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Sample records for ameliorate nonalcoholic fatty

  1. Ginkgolide A ameliorates non-alcoholic fatty liver diseases on high fat diet mice.

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    Jeong, Hyeon-Soo; Kim, Kang-Hoon; Lee, In-Seung; Park, Ji Young; Kim, Yumi; Kim, Ki-Suk; Jang, Hyeung-Jin

    2017-04-01

    Non-alcoholic fatty liver disease (NAFLD) is one of the most common diseases worldwide and has continuously increased. NAFLD refers to a spectrum of diseases ranging from fatty liver to steatohepatitis, cirrhosis, and even to hepatocyte carcinoma. Excessive fatty acid enters the cell and the mitochondria undergo stress and unremoved ROS can trigger a form of cell apoptosis known as 'lipoapoptosis'. NASH arises from damaged liver hepatocytes due to lipotoxicity. NASH not only involves lipid accumulation and apoptosis but also inflammation. Ginkgo biloba has been tested clinical trials as a traditional medicine for asthma, bronchitis and cardiovascular disease. The effects of Ginkgolide A (GA), derived from the ginkgo biloba leaf, are still unknown in NAFLD. To determine the protective effects of GA in NAFLD, we examined the fatty liver disease condition in the non-esterified fatty acid (NEFA)-induced HepG2 cell line and in a high fat diet mouse model. The findings of this study suggest that GA is non-toxic at high concentrations in hepatocytes. Moreover, GA was found to inhibit cellular lipogenesis and lipid accumulation by causing mitochondrial oxidative stress. GA showed hepatoprotective efficacy by inducing cellular lipoapoptosis and by inhibiting cellular inflammation. The results demonstrated that GA may be feasible as a therapeutic agent for NAFLD patients. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  2. Antiresistin RNA Oligonucleotide Ameliorates Diet-Induced Nonalcoholic Fatty Liver Disease in Mice through Attenuating Proinflammatory Cytokines

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    Yi Tan

    2015-01-01

    Full Text Available The aim of this study was to determine whether inhibition of resistin by a synthetic antiresistin RNA (oligonucleotide oligo ameliorates metabolic and histological abnormalities in nonalcoholic fatty liver disease (NAFLD induced by high-fat diet (HFD in mice. The antiresistin RNA oligo and a scrambled control oligo (25 mg/kg of body weight were i.p. injected to HFD mice. Serum metabolic parameters and hepatic enzymes were measured after 4-week treatment. The treatment significantly reduced epididymal fat and attenuated the elevated serum resistin, cholesterol, triglycerides, glucose, and insulin with an improved glucose tolerance test. Antiresistin RNA oligo also normalized serum AST and ALT levels with improved pathohistology of NAFLD. Immunoblotting and qRT-PCR revealed that decreased protein and mRNA expression of resistin in fat and liver tissues of the treated mice were associated with reduction of adipose TNF-α and IL-6 expression and secretion into circulation. mRNA and protein expression of hepatic phosphoenolpyruvate carboxykinase (PEPCK and sterol regulatory element-binding protein-1c (SREBP-1c were also significantly decreased in the treated mice. Our results suggest that resistin may exacerbate NAFLD in metabolic syndrome through upregulating inflammatory cytokines and hepatic PEPCK and SREBP-1c. Antiresistin RNA oligo ameliorated metabolic abnormalities and histopathology of NAFLD through attenuating proinflammatory cytokines.

  3. Ginger Essential Oil Ameliorates Hepatic Injury and Lipid Accumulation in High Fat Diet-Induced Nonalcoholic Fatty Liver Disease.

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    Lai, Yi-Syuan; Lee, Wan-Ching; Lin, Yu-En; Ho, Chi-Tang; Lu, Kuan-Hung; Lin, Shih-Hang; Panyod, Suraphan; Chu, Yung-Lin; Sheen, Lee-Yan

    2016-03-16

    The objective of this study was to investigate the hepatoprotective efficacy and mechanism of action of ginger essential oil (GEO) against the development of nonalcoholic fatty liver disease (NAFLD). Mice were maintained on either a control diet or high-fat diet (HFD) supplemented with GEO (12.5, 62.5, and 125 mg/kg) or citral (2.5 and 25 mg/kg) for 12 weeks. We demonstrated that GEO and its major component (citral) lowered HFD-induced obesity in a dose-dependent manner, accompanied by anti-hyperlipidemic effects by reducing serum free fatty acid, triglyceride, and total cholesterol levels. Moreover, liver histological results showed that administration of 62.5 and 125 mg/kg GEO and 25 mg/kg citral significantly reduced hepatic lipid accumulation. Further assessment by Western blotting and investigation of the lipid metabolism revealed that hepatic protein expression of sterol regulatory element-binding protein-1c (SREBP-1c), acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), and cytochrome P450 2E1 (CYP2E1) were down-regulated by GEO and citral, indicating that GEO and citral suppressed HFD-stimulated lipid biosynthesis and oxidative stress. Furthermore, GEO and citral effectively enhanced the antioxidant capacities and reduced inflammatory response in mouse liver, which exerted protective effects against steatohepatitis. Collectively, GEO and citral exhibited potent hepatoprotective effects against NAFLD induced by HFD in obese mice. Thus, GEO might be an effective dietary supplement to ameliorate NAFLD-related metabolic diseases, and citral could play a vital role in its management.

  4. Ameliorative effects of lutein on non-alcoholic fatty liver disease in rats.

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    Qiu, Xiang; Gao, Dan-Hong; Xiang, Xiao; Xiong, Yu-Fang; Zhu, Teng-Shi; Liu, Lie-Gang; Sun, Xiu-Fa; Hao, Li-Ping

    2015-07-14

    To investigate the therapeutic effects of lutein against non-alcoholic fatty liver disease (NAFLD) and the related underlying mechanism. After 9 d of acclimation to a constant temperature-controlled room (20 °C-22 °C) under 12 h light/dark cycles, male Sprague-Darley rats were randomly divided into two groups and fed a standard commercial diet (n = 8) or a high-fat diet (HFD) (n = 32) for 10 d. Animals receiving HFD were then randomly divided into 4 groups and administered with 0, 12.5, 25, or 50 mg/kg (body weight) per day of lutein for the next 45 d. At the end of the experiment, the perinephric and abdominal adipose tissues of the rats were isolated and weighed. Additionally, serum and liver lipid metabolic condition parameters were measured, and liver function and insulin resistance state indexes were assessed. Liver samples were collected and stained with hematoxylin eosin and Oil Red O, and the expression of the key factors related to insulin signaling and lipid metabolism in the liver were detected using Western blot and real-time polymerase chain reaction analyses. Our data showed that after being fed a high-fat diet for 10 d, the rats showed a significant gain in body weight, energy efficiency, and serum total cholesterol (TC) and triglyceride (TG) levels. Lutein supplementation induced fat loss in rats fed a high-fat diet, without influencing body weight or energy efficiency, and decreased serum TC and hepatic TC and TG levels. Moreover, lutein supplementation decreased hepatic levels of lipid accumulation and glutamic pyruvic transaminase content, and also improved insulin sensitivity. Lutein administration also increased the expression of key factors in hepatic insulin signaling, such as insulin receptor substrate-2, phosphatidylinositol 3-kinase, and glucose transporter-2 at the gene and protein levels. Furthermore, high-dose lutein increased the expression of peroxisome proliferators activated receptor-α and sirtuin 1, which are associated with

  5. Swimming, but not vitamin E, ameliorates prothrombotic state and hypofibrinolysis in a rat model of nonalcoholic fatty liver disease.

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    Sakr, Hussein F; Abbas, Amr M; Haidara, Mohamed A

    2018-01-26

    Nonalcoholic fatty liver disease (NAFLD) is associated with a systemic procoagulant hypofibrinolysis state that is considered as a risk factor for microangiopathy and peripheral vascular diseases. Swimming exercise ameliorates the metabolic dysfunction in type 2 diabetes. Vitamin E is a natural antioxidant that reduces the risk of endothelial dysfunction in metabolic syndrome. The aim of the present study is to investigate the effect of combined swimming exercise with vitamin E on coagulation as well as blood fibrinolysis markers in rats with NAFLD. Eighty male rats were divided into control, control+vitamin E, control+exercise, high-fat diet (HFD), HFD+vitamin E, HFD+exercise, and HFD+vitamin E+exercise groups. Glucose, insulin, homeostatic model assessment for insulin resistance (HOMA-IR), triglycerides, cholesterol, low-density lipoprotein (LDL) and high-density lipoprotein (HDL), alanine transaminase (ALT) and aspartate transaminase (AST), intercellular adhesion molecule (ICAM-1), vascular cell adhesion molecule (VCAM-1), endothelin-1, von Willebrand factor (vWF), fibrinogen, plasminogen activator inhibitor (PAI-1), fibrin degradation products (FDP), platelet count and aggregation, bleeding and clotting times, activated partial thromboplastin time (aPTT), and prothrombin time (PT) were determined. HFD increased lipid profile, insulin, glucose, HOMA-IR, liver enzymes, adhesion molecules, endothelin-1, vWF, platelet aggregation, fibrinogen, FDP, and PAI-1, and decreased clotting and bleeding times and HDL. Although exercise reduced lipid profile, glucose, insulin, HOMA-IR, vWF, platelet aggregation, fibrinogen, FDP, and PAI-1 and increased PT, aPTT, bleeding and clotting times, and HDL, vitamin E had no effect. Exercise, but not vitamin E, ameliorated the HFD-induced prothrombotic state and enhanced fibrinolytic activity.

  6. Camel milk ameliorates steatohepatitis, insulin resistance and lipid peroxidation in experimental non-alcoholic fatty liver disease.

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    Korish, Aida A; Arafah, Maha M

    2013-10-13

    Camel milk (CM) is gaining increasing recognition due to its beneficial effects in the control and prevention of multiple health problems. The current study aimed to investigate the effects of CM on the hepatic biochemical and cellular alterations induced by a high-fat, cholesterol-rich diet (HCD), specifically, non-alcoholic fatty liver disease (NAFLD). Seventy male Wistar rats were divided into four groups: the Control (C) Group fed a standard diet; the Control + camel milk (CCM) Group fed a standard diet and CM, the Cholesterol (Ch) Group fed a HCD with no CM, and the Cholesterol + camel milk (ChM) Group fed a HCD and CM. The following parameters were investigated in the studied groups; basal, weekly random and final fasting blood glucose levels, intraperitoneal glucose tolerance test (GTT) and insulin tolerance test (ITT), serum insulin, serum lipids, liver functions, lipid peroxidation products, the antioxidant activity of catalase (CAT) and the levels of reduced glutathione (GSH). In addition, HOMA-IR as an index of insulin resistance (IR) and the histopathology of the hepatic tissue were assessed. The Ch Group developed features similar to those of non-alcoholic steatohepatitis (NASH), characterized by hepatic steatosis; inflammatory cellular infiltration in liver tissue; altered liver functions; and increased total cholesterol, triglycerides, low-density lipoprotein cholesterol, very-low-density lipoprotein cholesterol, atherogenic index (AI), blood glucose, IR, and malondialdehyde (MDA) levels. Additionally, feeding the HCD to animals in the Ch Group decreased CAT activity and the GSH and high-density lipoprotein (HDL) cholesterol levels. Camel milk intake for eight weeks decreased hepatic fat accumulation and inflammatory cellular infiltration, preserved liver function, increased the GSH levels and CAT activity, decreased the MDA levels, and ameliorated the changes in the lipid profile, AI, and IR in animals from the ChM Group. CM has a unique composition

  7. Nonalcoholic Fatty Liver Disease & NASH

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    ... Eating, Diet, & Nutrition Clinical Trials Wilson Disease Nonalcoholic Fatty Liver Disease & NASH View or Print All Sections Definition & Facts Nonalcoholic fatty liver disease (NAFLD) is a condition in which fat ...

  8. Treatment with a novel oleic-acid-dihydroxyamphetamine conjugation ameliorates non-alcoholic fatty liver disease in obese Zucker rats.

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    Decara, Juan M; Pavón, Francisco Javier; Suárez, Juan; Romero-Cuevas, Miguel; Baixeras, Elena; Vázquez, Mariam; Rivera, Patricia; Gavito, Ana L; Almeida, Bruno; Joglar, Jesús; de la Torre, Rafael; Rodríguez de Fonseca, Fernando; Serrano, Antonia

    2015-10-01

    Fatty liver disease is one of the main hepatic complications associated with obesity. To date, there are no effective treatments for this pathology apart from the use of classical fibrates. In this study, we have characterized the in vivo effects of a novel conjugation of oleic acid with an amphetamine derivative (OLHHA) in an animal model of genetic obesity. Lean and obese Zucker rats received a daily intraperitoneal administration of OLHHA (5 mg kg(-1)) for 15 days. Plasma and liver samples were collected for the biochemical and molecular biological analyses, including both immunohistochemical and histological studies. The expression of key enzymes and proteins that are involved in lipid metabolism and energy homeostasis was evaluated in the liver samples. The potential of OLHHA to produce adverse drug reactions or toxicity was also evaluated through the monitoring of interactions with hERG channel and liver cytochrome. We found that OLHHA is a drug with a safe pharmacological profile. Treatment for 15 days with OLHHA reduced the liver fat content and plasma triglyceride levels, and this was accompanied by a general improvement in the profile of plasma parameters related to liver damage in the obese rats. A decrease in fat accumulation in the liver was confirmed using histological staining. Additionally, OLHHA was observed to exert anti-apoptotic effects. This hepatoprotective activity in obese rats was associated with an increase in the mRNA and protein expression of the cannabinoid type 1 receptor and a decrease in the expression of the lipogenic enzymes FAS and HMGCR primarily. However, changes in the mRNA expression of certain proteins were not associated with changes in the protein expression (i.e. L-FABP and INSIG2). The present results demonstrate that OLHHA is a potential anti-steatotic drug that ameliorates the obesity-associated fatty liver and suggest the potential use of this new drug for the treatment of non-alcoholic fatty liver disease.

  9. Nonalcoholic fatty liver disease

    DEFF Research Database (Denmark)

    Patrick-Melin, A J; Kalinski, M I; Kelly, K R

    2009-01-01

    Nonalcoholic fatty liver disease (NAFLD) is a rapidly emerging chronic liver disease and is reported to affect up to 70-80% of overweight and obese individuals. NAFLD represents a spectrum of liver diseases that range from simple hepatic steatosis, to a more severe and treatment resistant stage...... that features steatosis plus inflammation, termed nonalcoholic steatohepatitis (NASH), which may in turn progress to hepatic fibrosis, cirrhosis, and sub-acute liver failure. Thus, NAFLD and its subsequent complications create a significant health burden, and currently there is no effective treatment strategy...

  10. Nonalcoholic fatty liver disease

    DEFF Research Database (Denmark)

    Patrick-Melin, A J; Kalinski, M I; Kelly, K R

    2009-01-01

    Nonalcoholic fatty liver disease (NAFLD) is a rapidly emerging chronic liver disease and is reported to affect up to 70-80% of overweight and obese individuals. NAFLD represents a spectrum of liver diseases that range from simple hepatic steatosis, to a more severe and treatment resistant stage......) are not only implicated in the development of insulin resistance and type 2 diabetes, but are also related to NAFLD. Such inflammatory mechanisms are fundamental in the progression of NAFLD toward higher risk cirrhotic states. This review outlines the leading theories of pathogenesis of NAFLD and highlights...

  11. Therapeutic role of ursolic acid on ameliorating hepatic steatosis and improving metabolic disorders in high-fat diet-induced non-alcoholic fatty liver disease rats.

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    Li, Songtao; Liao, Xilu; Meng, Fanyu; Wang, Yemei; Sun, Zongxiang; Guo, Fuchuan; Li, Xiaoxia; Meng, Man; Li, Ying; Sun, Changhao

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent liver diseases around the world, and is closely associated with obesity, diabetes, and insulin resistance. Ursolic acid (UA), an ubiquitous triterpenoid with multifold biological roles, is distributed in various plants. This study was conducted to investigate the therapeutic effect and potential mechanisms of UA against hepatic steatosis in a high-fat diet (HFD)-induced obese non-alcoholic fatty liver disease (NAFLD) rat model. Obese NAFLD model was established in Sprague-Dawley rats by 8-week HFD feeding. Therapeutic role of UA was evaluated using 0.125%, 0.25%, 0.5% UA-supplemented diet for another 6 weeks. The results from both morphologic and histological detections indicated that UA significantly reversed HFD-induced hepatic steatosis and liver injury. Besides, hepatic peroxisome proliferator-activated receptor (PPAR)-α was markedly up-regulated at both mRNA and protein levels by UA. Knocking down PPAR-α significantly inhibited the anti-steatosis role of UA in vitro. HFD-induced adverse changes in the key genes, which participated in hepatic lipid metabolism, were also alleviated by UA treatment. Furthermore, UA significantly ameliorated HFD-induced metabolic disorders, including insulin resistance, inflammation and oxidative stress. These results demonstrated that UA effectively ameliorated HFD-induced hepatic steatosis through a PPAR-α involved pathway, via improving key enzymes in the controlling of lipids metabolism. The metabolic disorders were accordingly improved with the decrease of hepatic steatosis. Thereby, UA could be a promising candidate for the treatment of NAFLD.

  12. Therapeutic role of ursolic acid on ameliorating hepatic steatosis and improving metabolic disorders in high-fat diet-induced non-alcoholic fatty liver disease rats.

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    Songtao Li

    Full Text Available BACKGROUND: Non-alcoholic fatty liver disease (NAFLD is one of the most prevalent liver diseases around the world, and is closely associated with obesity, diabetes, and insulin resistance. Ursolic acid (UA, an ubiquitous triterpenoid with multifold biological roles, is distributed in various plants. This study was conducted to investigate the therapeutic effect and potential mechanisms of UA against hepatic steatosis in a high-fat diet (HFD-induced obese non-alcoholic fatty liver disease (NAFLD rat model. METHODOLOGY/PRINCIPAL FINDINGS: Obese NAFLD model was established in Sprague-Dawley rats by 8-week HFD feeding. Therapeutic role of UA was evaluated using 0.125%, 0.25%, 0.5% UA-supplemented diet for another 6 weeks. The results from both morphologic and histological detections indicated that UA significantly reversed HFD-induced hepatic steatosis and liver injury. Besides, hepatic peroxisome proliferator-activated receptor (PPAR-α was markedly up-regulated at both mRNA and protein levels by UA. Knocking down PPAR-α significantly inhibited the anti-steatosis role of UA in vitro. HFD-induced adverse changes in the key genes, which participated in hepatic lipid metabolism, were also alleviated by UA treatment. Furthermore, UA significantly ameliorated HFD-induced metabolic disorders, including insulin resistance, inflammation and oxidative stress. CONCLUSIONS/SIGNIFICANCE: These results demonstrated that UA effectively ameliorated HFD-induced hepatic steatosis through a PPAR-α involved pathway, via improving key enzymes in the controlling of lipids metabolism. The metabolic disorders were accordingly improved with the decrease of hepatic steatosis. Thereby, UA could be a promising candidate for the treatment of NAFLD.

  13. MiR-150 deficiency ameliorated hepatosteatosis and insulin resistance in nonalcoholic fatty liver disease via targeting CASP8 and FADD-like apoptosis regulator.

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    Zhuge, Baozhong; Li, Guohong

    2017-12-16

    The prevalence of Non-alcoholic fatty liver diseases (NAFLD) increased rapidly in the world. However, the pathogenesis of is still unclear. Hepatic steatosis and insulin resistance are considered to be central to the pathophysiology of NAFLD. MicroRNAs are short non-coding RNAs and has been reported to be involved in pathogenesis of NAFLD and related metabolic diseases. Here, we investigated the mechanisms by which miR-150 regulate hepatic steatosis and insulin resistance in high fat diet (HFD) induced NAFLD model. The expression of miR-150 was up-regulated dramatically in both human NAFLD patients and HFD mice model, as well as in hepatocytes treated with oleic acid. miR-150 deficiency ameliorated the hepatic steatosis and insulin resistance significantly in NAFLD mice. miR-150 deficiency decreased the expression of genes related to fatty acid uptake, synthesis and gluconeogenesis, while increased the expression of genes related to fatty acid β-oxidation. Further, we identified that CFLAR is a direct downstream target of miR-150. Overexpression of miR-150 reduced both the mRNA and protein levels of CFLAR in vitro. And overexpression of miR-150 significantly inhibited the luciferase activity of CFLAR 3'-UTR, while the effect of miR-150 was blocked when the binding site of miR-150 within the CFLAR 3'-UTR was mutated. We also found that miR-150 deficiency decreased the expression of p-Jnk1 and p-Ask1, while the effect of miR-150 on steatosis and insulin signaling was blocked by CFLAR overexpression. In conclusion, our data indicated that miR-150 potentially contributes to the hepatic steatosis and insulin resistance in NAFLD. miR-150/CFLAR pathway may be a new therapeutic strategy against NAFLD. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Co-Administration of Cholesterol-Lowering Probiotics and Anthraquinone from Cassia obtusifolia L. Ameliorate Non-Alcoholic Fatty Liver.

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    Lu Mei

    Full Text Available Non-alcoholic fatty liver disease (NAFLD has become a common liver disease in recent decades. No effective treatment is currently available. Probiotics and natural functional food may be promising therapeutic approaches to this disease. The present study aims to investigate the efficiency of the anthraquinone from Cassia obtusifolia L. (AC together with cholesterol-lowering probiotics (P to improve high-fat diet (HFD-induced NAFLD in rat models and elucidate the underlying mechanism. Cholesterol-lowering probiotics were screened out by MRS-cholesterol broth with ammonium ferric sulfate method. Male Sprague-Dawley rats were fed with HFD and subsequently administered with AC and/or P. Lipid metabolism parameters and fat synthesis related genes in rat liver, as well as the diversity of gut microbiota were evaluated. The results demonstrated that, compared with the NAFLD rat, the serum lipid levels of treated rats were reduced effectively. Besides, cholesterol 7α-hydroxylase (CYP7A1, low density lipoprotein receptor (LDL-R and farnesoid X receptor (FXR were up-regulated while the expression of 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMGCR was reduced. The expression of peroxisome proliferator activated receptor (PPAR-α protein was significantly increased while the expression of PPAR-γ and sterol regulatory element binding protein-1c (SREBP-1c was down-regulated. In addition, compared with HFD group, in AC, P and AC+P group, the expression of intestinal tight-junction protein occludin and zonula occluden-1 (ZO-1 were up-regulated. Furthermore, altered gut microbiota diversity after the treatment of probiotics and AC were analysed. The combination of cholesterol-lowering probiotics and AC possesses a therapeutic effect on NAFLD in rats by up-regulating CYP7A1, LDL-R, FXR mRNA and PPAR-α protein produced in the process of fat metabolism while down-regulating the expression of HMGCR, PPAR-γ and SREBP-1c, and through normalizing the

  15. Adzuki bean ameliorates hepatic lipogenesis and proinflammatory mediator expression in mice fed a high-cholesterol and high-fat diet to induce nonalcoholic fatty liver disease.

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    Kim, Sera; Hong, Jihye; Jeon, Raok; Kim, Hyun-Sook

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) is a simple steatosis, in which fat accumulates more than 5% in the liver, and regarded as most common liver diseases worldwide. Because NAFLD can be developed to severe liver disease and correlated with metabolic disease, its importance is currently emphasized. Occurrence of NAFLD is strongly related to dietary patterns and lifestyles; therefore, the suggestion of physiologically beneficial food is essential. Based on these, adzuki beans containing anthocyanin, catechin, and adzukisaponin are suggested as a health-beneficial food. Moreover, the effects of adzuki beans on metabolic improvement are not well established through the in vivo studies. Therefore, this study hypothesized that adzuki beans can alleviate lipid accumulation and oxidative stress-mediated inflammation in high-cholesterol and high-fat diet-induced NALFD mice. To demonstrate its effects, 6-week-old C57BL/6 male mice were allocated into 4 groups and fed a normal diet (ND), a high-cholesterol and high-fat diet (HCD), and HCD with 10% and 20% adzuki bean for 10 weeks. The result shows that fasting blood glucose, serum and hepatic triglyceride and cholesterol levels, and antioxidative enzyme activity ameliorated in the adzuki bean groups (P fatty acid synthase, carnitine palmitoyltransferase 1, 3-hydroxy-3-methyl-glutaryl-CoA reductase, and apolipoprotein B, as well as proinflammatory mediators, such as tumor necrosis factor α, nuclear factor κB, and caspase-3, improved in both experimental groups (P < .05). These results suggested that adzuki beans attenuate lipid accumulation and oxidative stress-induced inflammation by suppressing hepatic messenger RNA expression of lipogenic and inflammatory mediators in NAFLD. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Green tea polyphenols ameliorate non-alcoholic fatty liver disease through upregulating AMPK activation in high fat fed Zucker fatty rats.

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    Tan, Yi; Kim, Jane; Cheng, Jing; Ong, Madeleine; Lao, Wei-Guo; Jin, Xing-Liang; Lin, Yi-Guang; Xiao, Linda; Zhu, Xue-Qiong; Qu, Xian-Qin

    2017-06-07

    To investigate protective effects and molecular mechanisms of green tea polyphenols (GTP) on non-alcoholic fatty liver disease (NAFLD) in Zucker fatty (ZF) rats. Male ZF rats were fed a high-fat diet (HFD) for 2 wk then treated with GTP (200 mg/kg) or saline (5 mL/kg) for 8 wk, with Zucker lean rat as their control. At the end of experiment, serum and liver tissue were collected for measurement of metabolic parameters, alanine aminotransferase (ALT) and aspartate aminotransferase (AST), inflammatory cytokines and hepatic triglyceride and liver histology. Immunoblotting was used to detect phosphorylation of AMP-activated protein kinase (AMPK) acetyl-CoA carboxylase (ACC), and sterol regulatory element-binding protein 1c (SREBP1c). Genetically obese ZF rats on a HFD presented with metabolic features of hepatic pathological changes comparable to human with NAFLD. GTP intervention decreased weight gain (10.1%, P = 0.052) and significantly lowered visceral fat (31.0%, P liver in GTP treated rats. The protective effects of GTP against HFD-induced NAFLD in genetically obese ZF rats are positively correlated to reduction in hepatic lipogenesis through upregulating the AMPK pathway.

  17. Maraviroc, a CCR5 antagonist, ameliorates the development of hepatic steatosis in a mouse model of non-alcoholic fatty liver disease (NAFLD).

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    Pérez-Martínez, Laura; Pérez-Matute, Patricia; Aguilera-Lizarraga, Javier; Rubio-Mediavilla, Susana; Narro, Judit; Recio, Emma; Ochoa-Callejero, Laura; Oteo, José-Antonio; Blanco, José-Ramón

    2014-07-01

    Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the general population. The NAFLD spectrum ranges from simple steatosis to cirrhosis. The chemokine CCL5/RANTES plays an important role in the progression of hepatic inflammation and fibrosis. The objective of this study was to examine the effects of maraviroc, a CCR5 antagonist, on liver pathology in a NAFLD mouse model. A total of 32 male C57BL/6 mice were randomly assigned to one of four groups: (i) control group (chow diet plus tap water); (ii) maraviroc group (chow diet plus maraviroc in drinking water); (iii) high-fat diet (HFD) group (HFD plus tap water); and (iv) maraviroc/HFD group (HFD plus maraviroc). All mice were sacrificed 16 weeks after the beginning of the experiment. Biochemical analyses and liver examinations were performed. Mice in the HFD group showed a tendency towards increased body mass gain and liver damage compared with the maraviroc/HFD group. Moreover, liver weight in the HFD group was significantly higher than in the maraviroc/HFD group. Hepatic triglyceride concentration in the maraviroc/HFD group was significantly lower than in the HFD group. Interestingly, the maraviroc/HFD group exhibited a lower degree of steatosis. Furthermore, hepatic CCL5/RANTES expression was significantly lower in the maraviroc/HFD group than in the HFD group. Overall, no differences were observed between the control group and the maraviroc group. Maraviroc ameliorates hepatic steatosis in an experimental model of NAFLD. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  18. Nonalcoholic Fatty Liver Disease Treatment

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    M Sadeghian

    2014-04-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD is increasing in pediatric age group parallel to the growing prevalence of obesity and overweight all around the world. So changing in life style and   interventions on obesogenic environment is cornerstone of NAFLD therapy in obese children. Some experts recommend that children and adolescents be encouraged to follow a low-fat, low-glycemic-index diet that includes eating a minimum of 5 servings of vegetables and fruits daily, engaging in physical activity for at least 1 hour daily, and minimizing television/computer time to 2 hours daily.  In spite of effectiveness of weight loss and exercise in improvement NAFLD, this goal is very difficult to be achieved and pharmacological approaches have become necessary. Pharmacologic therapies against one or more specific factors and/or molecules involved in the development of NAFLD (i.e., insulin resistance, free fatty acid lipid toxicity, and oxidative stress also might slow the progression of NAFLD to NASH or cirrhosis.  On this basis, insulin sensitizers, antioxidants, cytoprotective agents, and dietary supplementations have been evaluated in pediatric clinical trials but there is no approved pharmacologic therapy for NAFLD or NASH. Not all obese children affected by NAFLD. Diet modification and regular exercise beside to serial medical follow up highly suggested for this group of children. Normal weight and thin children with NAFLD or NASH should be investigated appropriately in a logical manner based on causes of primary liver steatosis in children and treatment of underlying disease can cause improvement fatty liver in these patients.   Keywords: Non-alcoholic fatty liver disease; Non-alcoholic steatohepatitis; Children; Steatosis; Treatment

  19. Salicornia Extract Ameliorates Salt-Induced Aggravation of Nonalcoholic Fatty Liver Disease in Obese Mice Fed a High-Fat Diet.

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    Kim, Jae Hwan; Suk, Sujin; Jang, Woo Jung; Lee, Chang Hyung; Kim, Jong-Eun; Park, Jin-Kyu; Kweon, Mee-Hyang; Kim, Jong Hun; Lee, Ki Won

    2017-07-01

    High-fat and high-salt intakes are among the major risks of chronic diseases including obesity, nonalcoholic fatty liver disease (NAFLD), and nonalcoholic steatohepatitis (NASH). Salicornia is a halophytic plant known to exert antioxidant, antidiabetic, and hypolipidemic effects, and Salicornia-extracted salt (SS) has been used as a salt substitute. In this study, the effects of SS and purified salt (PS) on the aggravation of NAFLD/NASH were compared. C57BL/6J male mice (8-wk-old) were fed a high-fat diet (HFD) for 6 mo and divided into 3 dietary groups, which were additionally fed HFD, HFD + SS, and HFD + PS for 13 wk. PS induced aggravation of NAFLD/NASH in HFD-fed mice. Although the actual salt intake was same between the PS and SS groups as 1% of the diet (extrapolated from the World Health Organization [WHO] guideline), SS induced less liver injury and hepatic steatosis compared to PS. The hepatic mRNA expressions of inflammatory cytokines and fibrosis marker were significantly lower in the SS group than the PS group. Oxidative stress is one of the major causes of inflammation in NAFLD/NASH. Results of the component analysis showed that the major polyphenols that exhibited antioxidant activity in the Salicornia water extract were ferulic acid, caffeic acid, and isorhamnetin. These results suggest that even the level of salt intake recommended by WHO can accelerate the progression of liver disease in obese individuals consuming HFD. It is proposed that SS can be a salt substitute for obese individuals who consume HFD. © 2017 Institute of Food Technologists®.

  20. Genetics Home Reference: non-alcoholic fatty liver disease

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    ... Facebook Twitter Home Health Conditions NAFLD Non-alcoholic fatty liver disease Printable PDF Open All Close All Enable ... view the expand/collapse boxes. Description Non-alcoholic fatty liver disease ( NAFLD ) is a buildup of excessive fat ...

  1. Non-Alcoholic Fatty Liver Disease in HIV Infection.

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    Macías, Juan; Pineda, Juan A; Real, Luis M

    2017-01-01

    Non-alcoholic fatty liver disease is one of the most frequent chronic hepatic conditions worldwide. The spectrum of non-alcoholic fatty liver disease goes from hepatic steatosis to steatohepatitis, cirrhosis, and hepatocellular carcinoma. Risk factors for non-alcoholic fatty liver disease are metabolic, mainly obesity and the accompanying consequences. Treatment and prevention of non-alcoholic fatty liver disease should target those metabolic abnormalities. The frequency of and the factors associated with hepatic steatosis in HIV infection seem to be similar to those reported in the general population, though direct comparisons are lacking. Hepatic steatosis in HIV infection may also be secondary to antiretroviral drugs or HCV-related factors in HCV-coinfected subjects. However, more recent data suggest that hepatic steatosis in HIV infection represents true non-alcoholic fatty liver disease. As such, management of non-alcoholic fatty liver disease in HIV infection should follow the same principles as in the general population.

  2. Pediatric Non-alcoholic Fatty Liver Disease.

    Science.gov (United States)

    Uppal, Vikas; Mansoor, Sana; Furuya, Katryn N

    2016-05-01

    Childhood obesity has reached epidemic proportions, and by 2012, more than one third of American children were overweight or obese. As a result, increasingly, children are developing complications of obesity including liver disease. In fact, non-alcoholic fatty liver disease is the most common form of chronic liver disease seen in children today. Recently, there has been a burgeoning literature examining the pathogenesis, genetic markers, and role of the microbiome in this disease. On the clinical front, new modalities of diagnosing hepatic steatosis and hepatic fibrosis are being developed to provide non-invasive methods of surveillance in children. Lastly, the mainstay of treatment of pediatric non-alcoholic fatty liver disease (NAFLD) has been largely through lifestyle interventions, namely, dieting and exercise. Currently, there are a number of clinical trials examining novel lifestyle and drug therapies for NAFLD that are registered with the US National Institutes of Health ClinicalTrials.gov website.

  3. Nonalcoholic fatty liver and the severity of acute pancreatitis.

    Science.gov (United States)

    Mikolasevic, I; Orlic, L; Poropat, G; Jakopcic, I; Stimac, D; Klanac, A; Carovic, F; Milic, S

    2017-03-01

    To explore the effect of nonalcoholic fatty liver as a hepatic manifestation of metabolic syndrome on the severity of acute pancreatitis. We hypothesized that patients with nonalcoholic fatty liver would have a more severe form of acute pancreatitis. We retrospectively analyzed 822 patients hospitalized with acute pancreatitis. We diagnosed acute pancreatitis and determined its severity according the revised Atlanta classification criteria from 2012. We assessed nonalcoholic fatty liver with computed tomography. There were 198 (24.1%) patients out of 822 analyzed who had nonalcoholic fatty liver. Patients with nonalcoholic fatty liver had statistically higher incidence of moderately severe (35.4% vs. 14.6%; p=0.02) and severe acute pancreatitis (20.7% vs. 9.6%; pacute pancreatitis and nonalcoholic fatty liver (OR 2.13, 95%CI 1.236-3.689). Compared to patients without nonalcoholic fatty liver, patients with nonalcoholic fatty liver had a higher death rate, however not statistically significant (5.6% vs. 4.3%; p=NS). Presence of nonalcoholic fatty liver at admission can indicate a higher risk for developing more severe forms of acute pancreatitis and could be used as an additional prognostic tool. Copyright © 2016 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

  4. Non-alcoholic fatty pancreas disease.

    Science.gov (United States)

    Alempijevic, Tamara; Dragasevic, Sanja; Zec, Simon; Popovic, Dragan; Milosavljevic, Tomica

    2017-04-01

    Obesity is a growing problem worldwide and disorders associated with excess body fat including the metabolic syndrome, type 2 diabetes mellitus (T2DM), cardiovascular disease and malignant neoplasms are becoming a major cause of morbidity and mortality. Over the past decade, a vast amount of research has furthered our understanding of non-alcoholic fatty liver disease; however, only recently pancreatic fat infiltration is coming to the forefront of investigation. Termed non-alcoholic fatty pancreas disease (NAFPD), it is becoming evident that it has important associations with other diseases of obesity. It appears to arise as obesity progresses and after an initial phase of pancreatic hypertrophy and hyperplasia, fatty infiltration becomes apparent. Various studies have demonstrated that NAFPD may exacerbate the severity of acute pancreatitis, promote pancreatic dysfunction associated with insulin resistance and T2DM, and even have links to the development of pancreatic carcinoma, and therefore, it must be investigated in further detail. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  5. Nonalcoholic fatty liver disease and hepatocellular carcinoma.

    Science.gov (United States)

    Zoller, Heinz; Tilg, Herbert

    2016-08-01

    The fastest growing cause of cancer-related death is hepatocellular carcinoma (HCC), which is at least partly attributable to the rising prevalence of non-alcoholic fatty liver disease. Non-alcoholic fatty liver disease (NAFLD) encompasses a broad spectrum of conditions, ranging from non-progressive bland steatosis to malignant transformation into hepatocellular cancer. The estimated annual HCC incidence in the progressive form of NAFLD - non-alcoholic steatohepatitis (NASH) - is about 0.3%. The risk of HCC development is higher in men and increases with age, more advanced fibrosis, progressive obesity, insulin resistance and diabetes mellitus. Studies on the molecular mechanism of HCC development in NAFLD have shown that hepatocarcinogenesis is associated with complex changes at the immunometabolic interface. In line with these clinical risk factors, administration of a choline-deficient high-fat diet to mice over a prolonged period results in spontaneous HCC development in a high percentage of animals. The role of altered insulin signaling in tumorigenesis is further supported by the observation that components of the insulin-signaling cascade are frequently mutated in hepatocellular cancer cells. These changes further enhance insulin-mediated growth and cell division of hepatocytes. Furthermore, studies investigating nuclear factor kappa B (NF-κB) signaling and HCC development allowed dissection of the complex links between inflammation and carcinogenesis. To conclude, NAFLD reflects an important risk factor for HCC, develops also in non-cirrhotic livers and is a prototypic cancer involving inflammatory and metabolic pathways. STRENGTHS/WEAKNESSES AND SUMMARY OF THE TRANSLATIONAL POTENTIAL OF THE MESSAGES IN THE PAPER: The systematic review summarizes findings from unbiased clinical and translational studies on hepatocellular cancer in non-alcoholic fatty liver disease. This provides a concise overview on the epidemiology, risk factors and molecular

  6. Managing non-alcoholic fatty liver disease.

    Science.gov (United States)

    Ngu, Jing Hieng; Goh, George Boon Bee; Poh, Zhongxian; Soetikno, Roy

    2016-07-01

    The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing rapidly with the obesity and diabetes mellitus epidemics. It is rapidly becoming the most common cause of liver disease worldwide. NAFLD can progress to serious complications such as cirrhosis, hepatocellular carcinoma and death. Therefore, it is important to recognise this condition so that early intervention can be implemented. Lifestyle modifications and strict control of metabolic risk factors are the mainstay of treatment. As disease progression is slow in the majority of NAFLD patients, most can be managed well by primary care physicians. NAFLD patients with advanced liver fibrosis should be referred to specialist care for further assessment. Copyright: © Singapore Medical Association.

  7. Non-Alcoholic Fatty Liver Disease.

    Science.gov (United States)

    Engin, Atilla

    2017-01-01

    Non-alcoholic fatty liver disease (NAFLD) is in parallel with the obesity epidemic and it is the most common cause of liver diseases. The development of hepatic steatosis in majority of patients is linked to dietary fat ingestion. NAFLD is characterized by excess accumulation of triglyceride in the hepatocyte due to both increased inflow of free fatty acids and de novo hepatic lipogenesis. Insulin resistance with the deficiency of insulin receptor substrate-2 (IRS-2)-associated phosphatidylinositol 3-kinase (PI3K) activity causes an increase in intracellular fatty acid-derived metabolites such as diacylglycerol, fatty acyl CoA or ceramides. Lipotoxicity-related mechanism of NAFLD could be explained still best by the "double-hit" hypothesis. Insulin resistance is the major mechanism in the development and progression of NAFLD/Non-alcoholic steatohepatitis (NASH). Metabolic oxidative stress, autophagy, and inflammation induce NASH progression. In the "first hit" the hepatic concentrations of diacylglycerol increase with rising saturated liver fat content in human NAFLD. Activities of mitochondrial respiratory chain complexes are decreased in liver tissue of patients with NASH. Furthermore, hepatocyte lipoapoptosis is a critical feature of NASH. In "second hit" reduced glutathione levels due to oxidative stress lead to overactivation of c-Jun N-terminal kinase (JNK)/c-Jun signaling that induces cell death in the steatotic liver. Accumulation of toxic levels of reactive oxygen species (ROS) is caused by the ineffectual cycling of the endoplasmic reticulum (ER) oxidoreductin (Ero1)-protein disulfide isomerase oxidation cycle through the downstream of the inner membrane mitochondrial oxidative metabolism and Kelch like-ECH-associated protein 1 (Keap1)- Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway.

  8. Radiologic evaluation of nonalcoholic fatty liver disease

    Science.gov (United States)

    Lee, Seung Soo; Park, Seong Ho

    2014-01-01

    Nonalcoholic fatty liver disease (NAFLD) is a frequent cause of chronic liver diseases, ranging from simple steatosis to nonalcoholic steatohepatitis (NASH)-related liver cirrhosis. Although liver biopsy is still the gold standard for the diagnosis of NAFLD, especially for the diagnosis of NASH, imaging methods have been increasingly accepted as noninvasive alternatives to liver biopsy. Ultrasonography is a well-established and cost-effective imaging technique for the diagnosis of hepatic steatosis, especially for screening a large population at risk of NAFLD. Ultrasonography has a reasonable accuracy in detecting moderate-to-severe hepatic steatosis although it is less accurate for detecting mild hepatic steatosis, operator-dependent, and rather qualitative. Computed tomography is not appropriate for general population assessment of hepatic steatosis given its inaccuracy in detecting mild hepatic steatosis and potential radiation hazard. However, computed tomography may be effective in specific clinical situations, such as evaluation of donor candidates for hepatic transplantation. Magnetic resonance spectroscopy and magnetic resonance imaging are now regarded as the most accurate practical methods of measuring liver fat in clinical practice, especially for longitudinal follow-up of patients with NAFLD. Ultrasound elastography and magnetic resonance elastography are increasingly used to evaluate the degree of liver fibrosis in patients with NAFLD and to differentiate NASH from simple steatosis. This article will review current imaging methods used to evaluate hepatic steatosis, including the diagnostic accuracy, limitations, and practical applicability of each method. It will also briefly describe the potential role of elastography techniques in the evaluation of patients with NAFLD. PMID:24966609

  9. Nonalcoholic fatty liver disease and hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    LI Liangping

    2016-03-01

    Full Text Available As the etiology of hepatocellular carcinoma (HCC has been changing, the incidence of HCC related to nonalcoholic fatty liver disease (NAFLD is gradually increasing in developed countries in Europe and America and some countries in Asia. This article introduces the close association between NAFLD and HCC, risk factors, clinicopathological features, and prevention and screening, and points out that although the incidence of NAFLD is not as high as that of hepatitis B- or hepatitis C-related HCC, there are a large absolute number of NAFLD patients, especially the high-risk patients with diabetes and obesity, or liver fibrosis/cirrhosis, due to a huge base number of NAFLD patients. NAFLD-related HCC is commonly seen in the elderly with various comorbidities and a poor prognosis. This article also points out that the prevention should focus on the effective treatment of NAFLD. The strict screening of high-risk population is the strategy for the diagnosis of early-stage HCC. At present, the sensitivity of alpha-fetoprotein is relatively low, and imaging examinations including computed tomography are the main screening methods; however, there are no measures for early warning of NAFLD-related HCC.

  10. Endocrine causes of nonalcoholic fatty liver disease.

    Science.gov (United States)

    Marino, Laura; Jornayvaz, François R

    2015-10-21

    Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the industrialized world. The prevalence of NAFLD is increasing, becoming a substantial public health burden. NAFLD includes a broad spectrum of disorders, from simple conditions such as steatosis to severe manifestations such as fibrosis and cirrhosis. The relationship of NAFLD with metabolic alterations such as type 2 diabetes is well described and related to insulin resistance, with NAFLD being recognized as the hepatic manifestation of metabolic syndrome. However, NAFLD may also coincide with endocrine diseases such as polycystic ovary syndrome, hypothyroidism, growth hormone deficiency or hypercortisolism. It is therefore essential to remember, when discovering altered liver enzymes or hepatic steatosis on radiological exams, that endocrine diseases can cause NAFLD. Indeed, the overall prognosis of NAFLD may be modified by treatment of the underlying endocrine pathology. In this review, we will discuss endocrine diseases that can cause NALFD. Underlying pathophysiological mechanisms will be presented and specific treatments will be reviewed.

  11. Nonalcoholic fatty liver disease - A multisystem disease?

    Science.gov (United States)

    Mikolasevic, Ivana; Milic, Sandra; Turk Wensveen, Tamara; Grgic, Ivana; Jakopcic, Ivan; Stimac, Davor; Wensveen, Felix; Orlic, Lidija

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD) is one of the most common comorbidities associated with overweight and metabolic syndrome (MetS). Importantly, NAFLD is one of its most dangerous complications because it can lead to severe liver pathologies, including fibrosis, cirrhosis and hepatic cellular carcinoma. Given the increasing worldwide prevalence of obesity, NAFLD has become the most common cause of chronic liver disease and therefore is a major global health problem. Currently, NAFLD is predominantly regarded as a hepatic manifestation of MetS. However, accumulating evidence indicates that the effects of NAFLD extend beyond the liver and are negatively associated with a range of chronic diseases, most notably cardiovascular disease (CVD), diabetes mellitus type 2 (T2DM) and chronic kidney disease (CKD). It is becoming increasingly clear that these diseases are the result of the same underlying pathophysiological processes associated with MetS, such as insulin resistance, chronic systemic inflammation and dyslipidemia. As a result, they have been shown to be independent reciprocal risk factors. In addition, recent data have shown that NAFLD actively contributes to aggravation of the pathophysiology of CVD, T2DM, and CKD, as well as several other pathologies. Thus, NAFLD is a direct cause of many chronic diseases associated with MetS, and better detection and treatment of fatty liver disease is therefore urgently needed. As non-invasive screening methods for liver disease become increasingly available, detection and treatment of NAFLD in patients with MetS should therefore be considered by both (sub-) specialists and primary care physicians. PMID:27920470

  12. [Non-alcoholic fatty liver disease--new view].

