scholarly journals Multi-technique comparison of atherogenic and MCD NASH models highlights changes in sphingolipid metabolism

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Sophie A. Montandon ◽  
Emmanuel Somm ◽  
Ursula Loizides-Mangold ◽  
Claudio de Vito ◽  
Charna Dibner ◽  
...  
Keyword(s):  
Liver Damage ◽  
Liver Lipid ◽  
Phospholipid Composition ◽  
Significant Rise ◽  
Sphingolipid Metabolism ◽  
Similar Degree ◽  
Transcriptional Level ◽  
Nonalcoholic Fatty Liver ◽  
Technique Comparison ◽  
Strong Depletion

AbstractLipotoxicity is a key player in the pathogenesis of nonalcoholic steatohepatitis (NASH), a progressive subtype of nonalcoholic fatty liver disease (NAFLD). In the present study, we combine histological, transcriptional and lipidomic approaches to dissociate common and specific alterations induced by two classical dietary NASH models (atherogenic (ATH) and methionine/choline deficient (MCD) diet) in C57BL/6J male mice. Despite a similar degree of steatosis, MCD-fed mice showed more pronounced liver damage and a worsened pro-inflammatory and pro-fibrogenic environment than ATH-fed mice. Regarding lipid metabolism, the ATH diet triggered hepatic counter regulatory mechanisms, while the MCD diet worsened liver lipid accumulation by a concomitant increase in lipid import and reduction in lipid export. Liver lipidomics revealed sphingolipid enrichment in both NASH models that was accompanied by an upregulation of the ceramide biosynthesis pathway and a significant rise in dihydroceramide levels. In contrast, the phospholipid composition was not substantially altered by the ATH diet, whereas the livers of MCD-fed mice presented a reduced phosphatidylcholine to phosphatidylethanolamine (PC/PE) ratio and a strong depletion in phospholipids containing the sum of 34–36 carbons in their fatty acid chains. Therefore, the assessment of liver damage at the histological and transcriptional level combined with a lipidomic analysis reveals sphingolipids as shared mediators in liver lipotoxicity and pathogenesis of NASH.

NR1H4 rs35724 G>C Variant Modulates Liver Damage in Nonalcoholic Fatty Liver Disease

2020 ◽  
Author(s):  
Stefania Grimaudo ◽  
Paola Dongiovanni ◽  
Jussi Pihlajamäki ◽  
Mohammed Eslam ◽  
Hannele Yki-Järvinen ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Liver Damage ◽  
Fatty Liver Disease ◽  
Nonalcoholic Fatty Liver

scholarly journals Doxepin Exacerbates Renal Damage, Glucose Intolerance, Nonalcoholic Fatty Liver Disease and Urinary Chromium Loss in Obese Mice

2021 ◽  
Vol 14 (3) ◽  
pp. 267
Author(s):  
Geng-Ruei Chang ◽  
Po-Hsun Hou ◽  
Wei-Cheng Yang ◽  
Chao-Min Wang ◽  
Pei-Shan Fan ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Glucose Intolerance ◽  
Fatty Liver Disease ◽  
Renal Damage ◽  
Liver Lipid ◽  
Interleukin 1 ◽  
Mrna Levels ◽  
Nonalcoholic Fatty Liver

Doxepin is commonly prescribed for depression and anxiety treatment. Doxepin-related disruptions to metabolism and renal/hepatic adverse effects remain unclear; thus, the underlying mechanism of action warrants further research. Here, we investigated how doxepin affects lipid change, glucose homeostasis, chromium (Cr) distribution, renal impairment, liver damage, and fatty liver scores in C57BL6/J mice subjected to a high-fat diet and 5 mg/kg/day doxepin treatment for eight weeks. We noted that the treated mice had higher body, kidney, liver, retroperitoneal, and epididymal white adipose tissue weights; serum and liver triglyceride, alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, and creatinine levels; daily food efficiency; and liver lipid regulation marker expression. They also demonstrated exacerbated insulin resistance and glucose intolerance with lower Akt phosphorylation, GLUT4 expression, and renal damage as well as higher reactive oxygen species and interleukin 1 and lower catalase, superoxide dismutase, and glutathione peroxidase levels. The treated mice had a net-negative Cr balance due to increased urinary excretion, leading to Cr mobilization, delaying hyperglycemia recovery. Furthermore, they had considerably increased fatty liver scores, paralleling increases in adiponectin, FASN, PNPLA3, FABP4 mRNA, and SREBP1 mRNA levels. In conclusion, doxepin administration potentially worsens renal injury, nonalcoholic fatty liver disease, and diabetes.

