Inhibition of hepatic interleukin-18 production by rosiglitazone in a rat model of nonalcoholic fatty liver disease

Wang, Haining; Wang, Yanrong; Liu, Guoqiang; Liu, Zhe; Wu, Peixian; Wei, Xiao-Ling; Hong, Tianpei

doi:10.3748/wjg.14.7240

Cited by 31 publications

(22 citation statements)

References 39 publications

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“…These histological findings were similar to those seen in other studies [15,25]. These included accumulation of fat droplets in hepatocytes, which had vacuolated cytoplasm and pyknotic nuclei.…”

Section: Discussionsupporting

confidence: 90%

Histological study on the effect of metformin on high-fat-diet-induced liver injury in adult male albino rats

Shaker

Magdy

Abd-Elaziz

et al. 2014

The Egyptian Journal of Histology

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Changes in lifestyle and food habits increase the prevalence of nonalcoholic fatty liver disease (NAFLD). It is a chronic condition that has no or few symptoms. It may be accompanied by inflammation and insulin resistance. Moreover, it is closely linked to diabetes. Metformin is an antidiabetic agent that can improve insulin resistance. The aim of this studyThe study was conducted to investigate the effect of metformin on liver injury induced by a high-fat diet. Materials and methodsThe study lasted for 12 weeks. Thirty-six adult male albino rats were used and divided into four groups. Group I was the control group. Group II rats received metformin. Group III rats were fed a high-fat diet for induction of NAFLD. Group IV rats were fed a high-fat diet for induction of NAFLD and then administered metformin orally in the last 4 weeks of the study. Liver specimens were processed for light and electron microscopic examination. Moreover, liver weight index was determined, and biochemical, morphometric, and statistical studies were performed. ResultsInduction of NAFLD (group III) resulted in severe insulin resistance. Hepatocytes showed macrovesicular and microvesicular steatosis, ballooning, and lobular inflammation. The number of positive cells and the reaction for tumor necrosis factor-α in group III apparently increased as compared with group IV. Lipid droplets, loss of mitochondrial cristae, and dispersion of rER were detected in group III. Metformin improved insulin resistance, and liver histological changes were fewer than those in group III. ConclusionMetformin can greatly improve liver histological changes associated with a model of NAFLD.

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Section: Discussionsupporting

confidence: 90%

Histological study on the effect of metformin on high-fat-diet-induced liver injury in adult male albino rats

Shaker

Magdy

Abd-Elaziz

et al. 2014

The Egyptian Journal of Histology

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“…Proinflammatory cytokines IL-18 and IL-12 are closely related and act synergistically since the administration recombinant proteins IL-12 and IL-18 concurrently induces the production of elevated levels of IFN-γ and TNF-α in mice [41]. Interestingly, exogenous administration of IL-18 with IL-12 to BALB/c mice induces fatty liver in an IFN-γ dependent manner [42], suggesting that both cytokines play an important role in the inflammatory cascade leading to NAFLD.…”

Section: Discussionmentioning

confidence: 99%

Reduced Dietary Omega-6 to Omega-3 Fatty Acid Ratio and 12/15-Lipoxygenase Deficiency Are Protective against Chronic High Fat Diet-Induced Steatohepatitis