    Science.gov (United States)

    Raszeja-Wyszomirska, Joanna; Lawniczak, Małgorzata; Marlicz, Wojciech; Miezyńska-Kurtycz, Joanna; Milkiewicz, Piotr

    2008-06-01

    Non-alcoholic fatty liver disease (NAFLD) covers a wide spectrum of liver pathology--from steatosis alone, through the necroinflammatory disorder of non-alcoholic steatohepatitis (NASH) to cirrhosis and liver cancer. NAFLD/NASH is mostly related with visceral adiposity, obesity, type 2 diabetes melitus (DM t.2) and metabolic syndrome. Pathogenetic concepts of NAFLD include overnutrition and underactivity, insulin resistance (IR) and genetic factor. The prevalence of NAFLD has been estimated to be 17-33% in some countries, NASH may be present in about 1/3 of such cases, while 20-25% of NASH cases could progress to cirrhosis. NAFLD is now recognized as one of the most frequent reason of liver tests elevation without clinical symptoms. Insulin resistance is considering as having a central role in NAFLD pathogenesis. In hepatocytes, IR is related to hyperglycaemia and hyperinsulinaemia, formation of advanced glycation end-products, increased free fatty acids and their metabolites, oxidative stress and altered profiles of adipocytokines. Early stages of fatty liver are clinically silent and include elevation of ALT and GGTP, hyperechogenic liver in USG and/or hepatomegaly. Among clinical symptoms, abdominal discomfort is relatively common as well as chronic fatigue. NAFLD/NASH is not a benign disease, progressive liver biopsy have shown histological progression of fibrosis in 32%, the estimated rate of cirrhosis development is 20% and a liver--related death is 12% over 10 years. No treatment has scientifically proved to ameliorate NAFLD or to avoid its progression. The various therapeutic alternatives are aimed at interfering with the risk factors involved in the pathogenesis of the disorder in order to prevent the progression to end-stage liver disease. The most important therapeutic measure is increasing insulin sensitivity by an attempt to change a lifestyle mostly by dieting and physical activity in order to loose weight. The most used agent is metformin, the others

  13. Taurine and tea polyphenols combination ameliorate nonalcoholic steatohepatitis in rats.

    Science.gov (United States)

    Zhu, Wenhua; Chen, Siwen; Chen, Ronggui; Peng, Zhiqing; Wan, Jun; Wu, Benyan

    2017-09-08

    Nonalcoholic steatohepatitis (NASH) is a progressive form of nonalcoholic fatty liver disease, for which there is currently no safe and effective drug for therapy. In this study, we explored the effects of taurine, tea polyphenols (TPs), or a combination thereof, on NASH rats. Rats were divided into a normal group, a high-fat diet induced model group and a treatment group (including taurine, TPs, or taurine + TPs treatment for 8 weeks). Twelve weeks later, all rats were sacrificed, and serum transaminase, lipid and lipopolysaccharide levels and hepatic oxidative stress levels were determined. Histological changes were evaluated. In NASH rats, hepatocyte damage, lipid disturbance, oxidative stress and elevated lipopolysaccharide levels were confirmed. Taurine treatment alleviated hepatocyte damage and oxidative stress. TPs treatment improved lipid metabolism and increased hepatic antioxidant activity. The therapeutic effects of taurine + TPs treatment on hepatocyte damage, lipid disturbance, and oxidative stress were superior to those of taurine and TPs treatment, respectively. Taurine, TPs and their combination all decreased serum lipopolysaccharide levels in NASH rats, but the combination of the compounds caused these levels to decrease more significantly than taurine or TPs treatment alone. Taurine combined with TPs treatment could relieve NASH by alleviating hepatocyte damage, decreasing oxidative stress and improving lipid metabolism and gut flora disturbance partly. Taurine and TPs combination may act as a new effective medicine for treating NASH patients.

  14. [Non-alcoholic fatty liver disease and steatohepatitis].

    Science.gov (United States)

    Pár, Gabriella; Horváth, Gábor; Pár, Alajos

    2013-07-21

    Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis, the hepatic manifestations of metabolic syndrome with close association with inzulin resistance and obesity, are the most common liver diseases, affecting up to a third of the population worldwide. They confer increased risk for hepatocellular carcinoma as well as cardiovascular diseases. The review aims to summarize advances in epidemiology, pathogenesis and clinical management of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. Besides liver biopsy and biomarkers, a novel non-invasive diagnostic tool the called "controlled attenuation parameter" measuring the attenuation of ultrasound generated by the transient elastography transducer, can quantitatively assess the hepatic fat content and differentiate between steatosis grades. At the same time, liver stiffness (fibrosis) can also be evaluated. The authors present their own results obtained with the latter procedure. In non-alcoholic fatty liver disease, the lifestyle intervention, weight loss, diet and exercise supported by cognitive behavioural therapy represent the basis of management. Components of metabolic syndrome (obesity, dyslipidaemia, diabetes and arterial hypertension) have to be treated. Although there is no approved pharmacological therapy for NASH, it seems that long lasting administration of vitamin E in association with high dose ursodeoxycholic acid may be beneficial. In addition, omega-3 polyunsaturated fatty acid substitution can also decrease liver fat, however, the optimal dose is not known yet. Further controlled clinical studies are warranted to establish the real value of any suggested treatment modalities for non-alcoholic fatty liver disease and non-alcoholic steatohepatitis, although these are in experimental phase yet.

  15. Nonalcoholic fatty liver disease: Evolving paradigms

    Science.gov (United States)

    Lonardo, Amedeo; Nascimbeni, Fabio; Maurantonio, Mauro; Marrazzo, Alessandra; Rinaldi, Luca; Adinolfi, Luigi Elio

    2017-01-01

    In the last years new evidence has accumulated on nonalcoholic fatty liver disease (NAFLD) challenging the paradigms that had been holding the scene over the previous 30 years. NAFLD has such an epidemic prevalence as to make it impossible to screen general population looking for NAFLD cases. Conversely, focusing on those cohorts of individuals exposed to the highest risk of NAFLD could be a more rational approach. NAFLD, which can be diagnosed with either non-invasive strategies or through liver biopsy, is a pathogenically complex and clinically heterogeneous disease. The existence of metabolic as opposed to genetic-associated disease, notably including ”lean NAFLD” has recently been recognized. Moreover, NAFLD is a systemic condition, featuring metabolic, cardiovascular and (hepatic/extra-hepatic) cancer risk. Among the clinico-laboratory features of NAFLD we discuss hyperuricemia, insulin resistance, atherosclerosis, gallstones, psoriasis and selected endocrine derangements. NAFLD is a precursor of type 2 diabetes (T2D) and metabolic syndrome and progressive liver disease develops in T2D patients in whom the course of disease is worsened by NAFLD. Finally, lifestyle changes and drug treatment options to be implemented in the individual patient are also critically discussed. In conclusion, this review emphasizes the new concepts on clinical and pathogenic heterogeneity of NAFLD, a systemic disorder with a multifactorial pathogenesis and protean clinical manifestations. It is highly prevalent in certain cohorts of individuals who are thus potentially amenable to selective screening strategies, intensive follow-up schedules for early identification of liver-related and extrahepatic complications and in whom earlier and more aggressive treatment schedules should be carried out whenever possible. PMID:29085206

  16. β-glycosphingolipids ameliorated non-alcoholic steatohepatitis in the Psammomys obesus model

    Directory of Open Access Journals (Sweden)

    Zigmond E

    2014-10-01

    Full Text Available Ehud Zigmond,1,* Oshrat Tayer-Shifman,1,* Gadi Lalazar,1 Ami Ben Ya'acov,1 Sarah Weksler-Zangen,2 David Shasha,1 Miriam Sklair-Levy,3 Lidya Zolotarov,1 Zvi Shalev,1 Rony Kalman,2 Ehud Ziv,2 Itamar Raz,2 Yaron Ilan1 1Liver Unit, 2Diabetes Unit, 3Department of Radiology, Hebrew University-Hadassah Medical Center, Jerusalem, Israel *These authors contributed equally to this workAbstract: Liver steatosis is a common characteristic of obesity and type 2 diabetes, and fatty liver disease is increasingly recognized as a major health burden. Accumulating evidence suggests that β-glycosphingolipids play an important role in insulin sensitivity and thus could affect hepatic steatosis. To determine the effect associated with β-glycosphingolipid-mediated amelioration of liver injury, seven groups of Psammomys obesus on a high-energy diet were studied. Animals were treated with daily injections of β-glucosylceramide, β-lactosylceramide, or a combination of both. β-glycosphingolipids ameliorated the hepatic injury manifested by decreased liver enzymes, liver weight, and hepatic fat, and improved liver histology. Administration of both β-glucosylceramide and β-lactosylceramide also decreased interferon (IFN-γ serum levels. These effects were associated with improved serum cholesterol and triglyceride levels. These data suggest that β-glycosphingolipids ameliorate liver injury in an animal model of nonalcoholic steatohepatitis.Keywords: NAFLD, glycolipids, STAT, NASH, insulin resistance, diabetes

  17. [Non-alcoholic fatty liver disease and hepatocellular carcinoma - 2016].

    Science.gov (United States)

    Pár, Alajos; Pár, Gabriella

    2016-06-19

    In the past decade non-alcoholic liver disease became the most frequently diagnosed liver disease in developed countries. At the same time, the dramatic rise in the incidence of hepatocellular carcinoma is attributed to this common metabolic disorder, and mainly to its severe form, non-alcoholic steatohepatitis. The risk factors of these associated diseases are genetic predisposition, obesity and diabetes as well as chronic low grade necro-infammation, which often leads to liver fibrosis. Free fatty acids, cytokines, lipotoxicity, insulin resistance, microRNS dysregulation and alteration in intestinal microbiota play a pivotal role in the pathogenesis. Treatment of non-alcoholic fatty liver disease - weight reduction and physical exercise in obesity, metformin in diabetes, statins in dyslipidemia and, as a new option, obeticholic acid - may diminish the risk of the hepatocellular carcinoma related to this metabolic disease.

  18. Serum resistin levels in nonalcoholic fatty liver disease and their ...

    African Journals Online (AJOL)

    Background: Resistin is a hormone that is linked to the development of insulin resistance (IR), but information on the direct relationship of resistin levels in ... These findings support the link between resistin, insulin resistance and BMI in these patients. Keywords: resistin; nonalcoholic fatty liver disease; insulin resistance ...

  19. Nonalcoholic fatty liver disease: Synopsis of current developments

    African Journals Online (AJOL)

    2015-02-26

    Feb 26, 2015 ... Non-alcoholic fatty liver disease (NAFLD) which is defined as the accumulation of fat >5% of liver weight is increasingly becoming an important cause ..... visual analysis of the intensity of the echogenicity, provided the gain setting is .... adjustment resulted in a 7–10% weight loss with significant histological ...

  20. Non-Alcoholic Fatty Liver Disease (NAFLD) in Obesity

    OpenAIRE

    Patell, Rushad; Dosi, Rupal; Joshi, Harshal; Sheth, Smit; Shah, Purav; Jasdanwala, Sarfaraz

    2014-01-01

    Background and Objectives: Limited studies have been undertaken to characterize Non-Alcoholic Fatty Liver Disease (NAFLD) in the Indian population. The main objective of our study was to document the prevalence of NAFLD amongst a cohort of obese Indian patients and demonstrate its relationship with other components of the metabolic syndrome.

  1. Fructose Consumption, Lipogenesis, and Non-Alcoholic Fatty Liver Disease

    NARCIS (Netherlands)

    ter Horst, Kasper W.; Serlie, Mireille J.

    2017-01-01

    Increased fructose consumption has been suggested to contribute to non-alcoholic fatty liver disease (NAFLD), dyslipidemia, and insulin resistance, but a causal role of fructose in these metabolic diseases remains debated. Mechanistically, hepatic fructose metabolism yields precursors that can be

  2. ORIGINAL ARTICLE Non-Alcoholic Fatty Liver Disease and ...

    African Journals Online (AJOL)

    2018-01-01

    Jan 1, 2018 ... ABSTRACT. BACKGROUND: Non-alcoholic Fatty Liver Disease (NAFLD) among type 2 diabetic patients is completely ignored in developing regions like Africa paving the way for public health and economic burden in the region. Therefore, the main objective of this research was to evaluate non-alcoholic ...

  3. SCAP gene polymorphisms decrease the risk of nonalcoholic fatty ...

    Indian Academy of Sciences (India)

    disease in females with metabolic syndrome. SHANSHAN SUN1, MIAO WANG1 ... Keywords. genetic polymorphism; nonalcoholic fatty liver disease; metabolic syndrome; SCAP; SREBF-1; SREBF-2. Journal of Genetics, Vol. .... Clinical and biological characteristics of subjects in three groups. Total. MS. Healthy control. MS.

  4. The Adaptive Endoplasmic Reticulum Stress Response to Lipotoxicity in Progressive Human Nonalcoholic Fatty Liver Disease

    Czech Academy of Sciences Publication Activity Database

    Lake, A.D.; Novák, Petr; Hardwick, R.N.; Flores-Keown, B.; Zhao, F.; Klimecki, W. T.; Cherrington, N.J.

    2014-01-01

    Roč. 137, č. 1 (2014), s. 26-35 ISSN 1096-6080 Institutional support: RVO:60077344 Keywords : nonalcoholic fatty liver disease * lipotoxicity * nonalcoholic steatohepatitis Subject RIV: CE - Biochemistry Impact factor: 3.854, year: 2014

  5. Placental extract ameliorates non-alcoholic steatohepatitis (NASH by exerting protective effects on endothelial cells

    Directory of Open Access Journals (Sweden)

    Akihiro Yamauchi

    2017-09-01

    Full Text Available Non-alcoholic steatohepatitis (NASH is a severe form of fatty liver disease that is defined by the presence of inflammation and fibrosis, ultimately leading to cirrhosis and hepatocellular carcinoma. Treatment with human placental extract (HPE reportedly ameliorates the hepatic injury. We evaluated the effect of HPE treatment in a mouse model of NASH. In the methione- and choline-deficient (MCD diet-induced liver injury model, fibrosis started from regions adjacent to the sinusoids. We administered the MCD diet with high-salt loading (8% NaCl in the drinking water to mice deficient in the vasoprotective molecule RAMP2 for 5 weeks, with or without HPE. In both the HPE and control groups, fibrosis was seen in regions adjacent to the sinusoids, but the fibrosis was less pronounced in the HPE-treated mice. Levels of TNF-α and MMP9 expression were also significantly reduced in HPE-treated mice, and oxidative stress was suppressed in the perivascular region. In addition, HPE dose-dependently increased survival of cultured endothelial cells exposed to 100 μM H2O2, and it upregulated expression of eNOS and the anti-apoptotic factors bcl-2 and bcl-xL. From these observations, we conclude that HPE ameliorates NASH-associated pathologies by suppressing inflammation, oxidative stress and fibrosis. These beneficially effects of HPE are in part attributable to its protective effects on liver sinusoidal endothelial cells. HPE could thus be an attractive therapeutic candidate with which to suppress progression from simple fatty liver to NASH.

  6. Nonalcoholic Fatty Liver Disease: Focus on Lipoprotein and Lipid Deregulation

    Directory of Open Access Journals (Sweden)

    Klementina Fon Tacer

    2011-01-01

    Full Text Available Obesity with associated comorbidities is currently a worldwide epidemic and among the most challenging health conditions in the 21st century. A major metabolic consequence of obesity is insulin resistance which underlies the pathogenesis of the metabolic syndrome. Nonalcoholic fatty liver disease (NAFLD is the hepatic manifestation of obesity and metabolic syndrome. It comprises a disease spectrum ranging from simple steatosis (fatty liver, through nonalcoholic steatohepatitis (NASH to fibrosis, and ultimately liver cirrhosis. Abnormality in lipid and lipoprotein metabolism accompanied by chronic inflammation is the central pathway for the development of metabolic syndrome-related diseases, such as atherosclerosis, cardiovascular disease (CVD, and NAFLD. This paper focuses on pathogenic aspect of lipid and lipoprotein metabolism in NAFLD and the relevant mouse models of this complex multifactorial disease.

  7. Pathogenesis of non-alcoholic fatty liver disease

    OpenAIRE

    Dowman, J. K.; Tomlinson, J.W.; Newsome, P.N.

    2009-01-01

    Non-alcoholic fatty liver disease (NAFLD) represents a spectrum of disease ranging from hepatocellular steatosis through steatohepatitis to fibrosis and irreversible cirrhosis. The prevalence of NAFLD has risen rapidly in parallel with the dramatic rise in obesity and diabetes, and is rapidly becoming the most common cause of liver disease in Western countries. Indeed, NAFLD is now recognized to be the aetiology in many cases previously labelled as cryptogenic cirrhosis.

  8. Research advances in the pathogenesis of nonalcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    WANG Hu

    2017-04-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD has been developing rapidly in recent years and has become one of the most common liver diseases. However, its pathogenesis remains unclear, and there are no widely accepted therapeutic regimens. NAFLD has a complex pathogenesis with multiple factors involved, including insulin resistance, oxidative stress, bile acid metabolic disorders, and autophagy. This article reviews the pathogenesis of NAFLD in order to provide a reference for further research and clinical treatment in the future.

  9. Epidemiological modifiers of non-alcoholic fatty liver disease: focus on high-risk groups

    OpenAIRE

    Lonardo, A.; Bellentani, S.; Argo, C.K.; Ballestri, S.; Byrne, Christopher D.; Caldwell, S.H.; Cortez-Pinto, H.; Grieco, A.; Machado, M.V.; Miele, L.; Targher, G.

    2015-01-01

    An improved understanding of non-alcoholic fatty liver disease epidemiology would lead to identification of individuals at high risk of developing chronic liver disease and extra-hepatic complications, thus contributing to more effective case finding of non-alcoholic fatty liver disease among selected groups.We aimed to illustrate the epidemiology of non-alcoholic fatty liver disease in high-risk groups, which were identified based on existing literature. To this end, PubMed was searched to r...

  10. Epidemiological modifiers of non-alcoholic fatty liver disease: Focus on high-risk groups.

    Science.gov (United States)

    Lonardo, Amedeo; Bellentani, Stefano; Argo, Curtis K; Ballestri, Stefano; Byrne, Christopher D; Caldwell, Stephen H; Cortez-Pinto, Helena; Grieco, Antonio; Machado, Mariana V; Miele, Luca; Targher, Giovanni

    2015-12-01

    An improved understanding of non-alcoholic fatty liver disease epidemiology would lead to identification of individuals at high risk of developing chronic liver disease and extra-hepatic complications, thus contributing to more effective case finding of non-alcoholic fatty liver disease among selected groups. We aimed to illustrate the epidemiology of non-alcoholic fatty liver disease in high-risk groups, which were identified based on existing literature. To this end, PubMed was searched to retrieve original articles published until May 2015 using relevant and pertinent keywords "nonalcoholic fatty liver disease" and "diabetes", "obesity", "hyperlipidaemia", "familial heterozygous hypobetalipoproteinaemia", "hypertension", "metabolic syndrome", "ethnicity", "family history" or "genetic polymorphisms". We found that age, sex and ethnicity are major physiological modifiers of the risk of non-alcoholic fatty liver disease, along with belonging to "non-alcoholic fatty liver disease families" and carrying risk alleles for selected genetic polymorphisms. Metabolic syndrome, diabetes, obesity, mixed hyperlipidaemia and hypocholesterolaemia due to familial hypobetalipoproteinaemia are the major metabolic modifiers of non-alcoholic fatty liver disease risk. Compared with these metabolic conditions, however, arterial hypertension appears to carry a relatively more modest risk of non-alcoholic fatty liver disease. A better understanding of the epidemiology of non-alcoholic fatty liver disease may result in a more liberal policy of case finding among high-risk groups. Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  11. ω-3 Fatty acids reverse lipotoxity through induction of autophagy in nonalcoholic fatty liver disease.

    Science.gov (United States)

    Chen, Yi; Xu, Chengfu; Yan, Tianlian; Yu, Chaohui; Li, Youming

    2015-01-01

    The aim of this study was to evaluate the effect of ω-3 fatty acids on nonalcoholic fatty liver disease concerning hepatocyte lipid accumulation as well as apoptosis induced by free fatty acids (FFAs) and to explore the underlying mechanism involving autophagy. Hepatocytes were incubated with a mixture of free fatty acids (FFAs) to mimic in vitro lipotoxicity in the pathogenesis of nonalcoholic fatty liver disease, presented by lipid accumulation and cellular apoptosis. Chemical inhibitor or inducer of autophagy and genetic deficit cells, as well as ω-3 fatty acids were used as intervention. The autophagic role of ω-3 fatty acids was investigated using Western blot and immunofluorescence. The underlying mechanism of ω-3 fatty acids involving autophagy was preliminarily explored by quantitative real-time polymerase chain reaction and Western blot. FFAs induce lipid accumulation and apoptosis in hepatocytes. Inhibition or genetic defect of autophagy increases lipid accumulation induced by FFA, whereas induction acts inversely. ω-3 Fatty acids reduced lipid accumulation and inhibited apoptosis induced by FFA. ω-3 Fatty acids induced autophagy by downregulating stearoyl-CoA desaturase 1 expression in hepatocytes. ω-3 Fatty acids exert protective effects on hepatocytes against lipotoxicity through induction of autophagy, as demonstrated by inhibition of lipid accumulation and apoptosis. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Non-alcoholic fatty liver disease in 2016.

    Science.gov (United States)

    Townsend, S A; Newsome, Philip N

    2016-09-01

    Non-alcoholic fatty liver disease is the commonest cause of liver disease worldwide, and is rapidly becoming the leading indication for liver transplantation. Original articles, reviews and meta-analyses, guidelines. NAFLD strongly correlates with obesity and insulin resistance; currently, the best management strategy is weight loss and treatment of the metabolic syndrome. Recent data suggest that the presence of fibrosis and not non-alcoholic steatohepatitis (NASH) is the predictor of clinical outcome. Many phase 2 and 3 trials are underway. Drugs hoped to be effective are obeticholic acid, elafibranor, glucagon-like peptide-1 analogues and CCR2/5 inhibitors. Improved understanding of the pathophysiology of NAFLD should help us identify which patients progress to significant liver disease and to develop therapies to target this population. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  13. Multiparametric magnetic resonance imaging for the assessment of non-alcoholic fatty liver disease severity.

    Science.gov (United States)

    Pavlides, Michael; Banerjee, Rajarshi; Tunnicliffe, Elizabeth M; Kelly, Catherine; Collier, Jane; Wang, Lai Mun; Fleming, Kenneth A; Cobbold, Jeremy F; Robson, Matthew D; Neubauer, Stefan; Barnes, Eleanor

    2017-07-01

    The diagnosis of non-alcoholic steatohepatitis and fibrosis staging are central to non-alcoholic fatty liver disease assessment. We evaluated multiparametric magnetic resonance in the assessment of non-alcoholic steatohepatitis and fibrosis using histology as standard in non-alcoholic fatty liver disease. Seventy-one patients with suspected non-alcoholic fatty liver disease were recruited within 1 month of liver biopsy. Magnetic resonance data were used to define the liver inflammation and fibrosis score (LIF 0-4). Biopsies were assessed for steatosis, lobular inflammation, ballooning and fibrosis and classified as non-alcoholic steatohepatitis or simple steatosis, and mild or significant (Activity ≥2 and/or Fibrosis ≥2 as defined by the Fatty Liver Inhibition of Progression consortium) non-alcoholic fatty liver disease. Transient elastography was also performed. Magnetic resonance success rate was 95% vs 59% for transient elastography (Pliver inflammation and fibrosis (r s =.51, Pliver inflammation and fibrosis for the diagnosis of cirrhosis was 0.85. Liver inflammation and fibrosis score for ballooning grades 0, 1 and 2 was 1.2, 2.7 and 3.5 respectively (Pliver inflammation and fibrosis (1.3) compared to patients with non-alcoholic steatohepatitis (3.0) (PLiver inflammation and fibrosis scores for patients with mild and significant non-alcoholic fatty liver disease were 1.2 and 2.9 respectively (Pliver inflammation and fibrosis for the diagnosis of significant non-alcoholic fatty liver disease was 0.89. Multiparametric magnetic resonance is a promising technique with good diagnostic accuracy for non-alcoholic fatty liver disease histological parameters, and can potentially identify patients with non-alcoholic steatohepatitis and cirrhosis. © 2017 The Authors Liver International Published by John Wiley & Sons Ltd.

  14. Non-alcoholic fatty liver disease and associated factors among type ...

    African Journals Online (AJOL)

    Background: Non-alcoholic Fatty Liver Disease (NAFLD) among type 2 diabetic patients is completely ignored in developing regions like Africa paving the way for public health and economic burden in the region. Therefore, the main objective of this research was to evaluate non-alcoholic fatty liver disease and associated

  15. The gut microbiota of nonalcoholic fatty liver disease: current methods and their interpretation

    NARCIS (Netherlands)

    van Best, Niels; Jansen, Peter L.; Rensen, Sander S.

    2015-01-01

    The role of intestinal bacteria in the pathogenesis of nonalcoholic fatty liver disease is increasingly acknowledged. Recently developed microbial profiling techniques are beginning to shed light on the nature of gut microbiota alterations in nonalcoholic fatty liver disease. In this review, we

  16. Clinical approaches to non-alcoholic fatty liver disease

    Science.gov (United States)

    Schwenger, Katherine JP; Allard, Johane P

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) ranges from simple steatosis to nonalcoholic steatohepatitis (NASH), leading to fibrosis and potentially cirrhosis, and it is one of the most common causes of liver disease worldwide. NAFLD is associated with other medical conditions such as metabolic syndrome, obesity, cardiovascular disease and diabetes. NASH can only be diagnosed through liver biopsy, but noninvasive techniques have been developed to identify patients who are most likely to have NASH or fibrosis, reducing the need for liver biopsy and risk to patients. Disease progression varies between individuals and is linked to a number of risk factors. Mechanisms involved in the pathogenesis are associated with diet and lifestyle, influx of free fatty acids to the liver from adipose tissue due to insulin resistance, hepatic oxidative stress, cytokines production, reduced very low-density lipoprotein secretion and intestinal microbiome. Weight loss through improved diet and increased physical activity has been the cornerstone therapy of NAFLD. Recent therapies such as pioglitazone and vitamin E have been shown to be beneficial. Omega 3 polyunsaturated fatty acids and statins may offer additional benefits. Bariatric surgery should be considered in morbidly obese patients. More research is needed to assess the impact of these treatments on a long-term basis. The objective of this article is to briefly review the diagnosis, management and treatment of this disease in order to aid clinicians in managing these patients. PMID:24587650

  17. NON-ALCOHOLIC FATTY LIVER DISEASE IN CHILDREN

    Directory of Open Access Journals (Sweden)

    L.V. Chistova

    2010-01-01

    Full Text Available Metabolic syndrome that represents a totality of interrelated carbohydrate metabolism and lipid disorders, as well as a mechanism regulating arterial tension and endothelium function is one of the critical issues in pediatrics. In recent years, children with metabolic syndrome are increasingly diagnosed with liver injuries symptoms that are associated with a fatty transformation of the liver [1–3]. In this case, non-alcoholic fatty liver disease (NAFLD, a liver manifestation of metabolic syndrome is diagnosed. The diagnosis is confirmed in the absence of alcohol abuse in the past medical history, virus and autoimmune liver disease markers, elimination of toxic and drug influence, as wells as disorders of copper and iron exchange in the patient’s system. One of the key risk factors for developing NAFLD in children is overeating and reduced physical activities. It was believed in the past that NAFLD is relatively benign, however, there is evidence in current literature that this is a pathological condition that may develop and result in extreme fibrotic alterations in the liver parenchymatous tissue all the way to cirrhosis and hepatocellular carcinoma [4]. Early-stage identification and timely launch of therapy for NAFLD in children represents one of the most important objectives in modern healthcare. Key words: metabolic syndrome, non-alcoholic fatty liver disease, children, steatohepatosis. (Pediatric Pharmacology. – 2010; 7(6:68-72

  18. Nonalcoholic Fatty liver disease, diabetes, obesity, and hepatocellular carcinoma.

    Science.gov (United States)

    Noureddin, Mazen; Rinella, Mary E

    2015-05-01

    Diabetes and obesity are associated with nonalcoholic fatty liver disease (NAFLD) and an increased incidence of hepatocellular carcinoma (HCC). NAFLD is the commonest cause of chronic liver disease. HCC can develop in NAFLD patients even without cirrhosis, suggesting an association between the metabolic process and HCC and raising a concern that many cancers could be missed given high NAFLD prevalence and screening limitations. The increasing prevalence of these conditions and lack of effective treatments necessitate a better understanding of their connection. This article defines the known interrelationships and common pathways between NAFLD, diabetes, obesity and HCC and possible chemoprevention strategies. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Relationship between intestinal microflora imbalance and nonalcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    MA Ruijuan

    2015-01-01

    Full Text Available The intestinal microecosystem is composed of natural microflora, intestinal epithelial cells, and intestinal mucosal immune system. Nonalcoholic fatty liver disease (NAFLD is a metabolic stress-induced liver injury associated with insulin resistance and genetic susceptibility. In recent years, there has been increasing evidence showing the involvement of imbalanced intestinal microflora in the pathogenesis of NAFLD. Overgrowth of intestinal microflora, increased permeability of intestinal mucosa, intestinal endotoxemia, and production of inflammatory cytokines play important roles in the development of NAFLD. Further studies on the relationship between intestinal microflora imbalance and the pathogenesis of NAFLD may shed light on the treatment and prevention of NAFLD.

  20. Update on Berberine in Nonalcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Yang Liu

    2013-01-01

    Full Text Available Berberine (BBR, an active ingredient from nature plants, has demonstrated multiple biological activities and pharmacological effects in a series of metabolic diseases including nonalcoholic fatty liver disease (NAFLD. The recent literature points out that BBR may be a potential drug for NAFLD in both experimental models and clinical trials. This review highlights important discoveries of BBR in this increasing disease and addresses the relevant targets of BBR on NAFLD which links to insulin pathway, adenosine monophosphate-activated protein kinase (AMPK signaling, gut environment, hepatic lipid transportation, among others. Developing nuanced understanding of the mechanisms will help to optimize more targeted and effective clinical application of BBR for NAFLD.

  1. Diagnosis and Evaluation of Nonalcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Mikako Obika

    2012-01-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD is the most common cause of elevated liver function tests results, after the commonly investigated causes have been excluded, and frequently coexists with type 2 diabetes mellitus (T2DM because the conditions have common risk factors. As both T2DM and NAFLD are related to adverse outcomes of the other, diagnosis and valuation of fatty liver is an important part of the management of diabetes. Although noninvasive methods, such as biomarkers, panel markers, and imaging, may support a diagnostic evaluation of NAFLD patients, accurate histopathological findings cannot be achieved without a liver biopsy. As it is important to know whether steatohepatitis and liver fibrosis are present for the management of NAFLD, liver biopsy remains the gold standard for NAFLD diagnosis and evaluation. Therefore, new investigations of the pathogenesis of NAFLD are necessary to develop useful biomarkers that could provide a reliable noninvasive alternative to liver biopsy.

  2. Th17 involvement in nonalcoholic fatty liver disease progression to non-alcoholic steatohepatitis.

    Science.gov (United States)

    Chackelevicius, Carla Melisa; Gambaro, Sabrina Eliana; Tiribelli, Claudio; Rosso, Natalia

    2016-11-07

    The nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome. NAFLD encompasses a wide histological spectrum ranging from benign simple steatosis to non-alcoholic steatohepatitis (NASH). Sustained inflammation in the liver is critical in this process. Hepatic macrophages, including liver resident macropaghes (Kupffer cells), monocytes infiltrating the injured liver, as well as specific lymphocytes subsets play a pivotal role in the initiation and perpetuation of the inflammatory response, with a major deleterious impact on the progression of fatty liver to fibrosis. During the last years, Th17 cells have been involved in the development of inflammation not only in liver but also in other organs, such as adipose tissue or lung. Differentiation of a naïve T cell into a Th17 cell leads to pro-inflammatory cytokine and chemokine production with subsequent myeloid cell recruitment to the inflamed tissue. Th17 response can be mitigated by T regulatory cells that secrete anti-inflammatory cytokines. Both T cell subsets need TGF-β for their differentiation and a characteristic plasticity in their phenotype may render them new therapeutic targets. In this review, we discuss the role of the Th17 pathway in NAFLD progression to NASH and to liver fibrosis analyzing different animal models of liver injury and human studies.

  3. Helicobacter pylori infection in patients with nonalcoholic fatty liver disease.

    Science.gov (United States)

    Polyzos, Stergios A; Kountouras, Jannis; Papatheodorou, Athanasios; Patsiaoura, Kalliopi; Katsiki, Evangelia; Zafeiriadou, Efthimia; Zavos, Christos; Anastasiadou, Kyriaki; Terpos, Evangelos

    2013-01-01

    Clinical data regarding Helicobacter pylori (Hp) infection in nonalcoholic fatty liver disease (NAFLD) are limited. The aim was the evaluation of Hp infection in patients with NAFLD and its association with disease severity. 28 patients with biopsy-proven NAFLD (15 with simple nonalcoholic fatty liver [NAFL], 13 with nonalcoholic steatohepatitis [NASH]) and 25 matched healthy controls were recruited. Blood samples for anti-Hp Immunoglobulin G (IgG) and standard biochemical tests were obtained after overnight fasting, and (13)C urea breath test was performed before liver biopsy in NAFLD group. Higher rates of anti-Hp IgG (P=.038) were observed in NAFLD compared to control group. Only two NAFLD patients neither were Hp IgG seropositive nor did they have a history of eradication treatment compared to 11 control subjects (P=.002). Both Hp infection (assessed by history of Hp eradication treatment and/or Hp IgG seropositivity) (P=.034) and log(HOMA-IR) (P=.007) could independently predict NAFLD in logistic regression analysis. There were similar rates of Hp IgG seropositivity or positivity in (13)C urea breath test or their combination between NAFL and NASH patients. There were no significant differences in steatosis grade, fibrosis stage, lobular or portal inflammation, or ballooning, when NAFLD patients were divided according to Hp IgG seropositivity or (13)C urea breath test positivity. Hp infection may represent one more hit contributing to the pathogenesis of NAFL, though not to the progression from NAFL to NASH. These results warrant further validation. If confirmed, eradicating Hp infection may have certain therapeutic perspectives in NAFLD treatment. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Current Concepts and Management Approaches in Nonalcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Bashar M. Attar

    2013-01-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD is the most common cause of liver dysfunction worldwide. NAFLD may progress to nonalcoholic steatohepatitis (NASH and in turn cirrhosis. Importantly, hepatic cancer can occur in NASH in the absence of cirrhosis. The cardinal histologic feature of NAFLD is the presence of an excessive accumulation of triacylglycerols and diacylglycerols in hepatocytes. The presence of obesity and insulin resistance lead to an increased hepatic-free fatty acid (FFA flux creating an environment appropriate for the development of NAFLD. The generation of toxic reactive oxygen species with the production of hepatic injury and inflammation as a consequence of FFA oxidation will ultimately lead to the initiation and progression of fibrosis. Lifestyle modifications specifically weight loss, physical exercise, and cognitive behavior therapy have been recommended as treatments for NASH. Dietary fructose is an independent risk factor for the development of NAFLD. Pioglitazone can be used to treat biopsy-proven NASH; however, its safety risks should be considered carefully. Greater consumption for coffee, independent of its caffeine component, has been associated with a significant reduced risk of advanced fibrosis in NASH. Additional data are needed before recommending bariatric surgery as an established option for the specific treatment of NASH.

  5. Non-alcoholic fatty liver disease: The diagnosis and management

    Science.gov (United States)

    Abd El-Kader, Shehab M; El-Den Ashmawy, Eman M Salah

    2015-01-01

    Non-alcoholic fatty liver disease (NAFLD) is now the most frequent chronic liver disease that occurs across all age groups and is recognized to occur in 14%-30% of the general population, representing a serious and growing clinical problem due to the growing prevalence of obesity and overweight. Histologically, it resembles alcoholic liver injury but occurs in patients who deny significant alcohol consumption. NAFLD encompasses a spectrum of conditions, ranging from benign hepatocellular steatosis to inflammatory nonalcoholic steatohepatitis, fibrosis, and cirrhosis. The majority of hepatocellular lipids are stored as triglycerides, but other lipid metabolites, such as free fatty acids, cholesterol, and phospholipids, may also be present and play a role in disease progression. NAFLD is associated with obesity and insulin resistance and is considered the hepatic manifestation of the metabolic syndrome, a combination of medical conditions including type 2 diabetes mellitus, hypertension, hyperlipidemia, and visceral adiposity. Confirmation of the diagnosis of NAFLD can usually be achieved by imaging studies; however, staging the disease requires a liver biopsy. Current treatment relies on weight loss and exercise, although various insulin-sensitizing agents, antioxidants and medications appear promising. The aim of this review is to highlight the current information regarding epidemiology, diagnosis, and management of NAFLD as well as new information about pathogenesis, diagnosis and management of this disease. PMID:25937862

  6. Multidisciplinary Pharmacotherapeutic Options for Nonalcoholic Fatty Liver Disease

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    Kei Nakajima

    2012-01-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD and non-alcoholic steatohepatitis (NASH are multidisciplinary liver diseases that often accompany type 2 diabetes or metabolic syndrome, which are characterized by insulin resistance. Therefore, effective treatment of type 2 diabetes and metabolic syndrome should target not only the cardiometabolic abnormalities, but also the associated liver disorders. In the last decade, it has been shown that metformin, thiazolidinediones, vitamin E, ezetimibe, n-3 polyunsaturated fatty acids, renin-angiotensin system (RAS blockers, and antiobesity drugs may improve hepatic pathophysiological disorders as well as clinical parameters. Accordingly, insulin sensitizers, antioxidative agents, Niemann-Pick C1-like 1 (NPC1L1 inhibitors, RAS blockers, and drugs that target the central nervous system may represent candidate pharmacotherapies for NAFLD and possibly NASH. However, the efficacy, safety, and tolerability of long-term treatment (potentially for many years with these drugs have not been fully established. Furthermore, clinical trials have not comprehensively examined the efficacy of lipid-lowering drugs (i.e., statins, fibrates, and NPC1L1 inhibitors for the treatment of NAFLD. Although clinical evidence for RAS blockers and incretin-based agents (GLP-1 analogs and dipeptidyl peptidase-4 inhibitors is also lacking, these agents are promising in terms of their insulin-sensitizing and anti-inflammatory effects without causing weight gain.

  7. Nonalcoholic fatty liver disease in spinal and bulbar muscular atrophy.

    Science.gov (United States)

    Guber, Robert D; Takyar, Varun; Kokkinis, Angela; Fox, Derrick A; Alao, Hawwa; Kats, Ilona; Bakar, Dara; Remaley, Alan T; Hewitt, Stephen M; Kleiner, David E; Liu, Chia-Ying; Hadigan, Colleen; Fischbeck, Kenneth H; Rotman, Yaron; Grunseich, Christopher

    2017-12-12

    To determine the prevalence and features of fatty liver disease in spinal and bulbar muscular atrophy (SBMA). Two groups of participants with SBMA were evaluated. In the first group, 22 participants with SBMA underwent laboratory analysis and liver imaging. In the second group, 14 participants with SBMA were compared to 13 female carriers and 23 controls. Liver biopsies were done in 4 participants with SBMA. Evidence of fatty liver disease was detected by magnetic resonance spectroscopy in all participants with SBMA in the first group, with an average dome intrahepatic triacylglycerol of 27% (range 6%-66%, ref ≤5.5%). Liver dome magnetic resonance spectroscopy measurements were significantly increased in participants with SBMA in the second group relative to age- and sex-matched controls, with average disease and male control measurements of 17% and 3%, respectively. Liver biopsies were consistent with simple steatosis in 2 participants and nonalcoholic steatohepatitis in 2 others. We observed evidence of nonalcoholic liver disease in nearly all of the participants with SBMA evaluated. These observations expand the phenotypic spectrum of the disease and provide a potential biomarker that can be monitored in future studies. Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

  8. Molecular pathways in non-alcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    Berlanga A

    2014-07-01

    Full Text Available Alba Berlanga,1,* Esther Guiu-Jurado,1,* José Antonio Porras,1,2 Teresa Auguet1,21Group GEMMAIR (AGAUR and Applied Medicine Research Group, Department of Medicine and Surgery, Universitat Rovira i Virgili (URV, IISPV, Hospital Universitari Joan XXIII, Tarragona, Spain; 2Department of Internal Medicine, Hospital Universitari Joan XXIII Tarragona, Tarragona, Spain *These authors contributed equally to this workAbstract: Non-alcoholic fatty liver disease (NAFLD is a clinicopathological change characterized by the accumulation of triglycerides in hepatocytes and has frequently been associated with obesity, type 2 diabetes mellitus, hyperlipidemia, and insulin resistance. It is an increasingly recognized condition that has become the most common liver disorder in developed countries, affecting over one-third of the population and is associated with increased cardiovascular- and liver-related mortality. NAFLD is a spectrum of disorders, beginning as simple steatosis. In about 15% of all NAFLD cases, simple steatosis can evolve into non-alcoholic steatohepatitis, a medley of inflammation, hepatocellular injury, and fibrosis, often resulting in cirrhosis and even hepatocellular cancer. However, the molecular mechanism underlying NAFLD progression is not completely understood. Its pathogenesis has often been interpreted by the "double-hit" hypothesis. The primary insult or the "first hit" includes lipid accumulation in the liver, followed by a "second hit" in which proinflammatory mediators induce inflammation, hepatocellular injury, and fibrosis. Nowadays, a more complex model suggests that fatty acids (FAs and their metabolites may be the true lipotoxic agents that contribute to NAFLD progression; a multiple parallel hits hypothesis has also been suggested. In NAFLD patients, insulin resistance leads to hepatic steatosis via multiple mechanisms. Despite the excess hepatic accumulation of FAs in NAFLD, it has been described that not only de novo FA

  9. Non-alcoholic Fatty Liver Disease: Beneficial Effects of Flavonoids.

    Science.gov (United States)

    Akhlaghi, Masoumeh

    2016-10-01

    Non-alcoholic fatty liver disease (NAFLD) has been known as the hepatic feature of metabolic syndrome. Extra fat depots, especially in visceral areas, develop insulin resistance as a result of mild oxidation and inflammation. Insulin resistance induces lipolysis and releases free fatty acids into the circulation, where they are transported to the liver. In the liver, free fatty acids are converted to triglycerides and accumulate, causing simple steatosis that, if left untreated, can lead to steatohepatitis, and subsequently liver necrosis and cirrhosis.Flavonoids, a group of plant compounds with incredible biological characteristics, have shown advantages in pathological conditions. Beneficial effects of flavonoids against NAFLD and its related disorders have been observed in both animal and human studies. Various mechanisms have been found for their protection. Flavonoids prevent hepatosteatosis by increasing fatty acid oxidation in the liver. They can also reduce caloric intake and decrease body weight and fat deposition in visceral tissues. Flavonoids are unique antioxidants that exert their beneficial effects through inhibition of nuclear factor κB, thereby attenuating release of inflammatory cytokines, which are triggers of insulin resistance. Finally, flavonoids have shown to increase adiponectin, improve insulin sensitivity and glucose tolerance, correct dyslipidemia, and reduce blood pressure in patients with NAFLD. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  10. Practical approach to non-alcoholic fatty liver disease in patients with diabetes.

    Science.gov (United States)

    Tai, F W D; Syn, W-K; Alazawi, W

    2015-09-01

    The prevalence of Type 2 diabetes is expected to increase in parallel with obesity rates and the ageing population. Recent studies show that Type 2 diabetes is associated with a twofold increase in the risk of non-alcoholic fatty liver disease, a leading cause of chronic liver disease. Individuals with non-alcoholic steatohepatitis, a more advanced stage of non-alcoholic fatty liver disease, are specifically at risk of developing fibrosis/cirrhosis (end-stage liver disease) and hepatocellular carcinoma; therefore, identifying individuals (with Type 2 diabetes) who are likely to develop hepatic complications is paramount. In the present clinical review, we discuss the potential impact of non-alcoholic fatty liver disease diagnosis on Type 2 diabetes, and the putative risk factors for developing non-alcoholic steatohepatitis and non-alcoholic steatohepatitis fibrosis. We highlight the limitations of currently used tools in non-alcoholic fatty liver disease diagnosis and staging, and provide an insight into future developments in the field. We present an example of a non-alcoholic fatty liver disease screening protocol and discuss the therapeutic options currently available to our patients. © 2015 The Authors. Diabetic Medicine © 2015 Diabetes UK.

  11. The role of bile acids in nonalcoholic fatty liver disease and nonalcoholic steatohepatitis.

    Science.gov (United States)

    Chow, Monica D; Lee, Yi-Horng; Guo, Grace L

    2017-08-01

    Nonalcoholic fatty liver disease is growing in prevalence worldwide. It is marked by the presence of macrosteatosis on liver histology but is often clinically asymptomatic. However, it can progress into nonalcoholic steatohepatitis which is a more severe form of liver disease characterized by inflammation and fibrosis. Further progression leads to cirrhosis, which predisposes patients to hepatocellular carcinoma or liver failure. The mechanism by which simple steatosis progresses to steatohepatitis is not entirely clear. However, multiple pathways have been proposed. A common link amongst many of these pathways is disruption of the homeostasis of bile acids. Other than aiding in the absorption of lipids and lipid-soluble vitamins, bile acids act as ligands. For example, they bind to farnesoid X receptor, which is critically involved in many of the pathways responsible for maintaining bile acid, glucose, and lipid homeostasis. Alterations to these pathways can lead to dysregulation of energy balance and increased inflammation and fibrosis. Repeated insults over time may be the key to development of steatohepatitis. For this reason, current drug therapies target aspects of these pathways to try to reduce and halt inflammation and fibrosis. This review will focus on the role of bile acids in these various pathways and how changes in these pathways may result in steatohepatitis. While there is no approved pharmaceutical treatment for either hepatic steatosis or steatohepatitis, this review will also touch upon the multitude of potential therapies. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Nonalcoholic fatty liver disease in chronic obstructive pulmonary disease.

    Science.gov (United States)

    Viglino, Damien; Jullian-Desayes, Ingrid; Minoves, Mélanie; Aron-Wisnewsky, Judith; Leroy, Vincent; Zarski, Jean-Pierre; Tamisier, Renaud; Joyeux-Faure, Marie; Pépin, Jean-Louis

    2017-06-01

    Nonalcoholic fatty liver disease (NAFLD) is independently linked to cardiometabolic morbidity and mortality. Low-grade inflammation, oxidative stress and ectopic fat, common features of chronic obstructive pulmonary disease (COPD), might contribute to the development of NAFLD.We aimed to investigate the prevalence of NAFLD and to evaluate the relationship between various types of liver damage and COPD severity, comorbidities and circulating inflammatory cytokines. Validated noninvasive tests (FibroMax: SteatoTest, NashTest and FibroTest) were used to assess steatosis, nonalcoholic steatohepatitis (NASH) and liver fibrosis. Patients underwent an objective assessment of COPD comorbidities, including sleep studies. Biological parameters included a complete lipid profile and inflammatory markers.In COPD patients the prevalence of steatosis, NASH and fibrosis were 41.4%, 36.9% and 61.3%, respectively. In multivariate analysis, SteatoTest and FibroTest were significantly associated with sex, body mass index (BMI), untreated sleep apnoea and insulin resistance, and, in addition, COPD Global Initiative for Chronic Obstructive Lung Disease stage for SteatoTest. Patients with steatosis had higher tumour necrosis factor-α levels and those with NASH or a combination of liver damage types had raised leptin levels after adjustment for age, sex and BMI.We concluded that NAFLD is highly prevalent in COPD and might contribute to cardiometabolic comorbidities. Copyright ©ERS 2017.

  13. Autophagy and Non-Alcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Vanessa J. Lavallard

    2014-01-01

    Full Text Available Autophagy, or cellular self-digestion, is a catabolic process that targets cell constituents including damaged organelles, unfolded proteins, and intracellular pathogens to lysosomes for degradation. Autophagy is crucial for development, differentiation, survival, and homeostasis. Important links between the regulation of autophagy and liver complications associated with obesity, non-alcoholic fatty liver disease (NAFLD, have been reported. The spectrum of these hepatic abnormalities extends from isolated steatosis to non-alcoholic steatohepatitis (NASH, steatofibrosis, which sometimes leads to cirrhosis, and hepatocellular carcinoma. NAFLD is one of the three main causes of cirrhosis and increases the risk of liver-related death and hepatocellular carcinoma. The pathophysiological mechanisms of the progression of a normal liver to steatosis and then more severe disease are complex and still unclear. The regulation of the autophagic flux, a dynamic response, and the knowledge of the role of autophagy in specific cells including hepatocytes, hepatic stellate cells, immune cells, and hepatic cancer cells have been extensively studied these last years. This review will provide insight into the current understanding of autophagy and its role in the evolution of the hepatic complications associated with obesity, from steatosis to hepatocellular carcinoma.