NR1H4 rs35724 G>C Variant Modulates Liver Damage in Nonalcoholic Fatty Liver Disease

2021 ◽  
Author(s):  
Stefania Grimaudo ◽  
Paola Dongiovanni ◽  
Jussi Pihlajamäki ◽  
Mohammed Eslam ◽  
Hannele Yki‐Järvinen ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Liver Damage ◽  
Fatty Liver Disease ◽  
Nonalcoholic Fatty Liver

scholarly journals Circulating Levels of Pro-Neurotensin and Its Relationship with Nonalcoholic Steatohepatitis and Hepatic Lipid Metabolism

Metabolites ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 373
Author(s):  
Beatriz Villar ◽  
Laia Bertran ◽  
Carmen Aguilar ◽  
Jessica Binetti ◽  
Salomé Martínez ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Nonalcoholic Steatohepatitis ◽  
Liver Lipid ◽  
Normal Liver ◽  
Normal Weight ◽  
Published Data ◽  
Mrna Levels ◽  
Nonalcoholic Fatty Liver ◽  
Hepatic Expression ◽  
Liver Lipid Metabolism

Recent studies suggest a link between pro-neurotensin (pro-NT) and nonalcoholic fatty liver disease (NAFLD), but the published data are conflicting. Thus, we aimed to analyze pro-NT levels in women with morbid obesity (MO) and NAFLD to investigate if this molecule is involved in NAFLD and liver lipid metabolism. Plasma levels of pro-NT were determined in 56 subjects with MO and 18 with normal weight (NW). All patients with MO were subclassified according to their liver histology into the normal liver (NL, n = 20) and NAFLD (n = 36) groups. The NAFLD group had 17 subjects with simple steatosis (SS) and 19 with nonalcoholic steatohepatitis (NASH). We used a chemiluminescence sandwich immunoassay to quantify pro-NT in plasma and RT-qPCR to evaluate the hepatic mRNA levels of several lipid metabolism-related genes. We reported that pro-NT levels were significantly higher in MO with NAFLD than in MO without NAFLD. Additionally, pro-NT levels were higher in NASH patients than in NL. The hepatic expression of lipid metabolism-related genes was found to be altered in NAFLD, as previously reported. Additionally, although pro-NT levels correlated with LDL, there was no association with the main lipid metabolism-related genes. These findings suggest that pro-NT could be related to NAFLD progression.

scholarly journals Role of long-chain acyl-CoAs in the regulation of mycolic acid biosynthesis in mycobacteria

Open Biology ◽  
2017 ◽  
Vol 7 (7) ◽  
pp. 170087 ◽  
Author(s):  
Yi Ting Tsai ◽  
Valentina Salzman ◽  
Matías Cabruja ◽  
Gabriela Gago ◽  
Hugo Gramajo
Keyword(s):  
Cell Envelope ◽  
Phospholipid Composition ◽  
Mycolic Acid ◽  
Transcriptional Level ◽  
Direct Role ◽  
Conditional Mutant ◽  
In The Wild ◽  
Fas Ii

