scholarly journals Mouse models of hereditary hemochromatosis do not develop early liver fibrosis in response to a high fat diet

2018 ◽  
Author(s):  
John Wagner ◽  
Carine Fillebeen ◽  
Tina Haliotis ◽  
Jeannie Mui ◽  
Hojatollah Vali ◽  
...  
Keyword(s):  
Liver Disease ◽  
Liver Fibrosis ◽  
Liver Injury ◽  
Iron Overload ◽  
Mouse Models ◽  
High Fat Diet ◽  
Hereditary Hemochromatosis ◽  
Regulatory Function ◽  
High Fat ◽  
Ultrastructural Studies

AbstractHepatic iron overload, a hallmark of hereditary hemochromatosis (HH), triggers progressive liver disease. There is also increasing evidence for a pathogenic role of iron in non-alcoholic fatty liver disease (NAFLD), which may progress to non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis and hepatocellular cancer. Mouse models of HH and NAFLD can be used to explore potential interactions between iron and lipid metabolic pathways. Hfe−/− mice, a model of moderate iron overload, were reported to develop early liver fibrosis in response to a high fat diet. However, this was not the case with Hjv−/− mice, a model of severe iron overload. These data raised the possibility that the Hfe gene may protect against liver injury independently of its iron regulatory function. Herein, we addressed this hypothesis in a comparative study utilizing wild type, Hfe−/−, Hjv−/− and double Hfe−/−Hjv−/− mice. The animals, all in C57/BL6 background, were fed with a high fat diet for 14 weeks and developed hepatic steatosis, associated with mild iron overload. Hfe co-ablation did not sensitize steatotic Hjv-deficient mice to liver injury. Moreover, we did not observe any signs of liver inflammation or fibrosis even in single steatotic Hfe−/− mice. Ultrastructural studies revealed a reduced lipid and glycogen content in Hjv−/− hepatocytes, indicative of a metabolic defect. Interestingly, glycogen levels were restored in double Hfe−/−Hjv−/− mice, which is consistent with a metabolic function of Hfe. We conclude that hepatocellular iron excess does not aggravate diet-induced steatosis to steatohepatitis or early liver fibrosis in mouse models of HH, irrespectively of the presence or lack of Hfe.

scholarly journals Mouse models of hereditary hemochromatosis do not develop early liver fibrosis in response to a high fat diet

PLoS ONE ◽  
2019 ◽  
Vol 14 (8) ◽  
pp. e0221455 ◽  
Author(s):  
John Wagner ◽  
Carine Fillebeen ◽  
Tina Haliotis ◽  
Edouard Charlebois ◽  
Angeliki Katsarou ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Mouse Models ◽  
High Fat Diet ◽  
Hereditary Hemochromatosis ◽  
High Fat

scholarly journals Pengaruh Fraksi Air Buah Lemon terhadap Gambaran Morfologi Jaringan Hati Mencit Tua yang Diberi Pakan Tinggi Lemak

2019 ◽  
Vol 1 (1) ◽  
pp. 49-53
Author(s):  
Nur Azmiati Mundiri ◽  
Meta Maulida Damayanti ◽  
Maya Tejasari ◽  
Annisa Rahmah Furqaani ◽  
R.A. Retno Ekowati
Keyword(s):  
Liver Disease ◽  
Liver Injury ◽  
High Fat Diet ◽  
Fatty Liver Disease ◽  
Control Group ◽  
Citrus Limon ◽  
High Fat ◽  
Alcoholic Fatty Liver ◽  
Water Fraction ◽  
Alcoholic Fatty Liver Disease