  14. Autophagy and non-alcoholic fatty liver disease.

    Science.gov (United States)

    Lavallard, Vanessa J; Gual, Philippe

    2014-01-01

    Autophagy, or cellular self-digestion, is a catabolic process that targets cell constituents including damaged organelles, unfolded proteins, and intracellular pathogens to lysosomes for degradation. Autophagy is crucial for development, differentiation, survival, and homeostasis. Important links between the regulation of autophagy and liver complications associated with obesity, non-alcoholic fatty liver disease (NAFLD), have been reported. The spectrum of these hepatic abnormalities extends from isolated steatosis to non-alcoholic steatohepatitis (NASH), steatofibrosis, which sometimes leads to cirrhosis, and hepatocellular carcinoma. NAFLD is one of the three main causes of cirrhosis and increases the risk of liver-related death and hepatocellular carcinoma. The pathophysiological mechanisms of the progression of a normal liver to steatosis and then more severe disease are complex and still unclear. The regulation of the autophagic flux, a dynamic response, and the knowledge of the role of autophagy in specific cells including hepatocytes, hepatic stellate cells, immune cells, and hepatic cancer cells have been extensively studied these last years. This review will provide insight into the current understanding of autophagy and its role in the evolution of the hepatic complications associated with obesity, from steatosis to hepatocellular carcinoma.

  15. The Natural Course of Non-Alcoholic Fatty Liver Disease.

    Science.gov (United States)

    Calzadilla Bertot, Luis; Adams, Leon Anton

    2016-05-20

    Non-alcoholic fatty liver disease (NAFLD) is the most prevalent form of chronic liver disease in the world, paralleling the epidemic of obesity and Type 2 diabetes mellitus (T2DM). NAFLD exhibits a histological spectrum, ranging from "bland steatosis" to the more aggressive necro-inflammatory form, non-alcoholic steatohepatitis (NASH) which may accumulate fibrosis to result in cirrhosis. Emerging data suggests fibrosis, rather than NASH per se, to be the most important histological predictor of liver and non-liver related death. Nevertheless, only a small proportion of individuals develop cirrhosis, however the large proportion of the population affected by NAFLD has led to predictions that NAFLD will become a leading cause of end stage liver disease, hepatocellular carcinoma (HCC), and indication for liver transplantation. HCC may arise in non-cirrhotic liver in the setting of NAFLD and is associated with the presence of the metabolic syndrome (MetS) and male gender. The MetS and its components also play a key role in the histological progression of NAFLD, however other genetic and environmental factors may also influence the natural history. The importance of NAFLD in terms of overall survival extends beyond the liver where cardiovascular disease and malignancy represents additional important causes of death.

  16. Paediatric non-alcoholic fatty liver disease: an overview.

    Science.gov (United States)

    AlKhater, S A

    2015-05-01

    Non-alcoholic fatty liver disease (NAFLD) is a progressive disease that encompasses a spectrum of liver diseases, ranging from simple steatosis to non-alcoholic steatohepatitis (NASH). Data related to survival in children are scarce, but these data firmly associate NAFLD with higher risks of hepatic and non-hepatic morbidities and mortalities compared with the general population. More recently, the association between NAFLD and cardiovascular disease among children has increasingly been recognized. Given that obesity is a major risk factor for the disease, paediatric NAFLD is becoming a global issue, paralleling the dramatic rise in obesity worldwide. NASH, which is more common in obese children, has the potential to advance to liver fibrosis and failure. It is unclear why certain patients undergo such transformation but this susceptibility is likely related to an interaction between a genetically susceptible host and the surrounding environment. Currently, treatment is largely conservative and includes lifestyle modification, attainable through healthy weight reduction via diet and exercise. In this review, current knowledge about NAFLD in children is summarized. This review aims to increase the awareness of the medical community about a hidden public health issue and to identify current gaps in the literature while providing directions for future research. © 2015 World Obesity.

  17. Adipose tissue, obesity and non-alcoholic fatty liver disease.

    Science.gov (United States)

    Polyzos, Stergios A; Kountouras, Jannis; Mantzoros, Christos S

    2017-06-01

    The association of obesity with non-alcoholic fatty liver disease (NAFLD) has been established. Obesity has been linked not only to initial stages of the disease, i.e., simple steatosis (SS), but also to its severity. From an epidemiologic point of view, both diseases has an increasing prevalence worldwide. From a pathogenetic point of view, obesity and its associate IR contribute to the initial fat accumulation in the hepatocyte (SS), but also to the progression of SS to nonalcoholic steatohepatitis (NASH), NASH-related cirrhosis and hepatocellular carcinoma (HCC). From a clinical point of view, obesity has increased morbidity and mortality when combined with NAFLD, owing to cardiovascular and liver-specific mortality, including higher HCC risk. From a therapeutic point of view, weight loss is regarded as the cornerstone for the disease prevention and treatment. Although diet and exercise are the first choice to this aim, they are both difficult to achieve and sustain. Thus, the need for pharmacological treatment is considered of high importance. To treat obesity through pharmacologic weight loss, orlistat has been investigated, though with limited efficacy. Currently, liraglutide appears to be more efficacious, but it has not been officially approved for specifically NASH patients. Bariatric surgery is another alternative for severely obese patients showing histological improvement in NASH patients. However, since relative data from randomized trials are very limited, morbid obesity-related NASH patients may be subjected to bariatric surgery only after a careful individualized risk-benefit assessment.

  18. Branched chain amino acid metabolism profiles in progressive human nonalcoholic fatty liver disease

    Czech Academy of Sciences Publication Activity Database

    Lake, A.D.; Novák, Petr; Shipkova, P.; Aranibar, N.; Robertson, D.G.; Reily, M.D.; Lehman-McKeeman, L.D.; Vaillancourt, R.R.; Cherrington, N.J.

    2015-01-01

    Roč. 47, č. 3 (2015), s. 603-615 ISSN 0939-4451 Institutional support: RVO:60077344 Keywords : Branched chain amino acid * nonalcoholic fatty liver disease * nonalcoholic steatohepatitis * metabolomics and transcriptomics Subject RIV: CE - Biochemistry Impact factor: 3.196, year: 2015

  19. Characterization of Hepatocellular Carcinoma Related Genes and Metabolites in Human Nonalcoholic Fatty Liver Disease

    Czech Academy of Sciences Publication Activity Database

    Clarke, D. J.; Novák, Petr; Lake, A.D.; Shipkova, P.; Aranibar, N.; Robertson, D.; Severson, P.L.; Reily, M.D.; Futscher, B. W.; Lehman-McKeeman, L.D.; Cherrington, N.J.

    2014-01-01

    Roč. 59, č. 2 (2014), s. 365-374 ISSN 0163-2116 Institutional research plan: CEZ:AV0Z50510513 Institutional support: RVO:60077344 Keywords : nonalcoholic fatty liver disease * nonalcoholic steatohepatitis * hepatocellular carcinoma * metabolomics Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.613, year: 2014

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

    NARCIS (Netherlands)

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

    2011-01-01

    The major risk factors for non-alcoholic fatty liver disease (NAFLD) are obesity, insulin resistance and dyslipidemia. The cause for progression from the steatosis stage to the inflammatory condition (non-alcoholic steatohepatitis (NASH)) remains elusive at present. Aim of this study was to test

  1. Nonalcoholic fatty liver disease : A main driver of insulin resistance or a dangerous liaison?

    NARCIS (Netherlands)

    Gruben, Nanda; Shiri-Sverdlov, Ronit; Koonen, Debby P. Y.; Hofker, Marten H.

    2014-01-01

    Insulin resistance is one of the key components of the metabolic syndrome and it eventually leads to the development of type 2 diabetes, making it one of the biggest medical problems of modern society. Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are tightly

  2. Adipokines and Non-Alcoholic Fatty Liver Disease: Multiple Interactions.

    Science.gov (United States)

    Adolph, Timon E; Grander, Christoph; Grabherr, Felix; Tilg, Herbert

    2017-07-29

    Accumulating evidence links obesity with low-grade inflammation which may originate from adipose tissue that secretes a plethora of pro- and anti-inflammatory cytokines termed adipokines. Adiponectin and leptin have evolved as crucial signals in many obesity-related pathologies including non-alcoholic fatty liver disease (NAFLD). Whereas adiponectin deficiency might be critically involved in the pro-inflammatory state associated with obesity and related disorders, overproduction of leptin, a rather pro-inflammatory mediator, is considered of equal relevance. An imbalanced adipokine profile in obesity consecutively contributes to metabolic inflammation in NAFLD, which is associated with a substantial risk for developing hepatocellular carcinoma (HCC) also in the non-cirrhotic stage of disease. Both adiponectin and leptin have been related to liver tumorigenesis especially in preclinical models. This review covers recent advances in our understanding of some adipokines in NAFLD and associated HCC.

  3. Non-alcoholic fatty liver disease: A poorly known pandemic.

    Science.gov (United States)

    Augustin, Salvador; Graupera, Isabel; Caballeria, Juan

    2017-12-20

    Non-alcoholic fatty liver disease (NAFLD) consists of an excessive depositing of fat in the liver, which can end up by causing inflammation, fibrosis and also cirrhosis with the corresponding complications including liver cancer. NAFLD has become the most common liver disease worldwide. The incidence has increased in parallel with the obesity, diabetes and metabolic syndrome epidemic, thus resulting in becoming one of the main indications for liver transplant. The diagnosis has principally been through histology but with the development of non-invasive methods, these have helped in simplifying the management of these patients in clinical practice. The only therapeutic strategies currently available are focused on weight loss (lifestyle changes or bariatric surgery). There is still no approved pharmacological option for the treatment of NAFLD, however there are a number of molecular studies in advanced stages of development. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  4. Research advances in animal models of nonalcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    HUANG Haiyan

    2014-09-01

    Full Text Available In recent years, the incidence of nonalcoholic fatty liver disease (NAFLD has increased gradually along with the rising prevalence of obesity, type 2 diabetes, and hyperlipidemia, and NAFLD has become one of the most common chronic liver diseases in the world and the second major liver disease after chronic viral hepatitis in China. However, its pathogenesis has not yet been clarified. Animal models are playing an important role in researches on NAFLD due to the facts that the development and progression of NAFLD require a long period of time, and ethical limitations exist in conducting drug trials in patients or collecting liver tissues from patients. The animal models with histopathology similar to that of NAFLD patients are reviewed, and their modeling principle, as well as the advantages and disadvantages, are compared. Animal models provide a powerful tool for further studies of NAFLD pathogenesis and drug screening for prevention and treatment of NAFLD.

  5. Advances in the treatment of nonalcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    FENG Gong

    2017-12-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD has become a major liver disease in the world and its prevalence rate continues to increase. As a component of metabolic syndrome, it has become a risk factor for many serious cerebrovascular and cardiovascular diseases. Due to the complex pathogenesis of NAFLD or the combined/mutual effect of pathogenic factors, there are still no widely accepted effective therapies. In recent years, more and more studies have revealed new pathogeneses of NAFLD and the prospects of corresponding treatment. This article introduces the recent advances in the treatment of NAFLD, including lifestyle intervention, drug therapy, integrated traditional Chinese and Western medicine therapy, and bariatric surgery. In the aspect of drug therapy, this article introduces the drugs commonly used in clinical practice and new drugs in phase II and III clinical trials and their therapeutic effects.

  6. Nutrition and Physical Activity in Nonalcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Claudia P. Oliveira

    2016-01-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD is the most common liver disease worldwide and it is associated with other medical conditions such as diabetes mellitus, metabolic syndrome, and obesity. The mechanisms of the underlying disease development and progression are not completely established and there is no consensus concerning the pharmacological treatment. In the gold standard treatment for NAFLD weight loss, dietary therapy, and physical activity are included. However, little scientific evidence is available on diet and/or physical activity and NAFLD specifically. Many dietary approaches such as Mediterranean and DASH diet are used for treatment of other cardiometabolic risk factors such as insulin resistance and type-2 diabetes mellitus (T2DM, but on the basis of its components their role in NAFLD has been discussed. In this review, the implications of current dietary and exercise approaches, including Brazilian and other guidelines, are discussed, with a focus on determining the optimal nonpharmacological treatment to prescribe for NAFLD.

  7. Adipokines and Non-Alcoholic Fatty Liver Disease: Multiple Interactions

    Directory of Open Access Journals (Sweden)

    Timon E. Adolph

    2017-07-01

    Full Text Available Accumulating evidence links obesity with low-grade inflammation which may originate from adipose tissue that secretes a plethora of pro- and anti-inflammatory cytokines termed adipokines. Adiponectin and leptin have evolved as crucial signals in many obesity-related pathologies including non-alcoholic fatty liver disease (NAFLD. Whereas adiponectin deficiency might be critically involved in the pro-inflammatory state associated with obesity and related disorders, overproduction of leptin, a rather pro-inflammatory mediator, is considered of equal relevance. An imbalanced adipokine profile in obesity consecutively contributes to metabolic inflammation in NAFLD, which is associated with a substantial risk for developing hepatocellular carcinoma (HCC also in the non-cirrhotic stage of disease. Both adiponectin and leptin have been related to liver tumorigenesis especially in preclinical models. This review covers recent advances in our understanding of some adipokines in NAFLD and associated HCC.

  8. Non-alcoholic Fatty Liver Disease: East Versus West

    Science.gov (United States)

    Agrawal, Swastik; Duseja, Ajay K

    2012-01-01

    Non-alcoholic fatty liver disease (NAFLD) is an important cause of liver disease worldwide with prevalence ranging from 10% to 30% in various countries. It has become an important cause of unexplained rise in transaminases, cryptogenic cirrhosis, and cryptogenic hepatocellular carcinoma. Pathogenesis is related to obesity, insulin resistance, oxidative stress, lipotoxicity, and resultant inflammation in the liver progressing to fibrosis. Pharmacological treatment in patients with NAFLD is still evolving and the treatment of these patients rests upon lifestyle modification with diet and exercise being the cornerstones of therapy. While there are many similarities between patients with NAFLD from Asia and the West, there are certain features which make the patients with NAFLD from Asia stand apart. This review highlights the data on NAFLD from Asia comparing it with the data from the West. PMID:25755421

  9. Hypogonadism and non-alcoholic fatty liver disease.

    Science.gov (United States)

    Mintziori, Gesthimani; Poulakos, Pavlos; Tsametis, Christos; Goulis, Dimitrios G

    2017-06-01

    Non-alcoholic fatty liver disease (NAFLD) is more common in men than in women. Thus, it has been suggested that sex steroids do have a role in the development of NAFLD. The aim of the current paper is to illustrate the association between NAFLD and hypogonadism, by reviewing data derived from both human and animal studies. The prevalence of NAFLD is high in men with hypogonadism, including those with idiopathic hypogonadotropic hypogonadism (IHH), as well as in women in post-menopause, those under estrogen receptor antagonist treatment or women with Turner syndrome. Estrogens seem to play a pivotal role in hepatic lipid homeostasis, as demonstrated in animal models with diminished ovarian estrogens (i.e., ovariectomized mice) and low serum testosterone (T) concentration is independently associated with NAFLD. The elucidation of the exact role of sex steroids in NAFLD pathogenesis would create a unique opportunity to develop novel therapies to tackle NAFLD disease.

  10. Glycosyltransferases and non-alcoholic fatty liver disease

    Science.gov (United States)

    Zhan, Yu-Tao; Su, Hai-Ying; An, Wei

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease and its incidence is increasing worldwide. However, the underlying mechanisms leading to the development of NAFLD are still not fully understood. Glycosyltransferases (GTs) are a diverse class of enzymes involved in catalyzing the transfer of one or multiple sugar residues to a wide range of acceptor molecules. GTs mediate a wide range of functions from structure and storage to signaling, and play a key role in many fundamental biological processes. Therefore, it is anticipated that GTs have a role in the pathogenesis of NAFLD. In this article, we present an overview of the basic information on NAFLD, particularly GTs and glycosylation modification of certain molecules and their association with NAFLD pathogenesis. In addition, the effects and mechanisms of some GTs in the development of NAFLD are summarized. PMID:26937136

  11. Genetics of nonalcoholic Fatty liver disease: an overview.

    Science.gov (United States)

    Puppala, Jharna; Siddapuram, Siva Prasad; Akka, Jyothy; Munshi, Anjana

    2013-01-20

    Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in the world today. Its incidence in adults and children is rising rapidly due to the ongoing epidemics of obesity and type 2 diabetes. Hence, it has become a global public health issue. Environmental factors have been found to play a major role in the etiology of NAFLD, especially for genetically susceptible populations. Among these, one of the most important factors is junk food, especially the typical "Western-style" diet rich in simple carbohydrates, saturated fat, and highly processed food materials. Genetic predisposition to NAFLD does occur; however, a precise definition of genetic factors responsible for NAFLD is still lacking. Specific variants of different genes have been shown to present a risk for NAFLD. Genetic studies might be helpful in the management of the disease by developing novel treatment strategies based on individual's genotype. Copyright © 2013. Published by Elsevier Ltd.

  12. Molecular pathways in non-alcoholic fatty liver disease.

    Science.gov (United States)

    Berlanga, Alba; Guiu-Jurado, Esther; Porras, José Antonio; Auguet, Teresa

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) is a clinicopathological change characterized by the accumulation of triglycerides in hepatocytes and has frequently been associated with obesity, type 2 diabetes mellitus, hyperlipidemia, and insulin resistance. It is an increasingly recognized condition that has become the most common liver disorder in developed countries, affecting over one-third of the population and is associated with increased cardiovascular- and liver-related mortality. NAFLD is a spectrum of disorders, beginning as simple steatosis. In about 15% of all NAFLD cases, simple steatosis can evolve into non-alcoholic steatohepatitis, a medley of inflammation, hepatocellular injury, and fibrosis, often resulting in cirrhosis and even hepatocellular cancer. However, the molecular mechanism underlying NAFLD progression is not completely understood. Its pathogenesis has often been interpreted by the "double-hit" hypothesis. The primary insult or the "first hit" includes lipid accumulation in the liver, followed by a "second hit" in which proinflammatory mediators induce inflammation, hepatocellular injury, and fibrosis. Nowadays, a more complex model suggests that fatty acids (FAs) and their metabolites may be the true lipotoxic agents that contribute to NAFLD progression; a multiple parallel hits hypothesis has also been suggested. In NAFLD patients, insulin resistance leads to hepatic steatosis via multiple mechanisms. Despite the excess hepatic accumulation of FAs in NAFLD, it has been described that not only de novo FA synthesis is increased, but FAs are also taken up from the serum. Furthermore, a decrease in mitochondrial FA oxidation and secretion of very-low-density lipoproteins has been reported. This review discusses the molecular mechanisms that underlie the pathophysiological changes of hepatic lipid metabolism that contribute to NAFLD.

  13. Molecular pathways in non-alcoholic fatty liver disease

    Science.gov (United States)

    Berlanga, Alba; Guiu-Jurado, Esther; Porras, José Antonio; Auguet, Teresa

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) is a clinicopathological change characterized by the accumulation of triglycerides in hepatocytes and has frequently been associated with obesity, type 2 diabetes mellitus, hyperlipidemia, and insulin resistance. It is an increasingly recognized condition that has become the most common liver disorder in developed countries, affecting over one-third of the population and is associated with increased cardiovascular- and liver-related mortality. NAFLD is a spectrum of disorders, beginning as simple steatosis. In about 15% of all NAFLD cases, simple steatosis can evolve into non-alcoholic steatohepatitis, a medley of inflammation, hepatocellular injury, and fibrosis, often resulting in cirrhosis and even hepatocellular cancer. However, the molecular mechanism underlying NAFLD progression is not completely understood. Its pathogenesis has often been interpreted by the “double-hit” hypothesis. The primary insult or the “first hit” includes lipid accumulation in the liver, followed by a “second hit” in which proinflammatory mediators induce inflammation, hepatocellular injury, and fibrosis. Nowadays, a more complex model suggests that fatty acids (FAs) and their metabolites may be the true lipotoxic agents that contribute to NAFLD progression; a multiple parallel hits hypothesis has also been suggested. In NAFLD patients, insulin resistance leads to hepatic steatosis via multiple mechanisms. Despite the excess hepatic accumulation of FAs in NAFLD, it has been described that not only de novo FA synthesis is increased, but FAs are also taken up from the serum. Furthermore, a decrease in mitochondrial FA oxidation and secretion of very-low-density lipoproteins has been reported. This review discusses the molecular mechanisms that underlie the pathophysiological changes of hepatic lipid metabolism that contribute to NAFLD. PMID:25045276

  14. Experimental evidence for therapeutic potential of taurine in the treatment of nonalcoholic fatty liver disease

    Science.gov (United States)

    Gentile, Christopher L.; Nivala, Angela M.; Gonzales, Jon C.; Pfaffenbach, Kyle T.; Wang, Dong; Wei, Yuren; Jiang, Hua; Orlicky, David J.; Petersen, Dennis R.; Maclean, Kenneth N.

    2011-01-01

    The incidence of obesity is now at epidemic proportions and has resulted in the emergence of nonalcoholic fatty liver disease (NAFLD) as a common metabolic disorder that can lead to liver injury and cirrhosis. Excess sucrose and long-chain saturated fatty acids in the diet may play a role in the development and progression of NAFLD. One factor linking sucrose and saturated fatty acids to liver damage is dysfunction of the endoplasmic reticulum (ER). Although there is currently no proven, effective therapy for NAFLD, the amino sulfonic acid taurine is protective against various metabolic disturbances, including alcohol-induced liver damage. The present study was undertaken to evaluate the therapeutic potential of taurine to serve as a preventative treatment for diet-induced NAFLD. We report that taurine significantly mitigated palmitate-mediated caspase-3 activity, cell death, ER stress, and oxidative stress in H4IIE liver cells and primary hepatocytes. In rats fed a high-sucrose diet, dietary taurine supplementation significantly reduced hepatic lipid accumulation, liver injury, inflammation, plasma triglycerides, and insulin levels. The high-sucrose diet resulted in an induction of multiple components of the unfolded protein response in the liver consistent with ER stress, which was ameliorated by taurine supplementation. Treatment of mice with the ER stress-inducing agent tunicamycin resulted in liver injury, unfolded protein response induction, and hepatic lipid accumulation that was significantly ameliorated by dietary supplementation with taurine. Our results indicate that dietary supplementation with taurine offers significant potential as a preventative treatment for NAFLD. PMID:21957160

  15. [Retinal and carotid changes in non-alcoholic fatty liver disease].

    Science.gov (United States)

    Baloşeanu, Cristina; Rogoveanu, I; Mocanu, Carmen

    2013-01-01

    This article presents the results of a study on 85 patients with non-alcoholic fatty liver disease (NAFLD). We evaluate the retinal vascular changes using retinal photography and carotid vascular changes, by ultrasounds, occured in this group of patients.

  16. Strategies, models and biomarkers in experimental non-alcoholic fatty liver disease research

    OpenAIRE

    Willebrords, Joost; Pereira, Isabel Veloso Alves; Maes, Michaël; Yanguas, Sara Crespo; Colle, Isabelle; Van Den Bossche, Bert; Da silva, Tereza Cristina; Oliveira, Cláudia P; Andraus, Wellington; Alves, Venâncio Avancini Ferreira; Cogliati, Bruno; Vinken, Mathieu

    2015-01-01

    Non-alcoholic fatty liver disease encompasses a spectrum of liver diseases, including simple steatosis, steatohepatitis, liver fibrosis and cirrhosis and hepatocellular carcinoma. Non-alcoholic fatty liver disease is currently the most dominant chronic liver disease in Western countries due to the fact that hepatic steatosis is associated with insulin resistance, type 2 diabetes mellitus, obesity, metabolic syndrome and drug-induced injury. A variety of chemicals, mainly drugs, and diets is k...

  17. Nonalcoholic fatty liver disease, association with cardiovascular disease and treatment (II). The treatment of nonalcoholic fatty liver disease.

    Science.gov (United States)

    Brea, Ángel; Pintó, Xavier; Ascaso, Juan F; Blasco, Mariano; Díaz, Ángel; González-Santos, Pedro; Hernández-Mijares, Antonio; Mantilla, Teresa; Millán, Jesús; Pedro-Botet, Juan

    Disease nonalcoholic fatty liver disease (NAFLD) comprises a series of histologically similar to those induced by alcohol consumption in people with very little or no liver damage same. The importance of NAFLD is its high prevalence in our Western societies, from the point of view liver in its progressive evolution from steatosis to steatohepatitis, cirrhosis and liver cancer. During the last decade it has been observed that NAFLD leads to an increased cardiovascular risk with accelerated atherosclerosis and cardiovascular events, the leading cause of morbidity and mortality. This updated January 2016 revision consists of two parts. In this second part, the treatment of NAFLD and its influence on cardiovascular disease and drugs used in the control of cardiovascular risk factors showing a beneficial effect on the liver disease will be reviewed. Copyright © 2016 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

  18. Nonalcoholic Fatty Liver Disease in Children: a Modern View on the Diagnosis and Treatment (II Part

    Directory of Open Access Journals (Sweden)

    Y.M. Stepanov

    2015-09-01

    The rapid increase in the prevalence along with the progressive course of nonalcoholic fatty liver disease with the possibility of the formation of liver cirrhosis and hepatocellular carcinoma require a prompt diagnosis of this disease in children. In the absence of specific symptoms of nonalcoholic fatty liver disease diagnostic scree-ning ought to be performed in children with risk factors. Obesity is the leading indication for diagnostic search of nonalcoholic fatty liver disease in children. Identification of genetic predictors of nonalcoholic fatty liver disease allows distinguish a group of patients who require active monitoring because of the disease progression pro-bability. Diagnosis of nonalcoholic fatty liver disease is possible after careful exclusion of other steatosis’ causes based on the age of the child and relevant clinical and laboratory data. Imaging techniques allow detect and quantify the minimum degree of steatosis, but a liver biopsy remains the gold standard for determining the extent of liver tissue damage and fibrosis. Modification of the lifestyle is the first line treatment for nonalcoholic fatty liver disease in children. Drug correction using insulin sensitizing agents, hepatoprotectors, antioxidants, pre- and probiotics are administered in cases of ineffectiveness of the first-line therapy.

  19. Strategies, models and biomarkers in experimental non-alcoholic fatty liver disease research.

    Science.gov (United States)

    Willebrords, Joost; Pereira, Isabel Veloso Alves; Maes, Michaël; Crespo Yanguas, Sara; Colle, Isabelle; Van Den Bossche, Bert; Da Silva, Tereza Cristina; de Oliveira, Cláudia Pinto Marques Souza; Andraus, Wellington; Alves, Venâncio Avancini; Cogliati, Bruno; Vinken, Mathieu

    2015-07-01

    Non-alcoholic fatty liver disease encompasses a spectrum of liver diseases, including simple steatosis, steatohepatitis, liver fibrosis and cirrhosis and hepatocellular carcinoma. Non-alcoholic fatty liver disease is currently the most dominant chronic liver disease in Western countries due to the fact that hepatic steatosis is associated with insulin resistance, type 2 diabetes mellitus, obesity, metabolic syndrome and drug-induced injury. A variety of chemicals, mainly drugs, and diets is known to cause hepatic steatosis in humans and rodents. Experimental non-alcoholic fatty liver disease models rely on the application of a diet or the administration of drugs to laboratory animals or the exposure of hepatic cell lines to these drugs. More recently, genetically modified rodents or zebrafish have been introduced as non-alcoholic fatty liver disease models. Considerable interest now lies in the discovery and development of novel non-invasive biomarkers of non-alcoholic fatty liver disease, with specific focus on hepatic steatosis. Experimental diagnostic biomarkers of non-alcoholic fatty liver disease, such as (epi)genetic parameters and '-omics'-based read-outs are still in their infancy, but show great promise. In this paper, the array of tools and models for the study of liver steatosis is discussed. Furthermore, the current state-of-art regarding experimental biomarkers such as epigenetic, genetic, transcriptomic, proteomic and metabonomic biomarkers will be reviewed. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Strategies, models and biomarkers in experimental non-alcoholic fatty liver disease research

    Science.gov (United States)

    Willebrords, Joost; Pereira, Isabel Veloso Alves; Maes, Michaël; Yanguas, Sara Crespo; Colle, Isabelle; Van Den Bossche, Bert; Da silva, Tereza Cristina; Oliveira, Cláudia P; Andraus, Wellington; Alves, Venâncio Avancini Ferreira; Cogliati, Bruno; Vinken, Mathieu

    2015-01-01

    Non-alcoholic fatty liver disease encompasses a spectrum of liver diseases, including simple steatosis, steatohepatitis, liver fibrosis and cirrhosis and hepatocellular carcinoma. Non-alcoholic fatty liver disease is currently the most dominant chronic liver disease in Western countries due to the fact that hepatic steatosis is associated with insulin resistance, type 2 diabetes mellitus, obesity, metabolic syndrome and drug-induced injury. A variety of chemicals, mainly drugs, and diets is known to cause hepatic steatosis in humans and rodents. Experimental non-alcoholic fatty liver disease models rely on the application of a diet or the administration of drugs to laboratory animals or the exposure of hepatic cell lines to these drugs. More recently, genetically modified rodents or zebrafish have been introduced as non-alcoholic fatty liver disease models. Considerable interest now lies in the discovery and development of novel non-invasive biomarkers of non-alcoholic fatty liver disease, with specific focus on hepatic steatosis. Experimental diagnostic biomarkers of non-alcoholic fatty liver disease, such as (epi)genetic parameters and ‘-omics’-based read-outs are still in their infancy, but show great promise. . In this paper, the array of tools and models for the study of liver steatosis is discussed. Furthermore, the current state-of-art regarding experimental biomarkers such as epigenetic, genetic, transcriptomic, proteomic and metabonomic biomarkers will be reviewed. PMID:26073454

  1. Nonalcoholic fatty liver disease and bariatric surgery: a comprehensive review

    Directory of Open Access Journals (Sweden)

    Everton Cazzo

    2017-05-01

    Full Text Available ABSTRACT CONTEXT AND OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD has been increasingly diagnosed worldwide and is now recognized as a source of public health concern. It comprises a wide spectrum of histological features that range from simple steatosis to severe forms of fibrosis, steatohepatitis and even cirrhosis. The impact of bariatric surgery on the course of NAFLD in individuals with obesity has been extensively studied. DESIGN AND SETTING: Narrative review; public university hospital. METHODS: A comprehensive review was conducted based on an online search on the electronic databases MEDLINE and LILACS using the MeSH terms “fatty liver” and “bariatric surgery”. RESULTS: The exact mechanisms that lead to improvement in NAFLD following bariatric surgery are not completely understood. Since Roux-en-Y gastric bypass (RYGB is the bariatric surgical procedure most performed worldwide, it is also the one from which the effects on NAFLD have been most studied, although there is also consistent evidence regarding the effects from gastric banding, sleeve gastrectomy and biliopancreatic diversions. CONCLUSION: According to the currently available evidence, bariatric surgery leads to significant improvement in NAFLD. Further research, especially by means of randomized controlled trials enrolling larger cohorts of individuals, is needed to determine the optimal procedure for this group of subjects.

  2. Non-alcoholic fatty liver disease: An expanded review

    Science.gov (United States)

    Benedict, Mark; Zhang, Xuchen

    2017-01-01

    Non-alcoholic fatty liver disease (NAFLD) encompasses the simple steatosis to more progressive steatosis with associated hepatitis, fibrosis, cirrhosis, and in some cases hepatocellular carcinoma. NAFLD is a growing epidemic, not only in the United States, but worldwide in part due to obesity and insulin resistance leading to liver accumulation of triglycerides and free fatty acids. Numerous risk factors for the development of NAFLD have been espoused with most having some form of metabolic derangement or insulin resistance at the core of its pathophysiology. NAFLD patients are at increased risk of liver-related as well as cardiovascular mortality, and NAFLD is rapidly becoming the leading indication for liver transplantation. Liver biopsy remains the gold standard for definitive diagnosis, but the development of noninvasive advanced imaging, biochemical and genetic tests will no doubt provide future clinicians with a great deal of information and opportunity for enhanced understanding of the pathogenesis and targeted treatment. As it currently stands several medications/supplements are being used in the treatment of NAFLD; however, none seem to be the “magic bullet” in curtailing this growing problem yet. In this review we summarized the current knowledge of NAFLD epidemiology, risk factors, diagnosis, pathogenesis, pathologic changes, natural history, and treatment in order to aid in further understanding this disease and better managing NAFLD patients. PMID:28652891

  3. Non-Alcoholic Fatty Liver Disease: Lipids and Insulin Resistance

    Science.gov (United States)

    Berk, Paul D; Verna, Elizabeth C

    2016-01-01

    Abstract/Synopsis Obesity and its major co-morbidities, including type 2 diabetes mellitus, nonalcoholic fatty liver disease (NAFLD), obesity cardiomyopathy, and certain cancers, are major public health problems worldwide. They are responsible for substantial morbidity and mortality, to a degree that life expectancy in the United States has actually declined in recent years because of it. Obesity is the increased accumulation of fat, i.e. triglycerides (TG), which are synthesized from glycerol and long chain fatty acids (LCFA), throughout the body. Although long believed to enter cells solely by passive diffusion, it has been established over the past 30 years that LCFA enter adipocytes, hepatocytes and cardiomyocytes via specific, facilitated transport processes, and that these processes are hormonally up-regulated in obesity. Metabolism of increased cellular TG content in obesity may lead to cell-specific lipotoxicity, contributing to co-morbidities such as NAFLD and cardiomyopathy. In contrast to the popular perception, dietary control and bariatric surgery can each achieve major initial weight loss in many patients. However several mechanisms, including persistent up-regulation of LCFA transport, contribute to weight regain in the large majority of patients. Better understanding of these transport processes and their regulation may be a key to successful future strategies to treat obesity and NAFLD. PMID:27063267

  4. Genetic background in nonalcoholic fatty liver disease: A comprehensive review

    Science.gov (United States)

    Macaluso, Fabio Salvatore; Maida, Marcello; Petta, Salvatore

    2015-01-01

    In the Western world, nonalcoholic fatty liver disease (NAFLD) is considered as one of the most significant liver diseases of the twenty-first century. Its development is certainly driven by environmental factors, but it is also regulated by genetic background. The role of heritability has been widely demonstrated by several epidemiological, familial, and twin studies and case series, and likely reflects the wide inter-individual and inter-ethnic genetic variability in systemic metabolism and wound healing response processes. Consistent with this idea, genome-wide association studies have clearly identified Patatin-like phosholipase domain-containing 3 gene variant I148M as a major player in the development and progression of NAFLD. More recently, the transmembrane 6 superfamily member 2 E167K variant emerged as a relevant contributor in both NAFLD pathogenesis and cardiovascular outcomes. Furthermore, numerous case-control studies have been performed to elucidate the potential role of candidate genes in the pathogenesis and progression of fatty liver, although findings are sometimes contradictory. Accordingly, we performed a comprehensive literature search and review on the role of genetics in NAFLD. We emphasize the strengths and weaknesses of the available literature and outline the putative role of each genetic variant in influencing susceptibility and/or progression of the disease. PMID:26494964

  5. Non-alcoholic fatty liver disease: An expanded review.

    Science.gov (United States)

    Benedict, Mark; Zhang, Xuchen

    2017-06-08

    Non-alcoholic fatty liver disease (NAFLD) encompasses the simple steatosis to more progressive steatosis with associated hepatitis, fibrosis, cirrhosis, and in some cases hepatocellular carcinoma. NAFLD is a growing epidemic, not only in the United States, but worldwide in part due to obesity and insulin resistance leading to liver accumulation of triglycerides and free fatty acids. Numerous risk factors for the development of NAFLD have been espoused with most having some form of metabolic derangement or insulin resistance at the core of its pathophysiology. NAFLD patients are at increased risk of liver-related as well as cardiovascular mortality, and NAFLD is rapidly becoming the leading indication for liver transplantation. Liver biopsy remains the gold standard for definitive diagnosis, but the development of noninvasive advanced imaging, biochemical and genetic tests will no doubt provide future clinicians with a great deal of information and opportunity for enhanced understanding of the pathogenesis and targeted treatment. As it currently stands several medications/supplements are being used in the treatment of NAFLD; however, none seem to be the "magic bullet" in curtailing this growing problem yet. In this review we summarized the current knowledge of NAFLD epidemiology, risk factors, diagnosis, pathogenesis, pathologic changes, natural history, and treatment in order to aid in further understanding this disease and better managing NAFLD patients.

  6. [Effects of three Wenyang Jianpi Tang on cell proliferation and apoptosis of nonalcoholic fatty liver cells].

    Science.gov (United States)

    Yang, Jia-Yao; Tao, Dong-Qing; Liu, Song; Zhang, Shu; Ma, Wei; Shi, Zhao-Hong

    2017-04-01

    To investigate the effects of Sijunzi Tang, Lizhong Tang and Fuzi Lizhong Tang on the cell proliferation and apoptosis of nonalcoholic fatty liver cells through the nonalcoholic fatty liver cell model established by inducing L02 cells with oleic acid. Different concentrations of oleic acid were added into L02 cells to induce the nonalcoholic fatty liver cell model. Oil red O staining was used to observe fatty droplets of fatty liver cells. Automatic biochemical analyzer was used to detect the levels of aspartic transaminase(AST), alanine aminotransferase(ALT), total cholesterol(TC), and triglyceride(TG) in the cell supernatants. There were five groups, namely normal group, model group, model and Sijunzi Tang group, model and Lizhong Tang group, and model and Fuzi Lizhong Tang group. The cell proliferation and apoptosis of the five groups were detected by MTT colorimetry test and flow cytometer. The expressions of PCNA, cleaved caspase-3, cleaved caspase-8, cleaved caspase-9, Bax and Bcl-2 proteins of the five groups were detected by Western blot. The oil red O staining results showed that the optimum concentration of oleic acid that was used to induce nonalcoholic fatty liver cell models was 80 mg•L-1. The levels of AST, ALT, TC and TG in the nonalcoholic fatty liver cell supernatants were higher than that in normal liver cell supernatants(Pcell proliferation, and inhibit the cellular apoptosis of nonalcoholic fatty liver cells(Pcells. And Fuzi Lizhong Tang showed the best effect. In conclusion, all of Sijunzi Tang, Lizhong Tang and Fuzi Lizhong Tang could effectively promote the cell proliferation, and inhibit the cellular apoptosis of nonalcoholic fatty liver cells. And Fuzi Lizhong Tang showed the best effect. The pharmacodynamic mechanism may be related to the expressions of key factors in pathways related with proliferation and apoptosis mediated by the three decoctions. Copyright© by the Chinese Pharmaceutical Association.

  7. The Risk of Abdominal Obesity according to the Degree of Non-Alcoholic Fatty Liver Disease in Korean Men

    OpenAIRE

    Park, Sung Keun; Ryoo, Jae-Hong; Choi, Joong-Myung; Seo, Min Woo; Park, Chung Min

    2016-01-01

    Although non-alcoholic fatty liver disease has been reported as a cardiometabolic risk factor, the effect of non-alcoholic fatty liver is yet to be clarified on abdominal obesity. Therefore, this study was conducted to investigate the longitudinal relationship of non-alcoholic fatty liver on the development of abdominal obesity. The study participants were composed of 11,212 Korean men without abdominal obesity. They were followed up from 2005 to 2010 to be monitored for the development of ab...

  8. [Dietetary recommendation for non-alcoholic fatty liver disease].

    Science.gov (United States)

    Jeznach-Steinhagen, Anna; Ostrowska, Joanna; Czerwonogrodzka-Senczyna, Aneta; Boniecka, Iwona; Gronostajska, Wioletta

    2017-12-22

    Non-alcoholic Fatty Liver Disease (NAFLD) is currently the most common chronic liver disease in the developed world. Nowadays, in the adult population of Europe it is estimated at 14% to 21%. Its most important risk factors are obesity and metabolic syndrome. Introducing lifestyle changes such as: dietary intervention and increased physical activity are the first-line treatment and are intended to support not only NAFLD but also associated diseases such as obesity, insulin resistance, diabetes and dyslipidemia. Dietary management focuses on weight reduction of overweight or obese people by decreasing energy in diet. It is recommended to limit the intake of saturated fats and trans fatty acids as well as cholesterol. Instead, it is important to increase the proportion of polyunsaturated fatty acid diets, mainly from the n-3 family, which exhibit anti-inflammatory activity. It is also beneficial to eat nuts, despite their high energy value, as a source of alpha linolenic acid, which lowers LDL cholesterol. It is important to increase the share of vegetable protein (eg. soya) and limit the intake of fat meat, milk and the dairy products. A key role in the treatment and prevention of NAFLD is also a reduction of simple sugars and total exclusion of added sugar in the diet. The rise of NAFLD in developed countries is analogous to the increase of fructose consumption, which high intake is directly indicated as the main cause of the disease. Choosing foods with high fiber content, low glycemic index and meals composed with low glycemic load, is conducive to weight reduction. An important role in supporting NAFLD treatment is also attributed to vitamin D, C and E supplementation and some probiotic bacteria, as well as cinnamon and turmeric, which improve insulin sensitivity. Daily physical activity is strongly recommended as the supplement of healthy lifestyle.

  9. Evaluation of nonalcoholic fatty liver disease using magnetic resonance in obese children and adolescents.

    Science.gov (United States)

    Benetolo, Patrícia O; Fernandes, Maria I M; Ciampo, Ieda R L Del; Elias-Junior, Jorge; Sawamura, Regina

    2018-02-10

    To determine the frequency of nonalcoholic fatty liver disease using nuclear magnetic resonance as a noninvasive method. This was a cross-sectional study conducted on 50 children and adolescents followed up at an outpatient obesity clinic. The subjects were submitted to physical examination, laboratory tests (transaminases, liver function tests, lipid profile, glycemia, and basal insulin) and abdominal nuclear magnetic resonance (calculation of hepatic, visceral, and subcutaneous fat). Nonalcoholic fatty liver disease was diagnosed in 14 (28%) participants, as a severe condition in eight (percent fat >18%), and as non-severe in four (percent fat from 9% to 18%). Fatty liver was associated with male gender, triglycerides, AST, ALT, AST/ALT ratio, and acanthosis nigricans. Homeostasis model assessment of insulin resistance and metabolic syndrome did not show an association with fatty liver. The frequency of nonalcoholic fatty liver disease in the present population of children and adolescents was lower than that reported in the international literature. It is suggested that nuclear magnetic resonance is an imaging exam that can be applied to children and adolescents, thus representing an effective noninvasive tool for the diagnosis of nonalcoholic fatty liver disease in this age range. However, further national multicenter studies with longitudinal design are needed for a better analysis of the correlation between nonalcoholic fatty liver disease and its risk factors, as well as its consequences. Copyright © 2018 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  10. Effects of fenugreek, Nigella, and termis seeds in nonalcoholic fatty liver in obese diabetic albino rats.

    Science.gov (United States)

    Mohamed, Waleed S; Mostafa, Ashraf M; Mohamed, Khaled M; Serwah, Abdel Hamid

    2015-03-01

    Nonalcoholic fatty liver disease (NAFLD) occurs in approximately 80% of cases of type 2 diabetes mellitus (T2DM). This study investigated the effects of some plants used in Saudi Arabia as antidiabetic agents on T2DM and associated fatty liver. A total of 150 adult male albino rats were divided into six experimental groups, each consisting of 25 rats. Twenty-five rats were considered as the control group. Experimental diabetes was induced in the remaining rats by administering a subcutaneous injection of 120 mg/kg of freshly prepared alloxan solution; these rats were classified into five groups: one group did not receive any treatment; the second group was treated with an aqueous extract of a mixture containing fenugreek, Nigella, and termis seeds; the third group was treated with an aqueous extract of Nigella sativa seeds; the fourth group was treated with an aqueous extract of fenugreek seeds; and finally the fifth group was treated with an aqueous extract of termis seeds at a dose of 100 mg/kg body weight. After 4 weeks of treatment, biochemical parameters were calculated, including blood sugar and serum insulin levels. Pancreatic and liver samples were obtained and processed for microscopic evaluation. The usage of each plant alone or a mixture of the plants corrected the glucose and insulin levels. Microscopically, a definite improvement in the number and diameter of β-cells in the diabetic group was observed. Furthermore, considerable improvement in fatty changes occurring in the liver of experimental animals was observed. The activity of the mixture was the most effective. The aqueous extract of the seed mixture of the used plants appeared to be a useful agent in improving fatty changes in the liver texture associated with T2DM by reducing hyperglycaemia through an increase in insulin levels, regeneration of β-cells of the pancreas, and an amelioration of associated dyslipidemia. Copyright © 2014 Arab Journal of Gastroenterology. Published by Elsevier B

  11. Effects of Omega-3 Fatty Acid in Nonalcoholic Fatty Liver Disease: A Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Wenxia Lu

    2016-01-01

    Full Text Available A meta-analysis was conducted to assess the effect of omega-3 fatty acid supplementation (n-3 PUFAs in lowering liver fat, liver enzyme (alanine aminotransferase (ALT, aspartate aminotransferase (AST, and gamma-glutamyltransferase (GGT levels, and blood lipids (triglyceride (TG, total cholesterol (TC, high density lipoprotein (HDL, and low density lipoprotein (LDL in patients with nonalcoholic fatty liver disease (NAFLD or nonalcoholic steatohepatitis (NASH. Methods. MEDLINE/PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, CINAHL, Science Citation Index (ISI Web of Science, Chinese Biomedical Literature Database (CBM, and Chinese National Knowledge Infrastructure (CNKI were searched for relevant randomized controlled trials on the effects of n-3 polyunsaturated fatty acids (PUFAs in patients with NAFLD from inception to May 2015. Ten studies were included in this meta-analysis. Results. 577 cases of NAFLD/NASH in ten randomized controlled trials (RCTs were included. The results of the meta-analysis showed that benefit changes in liver fat favored PUFA treatment, and it was also beneficial for GGT, but it was not significant on ALT, AST, TC, and LDL. Conclusions. In this meta-analysis, omega-3 PUFAs improved liver fat, GGT, TG, and HDL in patients with NAFLD/NASH. Therefore, n-3 PUFAs may be a new treatment option for NAFLD.

  12. An update on non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in Asia.

    Science.gov (United States)

    Hsu, Ching-Sheng; Kao, Jia-Horng

    2017-08-01

    Non-alcoholic fatty liver disease (NAFLD) has become the most overwhelming liver disease in Asia. In consideration of its increasing medical and economic impact on Asian people, it is time for us to review the update data in Asian countries and formulate strategies to cope with this emerging health problem in Asia. Moreover, growing data indicates that NAFLD may be a systemic disease, not just confined to liver-specific morbidity and mortality, but also associated with several extra-hepatic manifestations, such as cardiovascular diseases, chronic renal diseases, and malignancy. As the co-occurrence of NAFLD and viral hepatitis is common in Asia, issues related to the impact of NAFLD on the clinical outcomes and management of viral hepatitis remain to be elucidated. Areas covered: In this article, a narrative review was conducted, searching for literature from PubMed, Ovid MEDLINE, and the Cochrane Library database till August 2016. Studies relevant to the emerging data of NAFLD in Asia, including the diagnosis, risk factors, the assessment and management of Asian NAFLD patients were examined and discussed. Expert commentary: Collaboration in Asian countries to develop an effective and practical measurement to assess the severity of NAFLD is urgently required.

  13. Non-alcoholic fatty liver disease and colorectal cancer.

    Science.gov (United States)

    Mikolasevic, I; Orlic, L; Stimac, D; Hrstic, I; Jakopcic, I; Milic, S

    2017-03-01

    As a significant cause of cancer death worldwide, colorectal cancer (CRC) is still one of the most common cancers in the world. The most efficient strategies to reduce CRC incidence include identifying risk factors for CRC and performing a preventive colonoscopy in high-risk populations. Some well-established risk factors for CRC development include hereditary syndromes and inflammatory bowel disease. Of note, in recent years, attention has been given to new evidence indicating that more than 75%-95% of CRC occurs in individuals with little or no genetic risk. For these individuals, the risk for CRC is associated with their lifestyle and dietary factors, including central obesity, overweight and physical inactivity. Recently, evidence demonstrated a connection between non-alcoholic fatty liver disease (NAFLD) and CRC. Insulin resistance and metabolic syndrome (MetS) are common risks that NAFLD and colorectal neoplasms share. The incidence of NAFLD is increasing in parallel with an increasing prevalence of MetS and obesity. Consequently, the question arises: will the incidence of CRC increase together with this dramatic increase in obesity, MetS and ultimately NAFLD prevalence? Recent studies of adenomatous polyps, CRC and NAFLD are discussed in this manuscript. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  14. Nonalcoholic fatty liver disease and mortality among cancer survivors.