One of the dominant features of the biology of Mycobacterium tuberculosis , and other mycobacteria, is the mycobacterial cell envelope with its exceptional complex composition. Mycolic acids are major and very specific components of the cell envelope and play a key role in its architecture and impermeability. Biosynthesis of mycolic acid (MA) precursors requires two types of fatty acid synthases, FAS I and FAS II, which should work in concert in order to keep lipid homeostasis tightly regulated. Both FAS systems are regulated at their transcriptional level by specific regulatory proteins. FasR regulates components of the FAS I system, whereas MabR and FadR regulate components of the FAS II system. In this article, by constructing a tight mabR conditional mutant in Mycobacterium smegmatis mc 2 155, we demonstrated that sub-physiological levels of MabR lead to a downregulation of the fasII genes, inferring that this protein is a transcriptional activator of the FAS II system. In vivo labelling experiments and lipidomic studies carried out in the wild-type and the mabR conditional mutant demonstrated that under conditions of reduced levels of MabR, there is a clear inhibition of biosynthesis of MAs, with a concomitant change in their relative composition, and of other MA-containing molecules. These studies also demonstrated a change in the phospholipid composition of the membrane of the mutant strain, with a significant increase of phosphatidylinositol. Gel shift assays carried out with MabR and P fasII as a probe in the presence of different chain-length acyl-CoAs strongly suggest that molecules longer than C 18 can be sensed by MabR to modulate its affinity for the operator sequences that it recognizes, and in that way switch on or off the MabR-dependent promoter. Finally, we demonstrated the direct role of MabR in the upregulation of the fasII operon genes after isoniazid treatment.

872 ADIPONECTIN IN NONALCOHOLIC FATTY LIVER DISEASE: CORRELATION WITH LIVER DAMAGE AND PNPLA3 GENOTYPE

2011 ◽  
Vol 54 ◽  
pp. S347-S348 ◽  
Author(s):  
L. Valenti ◽  
R. Rametta ◽  
E. Canavesi ◽  
M. Ruscica ◽  
A.L. Fracanzani ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Liver Damage ◽  
Fatty Liver Disease ◽  
Nonalcoholic Fatty Liver

scholarly journals Features of metabolic pathology of the liver under the influence of industrial aerosols

2021 ◽  
Vol 100 (9) ◽  
pp. 943-946
Author(s):  
Marina V. Sheenkova ◽  
Oksana P. Rushkevich ◽  
Irina V. Yatsyna
Keyword(s):  
Carbohydrate Metabolism ◽  
Biliary Tract ◽  
Liver Damage ◽  
Blood Analysis ◽  
Toxic Effects ◽  
Industrial Workers ◽  
Nonalcoholic Fatty Liver ◽  
Copper Nickel ◽  
Pathology Of The Liver ◽  
Carbon Based

Ntroduction. The article is devoted to the study of the features of the metabolic pathology of the liver under the influence of harmful industrial factors. The relevance of the study of nonalcoholic fatty liver disease of workers in contact with industrial aerosols is due to the high prevalence of the disease among the working-age population, the polyethological nature of the pathology, including the pathogenetic relationship with external household and occupational toxic effects. Materials and methods. The were examined two hundred four industrial production workers, divided into four groups according to the composition of the affected aerosol: copper-nickel ore dust, welding aerosol, quartz-containing dust, carbon-based dust. The survey was conducted using the AUDIT questionnaire, examination of patients, anthropometry, ultrasound examination of the abdominal organs, biochemical blood analysis, determination of viral hepatitis B and C markers, and serum immunoglobulins. Results. The frequency of detection of ultrasonic signs of liver damage in the examined patients who came into contact with copper-nickel aerosol dust significantly exceeds the same indicator of the studied patients who came into contact with quartz-containing dust (p<0.05) and also exceeds the frequency of detection in the group working under the influence of carbon-based and welding aerosol (p>0.05). Most often, an increase in the activity of liver enzymes was noted among those working in contact with copper-nickel ore dust. Significant differences were found between groups 1 and 3; 1 and 4 (p<0.05). There were no significant differences between the groups in the frequency of lipid and carbohydrate metabolism disorders and biliary tract pathology. Discussion. The results of the study may be related to the toxic effects of the copper-nickel aerosol but may also be associated with the climatogeographic features of the workers ‘ habitat. Conclusion. The prevalence of liver diseases in the group that came into contact with copper-nickel dust was established. The revealed changes do not depend on lipid and carbohydrate metabolism features, pathology of the biliary tract. For a detailed study of liver damage in industrial workers, it is necessary to conduct an in-depth study.

