Dietary iron restriction leads to a reduction in hepatic fibrosis in a rat model of non-alcoholic steatohepatitis

Abe, Naomichi; Tsuchida, Takuma; Yasuda, Shin-ichiro; Oka, Kozo

doi:10.1242/bio.040519

Cited by 15 publications

(19 citation statements)

References 29 publications

(44 reference statements)

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“…In addition, the systemic inflammatory state induced by NAFLD may predispose the organism to increased hepcidin levels. Serum iron levels previously reported in rats fed with the MCD diet, were comparable with those found in the MCD rats used in this study [39]. Furthermore, no significant increase in serum iron documented in the present study was comparable with results previously reported: significantly higher levels in serum iron occurred only after 4 weeks [39].…”

Section: Iron and Nafldsupporting

confidence: 92%

“…Serum iron levels previously reported in rats fed with the MCD diet, were comparable with those found in the MCD rats used in this study [39]. Furthermore, no significant increase in serum iron documented in the present study was comparable with results previously reported: significantly higher levels in serum iron occurred only after 4 weeks [39]. The lack in serum Fe alterations may be attributed to early NAFLD stage; this result could also explain the absence of significant correlations versus pro-inflammatory markers.…”

Section: Iron and Nafldsupporting

confidence: 90%

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Associations between serum trace elements and inflammation in two animal models of nonalcoholic fatty liver disease

et al. 2020

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Background The comparison of hepatic steatosis animal models has allowed the understanding of mechanisms involved in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) and the progression to nonalcoholic steatohepatitis (NASH). We investigated the changes in serum levels of trace elements and inflammation markers in fatty livers using two rat models of NAFLD, the methionine and choline deficient (MCD) diet model and Obese-Zucker rats. Material and methods NAFLD was induced in male Wistar rats by 3-week MCD diet administration, after which, blood samples were collected. 12-week old Obese (fa/fa) and Lean (fa/-) male Zucker rats were also used. Serum levels of hepatic enzymes, Urea, Uric acid, Ca2+, Cl, Fe, K, Na, Mg and Zn were quantified, as well as the inflammation markers TNF-alpha, IL-1beta and IL-6. Results In MCD rats, a serum increase in Cl, Mg and Na and a decrease in Ca2+, Zn were detected in comparison with control rats. An increase in only serum Ca2+ was found in Obese-Zucker rats. In MCD rat serum, Zn was inversely correlated with IL-1beta, IL-6, TNF-alpha, Urea and Uric Acid; Ca2+ was inversely correlated with IL-1beta, IL-6 and Urea; Cl and Mg were directly correlated with Uric Acid and Urea, respectively. In Obese-Zucker rats, Cl and IL-1beta were inversely correlated, whereas Ca2+ and Urea where directly correlated, as well Fe and TNF-alpha. Conclusions The serum concentrations of trace elements change significantly only in MCD rats, which spontaneously progress to NASH. The causes of these changes may be a result of defense strategies of the organism, which is regulated by immunoregulatory cytokines. These results might suggest that the impairment of trace element status should be taken into account when the effectiveness of a pharmacological treatment is under evaluation.

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Section: Iron and Nafldsupporting

confidence: 92%

Section: Iron and Nafldsupporting

confidence: 90%

Associations between serum trace elements and inflammation in two animal models of nonalcoholic fatty liver disease

et al. 2020

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“…The choline-deficient L-amino acid defined (CDAA) diet is similar to the MCDD, with a low quantity of methionine (0.1%) and an average caloric density of 4320 kcal/kg. This diet, administered to Fisher 344 or Wistar rats for 6–12 weeks, induced severe steatosis with inflammation but lacked ballooning phenotypes [ 39 , 40 ]. Animals were not overweight compared to the control group and did not develop metabolic syndrome.…”