Dislipidemia merupakan salah satu faktor risiko dari non alcoholic fatty liver disease (NAFLD). NAFLD mempunyai karakteristik steatosis hepatik, hepatocyte ballooning, inflamasi lobular, dan fibrosis.  Kandungan flavonoid pada Citrus limon dipercaya dapat mencegah steatosis hepatik. Tujuan penelitian ini mengetahui pengaruh fraksi air buah lemon terhadap gambaran morfologi jaringan hati mencit tua yang diberi pakan tinggi lemak. Penelitian ini merupakan penelitian eksperimental dengan subjek penelitian adalah mencit (Mus musculus) jantan galur DDY tua yang dibagi menjadi empat kelompok secara acak, terdiri atas kelompok kontrol dan tiga kelompok perlakuan dengan konsentrasi fraksi air buah lemon 20,6; 41,2; 82,4 mg/20 gram BB mencit. Data jumlah hepatosit dengan droplet lemak dan hepatocyte ballooning dianalisis menggunakan uji ANOVA dan Uji Kruskal Willis. Terdapat  perbedaan jumlah hepatosit dengan droplet lemak (p=0,063) dan hepatosit yang mengalami pembengkakan (p=0,109) antara kelompok kontrol dan kelompok perlakuan. Simpulan penelitian ini adalah fraksi air buah lemon dapat mencegah hepatocyte ballooning dan pembentukan droplet lemak pada hepatosit mencit tua yang diberikan pakan tinggi lemak.  PROTECTIVE EFFECT OF WATER FRACTION OF LEMON ON HIGH-FAT DIET-INDUCED LIVER INJURY IN OLD MICEDyslipidemia is one of the risk factors of non alcoholic fatty liver disease (NAFLD). NAFLD is characterized by hepatic steatosis, hepatocyte ballooning, lobular inflammation, and fibrosis. Flavonoid in Citrus limon is believed to prevent hepatic steatosis. The aim of this study is to know the protective effect of lemon’s water fraction on high-fat diet-induced liver injury in old mice. This was an experimental study with old male mice (Mus musculus) DDY strain divided into four groups randomly, consisting of control group and three groups given with water fraction of lemon at concentration 20.6; 41.2; 82.4 mg/20 gram mice body weight. Total count of hepatocytes with fat droplets and hepatocytes ballooning were analyzed using ANOVA and Kruskal Willis tests. There are differences in the amount of hepatocytes with fat droplets (p=0.063) and hepatocytes ballooning (p=0.109) between the control group and the treatment group. The conclusion of this study is lemon’s water fraction can prevent the formation of hepatocyte ballooning and fat droplet in old mice’s hepatocyte fed by high-fat diet.

Water extract of Ferula lehmanni Boiss. prevents high-fat diet-induced overweight and liver injury by modulating intestinal microbiota in mice

2022 ◽  
Author(s):  
Yuting Ye ◽  
Lin Shi ◽  
Peng Wang ◽  
Minmin Yang ◽  
Ping Zhan ◽  
...  
Keyword(s):  
Liver Disease ◽  
Liver Injury ◽  
Fatty Liver ◽  
Intestinal Microbiota ◽  
High Fat Diet ◽  
Fatty Liver Disease ◽  
Water Extract ◽  
High Fat ◽  
Increased Risk ◽  
Health Complications

Obesity, often accompanied by hepatic steatosis, has been associated with an increased risk of health complications such as fatty liver disease and certain cancers. Ferula lehmannii Boiss. a food and...

scholarly journals Effects of high fructose intake on liver injury progression in high fat diet induced fatty liver disease in ovariectomized female mice

2018 ◽  
Vol 118 ◽  
pp. 190-197 ◽  
Author(s):  
Tomoko Ohashi ◽  
Masaki Kato ◽  
Akihiro Yamasaki ◽  
Akifumi Kuwano ◽  
Hideo Suzuki ◽  
...  
Keyword(s):  
Liver Disease ◽  
Liver Injury ◽  
Fatty Liver ◽  
High Fat Diet ◽  
Fatty Liver Disease ◽  
High Fat ◽  
Female Mice ◽  
Fructose Intake ◽  
High Fructose ◽  
Injury Progression

scholarly journals Nanoformulated SOD1 ameliorates the combined NASH and alcohol-associated liver disease partly via regulating CYP2E1 expression in adipose tissue and liver

2020 ◽  
Vol 318 (3) ◽  
pp. G428-G438
Author(s):  
Thiyagarajan Gopal ◽  
Narendra Kumar ◽  
Curtis Perriotte-Olson ◽  
Carol A. Casey ◽  
Terrence M. Donohue ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Liver Disease ◽  
Free Fatty Acid ◽  
Liver Injury ◽  
Nonalcoholic Steatohepatitis ◽  
High Fat Diet ◽  
Control Diet ◽  
High Fat