    Science.gov (United States)

    Brown, Justin C; Harhay, Michael O; Harhay, Meera N

    2017-06-01

    Nonalcoholic fatty liver disease (NAFLD) may foster a tumor microenvironment that promotes cancer recurrence and progression. We examined the relationship between NAFLD and mortality among a sample of cancer survivors. Ultrasonography was used to assess hepatic steatosis, and standardized algorithms were used to define NAFLD. Study endpoints included all-cause, cancer-specific, and cardiovascular-specific mortality. Among 387 cancer survivors, 17.6% had NAFLD. During a median of 17.9 years of follow up, we observed 196 deaths from all causes. In multivariable-adjusted regression models, NAFLD was associated with an increased risk of all-cause mortality [HR: 2.52, 95% CI: 1.47-4.34; P=0.001]. We observed 86 cancer-specific deaths. In multivariable-adjusted regression models, NAFLD was associated with an increased risk of cancer-specific mortality [HR: 3.21, 95% CI: 1.46-7.07; P=0.004]. We observed 46 cardiovascular-specific deaths. In multivariable-adjusted regression models, NAFLD was not associated with an increased risk of cardiovascular-specific mortality [HR: 1.04, 95% CI: 0.30-3.64, P=0.951]. NAFLD is associated with an increased risk of all-cause and cancer-specific mortality among cancer survivors. This novel observation warrants replication. Evaluating the efficacy of interventions, such as lifestyle modification through weight loss and exercise, to improve NAFLD in this population may be considered. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Dietary Anthocyanins as Nutritional Therapy for Nonalcoholic Fatty Liver Disease

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    Luca Valenti

    2013-01-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD, defined by excessive lipid accumulation in the liver, is the hepatic manifestation of insulin resistance and the metabolic syndrome. Due to the epidemics of obesity, NAFLD is rapidly becoming the leading cause of altered liver enzymes in Western countries. NAFLD encompasses a wide spectrum of liver disease ranging from simple uncomplicated steatosis, to steatohepatitis, cirrhosis, and hepatocellular carcinoma. Diet may affect the development of NAFLD either by increasing risk or by providing protective factors. Therefore, it is important to investigate the role of foods and/or food bioactives on the metabolic processes involved in steatohepatitis for preventive strategies. It has been reported that anthocyanins (ACNs decrease hepatic lipid accumulation and may counteract oxidative stress and hepatic inflammation, but their impact on NAFLD has yet to be fully determined. ACNs are water-soluble bioactive compounds of the polyphenol class present in many vegetable products. Here, we summarize the evidence evaluating the mechanisms of action of ACNs on hepatic lipid metabolism in different experimental setting: in vitro, in vivo, and in human trials. Finally, a working model depicting the possible mechanisms underpinning the beneficial effects of ACNs in NAFLD is proposed, based on the available literature.

  16. Iron and non-alcoholic fatty liver disease.

    Science.gov (United States)

    Britton, Laurence J; Subramaniam, V Nathan; Crawford, Darrell Hg

    2016-09-28

    The mechanisms that promote liver injury in non-alcoholic fatty liver disease (NAFLD) are yet to be thoroughly elucidated. As such, effective treatment strategies are lacking and novel therapeutic targets are required. Iron has been widely implicated in the pathogenesis of NAFLD and represents a potential target for treatment. Relationships between serum ferritin concentration and NAFLD are noted in a majority of studies, although serum ferritin is an imprecise measure of iron loading. Numerous mechanisms for a pathogenic role of hepatic iron in NAFLD have been demonstrated in animal and cell culture models. However, the human data linking hepatic iron to liver injury in NAFLD is less clear, with seemingly conflicting evidence, supporting either an effect of iron in hepatocytes or within reticulo-endothelial cells. Adipose tissue has emerged as a key site at which iron may have a pathogenic role in NAFLD. Evidence for this comes indirectly from studies that have evaluated the role of adipose tissue iron with respect to insulin resistance. Adding further complexity, multiple strands of evidence support an effect of NAFLD itself on iron metabolism. In this review, we summarise the human and basic science data that has evaluated the role of iron in NAFLD pathogenesis.

  17. A Nutrigenomic Approach to Non-Alcoholic Fatty Liver Disease.

    Science.gov (United States)

    Dongiovanni, Paola; Valenti, Luca

    2017-07-16

    Following the epidemics of obesity due to the consumption of high-calorie diet and sedentary lifestyle, nonalcoholic fatty liver disease (NAFLD) is now the leading cause of liver disease in Western countries. NAFLD is epidemiologically associated with metabolic syndrome and insulin resistance, and in susceptible individuals it may progress to cirrhosis and hepatocellular carcinoma. Genetic factors play a key role in NAFLD predisposition by interacting with nutritional and other environmental factors. To date, there is no drug therapy for the treatment of NAFLD, and the main clinical recommendation is lifestyle modification. In the last years, nutrigenomics is promoting an increased understanding of how nutrition affects the switch from health to disease by altering the expression of an individual's genetic makeup. The present review tries to summarize the most recent data evidencing how the interactions between nutrients and genetic factors can influence NAFLD development. The final goal should be to develop tools to quantify these complex interactions. The definition of a "nutrigenomic risk score" for each individual may represent a novel therapeutic approach for the management of NAFLD patients.

  18. Nonalcoholic fatty liver disease and serum uric acid

    Directory of Open Access Journals (Sweden)

    XU Beibei

    2016-03-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD is considered the manifestation of metabolic syndrome (MS in the liver. Besides glucose and lipid metabolic disorders, the level of serum uric acid (SUA is also associated with the progression of NAFLD. This article reviews the research achievements in the association between SUA and NAFLD and points out that SUA can independently predict the risks of MS, type 2 diabetes, and cardiovascular disease in both healthy people and patients. Its mechanism may be that SUA increases the expression of reactive oxygen species (ROS/thioredoxin-interacting protein (TXNIP through inducing ROS, and then it activates the NLR pyrin domain containing 3 inflammasome and induces the secretion of interleukin. Both basic and clinical research show that the drugs reducing SUA can inhibit the TXNIP pathway, reduce the blood glucose level, and alleviate liver ROS, inflammation, steatosis, and fibrosis. This article suggests that SUA may be a promising therapeutic method for NAFLD and needs further basic and clinical research.

  19. Role of folate in nonalcoholic fatty liver disease.

    Science.gov (United States)

    Sid, Victoria; Siow, Yaw L; O, Karmin

    2017-10-01

    Nonalcoholic fatty liver disease (NAFLD) is a spectrum of chronic liver conditions that are characterized by steatosis, inflammation, fibrosis, and liver injury. The global prevalence of NAFLD is rapidly increasing in proportion to the rising incidence of obesity and type 2 diabetes. Because NAFLD is a multifaceted disorder with many underlying metabolic abnormalities, currently, there is no pharmacological agent that is therapeutically approved for the treatment of this disease. Folate is a water-soluble B vitamin that plays an essential role in one-carbon transfer reactions involved in nucleic acid biosynthesis, methylation reactions, and sulfur-containing amino acid metabolism. The liver is the primary organ responsible for storage and metabolism of folates. Low serum folate levels have been observed in patients with obesity and diabetes. It has been reported that a low level of endogenous folates in rodents perturbs folate-dependent one-carbon metabolism, and may be associated with development of metabolic diseases such as NAFLD. This review highlights the biological role of folate in the progression of NAFLD and its associated metabolic complications including obesity and type 2 diabetes. Understanding the role of folate in metabolic disease may position this vitamin as a potential therapeutic for NAFLD.

  20. MicroRNAs in Nonalcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    György Baffy

    2015-12-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD has become the most common liver disorder. Strongly linked to obesity and diabetes, NAFLD has the characteristics of complex diseases with substantial heterogeneity. Accordingly, our ability to predict the risk of advanced NAFLD and provide efficient treatment may improve by a better understanding of the relationship between genotype and phenotype. MicroRNAs (miRNAs play a major role in the fine-tuning of gene expression and they have recently emerged as novel biomarkers and therapeutic tools in the management of NAFLD. These short non-coding RNA sequences act by partial repression or degradation of targeted mRNAs. Deregulation of miRNAs has been associated with different stages of NAFLD, while their biological role in the pathogenesis remains to be fully understood. Systems biology analyses based on predicted target genes have associated hepatic miRNAs with molecular pathways involved in NAFLD progression such as cholesterol and lipid metabolism, insulin signaling, oxidative stress, inflammation, and pathways of cell survival and proliferation. Moreover, circulating miRNAs have been identified as promising noninvasive biomarkers of NAFLD and linked to disease severity. This rapidly growing field is likely to result in major advances in the pathomechanism, prognostication, and treatment of NAFLD.

  1. Establishment and management of nonalcoholic fatty liver disease biobank

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    CHEN Lizhen

    2014-09-01

    Full Text Available ObjectiveTo investigate the collection and preservation of blood specimens from patients with nonalcoholic fatty liver disease (NAFLD and the establishment and information management of biobank. MethodsWhole blood samples were collected from 1226 patients who were diagnosed with NAFLD based on B-mode ultrasound and blood tests from October 2009 to October 2013. Biochemical parameters were measured. Plasma and whole-blood genomic DNA was extracted from the samples, and the purity and concentration of DNA were determined. Specimens were preserved in a refrigerator (-80℃. An information management system for NAFLD biobank was established. ResultsSpecimens of 1226 NAFLD patients, including those of 83 twins and 100 families, were collected. The success rate was 100% for extraction of plasma and whole-blood genomic DNA. One hundred DNA samples were randomly selected for testing, and the results showed that the collected specimens met the requirements of following experiments. ConclusionThe NAFLD Biobank has been successfully established in this study. It has the standard information management system and enables the quality control and information management of specimens, laying a solid foundation for further research on NAFLD.

  2. Adrenal disorders and non-alcoholic fatty liver disease.

    Science.gov (United States)

    Papanastasiou, Labrini; Fountoulakis, Stelios; Vatalas, Ioannis-Anastasios

    2017-06-01

    Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the developed world and its pathogenesis is complex and multifactorial. It is considered the hepatic manifestation of the metabolic syndrome and is the leading cause of hepatic cirrhosis. This review aims to present current knowledge on the involvement of the adrenal glands in the development of NAFLD. Clinical and animal studies have shown that excess glucocorticoids (GC) have been implicated in the pathogenesis of NAFLD. Patients with NAFLD seem to have a subtle chronic activation of the hypothalamic pituitary adrenal axis leading to a state of subclinical hypercortisolism. Regulators of GC such as 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), an enzyme that regenerates cortisol from inactive cortisone, and 5α/5β-reductases, enzymes that increase cortisol clearance, are implicated in the development of NAFLD by amplifying local GC action. Adrenal androgen (dehydroepiandrosterone) abnormalities and increased aldosterone levels may also have a role in the development of NAFLD whereas the contribution of adrenergic signaling in NAFLD pathogenesis remains unclear.

  3. Fructose Consumption, Lipogenesis, and Non-Alcoholic Fatty Liver Disease.

    Science.gov (United States)

    Ter Horst, Kasper W; Serlie, Mireille J

    2017-09-06

    Increased fructose consumption has been suggested to contribute to non-alcoholic fatty liver disease (NAFLD), dyslipidemia, and insulin resistance, but a causal role of fructose in these metabolic diseases remains debated. Mechanistically, hepatic fructose metabolism yields precursors that can be used for gluconeogenesis and de novo lipogenesis (DNL). Fructose-derived precursors also act as nutritional regulators of the transcription factors, including ChREBP and SREBP1c, that regulate the expression of hepatic gluconeogenesis and DNL genes. In support of these mechanisms, fructose intake increases hepatic gluconeogenesis and DNL and raises plasma glucose and triglyceride levels in humans. However, epidemiological and fructose-intervention studies have had inconclusive results with respect to liver fat, and there is currently no good human evidence that fructose, when consumed in isocaloric amounts, causes more liver fat accumulation than other energy-dense nutrients. In this review, we aim to provide an overview of the seemingly contradicting literature on fructose and NAFLD. We outline fructose physiology, the mechanisms that link fructose to NAFLD, and the available evidence from human studies. From this framework, we conclude that the cellular mechanisms underlying hepatic fructose metabolism will likely reveal novel targets for the treatment of NAFLD, dyslipidemia, and hepatic insulin resistance. Finally, fructose-containing sugars are a major source of excess calories, suggesting that a reduction of their intake has potential for the prevention of NAFLD and other obesity-related diseases.

  4. Nonalcoholic fatty liver disease and polycystic ovary syndrome

    Science.gov (United States)

    Vassilatou, Evangeline

    2014-01-01

    Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the Western world comprising a spectrum of liver damage from fatty liver infiltration to end-stage liver disease, in patients without significant alcohol consumption. Increased prevalence of NAFLD has been reported in patients with polycystic ovary syndrome (PCOS), one of the most common endocrinopathies in premenopausal women, which has been redefined as a reproductive and metabolic disorder after the recognition of the important role of insulin resistance in the pathophysiology of the syndrome. Obesity, in particular central adiposity and insulin resistance are considered as the main factors related to NAFLD in PCOS. Moreover, existing data support that androgen excess, which is the main feature of PCOS and is interrelated to insulin resistance, may be an additional contributing factor to the development of NAFLD. Although the natural history of NAFLD remains unclear and hepatic steatosis seems to be a relatively benign condition in most patients, limited data imply that advanced stage of liver disease is possibly more frequent in obese PCOS patients with NAFLD. PCOS patients, particularly obese patients with features of the metabolic syndrome, should be submitted to screening for NAFLD comprising assessment of serum aminotransferase levels and of hepatic steatosis by abdominal ultrasound. Lifestyle modifications including diet, weight loss and exercise are the most appropriate initial therapeutic interventions for PCOS patients with NAFLD. When pharmacologic therapy is considered, metformin may be used, although currently there is no medical therapy of proven benefit for NAFLD. Long-term follow up studies are needed to clarify clinical implications and guide appropriate diagnostic evaluation, follow-up protocol and optimal treatment for PCOS patients with NAFLD. PMID:25024594

  5. Serum Osteocalcin Levels in Children With Nonalcoholic Fatty Liver Disease.

    Science.gov (United States)

    Amin, Saleh; El Amrousy, Doaa; Elrifaey, Shaymaa; Gamal, Rasha; Hodeib, Hossam

    2018-01-01

    The aim of the study was to investigate the relationship between osteocalcin and nonalcoholic fatty liver disease (NAFLD) in children with obesity. 60 obese children with NAFLD were taken as a patient group and 60 obese children and normal liver with matching age, sex, and body mass index were taken as a control group. Anthropometric measurements, abdominal ultrasonography for diagnosis and grading of NAFLD, and laboratory investigations in the form of liver function tests, lipid profile, fasting serum glucose and insulin, and serum osteocalcin levels were done for all children. Patients with NAFLD were further divided into patients with metabolic syndrome (MS) and patients without MS. Age of NAFLD children was (10.55 ± 2.71), 20 boys and 40 girls, whereas age of children in control group was (10.05 ± 3.51), 24 boys and 36 girls (P > 0.05). Patients with NAFLD showed significant increase in waist and hip circumference, alanine aminotransferase, alkaline phosphatase, total cholesterol, triglycerides, insulin resistance (IR), fasting serum glucose, and insulin, but lower serum osteocalcin level than control group. Serum osteocalcin level is inversely correlated with waist circumference, triglyceride, liver enzymes, fasting serum insulin, fasting serum glucose, IR, and grades of fatty liver. Increase in alanine aminotransferase, total cholesterol, triglycerides, fasting insulin, and IR went with increase in degree of hepatic steatosis. Serum osteocalcin level <44.5 ng/mL is a good predictor for severity of hepatic steatosis with sensitivity and specificity of 80%. Osteocalcin plays an important role in glucose and lipid metabolism for protection against NAFLD occurrence and progression. Moreover, it could be a useful marker for progression of NAFLD in children with obesity.

  6. Clinical characteristics of de novo nonalcoholic fatty liver disease following pancreaticoduodenectomy

    International Nuclear Information System (INIS)

    Tanaka, Naoki; Horiuchi, Akira; Yokoyama, Takahide

    2011-01-01

    Hepatic steatosis may develop after pancreatic resection, but its clinicopathological features remain unclear. We explored the clinical characteristics of newly appearing nonalcoholic fatty liver disease (NAFLD) after pancreaticoduodenectomy (PD), designated as de novo NAFLD after PD. Of 83 patients who underwent PD between 2001 and 2006, the patients with regular alcohol consumption after PD (n=3), those who were unavailable for regular abdominal computed tomography follow-up (n=12), and those who died within 6 months of PD (n=8) were excluded from the study. In the remaining 60 patients, the prevalence and clinical features of de novo NAFLD after PD were examined. NAFLD developed after PD in 14 (23%) patients in our cohort. Liver biopsy was performed in 8 patients and all showed typical steatohepatitis. Compared with the patients who had conventional nonalcoholic steatohepatitis (NASH), patients with post-PD de novo NASH demonstrated significant decreases in body mass index and lower levels of serum albumin, cholesterol, apolipoprotein B, and homeostasis model assessment for insulin resistance. Multivariate logistic regression analysis revealed that pancreatic head cancer was associated with an increased risk of developing NAFLD after PD (odds ratio 12.0, 95% confidence interval 2.0-71.4, P=0.006). Increased dosage of oral pancreatic enzymes significantly ameliorated the steatosis, as well as leading to the recovery of body weight loss and resolution of the biochemical abnormalities. De novo NAFLD/NASH after PD is characterized by non-obesity and lack of hyperlipidemia and insulin resistance and is associated with pancreatic exocrine insufficiency. In such patients, intensifying pancreatic enzyme supplementation may be useful. (author)

  7. SIRT3 as a Regulator of Non-alcoholic Fatty Liver Disease

    OpenAIRE

    Cho, Eun-Hee

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) is a hepatic presentation of obesity and metabolic syndrome. NAFLD includes a large spectrum of hepatic pathologies that range from simple steatosis and non-alcoholic steatohepatitis (NASH), to liver cirrhosis without an all-encompassing approved therapeutic strategy. Mitochondrial dysfunction is a key component of many metabolic diseases, such as obesity, type 2 diabetes, cancer, NAFLD, and aging. Sirtuin 3 (SIRT3) is a NAD+-dependent deacetylase tha...

  8. Roles of abnormal lipid metabolism in pathogenesis of non-alcoholic fatty liver disease

    OpenAIRE

    LU Ran; HONG Tianpei

    2015-01-01

    The prevalence of non-alcoholic fatty liver disease (NAFLD) keeps rising worldwide along with the increasing prevalence of metabolic diseases such as obesity, type 2 diabetes, and dyslipidemia. Although most NAFLD patients present with simple steatosis of hepatocytes, some patients progress to non-alcoholic steatohepatitis, liver cirrhosis, and even cancer. In the Western world, NAFLD is the most common cause of elevated liver enzymes, and hence there has been a growing interest in this disea...

  9. A combination of dietary N-3 fatty acids and a cyclooxygenase-1 inhibitor attenuates nonalcoholic fatty liver disease in mice.

    Science.gov (United States)

    Saraswathi, Viswanathan; Perriotte-Olson, Curtis; Ganesan, Murali; Desouza, Cyrus V; Alnouti, Yazen; Duryee, Michael J; Thiele, Geoffrey M; Nordgren, Tara M; Clemens, Dahn L

    2017-04-01

    We sought to determine whether a combination of purified n-3 fatty acids (n-3) and SC-560 (SC), a cyclooxygenase-1-specific inhibitor, is effective in ameliorating nonalcoholic fatty liver disease in obesity. Female wild-type mice were fed a high-fat and high-cholesterol diet (HF) supplemented with n-3 in the presence or absence of SC. Mice treated with SC alone exhibited no change in liver lipids, whereas n-3-fed mice tended to have lower hepatic lipids. Mice given n-3+SC had significantly lower liver lipids compared with HF controls indicating enhanced lipid clearance. Total and sulfated bile acids were significantly higher only in n-3+SC-treated mice compared with chow diet (CD) controls. Regarding mechanisms, the level of pregnane X receptor (PXR), a nuclear receptor regulating drug/bile detoxification, was significantly higher in mice given n-3 or n-3+SC. Studies in precision-cut liver slices and in cultured hepatoma cells showed that n-3+SC enhanced not only the expression/activation of PXR and its target genes but also the expression of farnesoid X receptor (FXR), another regulator of bile synthesis/clearance, indicating that n-3+SC can induce both PXR and FXR. The mRNA level of FGFR4 which inhibits bile formation showed a significant reduction in Huh 7 cells upon n-3 and n-3+SC treatment. PXR overexpression in hepatoma cells confirmed that n-3 or SC each induced the expression of PXR target genes and in combination had an enhanced effect. Our findings suggest that combining SC with n-3 potentiates its lipid-lowering effect, in part, by enhanced PXR and/or altered FXR/FGFR4 signaling. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Genome-Wide Associations Related to Hepatic Histology in Nonalcoholic Fatty Liver Disease in Hispanic Boys.

    Science.gov (United States)

    Wattacheril, Julia; Lavine, Joel E; Chalasani, Naga P; Guo, Xiuqing; Kwon, Soonil; Schwimmer, Jeffrey; Molleston, Jean P; Loomba, Rohit; Brunt, Elizabeth M; Chen, Yii-Der Ida; Goodarzi, Mark O; Taylor, Kent D; Yates, Katherine P; Tonascia, James; Rotter, Jerome I

    2017-11-01

    To identify genetic loci associated with features of histologic severity of nonalcoholic fatty liver disease in a cohort of Hispanic boys. There were 234 eligible Hispanic boys age 2-17 years with clinical, laboratory, and histologic data enrolled in the Nonalcoholic Steatohepatitis Clinical Research Network included in the analysis of 624 297 single nucleotide polymorphisms (SNPs). After the elimination of 4 outliers and 22 boys with cryptic relatedness, association analyses were performed on 208 DNA samples with corresponding liver histology. Logistic regression analyses were carried out for qualitative traits and linear regression analyses were applied for quantitative traits. The median age and body mass index z-score were 12.0 years (IQR, 11.0-14.0) and 2.4 (IQR, 2.1-2.6), respectively. The nonalcoholic fatty liver disease activity score (scores 1-4 vs 5-8) was associated with SNP rs11166927 on chromosome 8 in the TRAPPC9 region (P = 8.7 -07 ). Fibrosis stage was associated with SNP rs6128907 on chromosome 20, near actin related protein 5 homolog (p = 9.9 -07 ). In comparing our results in Hispanic boys with those of previously reported SNPs in adult nonalcoholic steatohepatitis, 2 of 26 susceptibility loci were associated with nonalcoholic fatty liver disease activity score and 2 were associated with fibrosis stage. In this discovery genome-wide association study, we found significant novel gene effects on histologic traits associated with nonalcoholic fatty liver disease activity score and fibrosis that are distinct from those previously recognized by adult nonalcoholic fatty liver disease genome-wide association studies. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. The Risk of Abdominal Obesity according to the Degree of Non-Alcoholic Fatty Liver Disease in Korean Men.

    Science.gov (United States)

    Park, Sung Keun; Ryoo, Jae-Hong; Choi, Joong-Myung; Seo, Min Woo; Park, Chung Min

    2016-03-01

    Although non-alcoholic fatty liver disease has been reported as a cardiometabolic risk factor, the effect of non-alcoholic fatty liver is yet to be clarified on abdominal obesity. Therefore, this study was conducted to investigate the longitudinal relationship of non-alcoholic fatty liver on the development of abdominal obesity. The study participants were composed of 11,212 Korean men without abdominal obesity. They were followed up from 2005 to 2010 to be monitored for the development of abdominal obesity according to their degree of non-alcoholic fatty liver disease (normal, mild, and moderate to severe). Cox-proportional hazard model was used to calculate the hazard ratios for abdominal obesity according to the degree of non-alcoholic fatty liver disease. While the average incidence was 15.5%, the incidence of abdominal obesity increased according to the degree of non-alcoholic fatty liver (normal: 11.6%, mild: 25.2%, moderate to severe: 41.0%, P obesity independently increased proportionally to the degree of NAFLD (mild [1.07; 0.94-1.23], moderate to severe [1.58; 1.11-2.26], P for trend obesity increased proportionally to the degree of non-alcoholic fatty liver disease. This finding guarantees further studies to reveal the incidental relationship of abdominal obesity with non-alcoholic fatty liver disease.

  12. Prevalence and determinants of non-alcoholic fatty liver disease in lifelines : A large Dutch population cohort

    NARCIS (Netherlands)

    van den Berg, Eline H.; Amini, Marzyeh; Dullaart, Robin P. F.; Faber, Klaas Nico; Alizadeh, Behrooz Z.; Blokzijl, Hans

    2017-01-01

    Background & aims Non-alcoholic fatty liver disease is an increasing health issue that develops rather unnoticed with obesity, type 2 diabetes mellitus and metabolic syndrome. We investigated prevalence, determinants and associated metabolic abnormalities of non-alcoholic fatty liver disease in the

  13. Silencing of Hepatic Fatty Acid Transporter Protein 5 in Vivo Reverses Diet-induced Non-alcoholic Fatty Liver Disease and Improves Hyperglycemia*S⃞

    OpenAIRE

    Doege, Holger; Grimm, Dirk; Falcon, Alaric; Tsang, Bernice; Storm, Theresa A.; Xu, Hui; Ortegon, Angelica M.; Kazantzis, Melissa; Kay, Mark A.; Stahl, Andreas

    2008-01-01

    Non-alcoholic fatty liver disease is a serious health problem linked to obesity and type 2 diabetes. To investigate the biological outcome and therapeutic potential of hepatic fatty acid uptake inhibition, we utilized an adeno-associated virus-mediated RNA interference technique to knock down the expression of hepatic fatty acid transport protein 5 in vivo prior to or after establishing non-alcoholic fatty liver disease in mice. Using this approach, we demonstrate here...

  14. Nuclear receptors and nonalcoholic fatty liver disease1

    Science.gov (United States)

    Cave, Matthew C.; Clair, Heather B.; Hardesty, Josiah E.; Falkner, K. Cameron; Feng, Wenke; Clark, Barbara J.; Sidey, Jennifer; Shi, Hongxue; Aqel, Bashar A.; McClain, Craig J.; Prough, Russell A.

    2016-01-01

    Nuclear receptors are transcription factors which sense changing environmental or hormonal signals and effect transcriptional changes to regulate core life functions including growth, development, and reproduction. To support this function, following ligand-activation by xenobiotics, members of subfamily 1 nuclear receptors (NR1s) may heterodimerize with the retinoid X receptor (RXR) to regulate transcription of genes involved in energy and xenobiotic metabolism and inflammation. Several of these receptors including the peroxisome proliferator-activated receptors (PPARs), the pregnane and xenobiotic receptor (PXR), the constitutive androstane receptor (CAR), the liver X receptor (LXR) and the farnesoid X receptor (FXR) are key regulators of the gut:liver:adipose axis and serve to coordinate metabolic responses across organ systems between the fed and fasting states. Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease and may progress to cirrhosis and even hepatocellular carcinoma. NAFLD is associated with inappropriate nuclear receptor function and perturbations along the gut:liver:adipose axis including obesity, increased intestinal permeability with systemic inflammation, abnormal hepatic lipid metabolism, and insulin resistance. Environmental chemicals may compound the problem by directly interacting with nuclear receptors leading to metabolic confusion and the inability to differentiate fed from fasting conditions. This review focuses on the impact of nuclear receptors in the pathogenesis and treatment of NAFLD. Clinical trials including PIVENS and FLINT demonstrate that nuclear receptor targeted therapies may lead to the paradoxical dissociation of steatosis, inflammation, fibrosis, insulin resistance, dyslipidemia and obesity. Novel strategies currently under development (including tissue-specific ligands and dual receptor agonists) may be required to separate the beneficial effects of nuclear receptor activation from unwanted metabolic

  15. Prevalence of Hypothyroidism in Nonalcoholic Fatty Liver disease

    Science.gov (United States)

    Pagadala, Mangesh R.; Zein, Claudia O.; Dasarathy, Srinivasan; Yerian, Lisa; Lopez, Rocio; McCullough, Arthur J.

    2014-01-01

    Background A possible association between nonalcoholic fatty liver disease (NAFLD) and hypothyroidism has been suggested. Possible explanations for this association are the recognized links between hypothyroidism and various elements of the metabolic syndrome which is often present in NAFLD. To further explore this association, we determined the prevalence of hypothyroidism in a cohort of patients with NAFLD and analyzed the potential factors associated with hypothyroidism in this patient population. Methods Two hundred and forty six patients with biopsy proven NAFLD attending hepatology clinics at the Cleveland Clinic between October 2006 to June 2009 and 430 age, gender, race and BMI matched control subjects seen in the general internal medicine clinic were included. Patients with a clinical diagnosis of hypothyroidism who were on thyroid replacement therapy were considered to be hypothyroid. Results Hypothyroidism was more frequent among patients with NAFLD (21%vs 9.5%.; Phypothyroidism were 2.1 (95% CI: 1.1, 3.9,P=0.02)) and 3.8 (95% CI:2,6.9, Phypothyroidism. NAFLD subjects who reported mild alcohol consumption were less likely to have hypothyroidism compared to those who reported complete abstinence (OR 0.37, P=0.008). Conclusions A higher prevalence of hypothyroidism was demonstrated in patients with NAFLD compared to controls. Patients with hypothyroidism were more likely to have NASH. Among subjects with NALFD, female gender, increased BMI and history of abstinence from alcohol were associated with hypothyroidism. Further studies are needed in order to confirm and better characterized these findings as well as the described associations and their pathogenesis. PMID:22183820

  16. A disease-specific quality of life instrument for non-alcoholic fatty liver disease and non-alcoholic steatohepatitis: CLDQ-NAFLD.

    Science.gov (United States)

    Younossi, Zobair M; Stepanova, Maria; Henry, Linda; Racila, Andrei; Lam, Brian; Pham, Huong T; Hunt, Sharon

    2017-08-01

    Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis are the most common causes of chronic liver disease with known negative impact on patients' health-related quality of life. Our aim was to validate a disease-specific health-related quality of life instrument useful for efficacy trials involving patients with non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. From a long item selection questionnaire, we selected relevant items which, by factor analysis, were grouped into domains constituting Chronic Liver Disease Questionnaire-Non-Alcoholic Fatty Liver Disease version. The developed instrument was subjected to internal validity, test-retest reliability and construct validity assessment using standard methods. For development of the Chronic Liver Disease Questionnaire-Non-Alcoholic Fatty Liver Disease version instrument, a 75-item-long item selection questionnaire was administered to 25 patients with non-alcoholic fatty liver disease. After item reduction, factor analysis found that 98.7% of variance in the remaining items would be explained by six factors. Thus, the resulting Chronic Liver Disease Questionnaire-Non-Alcoholic Fatty Liver Disease version instrument had 36 items grouped into six domains: Abdominal Symptoms, Activity, Emotional, Fatigue, Systemic Symptoms, and Worry. The independent validation group included another 104 patients with non-alcoholic fatty liver disease. The Cronbach's alphas of 0.74-0.90 suggested good to excellent internal consistency of the domains. Furthermore, the presence of obesity and history of depression were discriminated best by Chronic Liver Disease Questionnaire-Non-Alcoholic Fatty Liver Disease version scores (P.15, intraclass correlations .76-.88). The Chronic Liver Disease Questionnaire-Non-Alcoholic Fatty Liver Disease version is a disease-specific health-related quality of life instrument developed and validated using an established methodology and useful for clinical trials of non-alcoholic

  17. [Role of the endocrine system in the pathogenesis of non-alcoholic fatty liver disease].

    Science.gov (United States)

    Hagymási, Krisztina; Reismann, Péter; Rácz, Károly; Tulassay, Zsolt

    2009-11-29

    The most frequent liver disorder in metabolic syndrome is the nonalcoholic fatty liver disease. Its pathogenesis is a complex, multifactorial process, characterized by insulin resistance and involvement of the endocrine system. Hypothyroidism may lead to nonalcoholic steatohepatitis via hyperlipidemia and obesity. Adult patients with growth hormone deficiency have a metabolic syndrome-like phenotype with obesity and many characteristic metabolic alterations. The chronic activation of the hypothalamic-pituitary-adrenal axis results in metabolic syndrome as well. Cushing's syndrome has also features of metabolic syndrome. Mild elevation of transaminase activities is commonly seen in patients with adrenal failure. Non-alcoholic steatosis is twice as common in postmenopusal as in premenopausal women and hormonal replacement therapy decreases the risk of steatosis. Insulin resistance, diabetes mellitus type 2, sleeping apnoe syndrome, cardiovascular disorders and non-alcoholic fatty liver disease are more frequent in polycystic ovary syndrome. Hypoandrogenism in males and hyperandrogenism in females may lead to fatty liver via obesity and insulin resistance. Adipokines (leptin, acylation stimulating protein, adiponectin) have a potential role in the pathogenesis of nonalcoholic fatty liver. The alterations of endocrine system must be considered in the background of cryptogenic liver diseases. The endocrine perspective may help the therapeutic approaches in the future.

  18. Increased risk of non-alcoholic fatty liver disease after diagnosis of celiac disease.

    Science.gov (United States)

    Reilly, Norelle R; Lebwohl, Benjamin; Hultcrantz, Rolf; Green, Peter H R; Ludvigsson, Jonas F

    2015-06-01

    Non-alcoholic fatty liver disease is a common cause of chronic liver disease. Celiac disease alters intestinal permeability and treatment with a gluten-free diet often causes weight gain, but so far there are few reports of non-alcoholic fatty liver disease in patients with celiac disease. Population-based cohort study. We compared the risk of non-alcoholic fatty liver disease diagnosed from 1997 to 2009 in individuals with celiac disease (n = 26,816) to matched reference individuals (n = 130,051). Patients with any liver disease prior to celiac disease were excluded, as were individuals with a lifetime diagnosis of alcohol-related disorder to minimize misclassification of non-alcoholic fatty liver disease. Cox regression estimated hazard ratios for non-alcoholic fatty liver disease were determined. During 246,559 person-years of follow-up, 53 individuals with celiac disease had a diagnosis of non-alcoholic fatty liver disease (21/100,000 person-years). In comparison, we identified 85 reference individuals diagnosed with non-alcoholic fatty liver disease during 1,488,413 person-years (6/100,000 person-years). This corresponded to a hazard ratio of 2.8 (95% CI 2.0-3.8), with the highest risk estimates seen in children (HR = 4.6; 95% CI 2.3-9.1). The risk increase in the first year after celiac disease diagnosis was 13.3 (95% CI 3.5-50.3) but remained significantly elevated even beyond 15 years after the diagnosis of celiac disease (HR = 2.5; 95% CI 1.0-5.9). Individuals with celiac disease are at increased risk of non-alcoholic fatty liver disease compared to the general population. Excess risks were highest in the first year after celiac disease diagnosis, but persisted through 15 years after diagnosis with celiac disease. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  19. Interleukin-17 exacerbates hepatic steatosis and inflammation in non-alcoholic fatty liver disease.

    Science.gov (United States)

    Tang, Y; Bian, Z; Zhao, L; Liu, Y; Liang, S; Wang, Q; Han, X; Peng, Y; Chen, X; Shen, L; Qiu, D; Li, Z; Ma, X

    2011-11-01

    Mechanisms associated with the progression of simple steatosis to non-alcoholic fatty liver disease (NAFLD) remain undefined. Regulatory T cells (T(regs)) play a critical role in regulating inflammatory processes in non-alcoholic steatohepatitis (NASH) and because T helper type 17 (Th17) functionally oppose T(reg)-mediated responses, this study focused on characterizing the role of Th17 cells using a NAFLD mouse model. C57BL/6 mice were fed either a normal diet (ND) or high fat (HF) diet for 8 weeks. Mice in the HF group had a significantly higher frequency of liver Th17 cells compared to ND-fed mice. Neutralization of interleukin (IL)-17 in HF mice ameliorated lipopolysaccharide (LPS)-induced liver injury reflected by decreased serum alanine aminotransferase (ALT) levels and reduced inflammatory cell infiltrates in the liver. In vitro, HepG2 cells cultured in the presence of free fatty acids (FFA; oleic acid and palmitic acid) for 24 h and IL-17 developed steatosis via insulin-signalling pathway interference. IL-17 and FFAs synergized to induce IL-6 production by HepG2 cells and murine primary hepatocytes which, in combination with transforming growth factor (TGF-β), expanded Th17 cells. It is likely that a similar process occurs in NASH patients, as there were significant levels of IL-17(+) cell infiltrates in NASH patient livers. The hepatic expression of Th17 cell-related genes [retinoid-related orphan receptor gamma (ROR)γt, IL-17, IL-21 and IL-23] was also increased significantly in NASH patients compared to healthy controls. Th17 cells and IL-17 were associated with hepatic steatosis and proinflammatory response in NAFLD and facilitated the transition from simple steatosis to steatohepatitis. Strategies designed to alter the balance between Th17 cells and T(regs) should be explored as a means of preventing progression to NASH and advanced liver diseases in NAFLD patients. © 2011 The Authors. Clinical and Experimental Immunology © 2011 British Society for

  20. The Role of Skeletal Muscle in Development of Nonalcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Jun Sung Moon

    2013-08-01

    Full Text Available BackgroundNonalcoholic fatty liver disease (NAFLD is closely correlated with abnormal accumulation of visceral fat, but the role of skeletal muscle remains unclear. The aim of this study was to elucidate the role of skeletal muscle in development of NAFLD.MethodsAmong 11,116 subjects (6,242 males, we examined the effects of skeletal muscle mass and visceral fat area (VFA, by bioelectric impedance analysis on NAFLD using by the fatty liver index (FLI.ResultsOf the total subjects (9,565 total, 5,293 males included, 1,848 were classified as having NALFD (FLI ≥60. Body mass index, lipid profile, fasting plasma glucose, hemoglobin A1c, prevalence of type 2 diabetes (DM, hypertension (HTN, and metabolic syndrome were higher in males than females, but FLI showed no significant difference. The low FLI group showed the lowest VFA and highest skeletal muscle mass of all the groups. Skeletal muscle to visceral fat ratio (SVR and skeletal muscle index had inverse correlations with FLI, when adjusted for age and gender. In multivariate regression analysis, SVR was negatively associated with FLI. Among SVR quartiles, the highest quartile showed very low risk of NAFLD when adjusted for age, gender, lipid profile, DM, HTN, and high sensitivity C-reactive protein from the lowest quartiles (odds ratio, 0.037; 95% confidence interval, 0.029 to 0.049.ConclusionSkeletal muscle mass was inversely associated with visceral fat area, and higher skeletal muscle mass may have a beneficial effect in preventing NAFLD. These results suggest that further studies are needed to ameliorate or slow the progression of sarcopenia.

  1. Xanthine oxidase in non-alcoholic fatty liver disease and hyperuricemia: One stone hits two birds.

    Science.gov (United States)

    Xu, Chengfu; Wan, Xingyong; Xu, Lei; Weng, Honglei; Yan, Ming; Miao, Min; Sun, Yan; Xu, Genyun; Dooley, Steven; Li, Youming; Yu, Chaohui

    2015-06-01

    Hyperuricemia is a common feature of patients with non-alcoholic fatty liver disease (NAFLD). This study aimed to explore the causal relationship and underlying mechanisms between NAFLD and hyperuricemia. We evaluated the impact of NAFLD on the development of hyperuricemia in a cohort of 5541 baseline hyperuricemia-free individuals. We further analyzed xanthine oxidase (XO), a rate-limiting enzyme that catalyzes uric acid production, as a candidate to link NAFLD and hyperuricemia. In the first study, a 7-year prospective analysis found that NAFLD was strongly associated with subsequent development of hyperuricemia. Cox proportional hazards regression analyses showed that age, gender, and body mass index adjusted hazard ratio (95% confidence interval) for incident hyperuricemia was 1.609 (1.129-2.294) in individuals with NAFLD, as compared with those without NAFLD at baseline. In the second study, we observed that expression and activity of XO were significantly increased in cellular and mouse models of NAFLD. Knocking down XO expression or inhibiting XO activity significantly decreases uric acid production and attenuates free fatty acids-induced fat accumulation in HepG2 cells. Inhibiting XO activity also significantly prevents the development of and ameliorates established hepatic steatosis induced by a high-fat diet in mice. Further experiments indicated that XO regulates activation of the NLRP3 inflammasome, which may be essential for the regulatory effect of XO on NAFLD. NAFLD significantly increases the risk of incident hyperuricemia. XO is a mediator of the relationship between NAFLD and hyperuricemia, and may serve as a novel therapeutic target for the two linked diseases. Copyright © 2015 European Association for the Study of the Liver. All rights reserved.

  2. Psoralea corylifolia L. Seed Extract Attenuates Nonalcoholic Fatty Liver Disease in High-Fat Diet-Induced Obese Mice

    Directory of Open Access Journals (Sweden)

    Eunhui Seo

    2016-02-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD, along with obesity, is increasing world-wide and is one of the major causes of chronic hepatic disease. The present study evaluated the ameliorative effect of extract of Psoralea corylifolia L. seed (PCS on high fat diet-induced NAFLD in C57BL/6 mice after daily administration at 300 or 500 mg/kg for 12 weeks. Treatment with PCS extract significantly reduced body weight and blood glucose levels and improved glucose tolerance and insulin sensitivity. In addition, PCS extract treatment significantly attenuated lipid accumulation in liver and adipose tissue and reduced serum lipid and hepatic triglyceride levels. Furthermore, the expression of lipogenic genes and inflammatory genes were reduced, and the expression of fat oxidation-related genes was increased in the liver of PCS extract-treated mice compared with control mice. Our study suggests the therapeutic potential of PCS extract for NAFLD by inhibiting lipid accumulation and inflammation in liver.

  3. Involvement of a periodontal pathogen, Porphyromonas gingivalis on the pathogenesis of non-alcoholic fatty liver disease.

    Science.gov (United States)

    Yoneda, Masato; Naka, Shuhei; Nakano, Kazuhiko; Wada, Koichiro; Endo, Hiroki; Mawatari, Hironori; Imajo, Kento; Nomura, Ryota; Hokamura, Kazuya; Ono, Masafumi; Murata, Shogo; Tohnai, Iwai; Sumida, Yoshio; Shima, Toshihide; Kuboniwa, Masae; Umemura, Kazuo; Kamisaki, Yoshinori; Amano, Atsuo; Okanoue, Takeshi; Ooshima, Takashi; Nakajima, Atsushi

    2012-02-16

    Non-alcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome that is closely associated with multiple factors such as obesity, hyperlipidemia and type 2 diabetes mellitus. However, other risk factors for the development of NAFLD are unclear. With the association between periodontal disease and the development of systemic diseases receiving increasing attention recently, we conducted this study to investigate the relationship between NAFLD and infection with Porphyromonas gingivalis (P. gingivalis), a major causative agent of periodontitis. The detection frequencies of periodontal bacteria in oral samples collected from 150 biopsy-proven NAFLD patients (102 with non-alcoholic steatohepatitis (NASH) and 48 with non-alcoholic fatty liver (NAFL) patients) and 60 non-NAFLD control subjects were determined. Detection of P. gingivalis and other periodontopathic bacteria were detected by PCR assay. In addition, effect of P. gingivalis-infection on mouse NAFLD model was investigated. To clarify the exact contribution of P. gingivalis-induced periodontitis, non-surgical periodontal treatments were also undertaken for 3 months in 10 NAFLD patients with periodontitis. The detection frequency of P. gingivalis in NAFLD patients was significantly higher than that in the non-NAFLD control subjects (46.7% vs. 21.7%, odds ratio: 3.16). In addition, the detection frequency of P. gingivalis in NASH patients was markedly higher than that in the non-NAFLD subjects (52.0%, odds ratio: 3.91). Most of the P. gingivalis fimbria detected in the NAFLD patients was of invasive genotypes, especially type II (50.0%). Infection of type II P. gingivalis on NAFLD model of mice accelerated the NAFLD progression. The non-surgical periodontal treatments on NAFLD patients carried out for 3 months ameliorated the liver function parameters, such as the serum levels of AST and ALT. Infection with high-virulence P. gingivalis might be an additional risk factor for the

  4. Omega-3 fatty acids for treatment of non-alcoholic fatty liver disease: design and rationale of randomized controlled trial

    OpenAIRE

    Janczyk, Wojciech; Socha, Piotr; Lebensztejn, Dariusz; Wierzbicka, Aldona; Mazur, Artur; Neuhoff-Murawska, Joanna; Matusik, Pawel

    2013-01-01

    Background Non-alcoholic fatty liver disease (NAFLD) is a liver manifestation of metabolic syndrome since obesity and insulin resistance are the main pathogenic contributors for both conditions. NAFLD carries increased risk of atherosclerosis and cardiovascular diseases. There is an urgent need to find effective and safe therapy for children and adults with NAFLD. Data from research and clinical studies suggest that omega-3 fatty acids may be beneficial in metabolic syndrome-related condition...

  5. Dietary Omega-3 Fatty Acid Deficiency and High Fructose Intake in the Development of Metabolic Syndrome, Brain Metabolic Abnormalities, and Non-Alcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Artemis P. Simopoulos

    2013-07-01

    Full Text Available Western diets are characterized by both dietary omega-3 fatty acid deficiency and increased fructose intake. The latter found in high amounts in added sugars such as sucrose and high fructose corn syrup (HFCS. Both a low intake of omega-3 fatty acids or a high fructose intake contribute to metabolic syndrome, liver steatosis or non-alcoholic fatty liver disease (NAFLD, promote brain insulin resistance, and increase the vulnerability to cognitive dysfunction. Insulin resistance is the core perturbation of metabolic syndrome. Multiple cognitive domains are affected by metabolic syndrome in adults and in obese adolescents, with volume losses in the hippocampus and frontal lobe, affecting executive function. Fish oil supplementation maintains proper insulin signaling in the brain, ameliorates NAFLD and decreases the risk to metabolic syndrome suggesting that adequate levels of omega-3 fatty acids in the diet can cope with the metabolic challenges imposed by high fructose intake in Western diets which is of major public health importance. This review presents the current status of the mechanisms involved in the development of the metabolic syndrome, brain insulin resistance, and NAFLD a most promising area of research in Nutrition for the prevention of these conditions, chronic diseases, and improvement of Public Health.

  6. Exercise training reverses endothelial dysfunction in nonalcoholic fatty liver disease.

    Science.gov (United States)

    Pugh, Christopher J A; Spring, Victoria S; Kemp, Graham J; Richardson, Paul; Shojaee-Moradie, Fariba; Umpleby, A Margot; Green, Daniel J; Cable, N Timothy; Jones, Helen; Cuthbertson, Daniel J

    2014-11-01

    Nonalcoholic fatty liver disease (NAFLD) is an independent risk factor for cardiovascular disease (CVD). Endothelial dysfunction is an early manifestation of atherosclerosis and an important prognostic marker for future cardiovascular events. The aim of this study was twofold: to examine 1) the association between liver fat, visceral adipose tissue (VAT), and endothelial dysfunction in obese NAFLD patients and 2) the impact of supervised exercise training on this vascular defect. Brachial artery endothelial function was assessed by flow-mediated dilatation (FMD) in 34 obese NAFLD patients and 20 obese controls of similar age and cardiorespiratory fitness [peak oxygen uptake (V̇o2 peak)] (48 ± 2 vs. 47 ± 2 yr; 27 ± 1 vs. 26 ± 2 ml·kg−1·min−1−1). Magnetic resonance imaging and spectroscopy quantified abdominal and liver fat, respectively. Twenty-one NAFLD patients completed either 16 wk of supervised moderate-intensity exercise training (n = 13) or conventional care (n = 8). Differences between NAFLD and controls were compared using independent t-tests and effects of interventions by analysis of covariance. NAFLD patients had higher liver fat [11.6% (95% CI = 7.4, 18.1), P < 0.0005] and VAT [1.6 liters (95% CI = 1.2, 2.0), P < 0.0001] than controls and exhibited impaired FMD compared with controls [−3.6% (95% CI = −4.9, −2.2), P < 0.0001]. FMD was inversely correlated with VAT (r = −0.54, P = 0.001) in NAFLD, although the impairment in FMD remained following covariate adjustment for VAT [3.1% (95% CI = 1.8, 4.5), P < 0.001]. Exercise training, but not conventional care, significantly improved V̇o2 peak [9.1 ml·kg−1·min−1 (95% CI = 4.1, 14.1); P = 0.001] and FMD [3.6% (95% CI = 1.6, 5.7), P = 0.002]. Endothelial dysfunction in NAFLD cannot be fully explained by excess VAT but can be reversed with exercise training; this has potential implications for the primary prevention of CVD in NAFLD.

