following lactation, and on offspring within 24 h of birth. Sucrose and HFCS-55 consumption resulted in increased total energy intake compared with controls, however the increase from sucrose consumption was accompanied by a compensatory decrease in chow consumption. There was no effect of sucrose or HFCS-55 consumption on body weight, however sucrose consumption resulted in increased adiposity and elevated total plasma cholesterol in the dam, while HFCS-55 consumption resulted in increased plasma insulin and decreased plasma non-esterified fatty acids (NEFA). Maternal HFCS-55 consumption was associated with decreased relative liver weight and plasma NEFA in the offspring at birth. There was no effect of either treatment on pup weight at birth. These findings suggest that both sucrose and HFCS-55 consumption during pregnancy and lactation have the potential to impact negatively on maternal metabolic health, which may have adverse consequences for the long-term health of the offspring.

Deficiency in TDAG51 Decreases Atherosclerotic Lesion Development in ApoE-Deficient Mice.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3940-3940
Author(s):  
Gazi S. Hossain ◽  
Ji Zhou ◽  
Kenneth Maclean ◽  
Sarka Lhotak ◽  
Sudesh K. Sood ◽  
...  
Keyword(s):  
Cell Death ◽  
Hepatic Steatosis ◽  
Plasma Cholesterol ◽  
Control Diet ◽  
Atherosclerotic Lesion ◽  
Double Knockout ◽  
Lesion Development ◽  
Ppar Γ ◽  
Deficient Mice ◽  
Atherosclerotic Lesion Development

Abstract T-cell death associated gene 51 (TDAG51) is a pro-apoptotic gene that can be induced by endoplasmic reticulum (ER) stress agents, including homocysteine, tunicamycin, thapsigargin or dithiothreitol. Our previous studies have demonstrated that transient overexpression of TDAG51 elicited significant changes in cell morphology, decreased cell adhesion and promoted detachment-induced programmed cell death (PCD). In support of these in vitro findings, we have further shown that TDAG51 expression was increased and correlated with PCD in the atherosclerotic lesions from apolipoprotein E (apoE)-deficient mice fed hyperhomocysteinemic diets, compared to mice fed control diet. We designed the current study to investigate the effect of TDAG51 deficiency in the development and progression of atherosclerosis. To assess in vivo significance of TDAG51 on atherosclerosis, we have crossed TDAG51-deficient mice with apoE-deficient mice to obtain double knockout mice. Our findings have demonstrated that TDAG51/apoE-deficient mice have a significant decrease in atherosclerotic lesion area, compared to age- and sex-matched apoE-deficient mice. Total plasma cholesterol and triglycerides as well as lipoprotein profiles were similar in both groups. However, TDAG51/apoE-deficient mice presented with increased hepatic steatosis. Further, a significant upregulation of peroxisome proliferator-activated receptor γ (PPAR-γ), a transcription factor required for adipose tissue formation, was demonstrated in TDAG51-deficient mouse embryonic fibroblasts (MEFs), compared to control wildtype MEFs. Interestingly, earlier studies in mice have reported that overexpression of PPAR-γ decreases atherosclerotic lesion development and increases hepatic steatosis - a phenotype similar to that observed in the mouse deficient in both apoE and TDAG51. Collectively, these findings provide evidence that TDAG51 mediates atherosclerotic lesion development and hepatic steatosis through a mechanism involving PPAR-γ.

scholarly journals The effect of hepatic steatosis and fibrosis on liver weight and dimensions

2020 ◽  
Vol 47 ◽  
pp. 101781
Author(s):  
Gábor Simon ◽  
Veronika Heckmann ◽  
Dénes Tóth ◽  
Dénes Pauka ◽  
Karola Petrus ◽  
...  
Keyword(s):  
Hepatic Steatosis ◽  
Liver Weight

scholarly journals Diethanolamine-Induced Hepatic Steatosis in Mice and Its Amelioration by Curcumin

2019 ◽  
Vol 27 (1) ◽  
pp. 110-127
Author(s):  
Hetal I. Doctor ◽  
Sanman K. Samova ◽  
Ramtej J. Verma
Keyword(s):  
Body Weight ◽  
Hepatic Steatosis ◽  
Antioxidant Properties ◽  
Body Weight Loss ◽  
Liver Weight ◽  
Histological Structure ◽  
High Dose ◽  
Health Issues ◽  
Toxicological Evaluation ◽  
Dose Dependent Increase

Abstract Extensive use of chemicals in personal care products has led to many health issues. Diethanolamine is one of such harmful chemicals containing two highly functional groups alcohol and amine that requires toxicological evaluation and its mitigation. Swiss strain albino mice were used and divided into different control and treated groups. Different doses of DEA (110, 165 and 330 mg/kg body weight/day) were orally administered for 30 days. Biochemical and histopathological assessments were performed at the end of the treatment. Results collectively revealed body weight loss as well as significant increase in absolute and relative liver weight in DEA-treated groups. Biochemical analysis revealed that DEA treatment further promotes significant (P<0.05), dose-dependent increase in lipid and cholesterol contents and also cause decrease in protein and glycogen content. Histopathological assessment confirms vacuole formation due to accumulation of lipid within the liver tissue. Administration of curcumin (10, 20 and 30 mg/kg body weight/day) along with high dose of DEA (330 mg/kg body weight/day) showed improved values of lipid, cholesterol, protein and glycogen contents. It also helped retaining normal histological structure of liver. Observations in all groups and results indicate DEA-treatment causes hepatic steatosis and treatment of curcumin attenuated effect of DEA that is due to its potential antioxidant properties.