scholarly journals Apolipoprotein CIII Overexpression-Induced Hypertriglyceridemia Increases Nonalcoholic Fatty Liver Disease in Association with Inflammation and Cell Death

2017 ◽  
Vol 2017 ◽  
pp. 1-18 ◽  
Author(s):  
Adriene A. Paiva ◽  
Helena F. Raposo ◽  
Amarylis C. B. A. Wanschel ◽  
Tarlliza R. Nardelli ◽  
Helena C. F. Oliveira
Keyword(s):  
Cell Death ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Lipid Content ◽  
Fatty Liver Disease ◽  
Liver Lipid ◽  
Hepatic Insulin Resistance ◽  
Nonalcoholic Fatty Liver ◽  
Liver Lipid Content

Nonalcoholic fatty liver disease (NAFLD) is the principal manifestation of liver disease in obesity and metabolic syndrome. By comparing hypertriglyceridemic transgenic mice expressing apolipoprotein (apo) CIII with control nontransgenic (NTg) littermates, we demonstrated that overexpression of apoCIII, independent of a high-fat diet (HFD), produces NAFLD-like features, including increased liver lipid content; decreased antioxidant power; increased expression of TNFα, TNFα receptor, cleaved caspase-1, and interleukin-1β; decreased expression of adiponectin receptor-2; and increased cell death. This phenotype is aggravated and additional NAFLD features are differentially induced in apoCIII mice fed a HFD. HFD induced glucose intolerance together with increased gluconeogenesis, indicating hepatic insulin resistance. Additionally, the HFD led to marked increases in plasma TNFα (8-fold) and IL-6 (60%) in apoCIII mice. Cell death signaling (Bax/Bcl2), effector (caspase-3), and apoptosis were augmented in apoCIII mice regardless of whether a HFD or a low-fat diet was provided. Fenofibrate treatment reversed several of the effects associated with diet and apoCIII expression but did not normalize inflammatory traits even when liver lipid content was fully corrected. These results indicate that apoCIII and/or hypertriglyceridemia plays a major role in liver inflammation and cell death, which in turn increases susceptibility to and the severity of diet-induced NAFLD.

β-Sitosterol mitigates the development of high-fructose diet-induced nonalcoholic fatty liver disease in growing male Sprague–Dawley rats

2020 ◽  
Vol 98 (1) ◽  
pp. 44-50 ◽  
Author(s):  
Nontobeko M. Gumede ◽  
Busisani W. Lembede ◽  
Pilani Nkomozepi ◽  
Richard L. Brooksbank ◽  
Kennedy H. Erlwanger ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Liver Lipid ◽  
Male Rat ◽  
Nonalcoholic Fatty Liver ◽  
High Fructose Diet ◽  
Group I ◽  
High Fructose

Fructose contributes to the development of nonalcoholic fatty liver disease (NAFLD). β-Sitosterol (Bst), a naturally occurring phytosterol, has antihyperlipidaemic and hepatoprotective properties. This study interrogated the potential protective effect of β-sitosterol against NAFLD in growing rats fed a high-fructose diet, modelling children fed obesogenic diets. Forty-four 21 day old male rat pups were randomly allocated to and administered the following treatments for 12 weeks: group I, standard rat chow (SRC) + plain drinking water (PW) + plain gelatine cube (PC); group II, SRC + 20% w/v fructose solution (FS) as drinking fluid + PC; group III, SRC + FS + 100 mg/kg fenofibrate in a gelatine cube; group IV, SRC + FS + 20 mg/kg β-sitosterol gelatine cube (Bst); group V, SRC + PW + Bst. Terminally, the livers were dissected out, weighed, total liver lipid content determined, and histological analyses done. Harvested plasma was used to determine the surrogate biomarkers of liver function. The high-fructose diet caused increased (p < 0.05) hepatic lipid (total) accretion (>10% liver mass), micro- and macrovesicular hepatic steatosis, and hepatic inflammation. β-Sitosterol and fenofibrate prevented the high-fructose diet-induced macrovesicular steatosis and prevented the progression of NAFLD to steatohepatitis. β-Sitosterol can prospectively be used to mitigate diet-induced NAFLD.

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