  7. Nonalcoholic fatty liver disease and cardiovascular risk in children with obesity

    NARCIS (Netherlands)

    Koot, Bart G. P.; de Groot, Eric; van der Baan-Slootweg, Olga H.; Bohte, Anneloes E.; Nederveen, Aart J.; Jansen, Peter L. M.; Stoker, Jaap; Benninga, Marc A.

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) has been recognized as an independent risk factor for cardiovascular disease in adults. It has not been established whether NAFLD is related to early atherosclerotic changes in children. In a cross-sectional study, 78 non diabetic, non smoking children with

  8. Nonalcoholic fatty liver disease in hispanic youth with dysglycemia: Risk for subclinical atherosclerosis?

    Science.gov (United States)

    Obese Hispanic adolescents (OHAs) with dysglycemia have increased cardiovascular disease risk burden. To investigate if nonalcoholic fatty liver disease (NAFLD) confers added risk for endothelial dysfunction in these youth. Cross-sectional study. Academic institution. Thirty-six OHAs (15.360.4 years...

  9. Phenotyping the effect of diet on non-alcoholic fatty liver disease

    NARCIS (Netherlands)

    Wit, de N.J.W.; Afman, L.A.; Mensink, M.R.; Muller, M.R.

    2012-01-01

    Non-alcoholic fatty liver disease (NAFLD) is associated with the growing incidence of metabolic syndrome. Diet is an important contributor to the pathogenesis of NAFLD. In this review, we focused on recent publications reporting on the effect of macro- and micronutrients on development and

  10. The contribution of metabolic and adipose tissue inflammation to non-alcoholic fatty liver disease

    NARCIS (Netherlands)

    Mulder, P.C.A.

    2017-01-01

    Non-alcoholic fatty liver disease (NAFLD) has rapidly become the most common cause of chronic liver disease, and its worldwide prevalence continues to increase in parallel of the obesity epidemic. NAFLD comprises a wide spectrum of liver damage ranging fat accumulation (steatosis) to steatosis with

  11. Screening for non-alcoholic fatty liver disease in children: do guidelines provide enough guidance?

    NARCIS (Netherlands)

    Koot, B. G. P.; Nobili, V.

    2017-01-01

    Background: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the industrialized world in children. Its high prevalence and important health risks make NAFLD highly suitable for screening. In practice, screening is widely, albeit not consistently, performed. Aim:

  12. Preserved hemostatic status in patients with non-alcoholic fatty liver disease

    NARCIS (Netherlands)

    Potze, Wilma; Siddiqui, Mohammad S.; Boyett, Sherry L.; Adelmeijer, Jelle; Daita, Kalyani; Sanyal, Arun J.; Lisman, Ton

    2016-01-01

    Background & Aims: Non-alcoholic fatty liver disease (NAFLD) is associated with an increased risk of thrombosis. However, it remains unclear if hypercoagulability contributes to this risk. We, therefore, determined an in-depth hemostatic profile in a cohort of well-defined patients with NAFLD.

  13. Diet-induced dyslipidemia leads to nonalcoholic fatty liver disease and oxidative stress in guinea pigs

    DEFF Research Database (Denmark)

    Tveden-Nyborg, Pernille; Birck, Malene Muusfeldt; Ipsen, David Højland

    2016-01-01

    Chronic dyslipidemia imposed by a high-fat and high-caloric dietary regime leads to debilitating disorders such as obesity, nonalcoholic fatty liver disease (NAFLD), and insulin resistance. As disease rates surge, so does the need for high validity animal models to effectively study the causal re...

  14. 'Non-alcoholic fatty liver disease' bij kinderen : een nieuwe complicatie van obesitas

    NARCIS (Netherlands)

    Bocca, Gianni; Stolk, R.P.; Scheenstra, R.; Sauer, P.J.

    2008-01-01

    Non-alcoholic fatty liver disease (NAFLD) comprises a range of chronic liver diseases from simple steatosis to steatohepatitis and cirrhosis with liver failure. In children, NAFLD is mainly associated with obesity and metabolic syndrome, the results of an unhealthy lifestyle. Insulin resistance and

  15. New insights in the pathogenesis of non-alcoholic fatty liver disease

    NARCIS (Netherlands)

    Gaemers, Ingrid C.; Groen, Albert K.

    2006-01-01

    PURPOSE OF REVIEW: The hallmark of non-alcoholic fatty liver disease is hepatic steatosis. This is mostly a benign condition, but for largely unknown reasons it progresses to liver fibrosis, cirrhosis, and ultimately hepatocellular carcinoma in about 10% of patients. In this review we discuss recent

  16. Accuracy of prediction scores and novel biomarkers for predicting nonalcoholic fatty liver disease in obese children

    NARCIS (Netherlands)

    Koot, Bart G. P.; van der Baan-Slootweg, Olga H.; Bohte, Anneloes E.; Nederveen, Aart J.; van Werven, Jochem R.; Tamminga-Smeulders, Christine L. J.; Merkus, Maruschka P.; Schaap, Frank G.; Jansen, Peter L. M.; Stoker, Jaap; Benninga, Marc A.

    2013-01-01

    Accurate prediction scores for liver steatosis are demanded to enable clinicians to noninvasively screen for nonalcoholic fatty liver disease (NAFLD). Several prediction scores have been developed, however external validation is lacking. The aim was to determine the diagnostic accuracy of four

  17. Implications for the pathogenesis of non-alcoholic fatty liver disease

    African Journals Online (AJOL)

    Aim. Explore the possibility that increased gastrointestinal alcohol production may play a role in the pathogenesis of non-alcoholic fatty liver disease in patients with the metabolic syndrome. Methods. Blood, urine and breath levels of alcohol measured in 20 patients with the metabolic syndrome were compared with those of ...

  18. Modulation of the gut microbiota impacts nonalcoholic fatty liver disease : A potential role for bile acids

    NARCIS (Netherlands)

    Janssen, Aafke Wf; Houben, Tom; Katiraei, Saeed; Dijk, Wieneke; Boutens, Lily; van der Bolt, Nieke; Wang, Zeneng; Brown, J Mark; Hazen, Stanley L; Mandard, Stéphane; Shiri-Sverdlov, Ronit; Kuipers, Folkert; Willems van Dijk, Ko; Vervoort, Jacques; Stienstra, Rinke; Hooiveld, Guido Jej; Kersten, Sander

    Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide, yet the pathogenesis of NAFLD is only partially understood. Here, we investigated the role of the gut bacteria in NAFLD by stimulating the gut bacteria via feeding mice the fermentable dietary fiber, guar gum (GG),

  19. Modulation of the gut microbiota impacts nonalcoholic fatty liver disease: a potential role for bile acids

    NARCIS (Netherlands)

    Janssen, Aafke W.F.; Houben, Tom; Katiraei, Saeed; Dijk, Wieneke; Boutens, Lily; Bolt, van der Nieke; Wang, Zeneng; Brown, J.M.; Hazen, Stanley L.; Mandard, Stéphane; Shiri-Sverdlov, Ronit; Kuipers, Folkert; Willems van Dijk, Ko; Vervoort, Jacques; Stienstra, Rinke; Hooiveld, Guido J.E.J.; Kersten, Sander

    2017-01-01

    Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide, yet the pathogenesis of NAFLD is only partially understood. Here, we investigated the role of the gut bacteria in NAFLD by stimulating the gut bacteria via feeding mice the fermentable dietary fiber, guar gum (GG),

  20. Maternal western diet primes non-alcoholic fatty liver disease in adult mouse offspring

    NARCIS (Netherlands)

    Pruis, M. G. M.; Lendvai, A.; Bloks, V. W.; Zwier, M. V.; Baller, J. F. W.; de Bruin, A.; Groen, A. K.; Plosch, T.

    AimMetabolic programming via components of the maternal diet during gestation may play a role in the development of different aspects of the metabolic syndrome. Using a mouse model, we aimed to characterize the role of maternal western-type diet in the development of non-alcoholic fatty liver

  1. GRADING SCALE OF VISCERAL ADIPOSE TISSUE THICKNESS AND THEIR RELATION TO THE NONALCOHOLIC FATTY LIVER DISEASE

    OpenAIRE

    ANDRADE, Luís Jesuino de Oliveira; MELO, Paulo Roberto Santana de; PARANÁ, Raymundo; DALTRO, Carla

    2014-01-01

    ContextThe mesenteric fat is drained by the portal system, being related to the metabolic syndrome which is an important risk factor for non-alcoholic fatty liver disease (NAFLD).ObjectivesGraduate of visceral fat thickness and correlate with the NAFLD degree through ultrasonography method.MethodsWe studied 352 subjects for age, gender, measures of subcutaneous fat thickness and visceral fat thickness as well as the presence and degree of liver fatty. Was analyzed the independent relationship...

  2. Eicosapentaenoic acid ameliorates non-alcoholic steatohepatitis in a novel mouse model using melanocortin 4 receptor-deficient mice.

    Science.gov (United States)

    Konuma, Kuniha; Itoh, Michiko; Suganami, Takayoshi; Kanai, Sayaka; Nakagawa, Nobutaka; Sakai, Takeru; Kawano, Hiroyuki; Hara, Mitsuko; Kojima, Soichi; Izumi, Yuichi; Ogawa, Yoshihiro

    2015-01-01

    Many attempts have been made to find novel therapeutic strategies for non-alcoholic steatohepatitis (NASH), while their clinical efficacy is unclear. We have recently reported a novel rodent model of NASH using melanocortin 4 receptor-deficient (MC4R-KO) mice, which exhibit the sequence of events that comprise hepatic steatosis, liver fibrosis, and hepatocellular carcinoma with obesity-related phenotypes. In the liver of MC4R-KO mice, there is a unique histological feature termed hepatic crown-like structures (hCLS), where macrophages interact with dead hepatocytes and fibrogenic cells, thereby accelerating inflammation and fibrosis. In this study, we employed MC4R-KO mice to examine the effect of highly purified eicosapentaenoic acid (EPA), a clinically available n-3 polyunsaturated fatty acid, on the development of NASH. EPA treatment markedly prevented the development of hepatocyte injury, hCLS formation and liver fibrosis along with lipid accumulation. EPA treatment was also effective even after MC4R-KO mice developed NASH. Intriguingly, improvement of liver fibrosis was accompanied by the reduction of hCLS formation and plasma kallikrein-mediated transforming growth factor-β activation. Moreover, EPA treatment increased the otherwise reduced serum concentrations of adiponectin, an adipocytokine with anti-inflammatory and anti-fibrotic properties. Collectively, EPA treatment effectively prevents the development and progression of NASH in MC4R-KO mice along with amelioration of hepatic steatosis. This study unravels a novel anti-fibrotic mechanism of EPA, thereby suggesting a clinical implication for the treatment of NASH.

  3. Eicosapentaenoic acid ameliorates non-alcoholic steatohepatitis in a novel mouse model using melanocortin 4 receptor-deficient mice.

    Directory of Open Access Journals (Sweden)

    Kuniha Konuma

    Full Text Available Many attempts have been made to find novel therapeutic strategies for non-alcoholic steatohepatitis (NASH, while their clinical efficacy is unclear. We have recently reported a novel rodent model of NASH using melanocortin 4 receptor-deficient (MC4R-KO mice, which exhibit the sequence of events that comprise hepatic steatosis, liver fibrosis, and hepatocellular carcinoma with obesity-related phenotypes. In the liver of MC4R-KO mice, there is a unique histological feature termed hepatic crown-like structures (hCLS, where macrophages interact with dead hepatocytes and fibrogenic cells, thereby accelerating inflammation and fibrosis. In this study, we employed MC4R-KO mice to examine the effect of highly purified eicosapentaenoic acid (EPA, a clinically available n-3 polyunsaturated fatty acid, on the development of NASH. EPA treatment markedly prevented the development of hepatocyte injury, hCLS formation and liver fibrosis along with lipid accumulation. EPA treatment was also effective even after MC4R-KO mice developed NASH. Intriguingly, improvement of liver fibrosis was accompanied by the reduction of hCLS formation and plasma kallikrein-mediated transforming growth factor-β activation. Moreover, EPA treatment increased the otherwise reduced serum concentrations of adiponectin, an adipocytokine with anti-inflammatory and anti-fibrotic properties. Collectively, EPA treatment effectively prevents the development and progression of NASH in MC4R-KO mice along with amelioration of hepatic steatosis. This study unravels a novel anti-fibrotic mechanism of EPA, thereby suggesting a clinical implication for the treatment of NASH.

  4. Acceleration training for managing nonalcoholic fatty liver disease: a pilot study.

    Science.gov (United States)

    Oh, Sechang; Shida, Takashi; Sawai, Akemi; Maruyama, Tsuyoshi; Eguchi, Kiyoshi; Isobe, Tomonori; Okamoto, Yoshikazu; Someya, Noriko; Tanaka, Kiyoji; Arai, Emi; Tozawa, Akiko; Shoda, Junichi

    2014-01-01

    While aerobic training is generally recommended as therapeutic exercise in guidelines, the effectiveness of resistance training has recently been reported in the management of nonalcoholic fatty liver disease (NAFLD). Acceleration training (AT) is a new training method that provides a physical stimulation effect on skeletal muscles by increasing gravitational acceleration with vibration. AT has recently been indicated as a component of medicine. In this study, we evaluated the effectiveness of AT in the management of NAFLD in obese subjects. A total of 18 obese patients with NAFLD who had no improvement in liver function test abnormalities and/or steatosis grade after 12 weeks of lifestyle counseling were enrolled in an AT program. These patients attended a 20-minute session of AT twice a week for 12 consecutive weeks. During the AT program, the NAFLD patients showed a modest increase in the strength (+12.6%) and cross-sectional area (+3.1%) of the quadriceps, coupled with a significant reduction in intramyocellular lipids (-26.4%). Notably, they showed a modest reduction in body weight (-1.9%), abdominal visceral fat area (-3.4%), and hepatic fat content (-8.7%), coupled with a significant reduction in levels of aminotransferase (-15.7%), γ-glutamyltransferase (-14.4%), leptin (-9.7%), interleukin-6 (-26.8%), and tumor necrosis factor-α (-17.9%), and a significant increase of adiponectin (+8.7%). On a health-related quality of life survey, the patients showed an improvement in physical functioning (+17.3%), physical role (+9.7%), general health (+22.1), and social functioning (+6.0%). AT reduced hepatic and intramyocellular fat contents and ameliorated liver function test abnormalities in obese patients with NAFLD, which was coupled with improved physical function and body adiposity. AT is clinically beneficial for the management of NAFLD.

  5. Nonalcoholic fatty liver disease and hepatic cirrhosis: Comparison with viral hepatitis-associated steatosis.

    Science.gov (United States)

    Haga, Yuki; Kanda, Tatsuo; Sasaki, Reina; Nakamura, Masato; Nakamoto, Shingo; Yokosuka, Osamu

    2015-12-14

    Nonalcoholic fatty liver disease (NAFLD) including nonalcoholic steatohepatitis (NASH) is globally increasing and has become a world-wide health problem. Chronic infection with hepatitis B virus or hepatitis C virus (HCV) is associated with hepatic steatosis. Viral hepatitis-associated hepatic steatosis is often caused by metabolic syndrome including obesity, type 2 diabetes mellitus and/or dyslipidemia. It has been reported that HCV genotype 3 exerts direct metabolic effects that lead to hepatic steatosis. In this review, the differences between NAFLD/NASH and viral hepatitis-associated steatosis are discussed.

  6. The benefits of exercise for patients with non-alcoholic fatty liver disease.

    Science.gov (United States)

    Keating, Shelley E; George, Jacob; Johnson, Nathan A

    2015-01-01

    As exercise is now an established therapy for the management of non-alcoholic fatty liver disease (NAFLD), recent investigations have sought to identify the optimal dose (type, intensity and amount) of exercise for hepatic benefit. Here, the authors discuss the following: the role of aerobic exercise for the modulation of hepatic steatosis; the limited evidence for the role of resistance training in reducing liver fat; the lack of evidence from clinical trials on the role of exercise in non-alcoholic steatohepatitis; and the benefits of exercise for patients with NAFLD, beyond steatosis. Based on current evidence, the authors provide recommendations for exercise prescription for patients with NAFLD.

  7. Dietary patterns in Brazilian patients with nonalcoholic fatty liver disease: a cross-sectional study

    Directory of Open Access Journals (Sweden)

    Silvia Marinho Ferolla

    2013-01-01

    Full Text Available OBJECTIVE: Recent evidence suggests that non-alcoholic fatty liver disease is associated with diet. Our aim was to investigate the dietary patterns of a Brazilian population with this condition and compare them with the recommended diet. METHODS: A cross-sectional study was conducted on 96 non-alcoholic fatty liver disease patients before any dietetic counseling. All patients underwent abdominal ultrasound, biochemical tests, dietary evaluations, and anthropometric evaluations. Their food intake was assessed by a semi-quantitative food-frequency questionnaire and 24-hour food recall. RESULTS: The median patient age was 53 years, and 77% of the individuals were women. Most (67.7% participants were obese, and a large waist circumference was observed in 80.2% subjects. Almost 70% of the participants had metabolic syndrome, and 62.3% presented evidence of either insulin resistance or overt diabetes. Most patients (51.5, 58.5, and 61.7%, respectively exceeded the recommendations for energy intake, as well as total and saturated fat. All patients consumed less than the amount of recommended monounsaturated fatty acids, and 52.1 and 76.6% of them consumed less polyunsaturated fatty acids and fiber, respectively, than recommended. In most patients, the calcium, sodium, potassium, pyridoxine, and vitamin C intake did not meet the recommendations, and in 10.5-15.5% of individuals, the tolerable upper limit intake for sodium was exceeded. The patients presented a significantly high intake of meats, fats, sugars, legumes (beans, and vegetables and a low consumption of cereals, fruits, and dairy products compared with the recommendations. CONCLUSIONS: Although patients with non-alcoholic fatty liver disease exhibited high energy and lipid consumption, most of them had inadequate intake of some micronutrients. The possible role of nutrient-deficient intake in the development of non-alcoholic fatty liver disease warrants investigation.

  8. Melatonin ameliorates methionine- and choline-deficient diet-induced nonalcoholic steatohepatitis in rats.

    Science.gov (United States)

    Tahan, Veysel; Atug, Ozlen; Akin, Hakan; Eren, Fatih; Tahan, Gulgun; Tarcin, Ozlem; Uzun, Hafize; Ozdogan, Osman; Tarcin, Orhan; Imeryuz, Nese; Ozguner, Fehmi; Celikel, Cigdem; Avsar, Erol; Tozun, Nurdan

    2009-05-01

    Nonalcoholic steatohepatitis (NASH) may progress to advanced fibrosis and cirrhosis. Mainly, oxidative stress and excessive hepatocyte apoptosis are implicated in the pathogenesis of progressive NASH. Melatonin is not only a powerful antioxidant but also an anti-inflammatory and anti-apoptotic agent. We aimed to evaluate the effects of melatonin on methionine- and choline-deficient diet (MCDD)-induced NASH in rats. Thirty-two male Wistar rats were divided into four groups. Two groups were fed with MCDD while the other two groups were fed a control diet, pair-fed. One of the MCDD groups and one of the control diet groups were administered melatonin 50 mg/kg/day intraperitoneally, and the controls were given a vehicle. After 1 month the liver tissue oxidative stress markers, proinflammatory cytokines and hepatocyte apoptosis were studied by commercially available kits. For grading and staging histological lesions, Brunt et al.'s system was used. Melatonin decreased oxidative stress, proinflammatory cytokines and hepatocyte apoptosis. The drug ameliorated the grade of NASH. The present study suggests that melatonin functions as a potent antioxidant, anti-inflammatory and antiapoptotic agent in NASH and may be a therapeutic option.

  9. Relationship between nonalcoholic fatty liver disease and adipocyte fatty acid-binding protein

    Directory of Open Access Journals (Sweden)

    ZHOU Xiaoli

    2013-12-01

    Full Text Available ObjectiveTo investigate the relationship between nonalcoholic fatty liver disease (NAFLD and serum level of adipocyte fatty acid-binding protein (AFABP. MethodsA total of 160 patients who underwent physical examination in the Affiliated Hospital of Ningxia Medical University from July to November 2010 were included in our study. These subjects were divided into two groups according to the diagnostic criteria for NAFLD formulated by the Chinese Medical Association: control group (n=71 and NAFLD group (n=89. The two groups were compared with respect to general condition, body mass index (BMI, blood pressure, AFABP, serum insulin, and other serological indices. The relationship of serum AFABP with NAFLD and other metabolic parameters was analyzed using the Spearman linear correlation coefficient. Comparison of measurement data was made by t test and rank sum test; comparison of enumeration data was made by chi-square test. ResultsThere were more males than females in the NAFLD group. Compared with the control group, the NAFLD group had higher BMI and levels of blood glucose, triglyceride (TG, aspartate aminotransferase (AST, alanine aminotransferase (ALT, and uric acid and lower high-density lipoprotein (HDL level; in addition, the NAFLD group had significantly higher serum AFABP and insulin levels and homeostasis model assessment-estimated insulin resistance (HOMA-IR. The Spearman correlation analysis showed that serum AFABP was positively correlated with NAFLD, BMI, HOMA-IR, serum insulin, blood glucose, TG, ALT, AST, and uric acid but negatively correlated with HDL. After adjustment for sex, age, and BMI, serum AFABP was positively correlated with NAFLD, HOMA-IR, serum insulin, blood glucose, TG, ALT, and uric acid, but had no significant correlation with HDL and AST. ConclusionSerum AFABP is closely associated with NAFLD and may be an independent plasma marker of this disease. AFABP plays a causative role in the pathogenesis of NAFLD.

  10. A clinical and biochemical profile of biopsy-proven non-alcoholic fatty liver disease subjects

    International Nuclear Information System (INIS)

    Khurram, M.; Mushraf, M.

    2007-01-01

    To describe clinical and biochemical features of patients with biopsy-proven non-alcoholic fatty liver disease (NAFLD). Fifty patients of either and of all ages were included, who had ultrasound evidence of fatty liver, deranged liver enzymes, and negative history of alcohol uptake. Serological/biochemical tests/markers of other liver diseases were negative. Each subject underwent liver biopsy reported by a single histopathologist. Clinical (symptoms, hypertension, hepatomegaly, and obesity) and biochemical evaluation (for diabetes, lipid abnormalities, and aspartate to alanine aminotransferase ratio (AST/ALT)) of each subject was done. Chi-square and t-tests were used for p-value calculation for finding significant difference between fatty liver and non-alcoholic steato-hepatitis groups. Thirty three (66%) patients were female and 34% were male. Mean age was 45.50+-11.50 years. Histopathologically, 62% subjects had fatty liver alone, while 38% had nonalcoholic steatohepatitis (NASH). Fatigue (100%), hypertriglyceridemia (80%), hepatomegaly (72%), AST/ALT ratio <1 (72%), and obesity/overweight (54%) were common NAFLD-related features. Except for hypertriglycedemia (p-value 0.008), no statistically significant association was noted between these features and histopathological subtypes of NAFLD. NAFLD-related clinical and biochemical features included fatigue, obesity, hepatomegaly, AST/ALT ratio <1, and hypertriglycedemia. Significant relationship existed between hypertriglyceridemia and NASH. (author)

  11. External validation of the fatty liver index for identifying nonalcoholic fatty liver disease in a population-based study.

    Science.gov (United States)

    Koehler, Edith M; Schouten, Jeoffrey N L; Hansen, Bettina E; Hofman, Albert; Stricker, Bruno H; Janssen, Harry L A

    2013-09-01

    We aimed to validate the fatty liver index (FLI), an algorithm that is based on waist circumference, body mass index, and levels of triglyceride and γ-glutamyltransferase. We calculated its ability to identify fatty liver disease from any cause or nonalcoholic fatty liver disease (NAFLD) in a large population of white elderly persons. We collected ultrasonography and FLI data from participants of the Rotterdam Study from February 2009 to February 2012; 2652 subjects (mean age, 76.3 ± 6.0 years) were interviewed and received a clinical examination that included abdominal ultrasound, analysis of blood samples during fasting, and anthropometric assessment. The ability of the FLI to detect (nonalcoholic) fatty liver was assessed by using area under the receiver operator characteristic (AUROC) curve analysis. FLI score was associated with NAFLD in multivariable analysis (odds ratio, 1.05; 95% confidence interval [CI], 1.04-1.05; P < .001). FLI identified patients with NAFLD with an AUROC curve of 0.813 (95% CI, 0.797-0.830) and those with fatty liver from any cause with an AUROC curve of 0.807 (95% CI, 0.792-0.823). The FLI (an algorithm that is based on waist circumference, body mass index, and levels of triglyceride and γ-glutamyltransferase) accurately identifies NAFLD, confirmed via ultrasonography, in a large, white, elderly population. Published by Elsevier Inc.

  12. Prevalence of nonalcoholic fatty liver disease and its prognostic factors

    Directory of Open Access Journals (Sweden)

    NI Manman

    2016-03-01

    Full Text Available ObjectiveTo investigate the prevalence, natural history, and causes of death of nonalcoholic fatty liver disease (NAFLD, as well as related influencing factors. MethodsA total of 833 retired cadres and staff members who underwent physical examination in Shanghai Changzheng Hospital and Shanghai 85 Hospital of the PLA from January 1 to December 31, 2011 and received follow-up visits in either hospital every year since 2011 were enrolled as study subjects, and were divided into NAFLD group (459 patients who were diagnosed with NAFLD before December 31, 2011 and control group (374 patients without liver or biliary diseases. The patients′ clinical data were collected, including body height, body weight, systolic pressure, diastolic pressure, blood biochemical parameters, presence or absence of diabetes, hyperlipidemia, cerebrovascular and cardiovascular diseases, and malignant tumor, and smoking and drinking, and the death time and causes of death were clarified for the patients who died. The prevalence and natural course of NAFLD and related risk factors and prognostic factors were analyzed in this population. The t-test was applied for comparison of continuous data between groups, the chi-square test was applied for comparison of categorical data between groups, the multivariate binary logistic regression was applied to analyze the risk factors for the pathogenesis of NAFLD, and the multinomial logistic regression was applied to analyze the influencing factors for aggravation or alleviation of NAFLD. ResultsThe patients in NAFLD group accounted for 55.1% of all subjects, and the proportion of male patients was higher than that of female patients (58.0% vs 46.7%, χ2=4.962, P=0.026. Compared with the control group, the NAFLD group had significantly higher body mass index (BMI, systolic pressure, diastolic pressure, alanine aminotransferase (ALT, fasting blood glucose, serum uric acid, and triglyceride (TG, a significantly higher proportion of

  13. Role of Hedgehog signaling pathway in progression of non-alcoholic fatty liver fibrosis

    Directory of Open Access Journals (Sweden)

    AN Baiquan

    2015-03-01

    Full Text Available Obesity and related metabolic syndromes are prevalent on the global scale. Thus far, non-alcoholic fatty liver (NAFL disease has caused wide attention from domestic and overseas scholars. NAFL cirrhosis is considered to be the central part and inevitable stage of liver cirrhosis developed from simple fatty liver and non-alcoholic steatohepatitis. The effect of Hedgehog signaling pathway on hepatocytes in the progression of NAFL fibrosis was elucidated and investigated by a population study. Results showed that abnormal activation of the Hedgehog signaling pathway promoted the progression of NAFL fibrosis. In-depth study on the Hedgehog signaling pathway may provide a new approach for the treatment of NAFL fibrosis.

  14. [Fructose consumption and its health implications; fructose malabsorption and nonalcoholic fatty liver disease].

    Science.gov (United States)

    Riveros, María Jesús; Parada, Alejandra; Pettinelli, Paulina

    2014-03-01

    Fructose intake has increased considerably in recent years, especially in the form high fructose corn syrup, due its high sweetening power. Several studies have associated high intake of fructose to metabolic alterations, as nonalcoholic fatty liver disease and fructose malabsorption, among other pathologies. This review aims to update about the effect of high intake of fructose in the liver and intestine, mainly associated with processed foods with added fructose. An updated literature search was conducted using databases (Pubmed, Scopus and SciELO), selecting articles published after the year 2000, resulting from the keywords "fructose intake, fructose intolerance, nonalcoholic fatty liver and fructose, fructose malabsorption" Of 735 articles initially retrieved, 78 met the inclusion criteria. Fructose consumption has increased in recent decades, especially due to increased consumption of sweetened beverages and processed foods with added fructose. High fructose intake has been associated to pathologies as NAFLD and fructose malabsorption. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  15. Nutritional management of insulin resistance in nonalcoholic fatty liver disease (NAFLD).

    Science.gov (United States)

    Conlon, Beth A; Beasley, Jeannette M; Aebersold, Karin; Jhangiani, Sunil S; Wylie-Rosett, Judith

    2013-10-11

    Nonalcoholic fatty liver disease (NAFLD) is an emerging global health concern. It is the most common form of chronic liver disease in Western countries, affecting both adults and children. NAFLD encompasses a broad spectrum of fatty liver disease, ranging from simple steatosis (NAFL) to nonalcoholic steatohepatitis (NASH), and is strongly associated with obesity, insulin resistance, and dyslipidemia. First-line therapy for NAFLD includes weight loss achieved through diet and physical activity. However, there is a lack of evidenced-based dietary recommendations. The American Diabetes Association's (ADA) recommendations that aim to reduce the risk of diabetes and cardiovascular disease may also be applicable to the NAFLD population. The objectives of this review are to: (1) provide an overview of NAFLD in the context of insulin resistance, and (2) provide a rationale for applying relevant aspects of the ADA recommendations to the nutritional management of NAFLD.

  16. Nutrition: a promising route for prevention and management of obesity-related nonalcoholic fatty liver disease.

    Science.gov (United States)

    Tarantino, Giovanni

    2014-11-01

    When dealing with the treatment of obesity-linked illnesses - in particular nonalcoholic fatty liver disease - beyond diet, various nutritional ingredients are reported to be useful as silymarin, spirulina, choline, folic acid, methionine and vitamin E, all of them showing promising but not definite results. An emerging field of study is represented by prebiotics/probiotics and restoration of normal gut flora, which could play a fundamental role diet and various its components. It is noteworthy to point out that both improving or reducing the severity of nonalcoholic fatty liver disease bear a positive consequence on evolution of atherosclerosis and its cardiovascular-associated disease, such as coronary artery disease, even though the involved immunologic mechanisms are gaining greater credit in the most recent literature, without excluding the role of nutrition in modulating the acquired immunity in this condition.

  17. Dietary Flaxseed Oil Prevents Western-Type Diet-Induced Nonalcoholic Fatty Liver Disease in Apolipoprotein-E Knockout Mice

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    Hao Han

    2017-01-01

    Full Text Available The prevalence of nonalcoholic fatty liver disease (NAFLD has dramatically increased globally during recent decades. Intake of n-3 polyunsaturated fatty acids (PUFAs, mainly eicosapentaenoic acid (EPA, C20:5n-3 and docosahexaenoic acid (DHA, C22:6n-3, is believed to be beneficial to the development of NAFLD. However, little information is available with regard to the effect of flaxseed oil rich in α-linolenic acid (ALA, C18:3n-3, a plant-derived n-3 PUFA, in improving NAFLD. This study was to gain the effect of flaxseed oil on NAFLD and further investigate the underlying mechanisms. Apolipoprotein-E knockout (apoE-KO mice were given a normal chow diet, a western-type high-fat and high-cholesterol diet (WTD, or a WTD diet containing 10% flaxseed oil (WTD + FO for 12 weeks. Our data showed that consumption of flaxseed oil significantly improved WTD-induced NAFLD, as well as ameliorated impaired lipid homeostasis, attenuated oxidative stress, and inhibited inflammation. These data were associated with the modification effects on expression levels of genes involved in de novo fat synthesis (SREBP-1c, ACC, triacylglycerol catabolism (PPARα, CPT1A, and ACOX1, inflammation (NF-κB, IL-6, TNF-α, and MCP-1, and oxidative stress (ROS, MDA, GSH, and SOD.

  18. PARP1-mediated PPARα poly(ADP-ribosyl)ation suppresses fatty acid oxidation in non-alcoholic fatty liver disease.

    Science.gov (United States)

    Huang, Kun; Du, Meng; Tan, Xin; Yang, Ling; Li, Xiangrao; Jiang, Yuhan; Wang, Cheng; Zhang, Fengxiao; Zhu, Feng; Cheng, Min; Yang, Qinglin; Yu, Liqing; Wang, Lin; Huang, Dan; Huang, Kai

    2017-05-01

    PARP1 is a key mediator of cellular stress responses and critical in multiple physiological and pathophysiological processes of cells. However, whether it is involved in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) remains elusive. We analysed PARP1 activity in the liver of mice on a high fat diet (HFD), and samples from NAFLD patients. Gain- or loss-of-function approaches were used to investigate the roles and mechanisms of hepatic PARP1 in the pathogenesis of NAFLD. PARP1 is activated in fatty liver of HFD-fed mice. Pharmacological or genetic manipulations of PARP1 are sufficient to alter the HFD-induced hepatic steatosis and inflammation. Mechanistically we identified peroxisome proliferator-activated receptor α (PPARα) as a substrate of PARP1-mediated poly(ADP-ribosyl)ation. This poly(ADP-ribosyl)ation of PPARα inhibits its recruitment to target gene promoters and its interaction with SIRT1, a key regulator of PPARα signaling, resulting in suppression of fatty acid oxidation upregulation induced by fatty acids. Moreover, we show that PARP1 is a transcriptional repressor of PPARα gene in human hepatocytes, and its activation suppresses the ligand (fenofibrate)-induced PPARα transactivation and target gene expression. Importantly we demonstrate that liver biopsies of NAFLD patients display robust increases in PARP activity and PPARα poly(ADP-ribosyl)ation levels. Our data indicate that PARP1 is activated in fatty liver, which prevents maximal activation of fatty acid oxidation by suppressing PPARα signaling. Pharmacological inhibition of PARP1 may alleviate PPARα suppression and therefore have therapeutic potential for NAFLD. PARP1 is activated in the non-alcoholic fatty liver of mice and patients. Inhibition of PARP1 activation alleviates lipid accumulation and inflammation in fatty liver of mice. Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  19. Emerging role of obeticholic acid in the management of nonalcoholic fatty liver disease

    OpenAIRE

    Makri, Evangelia; Cholongitas, Evangelos; Tziomalos, Konstantinos

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) is the commonest chronic liver disease and its prevalence is increasing driven by the pandemic of obesity and type 2 diabetes mellitus. NAFLD can progress to cirrhosis and is associated with increased risk for cardiovascular disease and hepatocellular cancer. Diet and exercise are limited by suboptimal long-term adherence in patients with NAFLD. On the other hand, current pharmacological treatment of NAFLD has limited efficacy and unfavorable safety pr...

  20. A Guide to Non-Alcoholic Fatty Liver Disease in Childhood and Adolescence

    OpenAIRE

    Temple, J. L.; Cordero, P.; Li, J.; Vi, N.; Oben, J. A.

    2016-01-01

    Non-Alcoholic Fatty Liver Disease (NAFLD) is now the most prevalent form of chronic liver disease, affecting 10%–20% of the general paediatric population. Within the next 10 years it is expected to become the leading cause of liver pathology, liver failure and indication for liver transplantation in childhood and adolescence in the Western world. While our understanding of the pathophysiological mechanisms underlying this disease remains limited, it is thought to be the hepatic manifestation ...

  1. Can Diet Help Non-Obese Individuals with Non-Alcoholic Fatty Liver Disease (NAFLD)?

    OpenAIRE

    Merchant, Hamid A.

    2017-01-01

    Subjects diagnosed with non-alcoholic fatty liver disease (NAFLD) or hepatic steatosis are usually obese or overweight. NAFLD has also been reported in many non-obese healthy subjects as an incidental finding during imaging. Subjects with early-stage NAFLD who are otherwise healthy are often left unmanaged in current clinical practice; it is not clear if an early intervention in those individuals would be of any benefit in preventing NAFLD progression to more serious conditions. Since many of...

  2. Histopathologic Evaluation of Nonalcoholic Fatty Liver Disease in Hypothyroidism-Induced Rats

    OpenAIRE

    Demir, Şule; Ünübol, Mustafa; Aypak, Serap Ünübol; İpek, Emrah; Aktaş, Serdar; Ekren, Gamze Sevri; Yılmaz, Murat; Tunca, Recai; Güney, Engin

    2016-01-01

    It is speculated that thyroid hormones may be involved in nonalcoholic fatty liver disease (NAFLD) pathogenesis. A literature scan, however, demonstrated conflicting results from studies investigating the relationship between hypothyroidism and NAFLD. Therefore, our study aims to evaluate NAFLD, from the histopathologic perspective, in hypothyroidism-induced rats. Wistar rats were divided into 2 groups: the experimental group consumed water containing methimazole 0.025% (MMI, Sigma, USA) for ...

  3. Plasmatic higher levels of homocysteine in Non-alcoholic fatty liver disease (NAFLD)

    OpenAIRE

    Carvalho, Sylene Coutinho Rampche de; Muniz, Maria Tereza Cartaxo; Siqueira, Maria Deozete Vieira; Siqueira, Erika Rabelo Forte; Gomes, Adriana Vieira; Silva, Karina Alves; Bezerra, Lais Carvalho Luma; D'Almeida, Vania [UNIFESP; Oliveira, Claudia Pinto Marques Souza de; Pereira, Leila Maria M. Beltrao

    2013-01-01

    Abstract Background Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease, which includes a spectrum of hepatic pathology such as simple steatosis, steatohepatitis, fibrosis and cirrhosis. The increased serum levels of homocysteine (Hcy) may be associated with hepatic fat accumulation. Genetic mutations in the folate route may only mildly impair Hcy metabolism. The aim of this study was to investigate the relation between ...

  4. Dietary Composition Independent of Weight Loss in the Management of Non-Alcoholic Fatty Liver Disease

    OpenAIRE

    Eslamparast, Tannaz; Tandon, Puneeta; Raman, Maitreyi

    2017-01-01

    Poor dietary composition is an important factor in the progression of non-alcoholic fatty liver disease (NAFLD). The majority of NAFLD patients follow diets with overconsumption of simple carbohydrates, total and saturated fat, with reduced intake of dietary fiber and omega-3 rich foods. Although lifestyle modifications including weight loss and exercise remain the keystone of NAFLD management, modifying dietary composition with or without a calorie-restricted diet may also be a feasible and ...

  5. Similar Connotation in Chronic Hepatitis B and Nonalcoholic Fatty Liver Patients with Dampness-Heat Syndrome

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    Jianye Dai

    2013-01-01

    Full Text Available The phenomenon that the same syndrome turns up in different diseases appears in the sight of people around the world, which raises the thought for possibility of “Same Treatment for Different Diseases.” Actually, treatment based on ZHENG classification in Traditional Chinese Medicine could bring revelation for the former finding. The dampness-heat syndrome in chronic hepatitis B and nonalcoholic fatty liver is regarded as the breakthrough point. We discussed the molecular mechanism of similar connotation that exists in chronic hepatitis B and nonalcoholic fatty liver by metabonomics to give the modern understanding of dampness-heat syndrome. Both urine and serum metabolic profiling revealed that obvious differences existed between dampness-heat syndrome and non-dampness-heat syndrome but the commonality was proved to appear in chronic hepatitis B and nonalcoholic fatty liver patients with dampness-heat syndrome. Furthermore, disorder of body fluid metabolism, decline in digestive capacity, and imbalance of intestinal flora were found to be the new guiding for treatment, with the hope to provide the basis for Chinese personalized medicine.

  6. Efficacy of Qianggan capsule in treatment of non-alcoholic fatty liver disease complicated with hyperlipidemia

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    Zhi-Jun He

    2016-07-01

    Full Text Available Objective: To observe the clinical effects of Qianggan capsule and silibinin capsule in the treatment of non-alcoholic fatty liver disease complicated with hyperlipidemia. Methods: A total of 112 patients with non-alcoholic fatty liver disease were included in the study and divided into the control group (n=50 and the observation group (n=62. The patients in the control group were given silibinin capsule, while the patients in the observation group were given Qianggan capsule. The patients in the two groups were treated for 24 weeks. The liver/ spleen CT was performed before and after treatment. BMI was measured. The liver function, serum lipid, and leptin were detected. Results: TG, LDL-C, BMI, and liver/spleen CT ratio in the observation group were significantly reduced when compared with the control group. The levels of HDL-C and adiponectin in the observation group were significantly elevated when compared with the control group. The differences of ALT, GGT, and AST after treatment between the two groups were not statistically significant. Conclusions: Qianggan capsule and silibinin capsule has an accurate efficacy and high safety in the treatment of non-alcoholic fatty liver disease complicated with hyperlipidemia.

  7. GLP-1 Receptor Agonist and Non-Alcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Jinmi Lee

    2012-08-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD, one of the most common liver diseases, is caused by the disruption of hepatic lipid homeostasis. It is associated with insulin resistance as seen in type 2 diabetes mellitus. Glucagon-like peptide-1 (GLP-1 is an incretin that increases insulin sensitivity and aids glucose metabolism. In recent in vivo and in vitro studies, GLP-1 presents a novel therapeutic approach against NAFLD by increasing fatty acid oxidation, decreasing lipogenesis, and improving hepatic glucose metabolism. In this report, we provide an overview of the role and mechanism of GLP-1 in relieving NAFLD.

  8. Association between non-alcoholic fatty liver disease, insulin resistance and Helicobacter pylori.

    Science.gov (United States)

    Abenavoli, Ludovico; Milic, Natasa; Masarone, Mario; Persico, Marcello

    2013-11-01

    Here we report a case of a 55-year Caucasian man, who improved the metabolic profile after the treatment for Helicobacter pylori eradication. In particular, we report the changes in homeostatic model assessment of insulin resistance, fatty liver index and echographic liver pattern. We hypothesize the co-factorial role of H. pylori in the mechanisms involved in non-alcoholic fatty liver disease pathogenesis and insulin resistance, by the cytokine serum changes. If this correlation is confirmed, the H. pylori treatment may represent an option in the clinical management of liver steatosis. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Dorothy Hodgkin Lecture 2012: non-alcoholic fatty liver disease, insulin resistance and ectopic fat: a new problem in diabetes management.

    Science.gov (United States)

    Byrne, C D

    2012-09-01

    Non-alcoholic fatty liver disease is now recognized as the hepatic component of the metabolic syndrome. Non-alcoholic fatty liver disease is a spectrum of fat-associated liver conditions that can result in end-stage liver disease and the need for liver transplantation. Simple steatosis, or fatty liver, occurs early in non-alcoholic fatty liver disease and may progress to non-alcoholic steatohepatitis, fibrosis and cirrhosis with increased risk of hepatocellular carcinoma. Prevalence estimates for non-alcoholic fatty liver disease range from 17 to 33% in the general populations and it has been estimated that non-alcoholic fatty liver disease exists in up to 70% of people with Type 2 diabetes. Non-alcoholic fatty liver disease increases risk of Type 2 diabetes and cardiovascular disease. In people with Type 2 diabetes, non-alcoholic fatty liver disease is the most frequent cause (∼80%) of fatty liver diagnosed by ultrasound. As non-alcoholic fatty liver disease is strongly associated with insulin resistance, the presence of non-alcoholic fatty liver disease with diabetes often contributes to poor glycaemic control. Consequently, strategies that decrease liver fat and improve whole-body insulin sensitivity may both contribute to prevention of Type 2 diabetes and to better glycaemic control in people who already have developed diabetes. This review summarizes the Dorothy Hodgkin lecture given by the author at the 2012 Diabetes UK annual scientific conference, proposing that fatty acid fluxes through the liver are crucial for the pathogenesis of non-alcoholic fatty liver disease and for increasing insulin resistance. © 2012 The Author. Diabetic Medicine © 2012 Diabetes UK.

  10. Involvement of a periodontal pathogen, Porphyromonas gingivalis on the pathogenesis of non-alcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    Yoneda Masato

    2012-02-01

    Full Text Available Abstract Background Non-alcoholic fatty liver disease (NAFLD is a hepatic manifestation of metabolic syndrome that is closely associated with multiple factors such as obesity, hyperlipidemia and type 2 diabetes mellitus. However, other risk factors for the development of NAFLD are unclear. With the association between periodontal disease and the development of systemic diseases receiving increasing attention recently, we conducted this study to investigate the relationship between NAFLD and infection with Porphyromonas gingivalis (P. gingivalis, a major causative agent of periodontitis. Methods The detection frequencies of periodontal bacteria in oral samples collected from 150 biopsy-proven NAFLD patients (102 with non-alcoholic steatohepatitis (NASH and 48 with non-alcoholic fatty liver (NAFL patients and 60 non-NAFLD control subjects were determined. Detection of P. gingivalis and other periodontopathic bacteria were detected by PCR assay. In addition, effect of P. gingivalis-infection on mouse NAFLD model was investigated. To clarify the exact contribution of P. gingivalis-induced periodontitis, non-surgical periodontal treatments were also undertaken for 3 months in 10 NAFLD patients with periodontitis. Results The detection frequency of P. gingivalis in NAFLD patients was significantly higher than that in the non-NAFLD control subjects (46.7% vs. 21.7%, odds ratio: 3.16. In addition, the detection frequency of P. gingivalis in NASH patients was markedly higher than that in the non-NAFLD subjects (52.0%, odds ratio: 3.91. Most of the P. gingivalis fimbria detected in the NAFLD patients was of invasive genotypes, especially type II (50.0%. Infection of type II P. gingivalis on NAFLD model of mice accelerated the NAFLD progression. The non-surgical periodontal treatments on NAFLD patients carried out for 3 months ameliorated the liver function parameters, such as the serum levels of AST and ALT. Conclusions Infection with high-virulence P

  11. Modern approach to the clinical management of non-alcoholic fatty liver disease.

    Science.gov (United States)

    Del Ben, Maria; Polimeni, Licia; Baratta, Francesco; Pastori, Daniele; Loffredo, Lorenzo; Angelico, Francesco

    2014-07-14

    Non-alcoholic fatty liver disease (NAFLD) is the most common and emerging form of chronic liver disease worldwide. It includes a wide spectrum of liver diseases ranging from simple fatty liver to steatohepatitis, which may progress to cirrhosis, liver cancer, and liver mortality. Common metabolic diseases, which are well established cardiovascular risk factors, have been associated to NAFLD and cardiovascular disease is the single most important cause of morbidity and mortality in this patient population. The pathogenesis of NAFLD appears multifactorial and many mechanisms have been proposed as possible causes of fatty liver infiltration. Management of fatty liver has become a major challenge to healthcare systems as the consequence of the increasing rates of obesity worldwide. First-line management focuses on lifestyle modifications. Moderate weight reduction either by dietary restriction or by increased habitual physical activity is safe and highly recommended. Several therapeutic interventions have been proposed. These include insulin sensitizer agents, lipid lowering drugs, antioxidants such as vitamin E and supplementation of vitamin D3. However, therapeutic strategies have been largely empirical so far, and experimental trials have mostly been carried out in uncontrolled settings with small sample sizes. Metabolic conditions such as diabetes mellitus, obesity, hypertension and hyperlipidemia, should be strongly considered and a multidisciplinary approach should be personalized for individual patients. Treatment of co-morbidities should be regarded as of paramount importance in the management of these patients. The purpose of this review is to examine different approaches for the clinical management of non-alcoholic fatty liver disease.