Enhanced free fatty acid (FFA) flux from adipose tissue (AT) to liver plays an important role in the development of nonalcoholic steatohepatitis (NASH) and alcohol-associated liver disease (AALD). We determined the effectiveness of nanoformulated superoxide dismutase 1 (Nano) in attenuating liver injury in a mouse model exhibiting a combination of NASH and AALD. Male C57BL6/J mice were fed a chow diet (CD) or a high-fat diet (HF) for 10 wk followed by pair feeding of the Lieber-DeCarli control (control) or ethanol (ET) diet for 4 wk. Nano was administered once every other day for the last 2 wk of ET feeding. Mice were divided into 1) CD + control diet (CD + Cont), 2) high-fat diet (HF) + control diet (HF + Cont), 3) HF + Cont + Nano, 4) HF + ET diet (HF + ET), and 5) HF + ET + Nano. The total fat mass, visceral AT mass (VAT), and VAT perilipin 1 content were significantly lower only in HF + ET-fed mice but not in HF + ET + Nano-treated mice compared with controls. The HF + ET-fed mice showed an upregulation of VAT CYP2E1 protein, and Nano abrogated this effect. We noted a significant rise in plasma FFAs, ALT, and monocyte chemoattractant protein-1 in HF + ET-fed mice, which was blunted in HF + ET + Nano-treated mice. HF + ET-induced increases in hepatic steatosis and inflammatory markers were attenuated upon Nano treatment. Nano reduced hepatic CYP2E1 and enhanced catalase levels in HF + ET-fed mice with a concomitant increase in SOD1 protein and activity in liver. Nano was effective in attenuating AT and liver injury in mice exhibiting a combination of NASH and AALD, partly via reduced CYP2E1-mediated ET metabolism in these organs. NEW & NOTEWORTHY Increased free fatty acid flux from adipose tissue (AT) to liver accompanied by oxidative stress promotes nonalcoholic steatohepatitis (NASH) and alcohol-associated liver injury (AALD). Obesity increases the severity of AALD. Using a two-hit model involving a high-fat diet and chronic ethanol feeding to mice, and treating them with nanoformulated superoxide dismutase (nanoSOD), we have shown that nanoSOD improves AT lipid storage, reduces CYP2E1 in AT and liver, and attenuates the combined NASH/AALD in mice.

scholarly journals Iron-Induced Liver Injury: A Critical Reappraisal

2019 ◽  
Vol 20 (9) ◽  
pp. 2132 ◽  
Author(s):  
Steven A. Bloomer ◽  
Kyle E. Brown
Keyword(s):  
Liver Disease ◽  
Animal Models ◽  
Liver Injury ◽  
Iron Overload ◽  
Liver Damage ◽  
Human Liver ◽  
Hereditary Hemochromatosis ◽  
Hepatitis C Infection ◽  
Nonalcoholic Fatty Liver ◽  
Hepatocyte Necrosis

Iron is implicated in the pathogenesis of a number of human liver diseases. Hereditary hemochromatosis is the classical example of a liver disease caused by iron, but iron is commonly believed to contribute to the progression of other forms of chronic liver disease such as hepatitis C infection and nonalcoholic fatty liver disease. In this review, we present data from cell culture experiments, animal models, and clinical studies that address the hepatotoxicity of iron. These data demonstrate that iron overload is only weakly fibrogenic in animal models and rarely causes serious liver damage in humans, calling into question the concept that iron overload is an important cause of hepatotoxicity. In situations where iron is pathogenic, iron-induced liver damage may be potentiated by coexisting inflammation, with the resulting hepatocyte necrosis an important factor driving the fibrogenic response. Based on the foregoing evidence that iron is less hepatotoxic than is generally assumed, claims that assign a causal role to iron in liver injury in either animal models or human liver disease should be carefully evaluated.

