Lipotoxicity and steatohepatitis in an overfed mouse model for non-alcoholic fatty liver disease

Gaemers, Ingrid C.; Stallen, Jan; Kunne, Cindy; Wallner, Christian; Werven, Jochem van; Nederveen, Aart J.; Lamers, Wouter H.

doi:10.1016/j.bbadis.2011.01.003

Cited by 79 publications

(63 citation statements)

References 57 publications

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“…29 Oxidative stress is mirrored by the increase of lipid peroxidation products (ie, malondialdehyde and hydroxynonenal) in patients with NASH and in animal models. [30][31][32] The importance of oxidative stress in the pathogenesis of steatohepatitis is underscored by the use of several antioxidants, associated with variable success, in patients with NASH; 33 a recent randomized controlled trial showed the efficacy of vitamin E in counteracting liver injury progression. 34 There is evidence that both ROS and RNS contribute to hepatocyte damage and inflammatory/fibrogenic cells activation.…”

Section: Discussionmentioning

confidence: 99%

Silibinin modulates lipid homeostasis and inhibits nuclear factor kappa B activation in experimental nonalcoholic steatohepatitis

Salamone

Galvano

Cappello

et al. 2012

Translational Research

117

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Nonalcoholic steatohepatitis (NASH) is associated with increased liver-related mortality. Disturbances in hepatic lipid homeostasis trigger oxidative stress and inflammation (ie, lipotoxicity), leading to the progression of NASH. This study aimed at identifying whether silibinin may influence the molecular events of lipotoxicity in a mouse model of NASH. Eight-week-old db/db mice were fed a methioninecholine deficient (MCD) diet for 4 weeks and treated daily with silibinin (20 mg/kg intraperitoneally) or vehicle. Liver expression and enzyme activity of stearoyl-CoA desaturase-1 and acyl-CoA oxidase, and expression of liver fatty acid-binding protein were assessed. Hepatic levels of reactive oxygen species, thiobarbituric acidreactive substances (TBARS), 3-nitrotyrosine (3-NT), inducible nitric oxide synthase (iNOS), and nuclear factor kappa B (NFkB) activities were also determined. Silibinin administration decreased serum alanine aminotransferase and improved liver steatosis, hepatocyte ballooning, and lobular inflammation in db/db mice fed an MCD diet. Gene expression and activity of stearoyl-CoA desaturase-1 were reduced in db/db mice fed an MCD diet compared with lean controls and were increased by silibinin; moreover, silibinin treatment induced the expression and activity of acylCoA oxidase and the expression of liver fatty acid-binding protein. Vehicle-treated animals displayed increased hepatic levels of reactive oxygen species and TBARS, 3-NT staining, and iNOS expression; silibinin treatment markedly decreased reactive oxygen species and TBARS and restored 3-NT and iNOS to the levels of control mice. db/db mice fed an MCD diet consistently had increased NFkB p65 and p50 binding activity; silibinin administration significantly decreased the activity of both subunits. Silibinin treatment counteracts the progression of liver injury by modulating lipid homeostasis and suppressing oxidative stress-mediated lipotoxicity and NFkB activation in experimental NASH. (Translational Research 2012;159:477-486) Abbreviations: AOX ¼ acyl-CoA oxidase; ALT ¼ alanine aminotransferase; FFA ¼ free fatty acid; iNOS ¼ inducible nitric oxide synthase; L-FABP ¼ liver-fatty acid binding protein;

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Section: Discussionmentioning

confidence: 99%

Silibinin modulates lipid homeostasis and inhibits nuclear factor kappa B activation in experimental nonalcoholic steatohepatitis

Salamone

Galvano

Cappello

et al. 2012

Translational Research

117

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“…As NASH is characterized by liver damage involving inflammation paralleled with oxidative stress, this model also displays metabolic syndrome-like features. 24,27 MCD-induced NASH is considered to be a more severe NAFLD model, which develops irreversible damage of the liver in a short time.…”

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confidence: 99%

Metalloproteinases in liver fibrosis: current insights

Zbodakova¹,

Chalupský²,

Turečková³

et al. 2017

MNM

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Liver fibrosis is defined by excessive deposition of extracellular matrix. The fibrotic conditions result from the imbalance between synthesis and deposition of fibrous tissues and decomposition of these matrix proteins. This process can be reversed as a regular part of the healing process after hepatic damage or can become chronic. When the protein matrix synthesis predominates and the decomposition is suppressed, fibrosis will progress into irreversible cirrhosis or steatosis. Among the molecular players involved in fibrotic liver diseases, metalloproteinases of matrix metalloproteinase (MMP) and a disintegrin and metalloproteinase (ADAM) families are critical in the development of liver fibrosis and its resolution. Previously, MMPs were recognized as extracellular matrix degrading enzymes. Currently, they are also known as mediators in a variety of processes related to immunity and tissue repair. In this article, we have reviewed the models of liver fibrosis and findings on MMPs and ADAMs in hepatic fibrosis conditions.

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“…We could not find the symptom of NASH as the dietary intake of mice were under their control. Even earlier reports suggested that when rats were fed with a fat-rich diet both in liquid and solid forms, only those rats fed with highfat liquid diet progressed to NASH even though both the groups developed steatosis [22].…”

Section: Discussionmentioning

confidence: 96%

Long-term exposure to a butter-rich diet induces mild-to-moderate steatosis in Chang liver cells and Swiss albino mice models

Nalloor

Kumar

Kasinathan

et al. 2017

Journal of Basic and Clinical Physiology and Pharmacology

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Background:Butter is one of the widely used fats present in the diet. However, there is no satisfactory study available that evaluates the effect of a high-fat diet containing butter as the principal fat on the development of non-alcoholic fatty liver disease (NAFLD).Methods:In the present study, butter was used for the development of steatosis in Chang liver cells in an in vitro study and Swiss albino mice in an in vivo study. In vitro steatosis was established, and butter was compared with oleic acid in Chang liver cells using an oil red O (ORO)-based colorimetric assay. In the in vivo study, a butter-rich special diet was fed for 15 weeks to mice, who showed no significant change in body weight. The expression pattern of phosphatase and tensin homolog (Results and Conclusions:Special diet-fed animals showed downregulated

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Lipotoxicity and steatohepatitis in an overfed mouse model for non-alcoholic fatty liver disease

Abstract: this dietary mouse model displays the different stages and the metabolic settings often found in human NAFLD. Lipotoxicity due to compromised adipose tissue function is likely associated with the progression to NASH, but whether this is cause or consequence remains to be established.

Cited by 79 publications

References 57 publications

Silibinin modulates lipid homeostasis and inhibits nuclear factor kappa B activation in experimental nonalcoholic steatohepatitis

Silibinin modulates lipid homeostasis and inhibits nuclear factor kappa B activation in experimental nonalcoholic steatohepatitis

Metalloproteinases in liver fibrosis: current insights

Long-term exposure to a butter-rich diet induces mild-to-moderate steatosis in Chang liver cells and Swiss albino mice models

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