  12. GLCM algorithm image analysis of nonalcoholic fatty liver and focal fat sparing zone in the ultrasonography

    International Nuclear Information System (INIS)

    Cho, Jin Young; Ye, Soo Young

    2017-01-01

    There is a need for aggressive diagnosis and treatment in middle-aged and high-risk individuals who are more likely to progress from nonalcoholic fatty liver to hepatitis. In this study, nonalcoholic fatty liver was divided into severe, moderate, and severe, and classified by quantitative method using computer analysis of GLCM algorithm. The purpose of this study was to evaluate the characteristics of ultrasound images in the local fat avoidance region. Normal, mild, moderate, severe fatty liver, and focal fat sparing area, 80 cases, respectively. Among the parameters of the GLCM algorithm, the values of the Autocorrelation, Square of the deviation, Sum of averages and Sum of variances with high recognition rate of the liver ultrasound image were calculated. The average recognition rate of the GLCM algorithm was 97.5%. The result of local fat avoidance image analysis showed the most similar value to the normal parenchyma. Ultrasonography can be easily accessed by primary screening, but there may be differences in the accuracy of the test method or the correspondence of results depending on proficiency. GLCM algorithm was applied to quantitatively classify the degree of fatty liver. Local fat avoidance region was similar to normal parenchyma, so it could be predicted to be homogeneous liver parenchyma without fat deposition. We believe that GLCM computer image analysis will provide important information for differentiating not only fatty liver but also other lesions

  13. GLCM algorithm image analysis of nonalcoholic fatty liver and focal fat sparing zone in the ultrasonography

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Jin Young [Dept. of Radiological Science, Graduate School of Catholic University of Pusan, Busan (Korea, Republic of); Ye, Soo Young [Dept. of Radiological Science, Catholic University of Pusan, Busan (Korea, Republic of)

    2017-06-15

    There is a need for aggressive diagnosis and treatment in middle-aged and high-risk individuals who are more likely to progress from nonalcoholic fatty liver to hepatitis. In this study, nonalcoholic fatty liver was divided into severe, moderate, and severe, and classified by quantitative method using computer analysis of GLCM algorithm. The purpose of this study was to evaluate the characteristics of ultrasound images in the local fat avoidance region. Normal, mild, moderate, severe fatty liver, and focal fat sparing area, 80 cases, respectively. Among the parameters of the GLCM algorithm, the values of the Autocorrelation, Square of the deviation, Sum of averages and Sum of variances with high recognition rate of the liver ultrasound image were calculated. The average recognition rate of the GLCM algorithm was 97.5%. The result of local fat avoidance image analysis showed the most similar value to the normal parenchyma. Ultrasonography can be easily accessed by primary screening, but there may be differences in the accuracy of the test method or the correspondence of results depending on proficiency. GLCM algorithm was applied to quantitatively classify the degree of fatty liver. Local fat avoidance region was similar to normal parenchyma, so it could be predicted to be homogeneous liver parenchyma without fat deposition. We believe that GLCM computer image analysis will provide important information for differentiating not only fatty liver but also other lesions.

  14. Fatty liver index vs waist circumference for predicting non-alcoholic fatty liver disease.

    Science.gov (United States)

    Motamed, Nima; Sohrabi, Masoudreza; Ajdarkosh, Hossein; Hemmasi, Gholamreza; Maadi, Mansooreh; Sayeedian, Fatemeh Sima; Pirzad, Reza; Abedi, Khadijeh; Aghapour, Sivil; Fallahnezhad, Mojtaba; Zamani, Farhad

    2016-03-14

    To determine the discriminatory performance of fatty liver index (FLI) for non-alcoholic fatty liver disease (NAFLD). The data of 5052 subjects aged over 18 years were analyzed. FLI was calculated from body mass index, waist circumference (WC), triglyceride, and gamma glutamyl transferase data. Logistic regression analysis was conducted to determine the association between FLI and NAFLD. The discriminatory performance of FLI in the diagnosis of NAFLD was evaluated by receiver operating characteristic analysis. Area under the curves (AUCs) and related confidence intervals were estimated. Optimal cutoff points of FLI in the diagnosis of NAFLD were determined based on the maximum values of Youden's index. The mean age of men and women in the study population were 44.8 ± 16.8 and 43.78 ± 15.43, respectively (P = 0.0216). The prevalence of NAFLD was 40.1% in men and 44.2% in women (P < 0.0017). FLI was strongly associated with NAFLD, so that even a one unit increase in FLI increased the chance of developing NAFLD by 5.8% (OR = 1.058, 95%CI: 1.054-1.063, P < 0.0001). Although FLI showed good performance in the diagnosis of NAFLD (AUC = 0.8656 (95%CI: 0.8548-0.8764), there was no significant difference with regards to WC (AUC = 0.8533, 95%CI: 0.8419-0.8646). The performance of FLI was not significantly different between men (AUC = 0.8648, 95%CI: 0.8505-0.8791) and women (AUC = 0.8682, 95%CI: 0.8513-0.8851). The highest performance with regards to age was related to the 18-39 age group (AUC = 0.8930, 95%CI: 0.8766-0.9093). The optimal cutoff points of FLI were 46.9 in men (sensitivity = 0.8242, specificity = 0.7687, Youden's index = 0.5929) and 53.8 in women (sensitivity = 0.8233, specificity = 0.7655, Youden's index = 0.5888). Although FLI had acceptable discriminatory power in the diagnosis of NAFLD, WC was a simpler and more accessible index with a similar performance.

  15. Evaluation of the Effect of Exercise on Nonalcoholic Fatty Liver By Sonography

    International Nuclear Information System (INIS)

    Kim, Kyoung Yeon; Lim, Hyun Soo

    2012-01-01

    Nonalcoholic fatty liver disease (NAFLD) is accumulation state of fat in liver cells without excessive alcohol intake, and it has been studied that is closely related to obesity. The purpose of this study is to identify risk factors for NAFLD and may prevent or to manage risk factors. This study was in progress for six months (2011 May 1 to October 31), of the 83 people who underwent abdominal ultrasound 11 people eventually were selected. Research results was as follows : First, the decreased body weight and body mass index (BMI), and the second, a decrease of the deepening of fatty liver in ultrasound diagnosis, and the third, steady movement reduces the deepening of fatty liver regardless of calories. Thus, the implication of this research is that long-term exercise programs have positive effects in the treatment of fatty liver.

  16. Metabolic syndrome and risk factors for non-alcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    Mônica Rodrigues de Araújo Souza

    2012-03-01

    Full Text Available CONTEXT: Non-alcoholic fatty liver disease (NAFLD, hepatic manifestation of metabolic syndrome, has been considered the most common liver disease nowadays, which is also the most frequent cause of elevated transaminases and cryptogenic cirrhosis. The greatest input of fatty acids into the liver and consequent increased beta-oxidation contribute to the formation of free radicals, release of inflammatory cytokines and varying degrees of hepatocytic aggression, whose histological expression may vary from steatosis (HS to non-alcoholic steatohepatitis (NASH. The differentiation of these forms is required by the potential risk of progression to cirrhosis and development of hepatocellular carcinoma. OBJECTIVE: To review the literature about the major risk factors for NAFLD in the context of metabolic syndrome, focusing on underlying mechanisms and prevention. METHOD: PubMed, MEDLINE and SciELO data basis analysis was performed to identify studies describing the link between risk factors for metabolic syndrome and NAFLD. A combination of descriptors was used, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, metabolic syndrome and risk factors. At the end, 96 clinical and experimental studies, cohorts, meta-analysis and systematic reviews of great impact and scientific relevance to the topic, were selected. RESULTS: The final analysis of all these data, pointed out the central obesity, type 2 diabetes, dyslipidemia and hypertension as the best risk factors related to NAFLD. However, other factors were highlighted, such as gender differences, ethnicity, genetic factors and the role of innate immunity system. How these additional factors may be involved in the installation, progression and disease prognosis is discussed. CONCLUSION: Risk factors for NAFLD in the context of metabolic syndrome expands the prospects to 1 recognize patients with metabolic syndrome at high risk for NAFLD, 2 elucidate pathways common to other co-morbidities, 3

  17. Impact of bariatric surgery on non-alcoholic fatty liver disease.

    Science.gov (United States)

    Major, Piotr; Pędziwiatr, Michał; Rubinkiewicz, Mateusz; Stanek, Maciej; Głuszewska, Anna; Pisarska, Magdalena; Małczak, Piotr; Budzyński, Andrzej; Budzyński, Piotr

    2017-04-30

    Introduction; p to 300 million people have the body mass index (BMI) greater than 30 kg/m2. Obesity is the cause of many serious diseases, such as type 2 diabetes, hypertension, and non-alcoholic fatty liver disease (NAFLD). Bariatric surgery is the only effective method of achieving weight loss in patients with morbid obesity. The aim of the study was to assess the impact of bariatric surgery on non-alcoholic fatty liver disease in patients operated on due to morbid obesity. We included 20 patients who were qualified for bariatric procedures based on BMI > 40 kg/ m2 or BMI > 35kg/m2 with the presence of comorbidities. The average body weight in the group was 143.85kg, with an average BMI of 49.16kg/m2. Before the procedure, we evaluated the severity of non-alcoholic fatty liver disease in each patient using the Sheriff-Saadeh ultrasound scale. We also evaluated the levels of liver enzymes. Follow-up evaluation was performed twelve months after surgery. Twelve months after surgery, the average weight was 102.34 kg. The mean %WL was 33.01%, %EWL was 58.8%, and %EBMIL was 61.37%. All patients showed remission of fatty liver disease. Liver damage, evaluated with ultrasound imaging, decreased from an average of 1.85 on the Sheriff-Saadeh scale, before surgery, to 0.15 twelve months after surgery (p < 0.001). As regards liver enzymes, the level of alanine aminotransferase decreased from 64.5 (U/l) to 27.95 (U/l) (p < 0.001), and the level of aspartate aminotransferase decreased from 54.4 (U/l) to 27.2 (U/l). Bariatric procedures not only lead to a significant and lasting weight loss, but they also contribute to the reduction of fatty liver disease and improve liver function.

  18. Serum uric acid and non-alcoholic fatty liver disease in non-obesity Chinese adults.

    Science.gov (United States)

    Zheng, Xiaoya; Gong, Lilin; Luo, Rong; Chen, Hua; Peng, Bin; Ren, Wei; Wang, Yonghong

    2017-10-16

    Previous studies found elevated serum uric acid (SUA) was associated with the development or progression of non-alcoholic fatty liver disease (NAFLD) in general population; in this study we aim to investigate the association of SUA and the severity of NAFLD based on grade of fatty liver on ultrasonography in non-obese subjects. Data were obtained from subjects via routine physical examinations in the Public Health Center of our hospital between 2011 and 2014. The data included completed anthropometry and blood biochemical indicators and the results of abdominal ultrasound. The diagnosis of NAFLD was according to the clinical diagnosis of the Guidelines for the diagnosis and treatment of nonalcoholic fatty liver disease in 2008. In total, 95,924 subjects were analyzed in this study. The prevalence rate of lean-NAFLD was 8.16%, among which 7.58% had mild steatosis, and 0.58% had moderate and severe steatosis. The prevalence of fatty liver was increased progressively with SUA. Among which the prevalence of mild fatty liver from Q1 to Q4 were 10.33%, 18.39%, 23.11% and 25.93%; the prevalence of moderate and severe fatty liver from Q1 to Q4 were 1.06%, 2.82%, 5.05% and 7.27%. Lean-subjects with hyperuricemia had an OR of 1.718 (95% CI 1.622-1.820) to have NAFLD, after adjusted for other metabolic disorders. The area under curve (AUC) for detecting mild fatty liver based on SUA was 0.70; and the AUC for detecting moderate and severe fatty liver based on SUA was 0.78. Our data showed positive associations between elevated SUA levels and lean-NAFLD risk in the inland Chinese adults, independent of other metabolic factors. Our study also suggests that SUA could be considered as a simple and non-invasive method to follow up patients with lean-NAFLD.

  19. NON-ALCOHOLIC FATTY LIVER DISEASE AT OUR INSTITUTE

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    Madhavi

    2015-12-01

    Full Text Available INTRODUCTION A Correlation clinical observational hospital based clinical study with 50 patients were undertaken to study the Clinical Profile of incidentally detected Non Alcoholic Fatty Liver Disease. The cases for the study were selected retrospectively who were diagnosed as fatty liver by ultrasound imaging who attended the Department of General Medicine, Government General Hospital Kakinada Rangaraya Medical College. Data has been enumerated for those who fulfilled the inclusion criteria. This study was conducted between January 2013-January 2015. The study has limitations of observer variant dependent diagnostic ultrasound for inclusion in to study. A BMI of>25 kg/m2 taken as definition for obesity for analysis.

  20. Acceleration training for managing nonalcoholic fatty liver disease: a pilot study

    Directory of Open Access Journals (Sweden)

    Oh S

    2014-11-01

    Full Text Available Sechang Oh,1 Takashi Shida,1 Akemi Sawai,1 Tsuyoshi Maruyama,2 Kiyoshi Eguchi,2 Tomonori Isobe,1 Yoshikazu Okamoto,3 Noriko Someya,4 Kiyoji Tanaka,4 Emi Arai,1 Akiko Tozawa,5 Junichi Shoda1 1Department of Medical Sciences, Faculty of Medicine, University of Tsukuba, 2Department of Rehabilitation, Tsukuba University Hospital, 3Department of Diagnostic Radiology, 4Department of Sports Medicine, Faculty of Health and Sport Sciences, University of Tsukuba, Ibaraki, 5Protea Japan Co Ltd, Chiyoda, Tokyo, Japan Background: While aerobic training is generally recommended as therapeutic exercise in guidelines, the effectiveness of resistance training has recently been reported in the management of nonalcoholic fatty liver disease (NAFLD. Acceleration training (AT is a new training method that provides a physical stimulation effect on skeletal muscles by increasing gravitational acceleration with vibration. AT has recently been indicated as a component of medicine. In this study, we evaluated the effectiveness of AT in the management of NAFLD in obese subjects.Methods: A total of 18 obese patients with NAFLD who had no improvement in liver function test abnormalities and/or steatosis grade after 12 weeks of lifestyle counseling were enrolled in an AT program. These patients attended a 20-minute session of AT twice a week for 12 consecutive weeks.Results: During the AT program, the NAFLD patients showed a modest increase in the strength (+12.6% and cross-sectional area (+3.1% of the quadriceps, coupled with a significant reduction in intramyocellular lipids (−26.4%. Notably, they showed a modest reduction in body weight (−1.9%, abdominal visceral fat area (−3.4%, and hepatic fat content (−8.7%, coupled with a significant reduction in levels of aminotransferase (−15.7%, γ-glutamyltransferase (−14.4%, leptin (−9.7%, interleukin-6 (−26.8%, and tumor necrosis factor-α (−17.9%, and a significant increase of adiponectin (+8.7%. On a health

  1. Hepatic unsaturated fatty acids in patients with non-alcoholic fatty liver disease assessed by 3.0T MR spectroscopy

    NARCIS (Netherlands)

    van Werven, J. R.; Schreuder, T. C. M. A.; Nederveen, A. J.; Lavini, C.; Jansen, P. L. M.; Stoker, J.

    2010-01-01

    Non-alcoholic fatty liver disease (NAFLD) is related to the metabolic syndrome and obesity. Proton magnetic resonance spectroscopy ((1)H MRS) is a non-invasive technique to assess hepatic triglyceride content (HTGC) and allows assessment of unsaturated fatty acids (UFA). There is increasing evidence

  2. SCAP gene polymorphisms decrease the risk of nonalcoholic fatty ...

    Indian Academy of Sciences (India)

    5E-institute of Shanghai Municipal Education Commission, Shanghai University of Traditional Chinese Medicine,. Shanghai 201203, People's Republic of China. [Sun S., Wang M., Song H., .... no history of type II diabetes, hypertension, dyslipidaemia and fatty liver, and the remaining 263 individuals had been diagnosed ...

  3. Non-Alcoholic Fatty Liver Disease: From patient to population

    NARCIS (Netherlands)

    E.M. Koehler (Edith)

    2013-01-01

    textabstractNon-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease in Western countries, in parallel with epidemics in obesity and type 2 diabetes mellitus. NAFLD comprises a wide range of histological findings, extending from simple steatosis to

  4. Gene-metabolite network analysis in different nonalcoholic fatty liver disease phenotypes.

    Science.gov (United States)

    Liu, Xiao-Lin; Ming, Ya-Nan; Zhang, Jing-Yi; Chen, Xiao-Yu; Zeng, Min-De; Mao, Yi-Min

    2017-01-13

    We sought to identify common key regulators and build a gene-metabolite network in different nonalcoholic fatty liver disease (NAFLD) phenotypes. We used a high-fat diet (HFD), a methionine-choline-deficient diet (MCDD) and streptozocin (STZ) to establish nonalcoholic fatty liver (NAFL), nonalcoholic steatohepatitis (NASH) and NAFL+type 2 diabetes mellitus (T2DM) in rat models, respectively. Transcriptomics and metabolomics analyses were performed in rat livers and serum. A functional network-based regulation model was constructed using Cytoscape with information derived from transcriptomics and metabolomics. The results revealed that 96 genes, 17 liver metabolites and 4 serum metabolites consistently changed in different NAFLD phenotypes (>2-fold, Pmetabolism in HFD models, the inflammatory and immune response in MCDD models, and the AMPK signaling pathway and response to insulin in HFD+STZ models. Our study identified networks showing the general and specific characteristics in different NAFLD phenotypes, complementing the genetic and metabolic features in NAFLD with hepatic and extra-hepatic manifestations.

  5. Adipocytokines and cytokeratin-18 in patients with nonalcoholic fatty liver disease: Introduction of CHA index.

    Science.gov (United States)

    Polyzos, Stergios A; Kountouras, Jannis; Papatheodorou, Athanasios; Katsiki, Evangelia; Patsiaoura, Kalliopi; Zafeiriadou, Efthimia; Papadopoulou, Evridiki; Zavos, Christos; Terpos, Evangelos

    2013-01-01

    Insulin resistance (IR), adipocytokines, oxidative stress and hepatic apoptosis play a pathogenetic role in nonalcoholic fatty liver disease (NAFLD). The evaluation of specific adipocytokines and markers of IR, oxidative stress and apoptosis in NAFLD patients; the introduction of a combined non-invasive index for nonalcoholic steatohepatitis (NASH). Thirty patients with biopsy-proven NAFLD (15 with simple nonalcoholic fatty liver [NAFL], 15 with NASH) and 24 controls were recruited. Blood samples for total and high molecular weight (HMW) adiponectin, visfatin and tumor necrosis factor (TNF)-α, the apoptotic by-product cytokeratin (CK)-18, the reactive oxygen metabolites (ROMs) and standard biochemical tests were measured. Homeostatic model of assessment - insulin resistance (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI) were calculated. Total and HMW adiponectin were significantly lower and TNF-α higher in either NAFL or NASH group compared to control group; CK-18 was significantly higher in NASH compared to either NAFL or control group. CHAI (an acronym of CK-18, HOMA-IR, AST Index) was calculated as the product of parameters being significantly different between NAFL and NASH groups. CHAI was significantly higher in NASH (24.2 [15.1-214.0]) compared to either NAFL (15.7 [6.8-22.7]) or control (5.1 [2.4-7.6]) group (p validation study is needed before introducing CHAI in clinical practice.

  6. Bile Acids and Dysbiosis in Non-Alcoholic Fatty Liver Disease.

    Science.gov (United States)

    Mouzaki, Marialena; Wang, Alice Y; Bandsma, Robert; Comelli, Elena M; Arendt, Bianca M; Zhang, Ling; Fung, Scott; Fischer, Sandra E; McGilvray, Ian G; Allard, Johane P

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD) is characterized by dysbiosis. The bidirectional effects between intestinal microbiota (IM) and bile acids (BA) suggest that dysbiosis may be accompanied by an altered bile acid (BA) homeostasis, which in turn can contribute to the metabolic dysregulation seen in NAFLD. This study sought to examine BA homeostasis in patients with NAFLD and to relate that with IM data. This was a prospective, cross-sectional study of adults with biopsy-confirmed NAFLD (non-alcoholic fatty liver: NAFL or non-alcoholic steatohepatitis: NASH) and healthy controls (HC). Clinical and laboratory data, stool samples and 7-day food records were collected. Fecal BA profiles, serum markers of BA synthesis 7-alpha-hydroxy-4-cholesten-3-one (C4) and intestinal BA signalling, as well as IM composition were assessed. 53 subjects were included: 25 HC, 12 NAFL and 16 NASH. Levels of total fecal BA, cholic acid (CA), chenodeoxycholic acid (CDCA) and BA synthesis were higher in patients with NASH compared to HC (pLCA) (r = 0.526, p = 0.003) and inversely with unconjugated CA (r = -0.669, pinjury.

  7. Enhanced Amelioration of High-Fat Diet-Induced Fatty Liver by Docosahexaenoic Acid and Lysine Supplementations

    Directory of Open Access Journals (Sweden)

    Hsin-Yu Lin

    2014-01-01

    Full Text Available Fatty liver disease is the most common pathological condition in the liver. Here, we generated high-fat diet-(HFD- induced nonalcoholic fatty liver disease (NAFLD in mice and tested the effects of docosahexaenoic acid (DHA and lysine during a four-week regular chow (RCfeeding. Our results showed that 1% lysine and the combination of 1% lysine + 1% DHA reduced body weight. Moreover, serum triglyceride levels were reduced by 1% DHA and 1% lysine, whereas serum alanine transaminase activity was reduced by 1% DHA and 1% DHA + 0.5% lysine. Switching to RC reduced hepatic lipid droplet accumulation, which was further reduced by the addition of DHA or lysine. Furthermore, the mRNA expressions of hepatic proinflammatory cytokines were suppressed by DHA and combinations of DHA + lysine, whereas the mRNA for the lipogenic gene, acetyl-CoA carboxylase 1 (ACC1, was suppressed by DHA. In the gonadal adipose tissues, combinations of DHA and lysine inhibited mRNA expression of lipid metabolism-associated genes, including ACC1, fatty acid synthase, lipoprotein lipase, and perilipin. In conclusion, the present study demonstrated that, in conjunction with RC-induced benefits, supplementation with DHA or lysine further ameliorated the high-fat diet-induced NAFLD and provided an alternative strategy to treat, and potentially prevent, NAFLD.

  8. Nonalcoholic fatty liver in patients with Laron syndrome and GH gene deletion - preliminary report.

    Science.gov (United States)

    Laron, Zvi; Ginsberg, Shira; Webb, Muriel

    2008-10-01

    There is little information on the relationship between growth hormone/insulin-like growth factor-I (GH/IGF-I) deficiency or IGF-I treatment on nonalcoholic fatty liver disease (NAFLD) a disorder linked to obesity and insulin resistance. To find out whether the markedly obese patients with Laron syndrome (LS) and GH gene deletion have fatty livers. We studied 11 untreated adult patients with LS (5M, 6F), five girls with LS treated by IGF-I and five adult patients with GH gene deletion (3M, 3F), four previously treated by hGH in childhood. Fatty liver was quantitatively evaluated by ultrasonography using a phase array US system (HITACHI 6500, Japan). Body adiposity was determined by DEXA, and insulin resistance was estimated by HOMA-IR using the fasting serum glucose and insulin values. Six out of 11 adult patients with LS, two out of the five IGF-I treated girls with LS and three out of five adult hGH gene deletion patients were found to have NAFLD (nonalcoholic fatty liver disease). NAFLD is a frequent complication in untreated and treated congenital IGF-I deficiency. No correlation between NAFLD and age, sex, degree of obesity, blood lipids, or degree of insulin resistance was observed.

  9. Effects of sulfate chitosan derivatives on nonalcoholic fatty liver disease

    Science.gov (United States)

    Yu, Mingming; Wang, Yuanhong; Jiang, Tingfu; Lv, Zhihua

    2014-06-01

    Sulfate chitosan derivatives have good solubility and therapeutic effect on the cell model of NAFLD. The aim of this study was to examine the therapeutic effect of sulfate chitosan derivatives on NAFLD. The male Wistar rats were orally fed high fat emulsion and received sulfate chitosan derivatives for 5 weeks to determine the pre-treatment effect of sulfate chitosan derivatives on NAFLD. To evaluate the therapeutic effect of sulfate chitosan derivatives on NAFLD, the rats were orally fed with high concentration emulsion for 5 weeks, followed by sulfate chitosan derivatives for 3 weeks. Histological analysis and biomedical assays showed that sulfate chitosan derivatives can dramatically prevent the development of hepatic steatosis in hepatocyte cells. In animal studies, pre-treatment and treatment with sulfate chitosan derivatives significantly protected against hepatic steatohepatitis induced by high fat diet according to histological analysis. Furthermore, increased TC, ALT, MDA, and LEP in NAFLD were significantly ameliorated by pre-treatment and treatment with sulfate chitosan derivatives. Furthermore, increased TG, AST, and TNF-α in NAFLD were significantly ameliorated by treatment with sulfate chitosan derivatives. Sulfate chitosan derivatives have good pre-treatment and therapeutic effect on NAFLD.

  10. Secondhand tobacco exposure is associated with nonalcoholic fatty liver disease in children

    International Nuclear Information System (INIS)

    Lin, Connie; Rountree, Carl B.; Methratta, Sosamma; LaRusso, Salvatore; Kunselman, Allen R.; Spanier, Adam J.

    2014-01-01

    Background: Nonalcoholic fatty liver disease (NAFLD) is the leading cause of liver disease in children in the United States, and prevalence rates are rising. Smoking is associated with NAFLD, but the association of secondhand smoke exposure with NAFLD is unknown. Aims: To investigate the association of secondhand tobacco exposure with NAFLD in children. Methods: We surveyed parents/guardians of 304 children aged 3–12 years who had received an abdominal ultrasound at Penn State Hershey Medical Center. The survey addressed demographics, medical history, secondhand tobacco exposure, activity level, screen viewing time and other environmental exposures. A pediatric radiologist and sonographer reviewed the ultrasounds to grade the presence of bight liver compatible with NAFLD. We conducted logistic regression analysis to assess the association of secondhand tobacco exposure and NAFLD. Results: 54% of eligible potential participants responded to the survey. Fatty liver was present in 3% of the children. Increasing child age was associated with increased odds of NAFLD (OR 1.63 95% CI 1.1, 2.4). Reported child obesity was associated with increased odds of NAFLD (OR 44.5 95% CI 5.3, 371.7). The rate of NAFLD was higher in the smoke exposed group (6.7% vs. 1.7%). For every extra pack per day smoked at home, the odds of a child having NAFLD increased 1.8 times (AOR 1.8, 95% CI 1.2, 2.8), and any exposure increased a child's odds of NAFLD four-fold (AOR 4.0, 95% CI 1.02, 15.8). Conclusion: We found an association of secondhand smoke exposure and NAFLD in children. This may represent an area for future prevention efforts. - Highlights: • We evaluated the relation of tobacco exposure with nonalcoholic fatty liver disease. • Tobacco smoke exposure was associated with nonalcoholic fatty liver disease. • Tobacco smoke exposure may be an addressable risk factor

  11. Secondhand tobacco exposure is associated with nonalcoholic fatty liver disease in children

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Connie [College of Medicine, Penn State University Hershey Medical Center, 500 University Drive, PO Box 850, Hershey, PA 17033-0850 (United States); Rountree, Carl B. [Department of Pediatrics, Penn State University Hershey Medical Center, 500 University Drive, PO Box 850, Hershey, PA 17033-0850 (United States); Department of Pediatrics, Bon Secour St. Mary' s Hospital, 5801 Bremo Rd, Richmond, VA 23226 (United States); Methratta, Sosamma [Department of Pediatrics, Penn State University Hershey Medical Center, 500 University Drive, PO Box 850, Hershey, PA 17033-0850 (United States); Department of Radiology, Penn State University Hershey Medical Center, 500 University Drive, PO Box 850, Hershey, PA 17033-0850 (United States); LaRusso, Salvatore [Department of Radiology, Penn State University Hershey Medical Center, 500 University Drive, PO Box 850, Hershey, PA 17033-0850 (United States); Kunselman, Allen R. [Department of Public Health Sciences, Penn State University Hershey Medical Center, 500 University Drive, PO Box 850, Hershey, PA 17033-0850 (United States); Spanier, Adam J., E-mail: aspanier@hmc.psu.edu [Department of Pediatrics, Penn State University Hershey Medical Center, 500 University Drive, PO Box 850, Hershey, PA 17033-0850 (United States); Department of Public Health Sciences, Penn State University Hershey Medical Center, 500 University Drive, PO Box 850, Hershey, PA 17033-0850 (United States)

    2014-07-15

    Background: Nonalcoholic fatty liver disease (NAFLD) is the leading cause of liver disease in children in the United States, and prevalence rates are rising. Smoking is associated with NAFLD, but the association of secondhand smoke exposure with NAFLD is unknown. Aims: To investigate the association of secondhand tobacco exposure with NAFLD in children. Methods: We surveyed parents/guardians of 304 children aged 3–12 years who had received an abdominal ultrasound at Penn State Hershey Medical Center. The survey addressed demographics, medical history, secondhand tobacco exposure, activity level, screen viewing time and other environmental exposures. A pediatric radiologist and sonographer reviewed the ultrasounds to grade the presence of bight liver compatible with NAFLD. We conducted logistic regression analysis to assess the association of secondhand tobacco exposure and NAFLD. Results: 54% of eligible potential participants responded to the survey. Fatty liver was present in 3% of the children. Increasing child age was associated with increased odds of NAFLD (OR 1.63 95% CI 1.1, 2.4). Reported child obesity was associated with increased odds of NAFLD (OR 44.5 95% CI 5.3, 371.7). The rate of NAFLD was higher in the smoke exposed group (6.7% vs. 1.7%). For every extra pack per day smoked at home, the odds of a child having NAFLD increased 1.8 times (AOR 1.8, 95% CI 1.2, 2.8), and any exposure increased a child's odds of NAFLD four-fold (AOR 4.0, 95% CI 1.02, 15.8). Conclusion: We found an association of secondhand smoke exposure and NAFLD in children. This may represent an area for future prevention efforts. - Highlights: • We evaluated the relation of tobacco exposure with nonalcoholic fatty liver disease. • Tobacco smoke exposure was associated with nonalcoholic fatty liver disease. • Tobacco smoke exposure may be an addressable risk factor.

  12. Lifestyle Modification through Dietary Intervention: Health Promotion of Patients with Non-Alcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Manoochehr Khoshbaten

    2011-12-01

    Full Text Available Background: Prevalence of non-alcoholic fatty liver disease (NAFLD is more common worldwide and no certain treatment apart from lifestyle modification has been established yet. Available data consistently show that energy intake is significantly higher in patients with NAFLD than in individuals with no evidence of fatty liver. Changing nutritional behaviors seems to be the primary approach for treatment, simultaneously addressing all the clinical and biochemical defects. This study was aimed to examine the effects of two different composition of low energy diet (diet I vs. diet II on non-alcoholic fatty liver disease patients.Methods: In this double-blind randomized controlled trial, 44 ultrasonography-proven overweight non-alcoholic fatty liver disease patients were divided into two groups and received two low-energy diets (-500 kcal less than energy requirement individually inc. diet I (Carbohydrate: Fat: Protein: 55:25:20 and diet II (Carbohydrate: Fat: Protein: 40:40:20 for six weeks. Anthropometric and biochemical measures as well as liver enzymes were assessed after 12 hours fasting.Results: After diet I and diet II, weight decreased significantly (%1.82 and %2.45, respectively. Liver enzymes and echogenicity decreased significantly by both diet I and diet II. Mean of triglyceride concentration decreased (%18.09 after diet II (P=0.023, while there was no significant change after diet I. Significant correlations were found between changes in aspartate aminotransferase with triglyceride and LDL-C diet I.Conclusion: Low energy diets can decrease liver enzymes regardless of their composition, while diet II seems to be more effective than diet I in reduction of weight and triglyceride level.

  13. Global Epidemiology of Non-Alcoholic Fatty Liver Disease and Perspectives on US Minority Populations

    Science.gov (United States)

    Sherif, Zaki A.; Saeed, Armana; Ghavimi, Shima; Nouraie, Seyed-Mehdi; Laiyemo, Adeyinka O.; Brim, Hassan; Ashktorab, Hassan

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD), a clinical syndrome that is predicted to affect millions of people worldwide, will become the next global epidemic. The natural course of this disease, including its subtype, non-alcoholic steatohepatitis (NASH), is not clearly defined, especially in the US minority populations. The aim of this review is to report the global epidemiology of NAFLD, with emphasis on US minority populations on the basis of database searches using using Pubmed and other online databases. The US Hispanic population is the most disproportionately affected ethnic group with hepatic steatosis whereas African-Americans are the least affected. Genetic disparities involved in lipid metabolism seem to be the leading explanation for the lowest incidence and prevalence of both NAFLD and NASH in African-Americans. PMID:27038448

  14. Roles of abnormal lipid metabolism in pathogenesis of non-alcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    LU Ran

    2015-07-01

    Full Text Available The prevalence of non-alcoholic fatty liver disease (NAFLD keeps rising worldwide along with the increasing prevalence of metabolic diseases such as obesity, type 2 diabetes, and dyslipidemia. Although most NAFLD patients present with simple steatosis of hepatocytes, some patients progress to non-alcoholic steatohepatitis, liver cirrhosis, and even cancer. In the Western world, NAFLD is the most common cause of elevated liver enzymes, and hence there has been a growing interest in this disease. Given that fat deposition in the liver is the hallmark of NAFLD, we review the roles and the underlying mechanism of disturbed lipid metabolism in the development of NAFLD and suggest that more insights into the pathogenesis of NAFLD will help develop targeted strategies for the prevention and treatment of this disease.

  15. Translational Aspects of Diet and Non-Alcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Nicolas Goossens

    2017-09-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD is a spectrum of diseases ranging from simple steatosis without inflammation or fibrosis to nonalcoholic steatohepatitis (NASH. Despite the strong association between dietary factors and NAFLD, no dietary animal model of NAFLD fully recapitulates the complex metabolic and histological phenotype of the disease, although recent models show promise. Although animal models have significantly contributed to our understanding of human diseases, they have been less successful in accurate translation to predict effective treatment strategies. We discuss strategies to overcome this challenge, in particular the adoption of big data approaches combining clinical phenotype, genomic heterogeneity, transcriptomics, and metabolomics changes to identify the ideal NAFLD animal model for a given scientific question or to test a given drug. We conclude by noting that novel big data approaches may help to bridge the translational gap for selecting dietary models of NAFLD.

  16. Research progress in association between nonalcoholic fatty liver disease and gallstone disease

    Directory of Open Access Journals (Sweden)

    HUANG Ying

    2014-11-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD and gallstone disease (GD are considered the manifestations of metabolic syndrome in the liver and gallbladder. NAFLD and GD are closely related to insulin resistance (IR, obesity, dyslipidemia, abnormal glucose metabolism, and so on. Worldwide studies, which have been reviewed, show that both NAFLD and GD have the common risk factors, such as IR, obesity, dyslipidemia, abnormal glucose metabolism, and middle-aged and elderly women. NAFLD is the risk factor for GD. GD, closely related to nonalcoholic steatohepatitis and liver fibrosis, accelerates the progression of NAFLD. Thus, it is considered that the prevention and treatment of NAFLD can reduce the incidence of GD, and the progression of NAFLD can be delayed by the prevention and treatment of GD.

  17. The Role of Intestinal Bacteria Overgrowth in Obesity-Related Nonalcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Silvia M. Ferolla

    2014-12-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD is the most common chronic liver disease worldwide. It is a progressive disorder involving a spectrum of conditions that include pure steatosis without inflammation, nonalcoholic steatohepatitis (NASH, fibrosis and cirrhosis. The key factor in the pathophysiology of NAFLD is insulin resistance that determines lipid accumulation in the hepatocytes, which may be followed by lipid peroxidation, production of reactive oxygen species and consequent inflammation. Recent studies suggest that the characteristics of the gut microbiota are altered in NAFLD, and also, that small intestinal bacterial overgrowth (SIBO contributes to the pathogenesis of this condition. This review presents the chief findings from all the controlled studies that evaluated SIBO, gut permeability and endotoxemia in human NAFLD. We also discuss the possible mechanisms involving SIBO, lipid accumulation and development of NASH. The understanding of these mechanisms may allow the development of new targets for NASH treatment in the future.

  18. Plasma fibrinogen-like protein 2 levels in patients with non-alcoholic fatty liver disease.

    Science.gov (United States)

    Colak, Yasar; Senates, Ebubekir; Ozturk, Oguzhan; Yilmaz, Yusuf; Coskunpinar, Ender; Kahraman, Ozlem Timirci; Sahin, Onder; Zemheri, Ebru; Enc, Feruze Yilmaz; Ulasoglu, Celal; Kiziltas, Safak; Kurdas, Oya Ovunc; Tuncer, Ilyas

    2011-01-01

    Fibrinogen-like protein 2 (fgl2), has recently been identified as a new member of the fibrinogen-like family of proteins. In this study we assayed plasma levels of fgl2 in patients with biopsy proven non-alcoholic fatty liver disease (NAFLD) and examined their association with clinical, biochemical and histological phenotypes. Levels of plasma fgl2 were measured by enzyme linked immunosorbent assay and compared between the study groups. Moreover, concentrations of fgl2 were assessed in relation to the general characteristics of the study participants and the results of the liver biopsy. Levels of fgl2 were significantly higher in patients with definite non-alcoholic steatohepatitis (NASH) (788±190pg/mL, psubject to future confirmation, our data suggest that fgl2 levels are elevated in the more severe forms of NAFLD.

  19. Non-Alcoholic Fatty Liver Disease: The Emerging Burden in Cardiometabolic and Renal Diseases

    Directory of Open Access Journals (Sweden)

    Eugene Han

    2017-11-01

    Full Text Available As the number of individuals with non-alcoholic fatty liver disease (NAFLD has increased, the influence of NAFLD on other metabolic diseases has been highlighted. Accumulating epidemiologic evidence indicates that NAFLD not only affects the liver but also increases the risk of extra-hepatic diseases such as type 2 diabetes mellitus, metabolic syndrome, dyslipidemia, hypertension, cardiovascular or cerebrovascular diseases, and chronic kidney disease. Non-alcoholic steatohepatitis, an advanced type of NAFLD, can aggravate these inter-organ relationships and lead to poorer outcomes. NAFLD induces insulin resistance and exacerbates systemic chronic inflammation and oxidative stress, which leads to organ dysfunction in extra-hepatic tissues. Although more research is needed to identify the pathophysiological mechanisms and causal relationship between NAFLD and cardiometabolic and renal diseases, screening for heart, brain, and kidney diseases, risk assessment for diabetes, and a multidisciplinary approach for managing these patients should be highly encouraged.

  20. C-reactive protein levels in relation to various features of non-alcoholic fatty liver disease among obese patients

    DEFF Research Database (Denmark)

    Zimmermann, Esther; Anty, Rodolphe; Tordjman, Joan

    2011-01-01

    Non-alcoholic fatty liver disease (NAFLD) is a major hepatic consequence of obesity. It has been suggested that the high sensitivity C-reactive protein (hs-CRP) is an obesity-independent surrogate marker of severity of NAFLD, especially development of non-alcoholic steato-hepatitis (NASH......), but this remains controversial. We aimed to investigate whether associations between various features of NAFLD and hs-CRP are independent of body mass index (BMI) in its broad range among obese patients....

  1. Non-Alcoholic Fatty Liver Disease in Children: Focus on Nutritional Interventions

    Directory of Open Access Journals (Sweden)

    Min Yang

    2014-10-01

    Full Text Available With increasing prevalence of childhood obesity, non-alcoholic fatty liver disease (NAFLD has emerged as the most common cause of liver disease among children and adolescents in industrialized countries. It is generally recognized that both genetic and environmental risk factors contribute to the pathogenesis of NAFLD. Recently, there has been a growing body of evidence to implicate altered gut microbiota in the development of NAFLD through the gut-liver axis. The first line of prevention and treatment of NAFLD in children should be intensive lifestyle interventions such as changes in diet and physical activity. Recent advances have been focused on limitation of dietary fructose and supplementation of antioxidants, omega-3 fatty acids, and prebiotics/probiotics. Convincing evidences from both animal models and human studies have shown that reduction of dietary fructose and supplement of vitamin E, omega-3 fatty acids, and prebiotics/probiotics improve NAFLD.

  2. Practice guidelines for the diagnosis and management of nonalcoholic fatty liver disease. A decalogue from the Italian Association for the Study of the Liver (AISF) Expert Committee.

    Science.gov (United States)

    Loria, P; Adinolfi, L E; Bellentani, S; Bugianesi, E; Grieco, A; Fargion, S; Gasbarrini, A; Loguercio, C; Lonardo, A; Marchesini, G; Marra, F; Persico, M; Prati, D; Baroni, G Svegliati-

    2010-04-01

    We report the evidence-based Italian Association for the Study of Liver guidelines for the appropriate diagnosis and management of patients with nonalcoholic fatty liver disease in clinical practice and its related research agenda. The prevalence of nonalcoholic fatty liver disease varies according to age, gender and ethnicity. In the general population, the prevalence of nonalcoholic fatty liver disease is about 25% and the incidence is of two new cases/100 people/year. 2-3% of individuals in the general population will suffer from nonalcoholic steatohepatitis. Uncomplicated steatosis will usually follow a benign course. Individuals with nonalcoholic steatohepatitis, however, have a reduced life expectancy, mainly owing to vascular diseases and liver-related causes. Moreover, steatosis has deleterious effects on the natural history of HCV infection. Nonalcoholic fatty liver disease is usually diagnosed in asymptomatic patients prompted by the occasional discovery of increased liver enzymes and/or of ultrasonographic steatosis. Medical history, complete physical examination, etiologic screening of liver injury, liver biochemistry tests, serum lipids and insulin sensitivity tests should be performed in every patient. Occult alcohol abuse should be ruled out. Ultrasonography is the first-line imaging technique. Liver biopsy, the gold standard in diagnosis and prognosis of nonalcoholic fatty liver disease, is an invasive procedure and its results will not influence treatment in most cases but will provide prognostic information. Assessment of fibrosis by composite scores, specific laboratory parameters and transient elastography might reduce the number of nonalcoholic fatty liver disease patients requiring liver biopsy. Dieting and physical training reinforced by behavioural therapy are associated with improved nonalcoholic fatty liver disease. Diabetes and the metabolic syndrome should be ruled out at timed intervals in nonalcoholic fatty liver disease. Nonalcoholic

  3. Polyphenol-Rich Fraction of Ecklonia cava Improves Nonalcoholic Fatty Liver Disease in High Fat Diet-Fed Mice

    Directory of Open Access Journals (Sweden)

    Eun-Young Park

    2015-11-01

    Full Text Available Ecklonia cava (E. cava; CA is an edible brown alga with beneficial effects in diabetes via regulation of various metabolic processes such as lipogenesis, lipolysis, inflammation, and the antioxidant defense system in liver and adipose tissue. We investigated the effect of the polyphenol-rich fraction of E. cava produced from Gijang (G-CA on nonalcoholic fatty liver disease (NAFLD in high-fat diet (HFD-fed mice. C57BL6 mice were fed a HFD for six weeks and then the HFD group was administered 300 mg/kg of G-CA extracts by oral intubation for 10 weeks. Body weight, fat mass, and serum biochemical parameters were reduced by G-CA extract treatment. MRI/MRS analysis showed that liver fat and liver volume in HFD-induced obese mice were reduced by G-CA extract treatment. Further, we analyzed hepatic gene expression related to inflammation and lipid metabolism. The mRNA expression levels of inflammatory cytokines and hepatic lipogenesis-related genes were decreased in G-CA-treated HFD mice. The mRNA expression levels of cholesterol 7 alpha-hydroxylase 1 (CYP7A1, the key enzyme in bile acid synthesis, were dramatically increased by G-CA treatment in HFD mice. We suggest that G-CA treatment ameliorated hepatic steatosis by inhibiting inflammation and improving lipid metabolism.

  4. Comparative Study on the Effect of Plantago psyllium and Ocimum basilicum Seeds on Anthropometric Measures in Nonalcoholic Fatty Liver Patients

    OpenAIRE

    Akbarian, Shahab-Aldin; Asgary, Sedigheh; Feizi, Awat; Iraj, Bijan; Askari, Gholamreza

    2016-01-01

    Background: Due to the attribution of fatty liver with some chronic diseases such as obesity, finding a way to control obesity can be useful for the management of fatty liver. This study was performed to assess the effects of Plantago psyllium (PP) and Ocimum basilicum (OB) on anthropometric measurements in people with hepatic steatosis. Methods: All patients with nonalcoholic fatty liver disease (NAFLD) were enrolled in this four-arm parallel, randomized, and single blind trial. They ran...

  5. Knowing What's Out There: Awareness of Non-Alcoholic Fatty Liver Disease.

    Science.gov (United States)

    Ghevariya, Vishal; Sandar, Nan; Patel, Kishor; Ghevariya, Nehal; Shah, Ruchit; Aron, Joshua; Anand, Sury

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) is the most common hepatic disorder, which poses a significant health burden in the western countries. As the epidemic of obesity slides health downward, the incidence of NAFLD is evidently increasing. We aimed to ascertain the awareness of NAFLD and its risk factors in the general population, which may be helpful in designing educational tools to promote prevention, early detection, and treatment of this disorder. A survey of 5000 non-institutionalized residents of Brooklyn, NY, USA was conducted. Sixteen items were included in the survey questionnaire including awareness of fatty liver, predisposing factors of NAFLD, awareness of cirrhosis, and conditions that advance to cirrhosis. The questionnaire also addressed awareness of prevention, diagnostic methods and treatment of NAFLD, and education of physicians to their patients about NAFLD. Overwhelming majority of the subjects was not aware of NAFLD and stated that their physicians did not have a discussion about NAFLD. Non-alcoholic fatty liver disease is a preventable liver disorder with limited treatment options. Thorough counseling by primary care physicians can be of paramount importance in preventive strategy for NAFLD. We should target our teenage population in an era of obesity epidemics of all times.

  6. Practical approaches to the nutritional management of nonalcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    Leila Freidoony

    2014-12-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD is the hepatic manifestation of metabolic syndrome and a serious health burden worldwide which increases risk of cirrhosis, type 2 diabetes mellitus (T2DM, and cardiovascular complications. Current epidemics of obesity, unhealthy dietary patterns, and sedentary lifestyles, all contribute to the high prevalence of NAFLD. Dietary patterns and nutrients are important contributors to the development, progression, and treatment of NAFLD. A healthy diet is beneficial for all NAFLD patients beyond weight reduction. Generally, hypercaloric diets, especially rich in trans/saturated fat and cholesterol, high consumption of red and processed meat, and fructose-sweetened beverages seem to increase the risk of progression toward nonalcoholic steatohepatitis (NASH, whereas reducing caloric intake and high-glycemic index (GI foods, increasing consumption of monounsaturated fatty acids, omega-3 fatty acids, fibers, and specific protein sources such as fish and poultry have preventive and therapeutic effects. Therefore, nutrition serves as a major route of prevention and treatment of NAFLD, and patients with NAFLD should have an individualized diet recommendation. In this review, the evidence linking macronutrients to NAFLD are discussed.