et al. 2014

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Obesity is associated with metabolic perturbations including liver and adipose tissue inflammation, insulin resistance, and type 2 diabetes. Omega-6 fatty acids (ω6) promote and omega-3 fatty acids (ω3) reduce inflammation as they can be metabolized to pro- and anti-inflammatory eicosanoids, respectively. 12/15-lipoxygenase (12/15-LO) enzymatically produces some of these metabolites and is induced by high fat (HF) diet. We investigated the effects of altering dietary ω6/ω3 ratio and 12/15-LO deficiency on HF diet-induced tissue inflammation and insulin resistance. We examined how these conditions affect circulating concentrations of oxidized metabolites of ω6 arachidonic and linoleic acids and innate and adaptive immune system activity in the liver. For 15 weeks, wild-type (WT) mice were fed either a soybean oil-enriched HF diet with high dietary ω6/ω3 ratio (11∶1, HFH), similar to Western-style diet, or a fat Kcal-matched, fish oil-enriched HF diet with a low dietary ω6/ω3 ratio of 2.7∶1 (HFL). Importantly, the total saturated, monounsaturated and polyunsaturated fat content was matched in the two HF diets, which is unlike most published fish oil studies in mice. Despite modestly increased food intake, WT mice fed HFL were protected from HFH-diet induced steatohepatitis, evidenced by decreased hepatic mRNA expression of pro-inflammatory genes and genes involved in lymphocyte homing, and reduced deposition of hepatic triglyceride. Furthermore, oxidized metabolites of ω6 arachidonic acid were decreased in the plasma of WT HFL compared to WT HFH-fed mice. 12/15-LO knockout (KO) mice were also protected from HFH-induced fatty liver and elevated mRNA markers of inflammation and lymphocyte homing. 12/15-LOKO mice were protected from HFH-induced insulin resistance but reducing dietary ω6/ω3 ratio in WT mice did not ameliorate insulin resistance or adipose tissue inflammation. In conclusion, lowering dietary ω6/ω3 ratio in HF diet significantly reduces steatohepatitis.

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“…38,39 The development of steatohepatitis in a NASH model, induced by a methionine-and choline-deficient diet, was partly inhibited in TLR4 mutant mice, 40,41 suggesting a role for TLR4-dependent signaling in the occurrence of this type of liver damage. In addition, the lipoprotein component of endotoxin from Gram-negative and -positive bacteria activates TLR2 and/or TLR4, which leads to common downstream activation of TRAF6 via the adapter molecule MyD88.…”

Section: Discussionmentioning

confidence: 99%

A Human-Type Nonalcoholic Steatohepatitis Model with Advanced Fibrosis in Rabbits

Ogawa

Fujii

Yoshizato

et al. 2010

The American Journal of Pathology

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Nonalcoholic steatohepatitis (NASH) progresses to liver fibrosis and cirrhosis, which can lead to lifethreatening liver failure and the development of hepatocellular carcinoma. The aim of the present study was to create a rabbit model of NASH with advanced fibrosis (almost cirrhosis) by feeding the animals a diet supplemented with 0.75% cholesterol and 12% corn oil. After 9 months of feeding with this diet, the rabbits showed high total cholesterol levels in serum and liver tissues in the absence of insulin resistance. The livers became whitish and nodular. In addition, the number of rabbit macrophage antigen-positive cells and the expression of mRNAs for inflammatory cytokines showed a significant increase. Moreover, fibrotic septa composed of collagens and ␣-smooth muscle actin-positive cells were found between the central and portal veins, indicating alteration of the parenchymal architecture. There was also a marked increase of mRNAs for transforming growth factor-␤1 and collagen 1A1. Comprehensive analysis of protein and gene expression revealed an imbalance of the antioxidant system and methionine metabolism. We also found that ezetimibe attenuated steatohepatitis in this model. In conclusion , the present rabbit model of NASH features advanced fibrosis that is close to cirrhosis and may be useful for analyzing the molecular mechanisms of human NASH. Ezetimibe blunted the development of NASH in this model, suggesting its potential clinical usefulness for human steatohepatitis.

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Inhibition of hepatic interleukin-18 production by rosiglitazone in a rat model of nonalcoholic fatty liver disease

Cited by 31 publications

References 39 publications

Histological study on the effect of metformin on high-fat-diet-induced liver injury in adult male albino rats

Histological study on the effect of metformin on high-fat-diet-induced liver injury in adult male albino rats

Reduced Dietary Omega-6 to Omega-3 Fatty Acid Ratio and 12/15-Lipoxygenase Deficiency Are Protective against Chronic High Fat Diet-Induced Steatohepatitis

A Human-Type Nonalcoholic Steatohepatitis Model with Advanced Fibrosis in Rabbits

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