Role of immunodeficient animal models in the development of fructose induced NAFLD

Bhattacharjee, Jashdeep; Kumar, Jerald Mahesh; Arindkar, Shailendra; Das, Balaram; Upadhyay, Pramod; Juyal, Ramesh C.; Majumdar, Subeer S.; Nagarajan, Priyadharsini

doi:10.1016/j.jnutbio.2013.10.010

Cited by 38 publications

(45 citation statements)

References 20 publications

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“…However, this response was also suppressed relative to the PF groups after EtOH treatment in both groups of mice lacking PPAR-␣ (P Ͻ 0.05). Expression of mRNA encoding B220, a marker of B cells (6), was decreased in PF GSTA4Ϫ/Ϫ mice relative to PF WT mice but was increased in PPAR-␣Ϫ/Ϫ mice and dKO mice from the PF groups compared with either PF WT or GSTA4Ϫ/Ϫ mice (P Ͻ 0.05). Expression of B220 mRNA was suppressed relative to PF in EtOH-treated WT and dKO mice (P Ͻ 0.05).…”

Section: Inflammation and Infiltrationmentioning

confidence: 95%

Increased 4-hydroxynonenal protein adducts in male GSTA4–4/PPAR-α double knockout mice enhance injury during early stages of alcoholic liver disease

Ronis

Mercer

Gannon

et al. 2015

American Journal of Physiology-Gastrointestinal and Liver Physi

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To test the significance of lipid peroxidation in the development of alcoholic liver injury, an ethanol (EtOH) liquid diet was fed to male 129/SvJ mice (wild-type, WT) and glutathione S-transferase A4–4-null (GSTA4−/−) mice for 40 days. GSTA4−/− mice were crossed with peroxisome proliferator-activated receptor-α-null mice (PPAR-α−/−), and the effects of EtOH in the resulting double knockout (dKO) mice were compared with the other strains. EtOH increased lipid peroxidation in all except WT mice ( P < 0.05). Increased steatosis and mRNA expression of the inflammatory markers CXCL2, tumor necrosis factor-α (TNF-α), and α-smooth muscle actin (α-SMA) were observed in EtOH GSTA4−/− compared with EtOH WT mice ( P < 0.05). EtOH PPAR-α−/− mice had increased steatosis, serum alanine aminotransferase (ALT), and hepatic CD3+ T cell populations and elevated mRNA encoding CD14, CXCL2, TNF-α, IL-6, CD138, transforming growth factor-β, platelet-derived growth factor receptor-β (PDGFR-β), matrix metalloproteinase (MMP)-9, MMP-13, α-SMA, and collagen type 1 compared with EtOH WT mice. EtOH-fed dKO mice displayed elevation of periportal hepatic 4-hydroxynonenal adducts and serum antibodies against malondialdehyde adducts compared with EtOH feeding of GSTA4−/−, PPAR-α−/−, and WT mice ( P < 0.05). ALT was higher in EtOH dKO mice compared with all other groups ( P < 0.001). EtOH-fed dKO mice displayed elevated mRNAs for TNF-α and CD14, histological evidence of fibrosis, and increased PDGFR, MMP-9, and MMP-13 mRNAs compared with the EtOH GSTA4−/− or EtOH PPAR-α−/− genotype ( P < 0.05). These findings demonstrate the central role lipid peroxidation plays in mediating progression of alcohol-induced necroinflammatory liver injury, stellate cell activation, matrix remodeling, and fibrosis.