  7. The Role of Tumor Necrosis Factor- alpha and Resistin in Nonalcoholic Fatty Liver Disease

    International Nuclear Information System (INIS)

    Alkady, M.M.

    2011-01-01

    Nonalcoholic fatty liver disease (NAFLD) represents one of the most common liver diseases. It is strongly associated with obesity and insulin resistance and is thought to be a part of the metabolic syndrome. It can progress from simple fatty liver to steatohepatitis, cirrhosis and liver failure. Adipocytokines, synthesized in adipose tissue, are involved in the pathophysiology of many acute and chronic liver diseases. The aim of this study was to investigate the role of Tumor Necrosis Factor-alpha (TNF-alpha) and resistin in the pathogenesis of NAFLD and their correlation to the severity of the disease. Serum concentration of TNF-alpha and resistin were measured in 20 patients with NAFLD and 20 healthy controls with ELISA method. The results of this study revealed that serum levels of both adipokines were significantly elevated in NAFLD patients than controls (P<0.01). Moreover, they were significantly higher in patients with nonalcoholic steatohepatitis than in patients with simple fatty liver. There was a significant positive correlation between TNF-alpha, resistin and each of AST, ALT and HOMA. Similarly, the results showed a significant positive correlation between the two studied adipokines, TNF-alpha and resistin (P<0.001). We conclude that TNF-alpha and resistin have a role in the pathogenesis of NAFLD and they may be promising markers for the progressin to steatohepatitis and inhibition of their activities by drugs may be a new approach for the treatment of NAFLD

  8. Neutrophil depletion improves diet-induced non-alcoholic fatty liver disease in mice.

    Science.gov (United States)

    Ou, Rongying; Liu, Jia; Lv, Mingfen; Wang, Jingying; Wang, Jinmeng; Zhu, Li; Zhao, Liang; Xu, Yunsheng

    2017-07-01

    Non-alcoholic fatty liver disease is highly associated with morbidity and mortality in population. Although studies have already demonstrated that the immune response plays a pivotal role in the development of non-alcoholic fatty liver disease, the comprehensive regulation is unclear. Therefore, present study was carried out to investigate the non-alcoholic fatty liver disease development under neutrophil depletion. To achieve the aim of the study, C57BL/6 J mice were fed with high fat diet for 6 weeks before treated with neutrophil deplete antibody 1A8 or isotype control (200 μg/ mouse every week) for another 4 weeks. Treated with 1A8 antibody, obese mice exhibited better whole body metabolic parameters, including reduction of body weight gain and fasting blood glucose levels. Neutrophil depletion also effectively reduced hepatic structural disorders, dysfunction and lipid accumulation. Lipid β-oxidative markers, phosphorylated-AMP-activated protein kinase α and phosphorylated-acetyl-CoA carboxylase levels were increased in 1A8 antibody-treated obese mouse group. The mitochondrial number and function were also reversed after 1A8 antibody treatment, including increased mitochondrial number, reduced lipid oxidative damage and enhanced mitochondrial activity. Furthermore, the expression of inflammatory cytokines, tumor necrosis factor-α, interleukin-6, and monocyte chemoattractant protein-1 were obviously reduced after neutrophil depletion, accompanied with decreased F4/80 mRNA level and macrophage percentage in liver. The decreased NF-κB signaling activity was also involved in the beneficial effect of neutrophil depletion. Taken together, neutrophil depletion could attenuate metabolic syndromes and hepatic dysfunction.

  9. Multicausality in fatty liver disease: is there a rationale to distinguish between alcoholic and non-alcoholic origin?

    Science.gov (United States)

    Völzke, Henry

    2012-07-21

    Apart from alcohol, there are other factors that may induce complications, which resemble alcohol-related liver disorders. In particular, obesity has been brought into focus as a risk factor for fatty liver disease. The term "non-alcoholic" fatty liver disease is commonly used to distinguish between obesity-related and alcohol-related hepatic steatosis. This review uses the epidemiological perspective to critically assess whether it is necessary and useful to differentiate between alcoholic and "non-alcoholic" fatty liver disease. The MEDLINE database was searched using the PubMed search engine, and a review of reference lists from original research and review articles was conducted. The concept to distinguish between alcoholic and "non-alcoholic" fatty liver disease is mainly based on specific pathomechanisms. This concept has, however, several limitations including the common overlap between alcohol misuse and obesity-related metabolic disorders and the non-consideration of additional causal factors. Both entities share similar histopathological patterns. Studies demonstrating differences in clinical presentation and outcome are often biased by selection. Risk factor reduction is the main principle of prevention and treatment of both disease forms. In conclusion, alcoholic and "non-alcoholic" fatty liver diseases are one and the same disease caused by different risk factors. A shift from artificial categories to a more general approach to fatty liver disease as a multicausal disorder may optimize preventive strategies and help clinicians more effectively treat patients at the individual level.

  10. The Association between Non-Alcoholic Fatty Liver Disease and Cardiovascular Risk in Children

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    Anna Di Sessa

    2017-07-01

    Full Text Available The rising prevalence of childhood obesity in the past decades has made Non-Alcoholic Fatty Liver Disease (NAFLD the most common cause of pediatric chronic liver disease worldwide. Currently, a growing body of evidence links NAFLD with cardiovascular disease (CVD even at an early age. Data on the pediatric population have shown that NAFLD could represent an independent risk factor not only for cardiovascular events but also for early subclinical abnormalities in myocardial structure and function. Briefly, we review the current knowledge regarding the relationship between pediatric NAFLD and cardiovascular risk in an attempt to clarify our understanding of NAFLD as a possible cardiovascular risk factor in childhood.

  11. Omic studies reveal the pathogenic lipid droplet proteins in non-alcoholic fatty liver disease

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    Xuelin Zhang

    2016-10-01

    Full Text Available Abstract Non-alcoholic fatty liver disease (NAFLD is an epidemic metabolic condition driven by an underlying lipid homeostasis disorder. The lipid droplet (LD, the main organelle involved in neutral lipid storage and hydrolysis, is a potential target for NAFLD therapeutic treatment. In this review, we summarize recent progress elucidating the connections between LD-associated proteins and NAFLD found by genome-wide association studies (GWAS, genomic and proteomic studies. Finally, we discuss a possible mechanism by which the protein 17β-hydroxysteroid dehydrogenase 13 (17β-HSD13 may promote the development of NAFLD.

  12. Nonalcoholic fatty liver disease: A comprehensive review of a growing epidemic

    Science.gov (United States)

    Hassan, Kareem; Bhalla, Varun; Ezz El Regal, Mohammed; A-Kader, H Hesham

    2014-01-01

    Nonalcoholic fatty liver disease (NAFLD) is quickly becoming one of the most prominent causes of liver disease worldwide. The increasing incidence of NAFLD is tied to the obesity epidemic and the subsequent metabolic derangements brought along with it. Current efforts to elucidate the mechanism and causes of the disease have answered some questions, but much remains unknown about NAFLD. The aim of this article is to discuss the current knowledge regarding the pathogenesis of the disease, as well as the current and future diagnostic, preventative, and therapeutic options available to clinicians for the management of NAFLD. PMID:25232245

  13. Bioinformatics-Driven Identification and Examination of Candidate Genes for Non-Alcoholic Fatty Liver Disease

    DEFF Research Database (Denmark)

    Banasik, Karina; Justesen, Johanne M.; Hornbak, Malene

    2011-01-01

    Objective: Candidate genes for non-alcoholic fatty liver disease (NAFLD) identified by a bioinformatics approach were examined for variant associations to quantitative traits of NAFLD-related phenotypes. Research Design and Methods: By integrating public database text mining, trans-organism protein......-protein interaction transferal, and information on liver protein expression a protein-protein interaction network was constructed and from this a smaller isolated interactome was identified. Five genes from this interactome were selected for genetic analysis. Twenty-one tag single-nucleotide polymorphisms (SNPs...

  14. Improved hepatic lipid composition following short-term exercise in nonalcoholic fatty liver disease

    DEFF Research Database (Denmark)

    Haus, Jacob M; Solomon, Thomas; Kelly, Karen R

    2013-01-01

    Hepatic steatosis, insulin resistance, inflammation, low levels of polyunsaturated lipids, and adiponectin are implicated in the development and progression of nonalcoholic fatty liver disease (NAFLD). Objective: We examined the effects of short-term aerobic exercise on these metabolic risk factors...... measures included hepatic triglyceride content, and a lipid saturation index and polyunsaturated lipid index (PUI) of the liver, obtained by 1H magnetic resonance spectroscopy (N = 14). Insulin sensitivity was estimated from an oral glucose tolerance test (OGTT), and mononuclear cells were isolated...... resulted in an increase in liver PUI (P

  15. Action of mechanism of traditional Chinese medicine in prevention and treatment of nonalcoholic fatty liver disease

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    HOU Yixin

    2016-04-01

    Full Text Available In recent years, extensive studies have been conducted on the pathogenesis of nonalcoholic fatty liver disease (NAFLD, and the action of mechanism of traditional Chinese medicine (TCM in NAFLD has become a new research topic. TCM has achieved good clinical efficacy in the treatment of NAFLD, with the advantages of specific, flexible, multilevel, and multi-target treatment. This article introduces the role of TCM in improving insulin, regulating lipid metabolism, preventing lipid peroxidation, regulating cytokines, regulating and maintaining the dynamic balance of factors involved in lipid metabolism, and maintaining the balance of intestinal microflora, and analyzes the major problems in TCM research.

  16. Cordyceps militaris alleviates non-alcoholic fatty liver disease in ob/ob mice

    OpenAIRE

    Choi, Ha-Neul; Jang, Yang-Hee; Kim, Min-Joo; Seo, Min Jeong; Kang, Byoung Won; Jeong, Yong Kee; Kim, Jung-In

    2014-01-01

    BACKGROUND/OBJECTIVES Non-alcoholic fatty liver disease (NAFLD) is becoming an important public health problem as metabolic syndrome and type 2 diabetes have become epidemic. In this study we investigated the protective effect of Cordyceps militaris (C. militaris) against NAFLD in an obese mouse model. MATERIALS/METHODS Four-week-old male ob/ob mice were fed an AIN-93G diet or a diet containing 1% C. militaris water extract for 10 weeks after 1 week of adaptation. Serum glucose, insulin, free...

  17. Psychological and psychiatric aspects of treatment of obesity and nonalcoholic fatty liver disease.

    Science.gov (United States)

    Stewart, Karen E; Levenson, James L

    2012-08-01

    Chronic illnesses incur a tremendous cost to American lives in dollars and quality of life. Outcomes in these illnesses are often affected by psychological, behavioral, and pharmacologic issues related to mental illness and psychological symptoms. This article focuses on psychological and psychiatric issues related to the treatment of obesity and nonalcoholic fatty liver disease (NAFLD), including available weight-loss interventions, the complex relationship between psychiatric disorders and obesity, and special considerations regarding use of psychiatric drugs in patients with or at risk for NAFLD and obesity. Recommendations for collaborative care of individuals with comorbid NAFLD and psychological disorders/symptoms are discussed. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. An Animal Model for the Juvenile Non-Alcoholic Fatty Liver Disease and Non-Alcoholic Steatohepatitis.

    Science.gov (United States)

    Marin, Veronica; Rosso, Natalia; Dal Ben, Matteo; Raseni, Alan; Boschelle, Manuela; Degrassi, Cristina; Nemeckova, Ivana; Nachtigal, Petr; Avellini, Claudio; Tiribelli, Claudio; Gazzin, Silvia

    2016-01-01

    Non Alcoholic Fatty Liver Disease (NAFLD) and Non-Alcoholic Steatohepatitis (NASH) are the hepatic manifestations of the metabolic syndrome; worrisome is the booming increase in pediatric age. To recreate the full spectrum of juvenile liver pathology and investigate the gender impact, male and female C57Bl/6 mice were fed with high fat diet plus fructose in the drinking water (HFHC) immediately after weaning (equal to 3-years old human), and disease progression followed for 16 weeks, until adults (equal to 30-years old human). 100% of subjects of both genders on HFHC diet developed steatosis in 4weeks, and some degree of fibrosis in 8weeks, with the 86% of males and 15% of females presenting a stage 2 fibrosis at 16weeks. Despite a similar final liver damage both groups, a sex difference in the pathology progression was observed. Alterations in glucose homeostasis, dyslipidemia, hepatomegaly and obese phenotype were evident from the very beginning in males with an increased hepatic inflammatory activity. Conversely, such alterations were present in females only at the end of the HFHC diet (with the exception of insulin resistance and the hepatic inflammatory state). Interestingly, only females showed an altered hepatic redox state. This juvenile model appears a good platform to unravel the underlying gender dependent mechanisms in the progression from NAFLD to NASH, and to characterize novel therapeutic approaches.

  19. Non-alcoholic fatty liver disease and obesity: biochemical, metabolic and clinical presentations.

    Science.gov (United States)

    Milić, Sandra; Lulić, Davorka; Štimac, Davor

    2014-07-28

    Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the world. Presentation of the disease ranges from simple steatosis to non-alcoholic steatohepatitis (NASH). NAFLD is a hepatic manifestation of metabolic syndrome that includes central abdominal obesity along with other components. Up to 80% of patients with NAFLD are obese, defined as a body mass index (BMI) > 30 kg/m(2). However, the distribution of fat tissue plays a greater role in insulin resistance than the BMI. The large amount of visceral adipose tissue (VAT) in morbidly obese (BMI > 40 kg/m(2)) individuals contributes to a high prevalence of NAFLD. Free fatty acids derived from VAT tissue, as well as from dietary sources and de novo lipogenesis, are released to the portal venous system. Excess free fatty acids and chronic low-grade inflammation from VAT are considered to be two of the most important factors contributing to liver injury progression in NAFLD. In addition, secretion of adipokines from VAT as well as lipid accumulation in the liver further promotes inflammation through nuclear factor kappa B signaling pathways, which are also activated by free fatty acids, and contribute to insulin resistance. Most NAFLD patients are asymptomatic on clinical presentation, even though some may present with fatigue, dyspepsia, dull pain in the liver and hepatosplenomegaly. Treatment for NAFLD and NASH involves weight reduction through lifestyle modifications, anti-obesity medication and bariatric surgery. This article reviews the available information on the biochemical and metabolic phenotypes associated with obesity and fatty liver disease. The relative contribution of visceral and liver fat to insulin resistance is discussed, and recommendations for clinical evaluation of affected individuals is provided.

  20. Evaluation of Risk Factors of Nonalcoholic Fatty Liver Disease in the Adult Population of Zahedan, Iran

    Directory of Open Access Journals (Sweden)

    Alireza Ansari-Moghaddam

    2014-08-01

    Full Text Available Background: Non-alcoholic fatty liver disease (NAFLD is the most common form of chronic liver disease. It has been reported that visceral fat releases free fatty acids and arises fat accumulation in the liver. Therefore, this study aimed to evaluate the some biomarkers of NAFLD risk in adult general population. Materials and Methods: An analytical - descriptive study was carried out on a total of 1529 randomly selected individuals (797 male and 732 female aged 30–88 years in Zahedan. The characteristics of socio-demographic, medical history, food habits and lifestyle factors were obtained by a validated questionnaire, liver ultrasonography and routine laboratory tests were performed with the use of standard techniques. The assessment of waist circumference (WC and waist to hip ratio (WHR was performed as central obesity indices. Results: The mean levels of WC and WHR were 92±11.7 cm and 0.91±0.06 in men, and 91.2±12.4 cm and 0.88±0.07 in women, respectively. 39.7% and 37% of subjects had hypercholesterolemia and hypertriglyceridemia, respectively. Ultrasonography findings demonstrated diffuse fatty liver in 40.9% subjects. Data also showed low consumption of fruits and vegetables and fish, and high consumption of saturated fatty acids (SFAs and fast foods in the majority of obesity and NAFLD subjects compared with normal subjects. Conclusion: The results showed that a large proportion of the study population is at risk of central obesity and NAFLD. The formation of non-alcoholic fatty liver may be associated with obesity and unhealthy dietary patterns which warrants further research.

  1. CORRECTION OF MICROCIRCULATORY DISORDERS IN NON-ALCOHOLIC FATTY LIVER DISEASE IN PATIENTS WITH CHRONIC HEART FAILURE PATIENTS

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    M. E. Statsenko

    2016-01-01

    Full Text Available Combined liver damage in patients with chronic heart failure and non-alcoholic fatty liver disease leads to the formation of pathological hemodynamic types of microcirculation with prevalence of shunt blood flow, nutritional deficiency, that correlated with changes in the functional state of the liver. Using cytoprotector mexicor for 16 weeks as part of the basic treatment of patients with chronic heart failure and non-alcoholic fatty liver disease can correct these microcirculatory disorders, has a beneficial effect on endothelial function, autonomic tone of microvessels, which is accompanied by the positive dynamics of indicators of cytolysis and cholestasis.

  2. Bariatric surgery and nonalcoholic fatty liver disease: current and potential future treatments

    Directory of Open Access Journals (Sweden)

    Akira eSasaki

    2014-10-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD and nonalcoholic steatohepatitis (NASH are increasingly common cause of chronic liver disease worldwide. The diagnosis of NASH is challenging as most affected patients are symptom-free and the role of routine screening is not clearly established. Most patients with severe obesity who undergo bariatric surgery have NAFLD, which is associated insulin resistance, type 2 diabetes mellitus (T2DM, hypertension, and obesity-related dyslipidemia. The effective treatment for NAFLD is weight reduction through lifestyle modifications, antiobesity medication, or bariatric surgery. Among these treatments, bariatric surgery is the most reliable method for achieving substantial, sustained weight loss. This procedure is safe when performed by a skilled surgeon, and the benefits include reduced weight, improved quality of life, decreased obesity-related comorbidities, and increased life expectancy. Further research is urgently needed to determine the best use of bariatric surgery with NAFLD patients at high risk of developing liver cirrhosis and its role in modulating complications of NAFLD, such as T2DM and cardiovascular disease. The current evidence suggests that bariatric surgery for patients with severe obesity decreases the grade of steatosis, hepatic inflammation, and fibrosis. However, further long-term studies are required to confirm the true effects before recommending bariatric surgery as a potential treatment for nonalcoholic steatohepatitis.

  3. Fatty acid composition in serum correlates with that in the liver and non-alcoholic fatty liver disease activity scores in mice fed a high-fat diet.

    Science.gov (United States)

    Wang, Xing-He; Li, Chun-Yan; Muhammad, Ishfaq; Zhang, Xiu-Ying

    2016-06-01

    In this study, we investigated the correlation between the serum fatty acid composition and hepatic steatosis, inflammation, hepatocellular ballooning scores, and liver fatty acids composition in mice fed a high-fat diet. Livers were collected for non-alcoholic fatty liver disease score analysis. Fatty acid compositions were analysed by gas chromatography. Correlations were determined by Pearson correlation coefficient. Exposed to a high-fat diet, mice developed fatty liver disease with varying severity without fibrosis. The serum fatty acid variation became more severe with prolonged exposure to a high-fat diet. This variation also correlated significantly with the variation in livers, with the types of fatty acids corresponding to liver steatosis, inflammation, and hepatocellular ballooning scores. Results of this study lead to the following hypothesis: the extent of serum fatty acid variation may be a preliminary biomarker of fatty liver disease caused by high-fat intake. Copyright © 2016. Published by Elsevier B.V.

  4. Relationship between hepatocellular carcinoma, metabolic syndrome and non-alcoholic fatty liver disease: which clinical arguments?

    Science.gov (United States)

    Rosmorduc, Olivier

    2013-05-01

    Obesity and the metabolic syndrome are growing epidemics associated with an increased risk for many types of cancer. In the liver, inflammatory and angiogenic changes due to insulin resistance and fatty liver disease are associated with an increased incidence of liver cancer. Regardless of underlying liver disease, cirrhosis remains the most important risk factor for hepatocellular carcinoma (HCC) although are cases of HCC arising without cirrhosis raise the possibility of a direct carcinogenesis secondary to Non-alcoholic Fatty Liver Disease (NAFLD). Moreover, metabolic syndrome and its different features may also increase the risk of HCC in the setting of chronic liver diseases of other causes such as viral hepatitis or alcohol abuse. Taking into account all these data, it is necessary to better determine the risk of developing HCC in patients with metabolic syndrome to improve the screening guidelines and develop prophylactic treatments in this setting. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  5. Activation of CDK4 Triggers Development of Non-alcoholic Fatty Liver Disease

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    Jingling Jin

    2016-07-01

    Full Text Available The development of non-alcoholic fatty liver disease (NAFLD is a multiple step process. Here, we show that activation of cdk4 triggers the development of NAFLD. We found that cdk4 protein levels are elevated in mouse models of NAFLD and in patients with fatty livers. This increase leads to C/EBPα phosphorylation on Ser193 and formation of C/EBPα-p300 complexes, resulting in hepatic steatosis, fibrosis, and hepatocellular carcinoma (HCC. The disruption of this pathway in cdk4-resistant C/EBPα-S193A mice dramatically reduces development of high-fat diet (HFD-mediated NAFLD. In addition, inhibition of cdk4 by flavopiridol or PD-0332991 significantly reduces development of hepatic steatosis, the first step of NAFLD. Thus, this study reveals that activation of cdk4 triggers NAFLD and that inhibitors of cdk4 may be used for the prevention/treatment of NAFLD.

  6. Non-alcoholic fatty liver disease: the role of nuclear receptors and circadian rhythmicity.

    Science.gov (United States)

    Mazzoccoli, Gianluigi; Vinciguerra, Manlio; Oben, Jude; Tarquini, Roberto; De Cosmo, Salvatore

    2014-09-01

    Non-alcoholic fatty liver disease (NAFLD) is the accumulation of triglycerides in the hepatocytes in the absence of excess alcohol intake, and is caused by an imbalance between hepatic synthesis and breakdown of fats, as well as fatty acid storage and disposal. Liver metabolic pathways are driven by circadian biological clocks, and hepatic health is maintained by proper timing of circadian patterns of metabolic gene expression with the alternation of anabolic processes corresponding to feeding/activity during wake times, and catabolic processes characterizing fasting/resting during sleep. A number of nuclear receptors in the liver are expressed rhythmically, bind hormones and metabolites, sense energy flux and expenditure, and connect the metabolic pathways to the molecular clockwork throughout the 24-h day. In this review, we describe the role played by the nuclear receptors in the genesis of NAFLD in relationship with the circadian clock circuitry. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Mechanisms of hepatic triglyceride accumulation in non-alcoholic fatty liver disease.

    Science.gov (United States)

    Kawano, Yuki; Cohen, David E

    2013-04-01

    Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic lipid accumulation in the absence of excess alcohol intake. NAFLD is the most common chronic liver disease, and ongoing research efforts are focused on understanding the underlying pathobiology of hepatic steatosis with the anticipation that these efforts will identify novel therapeutic targets. Under physiological conditions, the low steady-state triglyceride concentrations in the liver are attributable to a precise balance between acquisition by uptake of non-esterified fatty acids from the plasma and by de novo lipogenesis, versus triglyceride disposal by fatty acid oxidation and by the secretion of triglyceride-rich lipoproteins. In NAFLD patients, insulin resistance leads to hepatic steatosis by multiple mechanisms. Greater uptake rates of plasma non-esterified fatty acids are attributable to increased release from an expanded mass of adipose tissue as a consequence of diminished insulin responsiveness. Hyperinsulinemia promotes the transcriptional upregulation of genes that promote de novo lipogenesis in the liver. Increased hepatic lipid accumulation is not offset by fatty acid oxidation or by increased secretion rates of triglyceride-rich lipoproteins. This review discusses the molecular mechanisms by which hepatic triglyceride homeostasis is achieved under normal conditions, as well as the metabolic alterations that occur in the setting of insulin resistance and contribute to the pathogenesis of NAFLD.

  8. Effectiveness of exercise in hepatic fat mobilization in non-alcoholic fatty liver disease: Systematic review.

    Science.gov (United States)

    Golabi, Pegah; Locklear, Cameron T; Austin, Patrick; Afdhal, Sophie; Byrns, Melinda; Gerber, Lynn; Younossi, Zobair M

    2016-07-21

    To investigate the efficacy of exercise interventions on hepatic fat mobilization in non-alcoholic fatty liver disease (NAFLD) patients. Ovid-Medline, PubMed, EMBASE and Cochrane database were searched for randomized trials and prospective cohort studies in adults aged ≥ 18 which investigated the effects of at least 8 wk of exercise only or combination with diet on NAFLD from 2010 to 2016. The search terms used to identify articles, in which exercise was clearly described by type, duration, intensity and frequency were: "NASH", "NAFLD", "non-alcoholic steatohepatitis", "non-alcoholic fatty liver disease", "fat", "steatosis", "diet", "exercise", "MR spectroscopy" and "liver biopsy". NAFLD diagnosis, as well as the outcome measures, was confirmed by either hydrogen-magnetic resonance spectroscopy (H-MRS) or biopsy. Trials that included dietary interventions along with exercise were accepted if they met all criteria. Eight studies met selection criteria (6 with exercise only, 2 with diet and exercise with a total of 433 adult participants). Training interventions ranged between 8 and 48 wk in duration with a prescribed exercise frequency of 3 to 7 d per week, at intensities between 45% and 75% of VO2 peak. The most commonly used imaging modality was H-MRS and one study utilized biopsy. The effect of intervention on fat mobilization was 30.2% in the exercise only group and 49.8% in diet and exercise group. There was no difference between aerobic and resistance exercise intervention, although only one study compared the two interventions. The beneficial effects of exercise on intrahepatic triglyceride (IHTG) were seen even in the absence of significant weight loss. Although combining an exercise program with dietary interventions augmented the reduction in IHTG, as well as improved measures of glucose control and/or insulin sensitivity, exercise only significantly decreased hepatic lipid contents. Prescribed exercise in subjects with NAFLD reduces IHTG independent of

  9. Nonalcoholic fatty liver disease induced by noncanonical Wnt and its rescue by Wnt3a

    Science.gov (United States)

    Wang, Shuxia; Song, Kangxing; Srivastava, Roshni; Dong, Chao; Go, Gwang-Woong; Li, Na; Iwakiri, Yasuko; Mani, Arya

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease, which begins with isolated steatosis and advances to nonalcoholic steatohepatitis (NASH), steatofibrosis, and cirrhosis. The pathways involved in disease progression are not understood. Loss-of-function mutations in Wnt coreceptor LDL receptor-related protein 6 (LRP6) underlie early-onset atherosclerosis, metabolic risk factors, and NAFLD in humans by unknown mechanisms. We generated mice with the human disease-associated LRP6R611C mutation and phenotypically characterized their liver. Homozygote LRP6R611C (LRP6mut/mut) mice exhibited both steatohepatitis and steatofibrosis. These traits were associated with increased activity of the noncanonical Wnt/Ras homolog family member A, Rho-associated protein kinase 2, and PKC-α/-μ pathways. Accordingly, there was increased TGF-β1 activity, coupled with enhanced expression of smooth muscle α-actin and vimentin that colocalized with albumin in LRP6mut/mut mouse liver. LRP6 knockdown reprogramed HepG2 cells to express both these markers, linking impaired Wnt signaling with hepatocyte transdifferentiation. The causal link between altered Wnt signaling and NASH was established by normalization of the disease pathways and rescue of the liver traits by Wnt3a administration to LRP6mut/mut mice. Thus, this study identifies diverse disease pathways that underlie a spectrum of NASH-related liver diseases and are linked by a single human genetic variant. LRP6 and noncanonical Wnt pathways are important potential therapeutic targets against NASH.—Wang, S., Song, K., Srivastava, R., Dong, C., Go, G.-W., Li, N., Iwakiri, Y., Mani, A. Nonalcoholic fatty liver disease induced by noncanonical Wnt and its rescue by Wnt3a. PMID:25917329

  10. Bile Acids and Dysbiosis in Non-Alcoholic Fatty Liver Disease.

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    Marialena Mouzaki

    Full Text Available Non-alcoholic fatty liver disease (NAFLD is characterized by dysbiosis. The bidirectional effects between intestinal microbiota (IM and bile acids (BA suggest that dysbiosis may be accompanied by an altered bile acid (BA homeostasis, which in turn can contribute to the metabolic dysregulation seen in NAFLD. This study sought to examine BA homeostasis in patients with NAFLD and to relate that with IM data.This was a prospective, cross-sectional study of adults with biopsy-confirmed NAFLD (non-alcoholic fatty liver: NAFL or non-alcoholic steatohepatitis: NASH and healthy controls (HC. Clinical and laboratory data, stool samples and 7-day food records were collected. Fecal BA profiles, serum markers of BA synthesis 7-alpha-hydroxy-4-cholesten-3-one (C4 and intestinal BA signalling, as well as IM composition were assessed.53 subjects were included: 25 HC, 12 NAFL and 16 NASH. Levels of total fecal BA, cholic acid (CA, chenodeoxycholic acid (CDCA and BA synthesis were higher in patients with NASH compared to HC (p<0.05 for all comparisons. The primary to secondary BA ratio was higher in NASH compared to HC (p = 0.004, but ratio of conjugated to unconjugated BAs was not different between the groups. Bacteroidetes and Clostridium leptum counts were decreased in in a subset of 16 patients with NASH compared to 25 HC, after adjusting for body mass index and weight-adjusted calorie intake (p = 0.028 and p = 0.030, respectively. C. leptum was positively correlated with fecal unconjugated lithocholic acid (LCA (r = 0.526, p = 0.003 and inversely with unconjugated CA (r = -0.669, p<0.0001 and unconjugated CDCA (r = - 0.630, p<0.0001. FGF19 levels were not different between the groups (p = 0.114.In adults with NAFLD, dysbiosis is associated with altered BA homeostasis, which renders them at increased risk of hepatic injury.

  11. Relevant Aspects of Nutritional and Dietary Interventions in Non-Alcoholic Fatty Liver Disease

    Science.gov (United States)

    Hernandez-Rodas, Maria Catalina; Valenzuela, Rodrigo; Videla, Luis A.

    2015-01-01

    Non-alcoholic fatty liver disease (NAFLD) is the main cause of liver disease worldwide. NAFLD is linked to circumstances such as type 2 diabetes, insulin resistance, obesity, hyperlipidemia, and hypertension. Since the obesity figures and related comorbidities are increasing, NAFLD has turned into a liver problem that has become progressively more common. Currently, there is no effective drug therapy for NAFLD; therefore, interventions in lifestyles remain the first line of treatment. Bearing in mind that adherence rates to this type of treatment are poor, great efforts are currently focused on finding novel therapeutic agents for the prevention in the development of hepatic steatosis and its progression to nonalcoholic steatohepatitis and cirrhosis. This review presents a compilation of the scientific evidence found in the last years showing the results of interventions in lifestyle, diet, and behavioral therapies and research results in human, animal and cell models. Possible therapeutic agents ranging from supplementation with vitamins, amino acids, prebiotics, probiotics, symbiotics, polyunsaturated fatty acids and polyphenols to interventions with medicinal plants are analyzed. PMID:26512643

  12. Focus on emerging drugs for the treatment of patients with non-alcoholic fatty liver disease

    Science.gov (United States)

    Federico, Alessandro; Zulli, Claudio; de Sio, Ilario; Del Prete, Anna; Dallio, Marcello; Masarone, Mario; Loguercio, Carmela

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) has become the most common liver disorder in Western countries and is increasingly being recognized in developing nations. Fatty liver disease encompasses a spectrum of hepatic pathology, ranging from simple steatosis to non-alcoholic steatohepatitis, cirrhosis, hepatocellular carcinoma and end-stage liver disease. Moreover, NAFLD is often associated with other metabolic conditions, such as diabetes mellitus type 2, dyslipidemia and visceral obesity. The most recent guidelines suggest the management and treatment of patients with NAFLD considering both the liver disease and the associated metabolic co-morbidities. Diet and physical exercise are considered the first line of treatment for patients with NAFLD, but their results on therapeutic efficacy are often contrasting. Behavior therapy is necessary most of the time to achieve a sufficient result. Pharmacological therapy includes a wide variety of classes of molecules with different therapeutic targets and, often, little evidence supporting the real efficacy. Despite the abundance of clinical trials, NAFLD therapy remains a challenge for the scientific community, and there are no licensed therapies for NAFLD. Urgently, new pharmacological approaches are needed. Here, we will focus on the challenges facing actual therapeutic strategies and the most recent investigated molecules. PMID:25492998

  13. Schisandrin B: A Double-Edged Sword in Nonalcoholic Fatty Liver Disease

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    Pou Kuan Leong

    2016-01-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD is a spectrum of liver lesions ranging from hepatic steatosis, nonalcoholic steatohepatitis, hepatic cirrhosis, and hepatocellular carcinoma. The high global prevalence of NAFLD has underlined the important public health implications of this disease. The pathogenesis of NAFLD involves the abnormal accumulation of free fatty acids, oxidative stress, endoplasmic reticulum (ER stress, and a proinflammatory state in the liver. Schisandrin B (Sch B, an active dibenzooctadiene lignan isolated from the fruit of Schisandra chinensis (a traditional Chinese herb, was found to possess antihyperlipidemic, antioxidant, anti-ER stress, and anti-inflammatory activities in cultured hepatocytes in vitro and in rodent livers in vivo. Whereas a long-term, low dose regimen of Sch B induces an antihyperlipidemic response in obese mice fed a high fat diet, a single bolus high dose of Sch B increases serum/hepatic lipid levels in mice. This differential action of Sch B is likely related to a dose/time-dependent biphasic response on lipid metabolism in mice. The hepatoprotection afforded by Sch B against oxidative stress, ER stress, and inflammation has been widely reported. The ensemble of results suggests that Sch B may offer potential as a therapeutic agent for NAFLD. The optimal dose and duration of Sch B treatment need to be established in order to ensure maximal efficacy and safety when used in humans.

  14. Increased Nitroxidative Stress Promotes Mitochondrial Dysfunction in Alcoholic and Nonalcoholic Fatty Liver Disease

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    Byoung-Joon Song

    2013-01-01

    Full Text Available Increased nitroxidative stress causes mitochondrial dysfunctions through oxidative modifications of mitochondrial DNA, lipids, and proteins. Persistent mitochondrial dysfunction sensitizes the target cells/organs to other pathological risk factors and thus ultimately contributes to the development of more severe disease states in alcoholic and nonalcoholic fatty liver disease. The incidences of nonalcoholic fatty liver disease continuously increase due to high prevalence of metabolic syndrome including hyperlipidemia, hypercholesterolemia, obesity, insulin resistance, and diabetes. Many mitochondrial proteins including the enzymes involved in fat oxidation and energy supply could be oxidatively modified (including S-nitrosylation/nitration under increased nitroxidative stress and thus inactivated, leading to increased fat accumulation and ATP depletion. To demonstrate the underlying mechanism(s of mitochondrial dysfunction, we employed a redox proteomics approach using biotin-N-maleimide (biotin-NM as a sensitive biotin-switch probe to identify oxidized Cys residues of mitochondrial proteins in the experimental models of alcoholic and acute liver disease. The aims of this paper are to briefly describe the mechanisms, functional consequences, and detection methods of mitochondrial dysfunction. We also describe advantages and limitations of the Cys-targeted redox proteomics method with alternative approaches. Finally, we discuss various applications of this method in studying oxidatively modified mitochondrial proteins in extrahepatic tissues or different subcellular organelles and translational research.

  15. Soft Drinks Consumption and the Risk of Nonalcoholic Fatty Liver Disease.

    Science.gov (United States)

    Siddiqi, Zeba; Karoli, Ritu; Fatima, Jalees; Khanduri, Sachin; Varshneya, Shishir; Ahmad, Sara Sabina

    2017-05-01

    The increased consumption of sugar-sweetened beverages (SSBs) has been implicated in the increased incidence of obesity and metabolic syndrome Little of the research on sugar-sweetened beverage intake has examined the consumption patterns of sugared beverages by college students, despite the vulnerabilities of this population to weight gain. The current study sought to characterize sugar-sweetened beverage intake of undergraduate students who belong to high socio-economic strata and to study its correlation with presence of non-alcoholic fatty liver disease. In a cross sectional, a self reported questionnaire based study about soft drink consumption (≥2/day, 1/day, drink consumption had positive correlation with presence of NAFLD. Substantial consumption of soft drinks is leading to increased obesity and cardio-metabolic risk factors in young adults. Artificially sweetened diet soft drinks have been posed as a healthier alternative due to their lack of calories but they do not guarantee protection against non-alcoholic fatty liver disease.

  16. Non-alcoholic fatty liver disease: What the clinician needs to know

    Science.gov (United States)

    Machado, Mariana Verdelho; Cortez-Pinto, Helena

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) is the most frequent cause of liver disease in the Western world. Furthermore, it is increasing worldwide, paralleling the obesity pandemic. Though highly frequent, only about one fifth of affected subjects are at risk of developing the progressive form of the disease, non-alcoholic steatohepatitis with fibrosis. Even in the latter, liver disease is slowly progressive, though, since it is so prevalent, it is already the third cause of liver transplantation in the United States, and it is predicted to get to the top of the ranking in few years. Of relevance, fatty liver is also associated with increased overall mortality and particularly increased cardiovascular mortality. The literature and amount of published papers on NAFLD is increasing as fast as its prevalence, which makes it difficult to keep updated in this topic. This review aims to summarize the latest knowledge on NAFLD, in order to help clinicians understanding its pathogenesis and advances on diagnosis and treatment. PMID:25278691

  17. Andrographolide Ameliorates Inflammation and Fibrogenesis and Attenuates Inflammasome Activation in Experimental Non-Alcoholic Steatohepatitis

    NARCIS (Netherlands)

    Cabrera, Daniel; Wree, Alexander; Povero, Davide; Solís, Nancy; Hernandez, Alejandra; Pizarro, Margarita; Moshage, Han; Torres, Javiera; Feldstein, Ariel E; Cabello-Verrugio, Claudio; Brandan, Enrique; Barrera, Francisco; Arab, Juan Pablo; Arrese, Marco

    2017-01-01

    Therapy for nonalcoholic steatohepatitis (NASH) is limited. Andrographolide (ANDRO), a botanical compound, has a potent anti-inflammatory activity due to its ability to inhibit NF-kB. ANDRO has been also shown to inhibit the NLRP3 inflammasome, a relevant pathway in NASH. Our aim was to evaluate the

  18. Serum adipokines might predict liver histology findings in non-alcoholic fatty liver disease.

    Science.gov (United States)

    Jamali, Raika; Razavizade, Mohsen; Arj, Abbas; Aarabi, Mohammad Hossein

    2016-06-07

    To assess significance of serum adipokines to determine the histological severity of non-alcoholic fatty liver disease. Patients with persistent elevation in serum aminotransferase levels and well-defined characteristics of fatty liver at ultrasound were enrolled. Individuals with a history of alcohol consumption, hepatotoxic medication, viral hepatitis or known liver disease were excluded. Liver biopsy was performed to confirm non-alcoholic liver disease (NAFLD). The degrees of liver steatosis, lobular inflammation and fibrosis were determined based on the non-alcoholic fatty liver activity score (NAS) by a single expert pathologist. Patients with a NAS of five or higher were considered to have steatohepatitis. Those with a NAS of two or lower were defined as simple fatty liver. Binary logistic regression was used to determine the independent association of adipokines with histological findings. Receiver operating characteristic (ROC) analysis was employed to determine cut-off values of serum adipokines to discriminate the grades of liver steatosis, lobular inflammation and fibrosis. Fifty-four participants aged 37.02 ± 9.82 were enrolled in the study. Higher serum levels of visfatin, IL-8, TNF-α levels were associated independently with steatosis grade of more than 33% [β = 1.08 (95%CI: 1.03-1.14), 1.04 (95%CI: 1.008-1.07), 1.04 (95%CI: 1.004-1.08), P < 0.05]. Elevated serum IL-6 and IL-8 levels were associated independently with advanced lobular inflammation [β = 1.4 (95%CI: 1.09-1.8), 1.07 (95%CI: 1.003-1.15), P < 0.05]. Similarly, higher TNF-α, resistin, and hepcidin levels were associated independently with advanced fibrosis stage [β = 1.06 (95%CI: 1.002-1.12), 19.86 (95%CI: 2.79-141.19), 560.72 (95%CI: 5.98-5255.33), P < 0.05]. Serum IL-8 and TNF-α values were associated independently with the NAS score, considering a NAS score of 5 as the reference value [β = 1.05 (95%CI: 1.01-1.1), 1.13 (95%CI: 1.04-1.22), P < 0.05]. Certain adipokines may

  19. Higher free triiodothyronine is associated with non-alcoholic fatty liver disease in euthyroid subjects : The Lifelines Cohort Study

    NARCIS (Netherlands)

    van den Berg, Eline H.; van Tienhoven-Wind, Lynnda J. N.; Amini, Marzyeh; Schreuder, Tim C.M.A.; Faber, Klaas Nico; Blokzijl, Hans; Dullaart, Robin P. F.

    Objective. Overt hypothyroidism confers an increased risk of non-alcoholic fatty liver disease (NAFLD). The liver plays a crucial role in the metabolism of cholesterol and triglycerides; thyroid hormones interact on hepatic lipid homeostasis. Thyroid function within the euthyroid range affects a

  20. Increased hepatic CD36 expression with age is associated with enhanced susceptibility to nonalcoholic fatty liver disease

    NARCIS (Netherlands)

    Sheedfar, Fareeba; Sung, Miranda My; Aparicio-Vergara, Marcela; Kloosterhuis, Niels J; Miquilena-Colina, Maria Eugenia; Vargas-Castrillón, Javier; Febbraio, Maria; Jacobs, René L; de Bruin, Alain|info:eu-repo/dai/nl/304837261; Vinciguerra, Manlio; García-Monzón, Carmelo; Hofker, Marten H; Dyck, Jason Rb; Koonen, Debby P Y

    CD36 has been associated with obesity and diabetes in human liver diseases, however, its role in age-associated nonalcoholic fatty liver disease (NAFLD) is unknown. Therefore, liver biopsies were collected from individuals with histologically normal livers (n=30), and from patients diagnosed with

  1. The hepatic response to FGF19 is impaired in patients with nonalcoholic fatty liver disease and insulin resistance

    NARCIS (Netherlands)

    Schreuder, Tim C. M. A.; Marsman, Hendrik A.; Lenicek, Martin; van Werven, Jochem R.; Nederveen, Aart J.; Jansen, Peter L. M.; Schaap, Frank G.

    2010-01-01

    Schreuder TC, Marsman HA, Lenicek M, van Werven JR, Nederveen AJ, Jansen PL, Schaap FG. The hepatic response to FGF19 is impaired in patients with nonalcoholic fatty liver disease and insulin resistance. Am J Physiol Gastrointest Liver Physiol 298: G440-G445, 2010. First published January 21, 2010;

  2. Intensive lifestyle treatment for non-alcoholic fatty liver disease in children with severe obesity: inpatient versus ambulatory treatment

    NARCIS (Netherlands)

    Koot, B. G. P.; van der Baan-Slootweg, O. H.; Vinke, S.; Bohte, A. E.; Tamminga-Smeulders, C. L. J.; Jansen, P. L. M.; Stoker, J.; Benninga, M. A.

    2016-01-01

    Lifestyle intervention is the only established therapy for non-alcoholic fatty liver disease (NAFLD). The optimal treatment schedule and predictors of response of this treatment have not been established in children. We aimed to evaluate the 2-year efficacy of an inpatient versus ambulatory

  3. SREBP-2 1784 G/C Genotype is Associated with Non-Alcoholic Fatty Liver Disease in North Indians

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    Surya Prakash Bhatt

    2011-01-01

    Full Text Available Background: Genetics of non-alcoholic fatty liver (NAFLD in Asian Indians has been inadequately investigated. This study aims to determine the association of the 1784G > C polymorphism in the SREBP-2 gene with NAFLD in Asian Indians in north India.

  4. Lifestyle intervention for non-alcoholic fatty liver disease: prospective cohort study of its efficacy and factors related to improvement

    NARCIS (Netherlands)

    Koot, B.G.P.; van der Baan-Slootweg, O.H.; Tamminga-Smeulders, C.L.J.; Pels Rijcken, T.H.; Korevaar, J.C.; van Aalderen, W.M.; Jansen, P.L.M.; Benninga, M.A.

    2011-01-01

    Background Non-alcoholic fatty liver disease (NAFLD) has a high prevalence in obese children. Lifestyle intervention is the primary treatment for NAFLD. However, limited data are available regarding the efficacy of lifestyle interventions. Objectives To prospectively determine the efficacy of a

  5. Lifestyle intervention for non-alcoholic fatty liver disease: prospective cohort study of its efficacy and factors related to improvement.

    NARCIS (Netherlands)

    Koot, B.G.P.; Baan-Slootweg, O.H. van der; Tamminga-Smeulders, C.L.J.; Pels Rijcken, T.H.; Korevaar, J.C.; Aalderen, W.M. van; Jansen, P.L.M.; Benninga, M.A.

    2011-01-01

    BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has a high prevalence in obese children. Lifestyle intervention is the primary treatment for NAFLD. However, limited data are available regarding the efficacy of lifestyle interventions. OBJECTIVES: To prospectively determine the efficacy of a

  6. Prediction of non-alcoholic fatty-liver disease and liver fat content by serum molecular lipids

    DEFF Research Database (Denmark)

    Orešic, Matej; Hyötyläinen, Tuulia; Kotronen, Anna

    2013-01-01

    We examined whether analysis of lipids by ultra-performance liquid chromatography (UPLC) coupled to MS allows the development of a laboratory test for non-alcoholic fatty-liver disease (NAFLD), and how a lipid-profile biomarker compares with the prediction of NAFLD and liver-fat content based...

  7. Genome-wide association analysis identifies variants associated with nonalcoholic fatty liver disease that have distinct effects on metabolic traits

    DEFF Research Database (Denmark)

    Speliotes, Elizabeth K; Yerges-Armstrong, Laura M; Wu, Jun

    2011-01-01

    Nonalcoholic fatty liver disease (NAFLD) clusters in families, but the only known common genetic variants influencing risk are near PNPLA3. We sought to identify additional genetic variants influencing NAFLD using genome-wide association (GWA) analysis of computed tomography (CT) measured hepatic...

  8. High prevalence of apolipoprotein B dyslipoproteinemias in non-alcoholic fatty liver disease : The lifelines cohort study

    NARCIS (Netherlands)

    Nass, Karlijn J.; van den Berg, Eline H.; Faber, Klaas Nico; Schreuder, Tim C.M.A.; Blokzijl, Hans; Dullaart, Robin P. F.

    Objective. Cardiovascular disease (CVD) is a major adverse consequence of non-alcoholic fatty liver disease (NAFLD). The association of NAFLD with various apolipoprotein B (apoB) dyslipoproteinemias is unclear. We determined the prevalence of specific apoB dyslipoproteinemias in subjects with

  9. Free triiodothyronine as determinant of non-alcoholic fatty liver disease in euthyroid subjects: The lifelines cohort study

    NARCIS (Netherlands)

    Van Den Berg, Eline; van Tienhoven-Wind, Lynnda; Amini, Marzyeh; Schreuder, Tim C.M.A.; Faber, Klaas Nico; Blokzijl, H.; Dullaart, Robin P.F.