Abstract 201: Maternal HDL-Cholesterol Levels in Women From the Gambia are Directly Related to Infant Birthweight

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Sandra L Rebholz ◽  
John T Melchior ◽  
Jeff Welge ◽  
Andrew M Prentice ◽  
Sophie E Moore ◽  
...  
Keyword(s):  
Fetal Growth ◽  
Growth Rates ◽  
Low Birthweight ◽  
Plasma Cholesterol ◽  
Hdl Cholesterol ◽  
Term Infants ◽  
Placental Function ◽  
Cholesterol Levels ◽  
Potential Biomarker ◽  
The Relationship

Babies born with low birthweight are often at a health disadvantage. Previous studies have shown direct relationships between maternal plasma cholesterol and infant birthweight in resource-rich countries. As plasma cholesterol levels are often decreased in resource-poor countries, the purpose of these studies was to evaluate the relationship between plasma cholesterol and birthweight in women enrolled in the ENID trial (ISRCTN49285450) in rural Gambia, West Africa. Plasma was obtained at enrolment (13.6±3.3 wk) and at 20 and 30 weeks of gestation; samples were obtained from women with term infants that weighed <2.75 kg or >3.25 kg at birth. Women with lower HDL-cholesterol (HDL-C) concentrations in mid-pregnancy had lower birthweight infants compared to women with higher HDL-C concentrations. There was no significant association between LDL-C or total cholesterol concentrations and birthweight. The relationship with HDL-C and birthweight was maintained when maternal BMI was included in the model. To begin to elucidate the processes involved in the regulation of fetal growth, placental function was examined in mice with increasing maternal HDL-C concentrations based on apoA-I levels; mice were lacking apoA-I (apoA-I -/- ), were wildtype (apoA-I +/+ ), or had excess apoA-I (apoA-I tg/tg ). HDL decreased in size as plasma apoA-I levels increased, and there were no statistical differences in the proteins carried by HDL, except for apoA-I, in pregnant mice of different genotypes. However, pregnancy alone led to changes in the HDL proteome. Importantly, fetuses of mice with lower concentrations of maternal HDL-C had reduced growth rates, not due to a lack of fetal apoA-I. The murine fetal growth rates were directly related to nutrient uptake by and transport across the placenta. This work suggests that maternal HDL affects placental function leading to enhanced nutrient supply and improved growth in utero, making HDL a potential biomarker for fetal growth and putative target for intervention.

Is there a role for the adrenals in the development of hypercholesterolemia in Zucker fatty rats?

1992 ◽  
Vol 263 (2) ◽  
pp. E287-E295
Author(s):  
F. Alarrayed ◽  
A. D. Hartman ◽  
J. R. Porter
Keyword(s):  
Adipose Tissue ◽  
Reductase Activity ◽  
Plasma Cholesterol ◽  
Density Lipoprotein ◽  
Liver Weight ◽  
Cholesterol Content ◽  
Zucker Rats ◽  
Tissue Storage ◽  
Hmg Coa Reductase ◽  
Coa Reductase

We tested the hypothesis that hypercorticosteronemia causes the hypercholesterolemia in young developing "fatty" rats. Obesity induced increases in corticosterone. Insulin, glucose, body weight, average daily food intake, plasma triglyceride, plasma phospholipids, liver weight, liver triglyceride, various adipose tissue parameters, and liver hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase activity were all ameliorated by adrenalectomy. Adrenalectomy exacerbated the hypercholesterolemia in obese animals and induced it in lean rats. Changes or lack of change in hepatic microsomal cholesterol, HMG-CoA reductase, and 7 alpha-hydroxylase, combined with the adrenalectomy-induced curtailment of tissue storage of cholesterol in adipose tissue, all contribute to the hypercholesterolemia caused by adrenalectomy. We suggest a mechanism whereby this may be related to elevated hepatic very low-density lipoprotein secretion rates. The elevated HMG-CoA reductase activity in obese rats results from the lower liver microsomal free cholesterol content. We conclude that the absence of glucocorticoids does not directly reduce plasma cholesterol in obese Zucker rats. The surprising elevation of cholesterol by adrenalectomy is due to other prevailing mechanisms in liver and adipose tissue, which curtail their capacity to store cholesterol.

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