A high-fat diet modulates iron metabolism but does not promote liver fibrosis in hemochromatotic Hjv−/− mice

2015 ◽  
Vol 308 (4) ◽  
pp. G251-G261 ◽  
Author(s):  
Ranjit Singh Padda ◽  
Konstantinos Gkouvatsos ◽  
Maria Guido ◽  
Jeannie Mui ◽  
Hojatollah Vali ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Iron Overload ◽  
Fatty Liver ◽  
Iron Metabolism ◽  
High Fat Diet ◽  
Smooth Muscle Actin ◽  
Liver Steatosis ◽  
Hepatic Iron ◽  
High Fat ◽  
Juvenile Hemochromatosis

Hemojuvelin (Hjv) is a membrane protein that controls body iron metabolism by enhancing signaling to hepcidin. Hjv mutations cause juvenile hemochromatosis, a disease of systemic iron overload. Excessive iron accumulation in the liver progressively leads to inflammation and disease, such as fibrosis, cirrhosis, or hepatocellular cancer. Fatty liver (steatosis) may also progress to inflammation (steatohepatitis) and liver disease, and iron is considered as pathogenic cofactor. The aim of this study was to investigate the pathological implications of parenchymal iron overload due to Hjv ablation in the fatty liver. Wild-type (WT) and Hjv−/− mice on C57BL/6 background were fed a standard chow, a high-fat diet (HFD), or a HFD supplemented with 2% carbonyl iron (HFD+Fe) for 12 wk. The animals were analyzed for iron and lipid metabolism. As expected, all Hjv−/− mice manifested higher serum and hepatic iron and diminished hepcidin levels compared with WT controls. The HFD reduced iron indexes and promoted liver steatosis in both WT and Hjv−/− mice. Notably, steatosis was attenuated in Hjv−/− mice on the HFD+Fe regimen. Hjv−/− animals gained less body weight and exhibited reduced serum glucose and cholesterol levels. Histological and ultrastructural analysis revealed absence of iron-induced inflammation or liver fibrosis despite early signs of liver injury (expression of α-smooth muscle actin). We conclude that parenchymal hepatic iron overload does not suffice to trigger progression of liver steatosis to steatohepatitis or fibrosis in C57BL/6 mice.

scholarly journals Obesity and binge alcohol intake are deadly combination to induce steatohepatitis: A model of high-fat diet and binge ethanol intake

2020 ◽  
Vol 26 (4) ◽  
pp. 586-594 ◽  
Author(s):  
Seonghwan Hwang ◽  
Tianyi Ren ◽  
Bin Gao
Keyword(s):  
Liver Injury ◽  
Binge Drinking ◽  
Mouse Models ◽  
High Fat Diet ◽  
Neutrophil Infiltration ◽  
Mitogen Activated Protein Kinase ◽  
High Fat ◽  
Hepatic Expression ◽  
Underlying Mechanisms ◽  
Binge Ethanol

Obesity and binge drinking often coexist and work synergistically to promote steatohepatitis; however, the underlying mechanisms remain obscure. In this mini-review, we briefly summarize clinical evidence of the synergistical effect of obesity and heavy drinking on steatohepatitis and discuss the underlying mechanisms obtained from the study of several mouse models. High-fat diet (HFD) feeding and binge ethanol synergistically induced steatohepatitis and fibrosis in mice with significant intrahepatic neutrophil infiltration; such HFD-plus-ethanol treatment markedly up-regulated the hepatic expression of many chemokines with the highest fold (approximately 30-fold) induction of chemokine (C-X-C motif) ligand 1 (<i>Cxcl1</i>), which contributes to hepatic neutrophil infiltration and liver injury. Furthermore, HFD feeding activated peroxisome proliferator-activated receptor gamma that subsequently inhibited CXCL1 upregulation in hepatocytes, thereby forming a negative feedback loop to prevent neutrophil overaction; whereas binge ethanol blocked this loop and then exacerbated CXCL1 elevation, neutrophil infiltration, and liver injury. Interestingly, inflamed mouse hepatocytes attracted neutrophils less effectively than inflamed human hepatocytes due to the lower induction of CXCL1 and the lack of the interleukin (IL)-8 gene in the mouse genome, which may be one of the reasons for difficulty in development of mouse models of alcoholic steatohepatitis and nonalcoholic steatohepatitis (NASH). Hepatic overexpression of <i>Cxcl1</i> and/or IL-8 promoted steatosis-to-NASH progression in HFD-fed mice by inducing neutrophil infiltration, oxidative stress, hepatocyte death, fibrosis, and p38 mitogen-activated protein kinase activation. Collectively, obesity and binge drinking synergistically promote steatohepatitis via the induction of CXCL1 and subsequent hepatic neutrophil infiltration.

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