Section: Diet-induced Nafld and Nash Models In Ratsmentioning

confidence: 99%

Modeling Diet-Induced NAFLD and NASH in Rats: A Comprehensive Review

et al. 2021

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Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, characterized by hepatic steatosis without any alcohol abuse. As the prevalence of NAFLD is rapidly increasing worldwide, important research activity is being dedicated to deciphering the underlying molecular mechanisms in order to define new therapeutic targets. To investigate these pathways and validate preclinical study, reliable, simple and reproducible tools are needed. For that purpose, animal models, more precisely, diet-induced NAFLD and nonalcoholic steatohepatitis (NASH) models, were developed to mimic the human disease. In this review, we focus on rat models, especially in the current investigation of the establishment of the dietary model of NAFLD and NASH in this species, compiling the different dietary compositions and their impact on histological outcomes and metabolic injuries, as well as external factors influencing the course of liver pathogenesis.

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“…Multiple murine models of NAFLD/NASH have been developed using obesogenic or nutrient-de cient diets, chemical induction, genetic modi cation, or a combination of these manipulations [11][12][13][14][15][16][17]. MS-NASH mouse, formerly published as FATZO [18], was developed by crossing C57Bl/6 and AKR/J strains with selection for dysmetabolic phenotypes.…”

Section: Introductionmentioning

confidence: 99%

Carbon tetrachloride (CCl4) accelerated development of non-alcoholic fatty liver disease (NAFLD)/steatohepatitis (NASH) in MS-NASH mice fed western diet supplemented with fructose (WDF)

Zhang

Wang

Chung

et al. 2020

Preprint

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Background: Multiple murine models of nonalcoholic fatty liver disease/steatohepatitis (NAFLD/NASH) have been established by using obesogenic diets and/or chemical induction. MS-NASH mouse (formally FATZO) is a spontaneously developed dysmetabolic strain that can progress from hepatosteatosis to moderate fibrosis when fed a western diet supplemented with 5% fructose (WDF). This study aimed to use carbon tetrachloride (CCl4) to accelerate and aggravate progression of NAFLD/NASH in MS-NASH mouse. Methods: Male MS-NASH mice at 8 weeks of age were fed WDF for the entire study. Starting at 16 weeks of age, CCl4 was intraperitoneally administered twice weekly at a dose of 0.2 mL/kg for 3 weeks or 0.08 mL/kg for 8 weeks. Obeticholic acid (OCA, 30 mg/kg, QD) was administered in both MS-NASH and C57Bl/6 mice fed WDF and treated with CCl4 (0.08 mL/kg).Results: WDF enhanced obesity and hepatosteatosis, as well as induced moderate fibrosis in MS-NASH mice similar to previous reports. Administration of CCl4 accelerated liver fibrosis with increased bridging and liver hydroxyproline contents, but had no significant impact on liver steatosis and lipid contents. High dose CCl4 caused high mortality and dramatic elevation of ALT and ASL, while low dose CCl4 resulted in a moderate elevation of ALT and AST with low mortality. Compared to C57BI/6 mice with WDF and CCl4 (0.08 mL/kg), MS-NASH mice had more prominent hepatosteatosis and fibrosis. OCA treatment significantly lowered liver triglycerides, steatosis and fibrosis in both MS-NASH and C57Bl/6 mice fed WDF with CCl4 treatment. Conclusions: CCl4 reduced induction time and exacerbated liver fibrosis in MS-NASH mice on WDF, proving a superior NASH model with more prominent liver pathology, which has been used favorably in pharmaceutical industry for testing novel NASH therapeutics.

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Dietary iron restriction leads to a reduction in hepatic fibrosis in a rat model of non-alcoholic steatohepatitis

Cited by 15 publications

References 29 publications

Associations between serum trace elements and inflammation in two animal models of nonalcoholic fatty liver disease

Associations between serum trace elements and inflammation in two animal models of nonalcoholic fatty liver disease

Modeling Diet-Induced NAFLD and NASH in Rats: A Comprehensive Review

Carbon tetrachloride (CCl4) accelerated development of non-alcoholic fatty liver disease (NAFLD)/steatohepatitis (NASH) in MS-NASH mice fed western diet supplemented with fructose (WDF)

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