Methionine- and choline-deficient diet induces hepatic changes characteristic of non-alcoholic steatohepatitis

Marcolin, Éder; Forgiarini, Luiz Felipe; Tieppo, Juliana; Dias, Alexandre Simões; Freitas, Luiz Antônio Rodrigues de; Marroni, Norma Possa

doi:10.1590/s0004-28032011000100015

Cited by 49 publications

(38 citation statements)

References 47 publications

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“…) and TBARS in liver from the NASH group in comparison with the control group (fig. ), corroborating previous studies which have shown a significant increase in liver lipoperoxidation in rodents with NASH induced by MCD diet .…”

Section: Discussionsupporting

confidence: 92%

Retracted: Quercetin Decreases Liver Damage in Mice with Non‐Alcoholic Steatohepatitis

Marcolin

Forgiarini

Rodrigues

et al. 2013

Basic Clin Pharma Tox

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Non-alcoholic steatohepatitis (NASH) is a frequent condition in obese patients that may progress to end-stage liver disease. This study was designed to evaluate the modulation of this condition by use of quercetin (Q), a flavonoid largely found in vegetable foods, with known anti-inflammatory and antioxidant properties, in the experimental model of non-alcoholic steatohepatitis (NASH) using a diet deficient in methionine and choline (MCD). Male C57BL6 mice were divided into four groups (n = 16): (i) Control plus vehicle (control ration plus carboxymethylcellulose 1% used as vehicle, CO + V); (ii) Control ration plus Q 50 mg/kg (CO + Q); (iii) MCD diet plus vehicle (NASH + V); and (iv) MCD diet plus Q (NASH + Q). Diets were administered for 4 weeks. At the end of the experimental period, liver alterations, bioindicators of oxidative stress and DNA damage were assessed. NASH was diagnosed in 100% of the mice that were fed the MCD diet. In addition, a significant increase in DNA damage in liver tissue from NASH + V group was observed in comparison with CO + V. The group NASH + Q showed a significant decrease in hepatic damage enzymes, lipoperoxidation, DNA damage and a lower degree of macrovesicular steatosis, ballooning and inflammatory process. These findings suggest that Q may have protective effects by improving liver integrity in NASH.

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Section: Discussionsupporting

confidence: 92%

Retracted: Quercetin Decreases Liver Damage in Mice with Non‐Alcoholic Steatohepatitis

Marcolin

Forgiarini

Rodrigues

et al. 2013

Basic Clin Pharma Tox

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“…Our results show that livers and plasma from HFHCC diet-fed mice have significant increases in FC and the different CEs in the liver. This is in contrast to MCD diet-fed mice in which cholesterol levels are not altered 49 , or in some cases have decreased 50 . Although liver FC levels progressively increase in obese NAFLD and NASH patients concurrent with TG, changes to CE levels are not observed 45 .…”

Section: Discussioncontrasting

confidence: 65%

Metabolomic characteristics of cholesterol-induced non-obese nonalcoholic fatty liver disease in mice

Showalter

Čajka

et al. 2017

Sci Rep

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Nonalcoholic fatty liver disease (NAFLD) in non-obese patients remains a clinical condition with unclear etiology and pathogenesis. Using a metabolomics approach in a mouse model that recapitulates almost all the characteristic features of non-obese NAFLD, we aimed to advance mechanistic understanding of this disorder. Mice fed high fat, high cholesterol, cholate (HFHCC) diet for three weeks consistently developed hepatic pathology similar to NAFLD and nonalcoholic steatohepatitis (NASH) without changes to body weight or fat pad weights. Gas- and liquid chromatography/mass spectrometry-based profiling of lipidomic and primary metabolism changes in the liver and plasma revealed that systemic mechanisms leading to steatosis and hepatitis in this non-obese NAFLD model were driven by a combination of effects directed by elevated free cholesterol, cholesterol esters and cholic acid, and associated changes to metabolism of sphingomyelins and phosphatidylcholines. These results demonstrate that mechanisms underlying cholesterol-induced non-obese NAFLD are distinct from NAFLD occurring as a consequence of metabolic syndrome. In addition, this investigation provides one of the first metabolite reference profiles for interpreting effects of dietary and hepatic cholesterol in human non-obese NAFLD/NASH patients.

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“…AChE expression in liver tissue is closely interconnected with oxidative stress (Ghareeb et al 2011). Methionine deficiency results in decrease of cysteine, the major precursor of glutathione (GSH), which is the main cellular antioxidant, while choline deprivation decreases phosphatidylcholine portion in very low-density lipoprotein particles (VLDL), with consequential accumulation of triacylglycerol (TAG) in liver (Marcolin et al 2011). However, various pathophysiological processes in liver were recognized as consequences of oxidative stress (Bianchi et al 2000;Jorgačević et al 2014).…”

Section: Discussionmentioning

confidence: 99%

“…In current study, increase in hepatic AChE activity is in agreement with hypothesis that this enzyme may serve as marker of inflammation in liver (Das 2012). MCD animal model, which is used in this experiment, is considered convenient basis for examining nonalcoholic steatohepatitis (NASH) (Marcolin et al 2011). Increased concentration of AChE lowers ACh level, leading to reduction or absence of its antiinflammatory activity (Das 2012).…”

Section: Discussionmentioning

confidence: 99%

Methionine-choline deprivation alters liver and brain acetylcholinesterase activity in C57BL6 mice

Vučević

Cerović²,

Mladenović³

et al. 2016

gpb

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Choline and methionine are precursors of acetylcholine, whose hydrolysis is catalyzed by acetylcholinesterase (AChE). Considering the possibility of their common deficiency, we investigated the influence of methionine-choline deprivation on AChE activity in liver and various brain regions (hypothalamus, hippocampus, cerebral cortex and striatum) in mice fed with methionine-choline deficient (MCD) diet. Male C57BL/6 mice (n = 28) were randomly and equally divided into following groups: control group fed with standard diet for 6 weeks (C) and groups fed with MCD diet for 2 weeks (MCD2), 4 weeks (MCD4) and for 6 weeks (MCD6). After the diet, mice were sacrificied and AChE activity in liver and brain was determined spectrophotometrically. Hepatic AChE activity was higher in MCD2, MCD4 and MCD6 compared to control (p < 0.01), with most prominent increase in MCD6. AChE activity in hypothalamus was higher in MCD4 and MCD6 vs. control (p < 0.05 and p < 0.01, respectively), as well as in MCD6 compared to MCD4 (p < 0.01). In hippocampus, increase in AChE activity was shown in MCD6 compared to control (p < 0.01). In cortex and striatum, increase in AChE activity was noted in MCD6 compared to control (p < 0.05). Our findings indicate the increase of hepatic and brain AChE activity in mice caused by methionine-choline deprivation.

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Methionine- and choline-deficient diet induces hepatic changes characteristic of non-alcoholic steatohepatitis

Abstract: The low cost and easily accessible methionine- and choline-deficient diet explored in this study is highly effective in inducing steatosis and steatohepatitis in animal model, alterations that are similar to those observed in human livers.

Cited by 49 publications

References 47 publications

Retracted: Quercetin Decreases Liver Damage in Mice with Non‐Alcoholic Steatohepatitis

Retracted: Quercetin Decreases Liver Damage in Mice with Non‐Alcoholic Steatohepatitis

Metabolomic characteristics of cholesterol-induced non-obese nonalcoholic fatty liver disease in mice

Methionine-choline deprivation alters liver and brain acetylcholinesterase activity in C57BL6 mice

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