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Section: Inflammation and Infiltrationmentioning

confidence: 95%

Increased 4-hydroxynonenal protein adducts in male GSTA4–4/PPAR-α double knockout mice enhance injury during early stages of alcoholic liver disease

Ronis

Mercer

Gannon

et al. 2015

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…Endotoxemia acts in part by activating the innate immune system, and inflammation is known to have a role in NAFLD, especially for the transition from steatosis to steatohepatitis and cirrhosis (95). In this regard, a role for T cells and NK cells (but not B lymphocytes) in fructose-induced NAFLD has been shown experimentally through the use of mice genetically modified that lack T cell or NK cell function (96). …”

Section: Fructokinase the Principal Enzyme Driving Fructose-induced mentioning

confidence: 99%

Fructose and sugar: A major mediator of non-alcoholic fatty liver disease

Jensen

Abdelmalek

Sullivan

et al. 2018

Journal of Hepatology

722

490

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Nonalcoholic Fatty Liver Disease (NAFLD) is the hepatic manifestation of metabolic syndrome, and its rising prevalence parallels the rise in obesity and diabetes. Historically thought to result from overnutrition and sedentary lifestyle, recent evidence suggests that diets high in sugar (from sucrose and/or high fructose corn syrup (HFCS)) not only increases the risk for NAFLD, but also, nonalcoholic steatohepatitis (NASH). Here we review the experimental and clinical evidence that fructose precipitates fat accumulation in the liver, due to both increased lipogenesis and impaired fat oxidation. Recent evidence suggests that the predisposition to fatty liver is linked with metabolism of fructose by fructokinase C, resulting in ATP consumption, nucleotide turnover and uric acid generation that mediate fat accumulation. Alterations in gut permeability, microbiome, and associated endotoxemia contributes to the risk of NAFLD and NASH. Early clinical studies suggest that reducing sugary beverages and total fructose intake, especially from added sugars, may have a significant benefit on reducing hepatic fat accumulation. We suggest larger, more definitive trials to determine if lowering sugar/HFCS intake, and/or blocking uric acid generation, may help reduce NAFLD and its downstream complications of cirrhosis and chronic liver disease.

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“…However, contradictory observations on the B-cell's contribution to insulin resistance and NAFLD have also emerged. Bhattacharjee et al found that B cell-deficient mice (xid mice) fed high fructose drinking water develop the same level of glucose intolerance and insulin resistance as wild-type mice [94], which suggests that B-cells do not play a role in NAFLD progression. The reason for these contradictory observations could be, in part, due to the differences in B-cell-deficient mutant mouse strains and different diet-induced NAFLD models.…”

Section: Inflammatory Mediators and Immune Alterationsmentioning

confidence: 99%

Pathogenesis of Nonalcoholic Steatohepatitis: Interactions between Liver Parenchymal and Nonparenchymal Cells

Magee

Zou

Zhang

2016

BioMed Research International

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Nonalcoholic fatty liver disease (NAFLD) is the most common type of chronic liver disease in the Western countries, affecting up to 25% of the general population and becoming a major health concern in both adults and children. NAFLD encompasses the entire spectrum of fatty liver disease in individuals without significant alcohol consumption, ranging from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH) and cirrhosis. NASH is a manifestation of the metabolic syndrome and hepatic disorders with the presence of steatosis, hepatocyte injury (ballooning), inflammation, and, in some patients, progressive fibrosis leading to cirrhosis. The pathogenesis of NASH is a complex process and implicates cell interactions between liver parenchymal and nonparenchymal cells as well as crosstalk between various immune cell populations in liver. Lipotoxicity appears to be the central driver of hepatic cellular injury via oxidative stress and endoplasmic reticulum (ER) stress. This review focuses on the contributions of hepatocytes and nonparenchymal cells to NASH, assessing their potential applications to the development of novel therapeutic agents. Currently, there are limited pharmacological treatments for NASH; therefore, an increased understanding of NASH pathogenesis is pertinent to improve disease interventions in the future.

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Role of immunodeficient animal models in the development of fructose induced NAFLD

Cited by 38 publications

References 20 publications

Increased 4-hydroxynonenal protein adducts in male GSTA4–4/PPAR-α double knockout mice enhance injury during early stages of alcoholic liver disease

Increased 4-hydroxynonenal protein adducts in male GSTA4–4/PPAR-α double knockout mice enhance injury during early stages of alcoholic liver disease

Fructose and sugar: A major mediator of non-alcoholic fatty liver disease

Pathogenesis of Nonalcoholic Steatohepatitis: Interactions between Liver Parenchymal and Nonparenchymal Cells

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