    2016-01-01

    Background: Non-alcoholic fatty live disease (NAFLD) is becoming the leading cause of chronic liver disease in de Western world. The liver plays a crucial role in the metabolism of cholesterol and triglycerides and thyroid hormones interact on hepatic lipid homeostasis. Given the importance of

  10. A nonalcoholic fatty liver disease cirrhosis model in gerbil : the dynamic relationship between hepatic lipid metabolism and cirrhosis

    NARCIS (Netherlands)

    Li, Wei; Guan, Zheng; Brisset, Jean C.; Shi, Qiaojuan; Lou, Qi; Ma, Yue; Suriguga, Su; Ying, Huazhong; Sa, Xiaoying; Chen, Zhenwen; Quax, Wim J.; Chu, Xiaofeng

    2018-01-01

    Nonalcoholic fatty liver disease (NAFLD) usually takes decades to develop into cirrhosis, which limits the longitudinal study of NAFLD. This work aims at developing a NAFLD-caused cirrhosis model in gerbil and examining the dynamic relationship between hepatic lipid metabolism and cirrhosis. We fed

  11. The Burden of Systemic Adiposity on Pancreatic Disease: Acute Pancreatitis, Non-Alcoholic Fatty Pancreas Disease, and Pancreatic Cancer.

    Science.gov (United States)

    Malli, Ahmad; Li, Feng; Conwell, Darwin L; Cruz-Monserrate, Zobeida; Hussan, Hisham; Krishna, Somashekar G

    2017-01-01

    Obesity is a global epidemic as recognized by the World Health Organization. Obesity and its related comorbid conditions were recognized to have an important role in a multitude of acute, chronic, and critical illnesses including acute pancreatitis, nonalcoholic fatty pancreas disease, and pancreatic cancer. This review summarizes the impact of adiposity on a spectrum of pancreatic diseases.

  12. Omega-3 fatty acids and non-alcoholic fatty liver disease: Evidence of efficacy and mechanism of action.

    Science.gov (United States)

    Scorletti, Eleonora; Byrne, Christopher D

    2018-03-22

    For many years it has been known that high doses of long chain omega-3 fatty acids are beneficial in the treatment of hypertriglyceridaemia. Over the last three decades, there has also been a wealth of in vitro and in vivo data that has accumulated to suggest that long chain omega-3 fatty acid treatment might be beneficial to decrease liver triacylglycerol. Several biological mechanisms have been identified that support this hypothesis; notably, it has been shown that long chain omega-3 fatty acids have a beneficial effect: a) on bioactive metabolites involved in inflammatory pathways, and b) on alteration of nuclear transcription factor activities such as peroxisome proliferator-activated receptors (PPARs), sterol regulatory element-binding protein 1c (SREBP-1c) and carbohydrate-responsive element-binding protein (ChREBP), involved in inflammatory pathways and liver lipid metabolism. Since the pathogenesis of non alcoholic fatty liver disease (NAFLD) begins with the accumulation of liver lipid and progresses with inflammation and then several years later with development of fibrosis; it has been thought in patients with NAFLD omega-3 fatty acid treatment would be beneficial in treating liver lipid and possibly also in ameliorating inflammation. Meta-analyses (of predominantly dietary studies and small trials) have tended to support the assertion that omega-3 fatty acids are beneficial in decreasing liver lipid, but recent randomised controlled trials have produced conflicting data. These trials have suggested that omega-3 fatty acid might be beneficial in decreasing liver triglyceride (docosahexanoic acid also possibly being more effective than eicosapentanoic acid) but not in decreasing other features of steatohepatitis (or liver fibrosis). The purpose of this review is to discuss recent evidence regarding biological mechanisms by which long chain omega-3 fatty acids might act to ameliorate liver disease in NAFLD; to consider the recent evidence from randomised

  13. Hepatoprotective Effect of Herb Formula KIOM2012H against Nonalcoholic Fatty Liver Disease

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    Hwayong Park

    2015-04-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD is a hepatic ailment with a rapidly increasing incidence due to dietary hypernutrition and subsequent obesity. Fatty liver disease can lead to steatohepatitis, fibrosis, cirrhosis, and even cancer, which is associated with various complications. Discovering effective natural materials and herbs can provide alternative and complementary medical treatments to current chemical pharmaceuticals. To develop an effective natural agent for NAFLD, we formulated a combination of four herb mixtures (KIOM2012H and observed lipid-lowering efficacy. The inhibitory effects of KIOM2012H on free fatty acid-induced lipid accumulation, triglyceride contents, and gene expressions were analyzed in HepG2 cells. Using high fat diet-fed mice, body weight changes, gross liver appearances, hepatic triglyceride contents, and gene expressions were evaluated. KIOM2012H dose-dependently inhibited lipid accumulation and gene expressions involved in lipogenesis and related regulators. Experimental animals also showed a decrease in body weight changes and lipid-associated physiological parameters. This study shows that KIOM2012H has an alleviating effect on fatty acid and lipid accumulation, and therefore can be applied for development of new therapeutic pharmaceuticals for treatment of NAFLD using natural products and herbs.

  14. Fatty Acid Elongation in Non-Alcoholic Steatohepatitis and Hepatocellular Carcinoma

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    Sonja M. Kessler

    2014-04-01

    Full Text Available Non-alcoholic steatohepatitis (NASH represents a risk factor for the development of hepatocellular carcinoma (HCC and is characterized by quantitative and qualitative changes in hepatic lipids. Since elongation of fatty acids from C16 to C18 has recently been reported to promote both hepatic lipid accumulation and inflammation we aimed to investigate whether a frequently used mouse NASH model reflects this clinically relevant feature and whether C16 to C18 elongation can be observed in HCC development. Feeding mice a methionine and choline deficient diet to model NASH not only increased total hepatic fatty acids and cholesterol, but also distinctly elevated the C18/C16 ratio, which was not changed in a model of simple steatosis (ob/ob mice. Depletion of Kupffer cells abrogated both quantitative and qualitative methionine-and-choline deficient (MCD-induced alterations in hepatic lipids. Interestingly, mimicking inflammatory events in early hepatocarcinogenesis by diethylnitrosamine-induced carcinogenesis (48 h increased hepatic lipids and the C18/C16 ratio. Analyses of human liver samples from patients with NASH or NASH-related HCC showed an elevated expression of the elongase ELOVL6, which is responsible for the elongation of C16 fatty acids. Taken together, our findings suggest a detrimental role of an altered fatty acid pattern in the progression of NASH-related liver disease.

  15. Mediterranean diet and non-alcoholic fatty liver disease: the need of extended and comprehensive interventions.

    Science.gov (United States)

    Trovato, Francesca M; Catalano, Daniela; Martines, G Fabio; Pace, Patrizia; Trovato, Guglielmo M

    2015-02-01

    Non-alcoholic fatty liver disease (NAFLD) is mostly related to increased BMI and sedentary life, even if it not directly attributable only to these or to single specific factors. Unhealthy lifestyle and obesity are the most probable causes, also in non-diabetic and without alcohol abuse patients, even if lean individuals can be involved. NAFLD treatment is currently warranted and driven by comprehensive lifestyle intervention, a valuable objective that is more often wished for than actually achieved. The aim is to re-assess the effectiveness of an intervention focused to increase the Adherence to Mediterranean Diet Score (AMDS) and the level of physical exercise, investigating the factors associated with failure and reporting the time that must elapse before such intervention becomes effective. The study included 90 (F 46, M 44) non-alcoholic non-diabetic patients, aged 50.13 ± 13.68 years, BMI 31.01 ± 5.18 with evidence of fatty liver by ultrasound. A significant decrease of Bright Liver Score (BLS) was observed only after 6 months of intervention: differently, at the first and third month of monitoring fatty liver changes were still not significant. By a multiple linear regression model Adherence to Mediterranean Diet change (p:0.015) and body mass index changes (p:Diet is a significant predictor of changes in the fat content of the liver in overweight patients with NAFLD. The effect of the diet is gradual and favorable and it is independent of other lifestyle changes. Copyright © 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  16. Liver mitochondrial dysfunction and oxidative stress in the pathogenesis of experimental nonalcoholic fatty liver disease

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    Oliveira C.P.M.S.

    2006-01-01

    Full Text Available Oxidative stress and hepatic mitochondria play a role in the pathogenesis of nonalcoholic fatty liver disease. The aim of the present study was to evaluate the role of hepatic mitochondrial dysfunction and oxidative stress in the pathogenesis of the disease. Fatty liver was induced in Wistar rats with a choline-deficient diet (CD; N = 7 or a high-fat diet enriched with PUFAs-omega-3 (H; N = 7 for 4 weeks. The control group (N = 7 was fed a standard diet. Liver mitochondrial oxidation and phosphorylation were measured polarographically and oxidative stress was estimated on the basis of malondialdehyde and glutathione concentrations. Moderate macrovacuolar liver steatosis was observed in the CD group and mild liver steatosis was observed in the periportal area in the H group. There was an increase in the oxygen consumption rate by liver mitochondria in respiratory state 4 (S4 and a decrease in respiratory control rate (RCR in the CD group (S4: 32.70 ± 3.35; RCR: 2.55 ± 0.15 ng atoms of O2 min-1 mg protein-1 when compared to the H and control groups (S4: 23.09 ± 1.53, 17.04 ± 2.03, RCR: 3.15 ± 0.15, 3.68 ± 0.15 ng atoms of O2 min-1 mg protein-1, respectively, P < 0.05. Hepatic lipoperoxide concentrations were significantly increased and the concentration of reduced glutathione was significantly reduced in the CD group. A choline-deficient diet causes moderate steatosis with disruption of liver mitochondrial function and increased oxidative stress. These data suggest that lipid peroxidation products can impair the flow of electrons along the respiratory chain, causing overreduction of respiratory chain components and enhanced mitochondrial reactive oxygen species. These findings are important in the pathogenesis of nonalcoholic fatty liver disease.

  17. The State of Pancreatobiliary System and Intestinal Microflora in Children with Nonalcoholic Fatty Liver Disease

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    N.Yu. Zavgorodnya

    2016-11-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD combines with a variety of liver pathologies, including hepatic steatosis, nonalcoholic steatohepatitis, fibrosis and cirrhosis, and acts as hepatic manifestation of metabolic syndrome. Not only the liver is a target organ in the formation of metabolic syndrome: also exist a possibility of gallbladder, pancreas and biliary tract steatosis. Fatty infiltration of the pancreatobiliary system associates with disturbance of digestive processes that promotes dysbiotic changes and intestinal disorders. Changes in intestinal microbiota, in turn, may induce systemic inflammatory response and promote NAFLD development and progression. Objective: to explore the structural and functional state of the pancreatobiliary system and changes of the enteric microflora in children with NAFLD. Methods. In 34 children with disorders of the gastrointestinal tract, we have determined controlled attenuation parameter by means of FibroScan. Assessment of functional status of biliary tract was performed using an ultrasound examination of the abdominal organs with test meal in order to determine gallbladder contractility and the sphincter of Oddi function. To characterize the state of the enteric microbiota, there was carried out a hydrogen breath test with glucose or lactose loading. Children were divided into groups according to the the transient elastography of the liver (FibroScan: the control group was represented by 21 patients without liver steatosis, the main group — 13 patients with liver steatosis. Results. Children with nonalcoholic fatty liver disease had signs of not only liver pathology, but also of the bile ducts and the pancreas. Biliary tract dysfunction in patients with NAFLD more often manifested as hypotension of the sphincter of Oddi and the gallbladder hypokinesia. Lesions of the pancreas function in children with NAFLD can be explained by the sphincter of Oddi disorders and manifestations of pancreatic

  18. L-carnitine ameliorated fatty liver in high-calorie diet/STZ-induced type 2 diabetic mice by improving mitochondrial function

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    Xia Yunqiu

    2011-11-01

    Full Text Available Abstract Background There are an increasing number of patients suffering from fatty liver caused by type 2 diabetes. We intended to study the preventive and therapeutic effect of L-carnitine (LC on nonalcoholic fatty liver disease (NAFLD in streptozotocin (STZ-induced type 2 diabetic mice and to explore its possible mechanism. Methods Thirty male Kungming mice were randomly divided into five groups: control group, diabetic group, pre-treatment group (125 mg/kg BW, low-dose (125 mg/kg BW therapeutic group and high-dose (250 mg/kg BW therapeutic group. The morphology of hepatocytes was observed by light and electron microscopy. LC and ALC (acetyl L-carnitine concentrations in the liver were determined by high-performance liquid chromatography (HPLC. Moreover, liver weight, insulin levels and free fatty acid (FFA and triglyceride (TG levels in the liver and plasma were measured. Results Average liver LC and ALC levels were 33.7% and 20% lower, respectively, in diabetic mice compared to control mice (P Conclusion LC supplements ameliorated fatty liver in type 2 diabetic mice by increasing fatty acid oxidation and decreasing the LC/ALC ratio in the liver. Therefore, oral administration of LC protected mitochondrial function in liver.

  19. Tim-3/galectin-9 regulate the homeostasis of hepatic NKT cells in a murine model of nonalcoholic fatty liver disease.

    Science.gov (United States)

    Tang, Zhao-Hui; Liang, Shuwen; Potter, James; Jiang, Xuan; Mao, Hai-Quan; Li, Zhiping

    2013-02-15

    T cell Ig and mucin domain (Tim)-3 is well known to interact with its natural ligand, Galectin-9 (Gal-9), to regulate T cell function. However, little is known about the function of Tim-3/Gal-9 signaling in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) mediated by hepatic NKT cells that also express Tim-3. In the current study, we define the role and the mechanism of Tim-3/Gal-9 signaling in hepatic NKT cell regulation in a mouse model of diet-induced NAFLD. Adult male wild-type or CD1d knockout C57BL/6 mice were fed a high-fat diet to induce steatosis. Some of the mice also received one or a combination of Gal-9, anti-IL-15R/IL-15 mAb, rIL-15, α-galactosylceramide, and multilamellar liposomes containing Cl(2)MDP. The expression of Tim-3 and various markers reflecting cell proliferation, activation, cytokine production, and apoptosis was analyzed. Liver histology, steatosis grade, and hepatic triglyceride content were also evaluated. In the liver, Tim-3(+) NKT cells are in an activated state, and Gal-9 directly induces Tim-3(+) NKT cell apoptosis and contributes to the depletion of NKT cells in diet-induced steatosis. However, Gal-9 also interacts with Tim-3-expressing Kupffer cells to induce secretion of IL-15, thus promoting NKT cell proliferation. Exogenous administration of Gal-9 significantly ameliorates diet-induced steatosis by modulating hepatic NKT cell function. In summary, the Tim-3/Gal-9-signaling pathway plays a critical role in the homeostasis of hepatic NKT cells through activation-induced apoptosis and secondary proliferation and, thus, contributes to the pathogenesis of NAFLD.

  20. Tim-3/Galectin-9 Regulate the Homeostasis of Hepatic NKT Cells in a Murine Model of Nonalcoholic Fatty Liver Disease

    Science.gov (United States)

    Liang, Shuwen; Potter, James; Jiang, Xuan; Mao, Hai-Quan

    2013-01-01

    T cell Ig and mucin domain (Tim)-3 is well known to interact with its natural ligand, Galectin-9 (Gal-9), to regulate T cell function. However, little is known about the function of Tim-3/Gal-9 signaling in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) mediated by hepatic NKT cells that also express Tim-3. In the current study, we define the role and the mechanism of Tim-3/Gal-9 signaling in hepatic NKT cell regulation in a mouse model of diet-induced NAFLD. Adult male wild-type or CD1d knockout C57BL/6 mice were fed a high-fat diet to induce steatosis. Some of the mice also received one or a combination of Gal-9, anti–IL-15R/IL-15 mAb, rIL-15, α-galactosylceramide, and multilamellar liposomes containing Cl2MDP. The expression of Tim-3 and various markers reflecting cell proliferation, activation, cytokine production, and apoptosis was analyzed. Liver histology, steatosis grade, and hepatic triglyceride content were also evaluated. In the liver, Tim-3+ NKT cells are in an activated state, and Gal-9 directly induces Tim-3+ NKT cell apoptosis and contributes to the depletion of NKT cells in diet-induced steatosis. However, Gal-9 also interacts with Tim-3–expressing Kupffer cells to induce secretion of IL-15, thus promoting NKT cell proliferation. Exogenous administration of Gal-9 significantly ameliorates diet-induced steatosis by modulating hepatic NKT cell function. In summary, the Tim-3/Gal-9–signaling pathway plays a critical role in the homeostasis of hepatic NKT cells through activation-induced apoptosis and secondary proliferation and, thus, contributes to the pathogenesis of NAFLD. PMID:23296703

  1. Non-alcoholic fatty liver disease, obesity and the metabolic syndrome.

    Science.gov (United States)

    Dietrich, Peter; Hellerbrand, Claus

    2014-08-01

    Nonalcoholic fatty liver disease (NAFLD) is now recognized as the most common cause of chronic liver disease worldwide. Its prevalence has increased to more than 30% of adults in developed countries and its incidence is still rising. The majority of patients with NAFLD have simple steatosis but in up to one third of patients, NAFLD progresses to its more severe form nonalcoholic steatohepatitis (NASH). NASH is characterized by liver inflammation and injury thereby determining the risk to develop liver fibrosis and cancer. NAFLD is considered the hepatic manifestation of the metabolic syndrome. However, the liver is not only a passive target but affects the pathogenesis of the metabolic syndrome and its complications. Conversely, pathophysiological changes in other organs such as in the adipose tissue, the intestinal barrier or the immune system have been identified as triggers and promoters of NAFLD progression. This article details the pathogenesis of NAFLD along with the current state of its diagnosis and treatment. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Epigenetic mechanisms in non-alcoholic fatty liver disease: An emerging field.

    Science.gov (United States)

    Gallego-Durán, Rocío; Romero-Gómez, Manuel

    2015-10-28

    Non-alcoholic fatty liver disease (NAFLD) is an emerging health concern in both developed and non-developed world, encompassing from simple steatosis to non-alcoholic steatohepatitis (NASH), cirrhosis and liver cancer. Incidence and prevalence of this disease are increasing due to the socioeconomic transition and change to harmful diet. Currently, gold standard method in NAFLD diagnosis is liver biopsy, despite complications and lack of accuracy due to sampling error. Further, pathogenesis of NAFLD is not fully understood, but is well-known that obesity, diabetes and metabolic derangements played a major role in disease development and progression. Besides, gut microbioma and host genetic and epigenetic background could explain considerable interindividual variability. Knowledge that epigenetics, heritable events not caused by changes in DNA sequence, contribute to development of diseases has been a revolution in the last few years. Recently, evidences are accumulating revealing the important role of epigenetics in NAFLD pathogenesis and in NASH genesis. Histone modifications, changes in DNA methylation and aberrant profiles or microRNAs could boost development of NAFLD and transition into clinical relevant status. PNPLA3 genotype GG has been associated with a more progressive disease and epigenetics could modulate this effect. The impact of epigenetic on NAFLD progression could deserve further applications on therapeutic targets together with future non-invasive methods useful for the diagnosis and staging of NAFLD.

  3. Emerging role of obeticholic acid in the management of nonalcoholic fatty liver disease.

    Science.gov (United States)

    Makri, Evangelia; Cholongitas, Evangelos; Tziomalos, Konstantinos

    2016-11-07

    Nonalcoholic fatty liver disease (NAFLD) is the commonest chronic liver disease and its prevalence is increasing driven by the pandemic of obesity and type 2 diabetes mellitus. NAFLD can progress to cirrhosis and is associated with increased risk for cardiovascular disease and hepatocellular cancer. Diet and exercise are limited by suboptimal long-term adherence in patients with NAFLD. On the other hand, current pharmacological treatment of NAFLD has limited efficacy and unfavorable safety profile. In this context, obeticholic acid (OCA), a selective agonist of the farnesoid X receptors, might represent a useful option in these patients. Preclinical studies suggest that OCA improves hepatic steatosis, inflammation and fibrosis. A proof-of-concept study and the randomized, placebo-controlled Farnesoid X Receptor Ligand Obeticholic Acid in non-alcoholic steatohepatitis Treatment (FLINT) trial also showed improvements in liver histology in patients with NAFLD who received OCA. Weight loss and reduction in blood pressure were also observed. However, the effects of OCA on insulin resistance are conflicting and the lipid profile is adversely affected by this agent. In addition, pruritus is frequently observed during treatment with OCA and might lead to treatment discontinuation. However, given the limitations of existing treatments for NAFLD, OCA might represent a useful therapeutic option in selected patients with NAFLD.

  4. Mitochondrial Molecular Pathophysiology of Nonalcoholic Fatty Liver Disease: A Proteomics Approach

    Directory of Open Access Journals (Sweden)

    Natalia Nuño-Lámbarri

    2016-03-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD is a chronic liver condition that can progress to nonalcoholic steatohepatitis, cirrhosis and cancer. It is considered an emerging health problem due to malnourishment or a high-fat diet (HFD intake, which is observed worldwide. It is well known that the hepatocytes’ apoptosis phenomenon is one of the most important features of NAFLD. Thus, this review focuses on revealing, through a proteomics approach, the complex network of protein interactions that promote fibrosis, liver cell stress, and apoptosis. According to different types of in vitro and murine models, it has been found that oxidative/nitrative protein stress leads to mitochondrial dysfunction, which plays a major role in stimulating NAFLD damage. Human studies have revealed the importance of novel biomarkers, such as retinol-binding protein 4, lumican, transgelin 2 and hemoglobin, which have a significant role in the disease. The post-genome era has brought proteomics technology, which allows the determination of molecular pathogenesis in NAFLD. This has led to the search for biomarkers which improve early diagnosis and optimal treatment and which may effectively prevent fatal consequences such as cirrhosis or cancer.

  5. Management of Nonalcoholic Fatty Liver Disease in Patients With Type 2 Diabetes: A Call to Action.

    Science.gov (United States)

    Bril, Fernando; Cusi, Kenneth

    2017-03-01

    Traditionally a disease of hepatologists, nonalcoholic fatty liver disease (NAFLD) has recently become a major concern for a broad spectrum of health care providers. Endocrinologists and those caring for patients with type 2 diabetes mellitus (T2DM) are at center stage, as T2DM appears to worsen the course of NAFLD and the liver disease makes diabetes management more challenging. However, the nature of this relationship remains incompletely understood. Although the increasing prevalence of NAFLD is frequently attributed to the epidemic of obesity and is often oversimplified as the "hepatic manifestation of the metabolic syndrome," it is a much more complex disease process that may also be observed in nonobese individuals and in patients without clinical manifestations of the metabolic syndrome. It carries both metabolic and liver-specific complications that make its approach unique among medical conditions. Diabetes appears to promote the development of nonalcoholic steatohepatitis (NASH), the more severe form of the disease, and increases the risk of cirrhosis and hepatocellular carcinoma. Patients and physicians face many uncertainties, including fragmented information on the natural history of the disease, challenges in the diagnosis of NASH, and few pharmacological agents with proven efficacy. However, recent advances in diagnosis and treatment, combined with the risk of serious consequences from inaction, call for health care providers to be more proactive in the management of patients with T2DM and NASH. © 2017 by the American Diabetes Association.

  6. Non-alcoholic fatty liver disease phosphoproteomics: A functional piece of the precision puzzle.

    Science.gov (United States)

    Wattacheril, Julia; Rose, Kristie L; Hill, Salisha; Lanciault, Christian; Murray, Clark R; Washington, Kay; Williams, Brandon; English, Wayne; Spann, Matthew; Clements, Ronald; Abumrad, Naji; Flynn, Charles Robb

    2017-12-01

    Molecular signaling events associated with the necroinflammatory changes in nonalcoholic steatohepatitis (NASH) are not well understood. To understand the molecular basis of NASH, we evaluated reversible phosphorylation events in hepatic tissue derived from Class III obese subjects by phosphoproteomic means with the aim of highlighting key regulatory pathways that distinguish NASH from non-alcoholic fatty liver disease (also known as simple steatosis; SS). Class III obese subjects undergoing bariatric surgery underwent liver biopsy (eight normal patients, eight with simple steatosis, and eight NASH patients). Our strategy was unbiased, comparing global differences in liver protein reversible phosphorylation events across the 24 subjects. Of the 3078 phosphorylation sites assigned (2465 phosphoserine, 445 phosphothreonine, 165 phosphotyrosine), 53 were altered by a factor of 2 among cohorts, and of those, 12 were significantly increased or decreased by ANOVA (P < 0.05). Statistical analyses of canonical signaling pathways identified carbohydrate metabolism and RNA post-transcriptional modification among the most over-represented networks. Collectively, these results raise the possibility of abnormalities in carbohydrate metabolism as an important trigger for the development of NASH, in parallel with already established abnormalities in lipid metabolism. © 2017 The Japan Society of Hepatology.

  7. Proteomic and genomic studies of non-alcoholic fatty liver disease - clues in the pathogenesis

    Science.gov (United States)

    Lim, Jun Wei; Dillon, John; Miller, Michael

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) is a widely prevalent hepatic disorder that covers wide spectrum of liver pathology. NAFLD is strongly associated with liver inflammation, metabolic hyperlipidaemia and insulin resistance. Frequently, NAFLD has been considered as the hepatic manifestation of metabolic syndrome. The pathophysiology of NAFLD has not been fully elucidated. Some patients can remain in the stage of simple steatosis, which generally is a benign condition; whereas others can develop liver inflammation and progress into non-alcoholic steatohepatitis, fibrosis, cirrhosis and hepatocellular carcinoma. The mechanism behind the progression is still not fully understood. Much ongoing proteomic researches have focused on discovering the unbiased circulating biochemical markers to allow early detection and treatment of NAFLD. Comprehensive genomic studies have also begun to provide new insights into the gene polymorphism to understand patient-disease variations. Therefore, NAFLD is considered a complex and mutifactorial disease phenotype resulting from environmental exposures acting on a susceptible polygenic background. This paper reviewed the current status of proteomic and genomic studies that have contributed to the understanding of NAFLD pathogenesis. For proteomics section, this review highlighted functional proteins that involved in: (1) transportation; (2) metabolic pathway; (3) acute phase reaction; (4) anti-inflammatory; (5) extracellular matrix; and (6) immune system. In the genomic studies, this review will discuss genes which involved in: (1) lipolysis; (2) adipokines; and (3) cytokines production. PMID:25024592

  8. Epigenetic Mechanisms Underlying the Link between Non-Alcoholic Fatty Liver Diseases and Nutrition

    Directory of Open Access Journals (Sweden)

    Joo Ho Lee

    2014-08-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD is defined as a pathologic accumulation of fat in the form of triglycerides (TG in the liver (steatosis that is not caused by alcohol. A subgroup of NAFLD patients shows liver cell injury and inflammation coupled with the excessive fat accumulation (steatohepatitis, which is referred to as non-alcoholic steatohepatitis (NASH. Patients with NASH may develop cirrhosis and hepatocellular carcinoma (HCC. NAFLD shares the key features of metabolic syndrome including obesity, hyperlipidemia, hypertension, and insulin resistance. The pathogenesis of NAFLD is multi-factorial, however the oxidative stress seems to plays a major role in the development and progression of the disease. The emerging field of epigenetics provides a new perspective on the pathogenesis of NAFLD. Epigenetics is an inheritable but reversible phenomenon that affects gene expression without altering the DNA sequence and refers to DNA methylation, histone modifications and microRNAs. Epigenetic manipulation through metabolic pathways such as one-carbon metabolism has been proposed as a promising approach to retard the progression of NAFLD. Investigating the epigenetic modifiers in NAFLD may also lead to the development of preventive or therapeutic strategies for NASH-associated complications.

  9. Liver fibrosis in non-alcoholic fatty liver disease - diagnostic challenge with prognostic significance.

    Science.gov (United States)

    Stål, Per

    2015-10-21

    Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the Western world, with a prevalence of 20%. In a subgroup of patients, inflammation, ballooning degeneration of hepatocytes and a varying degree of fibrosis may develop, a condition named non-alcoholic steatohepatitis. Advanced liver fibrosis (stage F3) and cirrhosis (stage F4) are histologic features that most accurately predict increased mortality in both liver-related and cardiovascular diseases. Patients with advanced fibrosis or cirrhosis are at risk for complications such as hepatocellular carcinoma and esophageal varices and should therefore be included in surveillance programs. However, liver disease and fibrosis are often unrecognized in patients with NAFLD, possibly leading to a delayed diagnosis of complications. The early diagnosis of advanced fibrosis in NAFLD is therefore crucial, and it can be accomplished using serum biomarkers (e.g., the NAFLD Fibrosis Score, Fib-4 Index or BARD) or non-invasive imaging techniques (transient elastography or acoustic radiation force impulse imaging). The screening of risk groups, such as patients with obesity and/or type 2 diabetes mellitus, for NAFLD development with these non-invasive methods may detect advanced fibrosis at an early stage. Additionally, patients with a low risk for advanced fibrosis can be identified, and the need for liver biopsies can be minimized. This review focuses on the diagnostic challenge and prognostic impact of advanced liver fibrosis in NAFLD.

  10. Non-alcoholic fatty liver disease in obese adults: clinical aspects and current management strategies.

    Science.gov (United States)

    Pallayova, M; Taheri, S

    2014-10-01

    Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder whose prevalence is strongly linked to the current epidemic of obesity in many western countries. The prevalence of NAFLD is two to four times higher in populations with pre-existing metabolic comorbidities than in the general population. The diagnosis of primary NAFLD involves establishing the presence of hepatic steatosis or steatohepatitis by imaging or histology, along with establishing the non-alcoholic nature of the disease process and excluding competing aetiologies for hepatic steatosis. Among the indirect serum biomarkers, the NAFLD fibrosis score can help to identify patients with NAFLD and with higher likelihood of having fibrosis or cirrhosis. A liver biopsy should be considered in NAFLD patients at increased risk for steatohepatitis/advanced fibrosis and in cases where a liver biopsy is necessary to exclude co-existing chronic liver diseases and other aetiologies for hepatic steatosis. The treatment and management recommendations for obesity-associated NAFLD are aimed towards weight reduction. The currently available interventions employed to promote weight loss and improve the metabolic responses in NAFLD include lifestyle modification, pharmacotherapy and bariatric surgery. © 2014 The Authors. Clinical Obesity © 2014 World Obesity.

  11. Early life programming and the risk of non-alcoholic fatty liver disease.

    Science.gov (United States)

    Lynch, C; Chan, C S; Drake, A J

    2017-06-01

    Non-alcoholic fatty liver disease (NAFLD) is associated with obesity, insulin resistance, type 2 diabetes and cardiovascular disease and can be considered the hepatic manifestation of the metabolic syndrome. NAFLD represents a spectrum of disease, from the relatively benign simple steatosis to the more serious non-alcoholic steatohepatitis, which can progress to liver cirrhosis, hepatocellular carcinoma and end-stage liver failure, necessitating liver transplantation. Although the increasing prevalence of NAFLD in developed countries has substantial implications for public health, many of the precise mechanisms accounting for the development and progression of NAFLD are unclear. The environment in early life is an important determinant of cardiovascular disease risk in later life and studies suggest this also extends to NAFLD. Here we review data from animal models and human studies which suggest that fetal and early life exposure to maternal under- and overnutrition, excess glucocorticoids and environmental pollutants may confer an increased susceptibility to NAFLD development and progression in offspring and that such effects may be sex-specific. We also consider studies aimed at identifying potential dietary and pharmacological interventions aimed at reducing this risk. We suggest that further human epidemiological studies are needed to ensure that data from animal models are relevant to human health.

  12. Nutritional Approaches to Achieve Weight Loss in Nonalcoholic Fatty Liver Disease.

    Science.gov (United States)

    Hsu, Christine C; Ness, Erik; Kowdley, Kris V

    2017-03-01

    Nonalcoholic fatty liver disease (NAFLD) can range in spectrum from simple hepatic steatosis to nonalcoholic steatohepatitis (NASH), which is characterized by lipotoxicity, hepatocellular ballooning, and inflammation and can progress to cirrhosis. Weight loss is the cornerstone treatment for NAFLD and NASH. Various randomized controlled trials have shown that weight loss of ≥5-10% leads to significant improvements in hepatic steatosis. Diets high in sodium and fructose have been implicated in the pathogenesis of NAFLD. Although some clinical studies suggest that an isocaloric high-fructose diet does not worsen NAFLD, these clinical studies are often short in duration. More recently, the Dietary Approaches to Stop Hypertension diet, a sodium-restricted diet, has been associated with less prevalence of NAFLD and has been shown to improve NAFLD. In addition, the Mediterranean diet has been promising in improving hepatic steatosis, and a larger randomized controlled trial is currently enrolling subjects. For those who are unable to pursue weight loss through dietary approaches, bariatric surgery has been shown to improve hepatic steatosis and steatohepatitis. This method has been variable in improving hepatic fibrosis. In conclusion, weight loss is crucial to the improvement of NAFLD and NASH, and patients should attempt various diets in an attempt to achieve weight loss. © 2017 American Society for Nutrition.

  13. Second Harmonic Generation Reveals Subtle Fibrosis Differences in Adult and Pediatric Nonalcoholic Fatty Liver Disease.

    Science.gov (United States)

    Liu, Feng; Zhao, Jing-Min; Rao, Hui-Ying; Yu, Wei-Miao; Zhang, Wei; Theise, Neil D; Wee, Aileen; Wei, Lai

    2017-11-20

    Investigate subtle fibrosis similarities and differences in adult and pediatric nonalcoholic fatty liver disease (NAFLD) using second harmonic generation (SHG). SHG/two-photon excitation fluorescence imaging quantified 100 collagen parameters and determined qFibrosis values by using the nonalcoholic steatohepatitis (NASH) Clinical Research Network (CRN) scoring system in 62 adult and 36 pediatric NAFLD liver specimens. Six distinct parameters identified differences among the NASH CRN stages with high accuracy (area under the curve, 0835-0.982 vs 0.885-0.981, adult and pediatric). All portal region parameters showed similar changes across early stages 0, 1C, and 2, in both groups. Parameter values decreased in adults with progression from stage 1A/B to 2 in the central vein region. In children, aggregated collagen parameters decreased, but nearly all distributed collagen parameters increased from stage 1A/B to 2. SHG analysis accurately reproduces NASH CRN staging in NAFLD, as well as reveals differences and similarities between adult and pediatric collagen deposition not captured by currently available quantitative methods. © American Society for Clinical Pathology, 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  14. Evaluation of circulating zonulin as a potential marker in the pathogenesis of nonalcoholic fatty liver disease.

    Science.gov (United States)

    Hendy, Olfat M; Elsabaawy, Maha M; Aref, Mona M; Khalaf, Fatma M; Oda, Abdel Moaty A; El Shazly, Helmy M

    2017-07-01

    Nonalcoholic fatty liver disease (NAFLD) is a spectrum of liver disorders ranging from simple hepatic steatosis up to nonalcoholic steatohepatitis (NASH) evolving to cirrhosis and hepatocellular carcinoma (HCC). Liver biopsy is still the gold standard modality for diagnosing and staging NAFLD. The linkage between intestinal microbiota and NAFLD, might suggest a potential role of serum zonulin in NAFLD diagnosis. To appraise the role of circulating zonulin in NAFLD pathogenesis, 56 subjects with proved NAFLD by ultrasonography and liver biopsy, as well as 20 healthy controls were tested. Liver function tests, serum glucose, fasting insulin, C peptide, lipid profile, homeostasis model assessment of insulin resistance (HOMA-IR), IL-6, and circulating zonulin were performed to all subjects. Aspartate transaminase (AST), alanine transaminase (ALT), gamma-glutamyl transferase (GGT), triglycerides, HDL-c, fasting insulin, C peptide, HOMA-IR, IL-6, and serum zonulin were higher in NAFLD group than in controls (p Zonulin was positively correlated with body mass index (BMI), ALT, triglycerides, fasting insulin, HOMA-IR, liver histopathology, and serum IL-6 (p zonulin was found to be of diagnostic value of NASH occurrence with 100% sensitivity and specificity (AUR = 1.000, p-value = zonulin levels in NAFLD patients with steep rise in NASH group denotes a possible role in pathogenesis of NAFLD occurrence and progression. This could open a new avenue of implicating zonulin antagonists as targeted therapies in NAFLD prevention. © 2017 APMIS. Published by John Wiley & Sons Ltd.

  15. Gallstone disease does not predict liver histology in nonalcoholic fatty liver disease.

    Science.gov (United States)

    Yilmaz, Yusuf; Ayyildiz, Talat; Akin, Hakan; Colak, Yasar; Ozturk, Oguzhan; Senates, Ebubekir; Tuncer, Ilyas; Dolar, Enver

    2014-05-01

    We sought to examine whether the presence of gallstone disease (GD) in patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD) is associated with liver fibrosis and histological nonalcoholic steatohepatitis (NASH) score. We included 441 Turkish patients with biopsy-proven NAFLD. GD was diagnosed in the presence of sonographic evidence of gallstones, echogenic material within the gallbladder with constant shadowing and little or no visualization of the gallbladder or absence of gallbladder at ultrasonography, coupled with a history of cholecystectomy. Fifty-four patients (12.2%) had GD (GD+ subjects). Compared with the GD- subjects, GD+ patients were older, had a higher body mass index and were more likely to be female and have metabolic syndrome. However, GD+ patients did not have a higher risk of advanced fibrosis or definite NASH on histology. After adjustment for potential confounding variables, the prevalence of GD in NAFLD patients was not associated with significant fibrosis (≥2) (odds ratio [OR], 1.06; 95% confidence interval [CI], 0.53 to 2.21; p=0.68) or definite NASH (OR, 1.03; 95% CI, 0.495 to 2.12; p=0.84). The presence of GD is not independently associated with advanced fibrosis and definite NASH in adult Turkish patients with biopsy-proven NAFLD.

  16. Novel Action of Carotenoids on Non-Alcoholic Fatty Liver Disease: Macrophage Polarization and Liver Homeostasis.

    Science.gov (United States)

    Ni, Yinhua; Zhuge, Fen; Nagashimada, Mayumi; Ota, Tsuguhito

    2016-06-24

    Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. It is characterized by a wide spectrum of hepatic changes, which may progress to non-alcoholic steatohepatitis (NASH) and cirrhosis. NAFLD is considered a hepatic manifestation of metabolic syndrome; however, mechanisms underlying the onset and progression of NAFLD are still unclear. Resident and recruited macrophages are key players in the homeostatic function of the liver and in the progression of NAFLD to NASH. Progress has been made in understanding the molecular mechanisms underlying the polarized activation of macrophages. New NAFLD therapies will likely involve modification of macrophage polarization by restraining M1 activation or driving M2 activation. Carotenoids are potent antioxidants and anti-inflammatory micronutrients that have been used to prevent and treat NAFLD. In addition to their antioxidative action, carotenoids can regulate macrophage polarization and thereby halt the progression of NASH. In this review, we summarize the molecular mechanisms of macrophage polarization and the function of liver macrophages/Kupffer cells in NAFLD. From our review, we propose that dietary carotenoids, such as β-cryptoxanthin and astaxanthin, be used to prevent or treat NAFLD through the regulation of macrophage polarization and liver homeostasis.

  17. Probiotics as a novel treatment for non-alcoholic Fatty liver disease; a systematic review on the current evidences.

    Science.gov (United States)

    Kelishadi, Roya; Farajian, Sanam; Mirlohi, Maryam

    2013-04-01

    Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease, with 5-10% of liver having extra fat. Increase in its prevalence in all age groups is linked with obesity and Type II diabetes. The treatment of NAFLD remains controversial. A growing body of evidence suggests a relation between overgrowth of gut microbiota with NAFLD and non-alcoholic steatohepatitis (NASH). The objective of this review is to provide an overview on experimental and clinical studies assessing all positive and negative effects of probiotics. We made a critical appraisal on various types of documents published from 1999 to March 2012 in journals, electronic books, seminars, and symposium contexts including Medline, PubMed, and Cochrane Central Register of Controlled Trials databases. We used the key words: "non-alcoholic fatty liver disease, probiotics, non-alcoholic steatohepatitis, liver disease, and fatty liver". Probiotics, as biological factors, control the gut microbiota and result in its progression. It is in this sense that they are suggestive of a new and a natural way of promoting liver function. Correspondingly, limited evidence suggests that probiotics could be considered as a new way of treatment for NAFLD. Various experimental studies and clinical trials revealed promising effects of probiotics in improving NAFLD; however given the limited experience in this field, generalization of probiotics as treatment of NAFLD needs substantiation through more trials with a larger sample sizes and with longer-term follow up.

  18. Nonalcoholic Fatty Liver Disease/Non-Alcoholic Steatohepatitis in Childhood: Endocrine-Metabolic “Mal-Programming”

    Science.gov (United States)

    Manti, Sara; Romano, Claudio; Chirico, Valeria; Filippelli, Martina; Cuppari, Caterina; Loddo, Italia; Salpietro, Carmelo; Arrigo, Teresa

    2014-01-01

    Context: Nonalcoholic Fatty Liver Disease (NAFLD) is the major chronic liver disease in the pediatric population. NAFLD includes a broad spectrum of abnormalities (inflammation, fibrosis and cirrhosis), ranging from accumulation of fat (also known as steatosis) towards non-alcoholic steatohepatitis (NASH). The development of NAFLD in children is significantly increased. Evidence Acquisition: A literature search of electronic databases was undertaken for the major studies published from 1998 to today. The databases searched were: PubMed, EMBASE, Orphanet, Midline and Cochrane Library. We used the key words: "non-alcoholic fatty liver disease, children, non-alcoholic steatohepatitis and fatty liver". Results: NAFLD/NASH is probably promoted by “multiple parallel hits”: environmental and genetic factors, systemic immunological disorders (oxidative stress, persistent-low grade of inflammation) as well as obesity and metabolic alterations (insulin resistance and metabolic syndrome). However its exact cause still underdiagnosed and unknown. Conclusions: Pediatric NAFLD/NASH is emerging problem. Longitudinal follow-up studies, unfortunately still insufficient, are needed to better understand the natural history and outcome of NAFLD in children. This review focuses on the current knowledge regarding the epidemiology, pathogenesis, environmental, genetic and metabolic factors of disease. The review also highlights the importance of studying the underlying mechanisms of pediatric NAFLD and the need for complete and personalized approach in the management of NAFLD/NASH. PMID:24829591

  19. Role of peroxisome proliferators-activated receptors in the pathogenesis and treatment of nonalcoholic fatty liver disease.

    Science.gov (United States)

    Kallwitz, Eric R; McLachlan, Alan; Cotler, Scott J

    2008-01-07

    Nonalcoholic fatty liver disease (NAFLD) is highly prevalent and can result in nonalcoholic steatohepatitis (NASH) and progressive liver disease including cirrhosis and hepatocellular carcinoma. A growing body of literature implicates the peroxisome proliferators-activated receptors (PPARs) in the pathogenesis and treatment of NAFLD. These nuclear hormone receptors impact on hepatic triglyceride accumulation and insulin resistance. The aim of this review is to describe the data linking PPAR alpha and PPAR gamma to NAFLD/NASH and to discuss the use of PPAR ligands for the treatment of NASH.

  20. Prevalence of Non-Alcoholic Fatty Liver Disease in Morbidly Obese Patients Undergoing Sleeve Bariatric Surgery in Iran and Association With Other Comorbid Conditions

    OpenAIRE

    Karimi-Sari; Mousavi-Naeini; Ramezani-Binabaj; Najafizadeh-Sari; Mir-Jalili; Dolatimehr

    2015-01-01

    Background Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease including simple steatosis to nonalcoholic steatohepatitis (NASH). NASH could progress to cirrhosis and liver cancer. The prevalence of NAFLD is increasing by increasing the prevalence of obesity. Objectives This study was designed to determine the prevalence of NASH in morbidly obese patients undergoing sleeve bariatric s...

  1. A new noninvasive technique for estimating hepatic triglyceride: will liver biopsy become redundant in diagnosing non-alcoholic fatty liver disease?

    NARCIS (Netherlands)

    Betzel, B.; Drenth, J.P.H.

    2014-01-01

    Obesity and metabolic syndrome are healthcare problems that continue to rise in frequency worldwide. Both phenotypes are a strong predictor for development of liver steatosis in the context of non-alcoholic fatty liver disease or non-alcoholic steatohepatitis. Ultrasound may detect steatosis, but

  2. Non-Alcoholic Fatty Liver Disease and Extra-Hepatic Cancers

    Directory of Open Access Journals (Sweden)

    Claudia Sanna

    2016-05-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD is a leading cause of chronic liver disease but the second cause of death among NAFLD patients are attributed to malignancies at both gastrointestinal (liver, colon, esophagus, stomach, and pancreas and extra-intestinal sites (kidney in men, and breast in women. Obesity and related metabolic abnormalities are associated with increased incidence or mortality for a number of cancers. NAFLD has an intertwined relationship with metabolic syndrome and significantly contributes to the risk of hepatocellular carcinoma (HCC, but recent evidence have fuelled concerns that NAFLD may be a new, and added, risk factor for extra-hepatic cancers, particularly in the gastrointestinal tract. In this review we critically appraise key studies on NAFLD-associated extra-hepatic cancers and speculate on how NAFLD may influence carcinogenesis at these sites.

  3. Non-Alcoholic Fatty Liver Disease and Extra-Hepatic Cancers.

    Science.gov (United States)

    Sanna, Claudia; Rosso, Chiara; Marietti, Milena; Bugianesi, Elisabetta

    2016-05-12

    Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease but the second cause of death among NAFLD patients are attributed to malignancies at both gastrointestinal (liver, colon, esophagus, stomach, and pancreas) and extra-intestinal sites (kidney in men, and breast in women). Obesity and related metabolic abnormalities are associated with increased incidence or mortality for a number of cancers. NAFLD has an intertwined relationship with metabolic syndrome and significantly contributes to the risk of hepatocellular carcinoma (HCC), but recent evidence have fuelled concerns that NAFLD may be a new, and added, risk factor for extra-hepatic cancers, particularly in the gastrointestinal tract. In this review we critically appraise key studies on NAFLD-associated extra-hepatic cancers and speculate on how NAFLD may influence carcinogenesis at these sites.

  4. Flaxseed supplementation in non-alcoholic fatty liver disease: a pilot randomized, open labeled, controlled study.

    Science.gov (United States)

    Yari, Zahra; Rahimlou, Mehran; Eslamparast, Tannaz; Ebrahimi-Daryani, Naser; Poustchi, Hossein; Hekmatdoost, Azita

    2016-06-01

    A two-arm randomized open labeled controlled clinical trial was conducted on 50 patients with non-alcoholic fatty liver disease (NAFLD). Participants were assigned to take either a lifestyle modification (LM), or LM +30 g/day brown milled flaxseed for 12 weeks. At the end of the study, body weight, liver enzymes, insulin resistance and hepatic fibrosis and steatosis decreased significantly in both groups (phepatic markers between flaxseed and control group, respectively: ALT [-11.12 compared with -3.7 U/L; Psteatosis score [-47 compared with -15.45 dB/m; p = 0.022]. In conclusion, flaxseed supplementation plus lifestyle modification is more effective than lifestyle modification alone for NAFLD management.

  5. The Possible Role of Helicobacter pylori Infection in Non-alcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Dan-dan Cheng

    2017-05-01

    Full Text Available Helicobacter pylori (H. pylori which colonizes the stomach can cause a wide array of gastric disorders, including chronic gastritis, peptic ulcer, and gastric cancer. Recently, accumulating evidence has implicated H. pylori infection in extragastrointestinal diseases such as cardiovascular diseases, neurological disorders, and metabolic diseases. At the same time, many scholars have noted the relationship between H. pylori infection and non-alcoholic fatty liver disease (NAFLD. Despite the positive association between H. pylori and NAFLD reported in some researches, there are opposite perspectives denying their relationship. Due to high prevalence, unclear etiology and difficult treatment of NAFLD, confirming the pathogenicity of H. pylori infection in NAFLD will undoubtedly provide insights for novel treatment strategies for NAFLD. This paper will review the relationship between H. pylori infection and NAFLD and the possible pathogenic mechanisms.

  6. Non-alcoholic fatty liver disease as a consequence of autonomic imbalance and circadian desynchronization.

    Science.gov (United States)

    Sabath, E; Báez-Ruiz, A; Buijs, R M

    2015-10-01

    The circadian system, headed by the suprachiasmatic nucleus, synchronizes behaviour and metabolism according to the external light-dark cycle through neuroendocrine and autonomic signals. Metabolic diseases, such as steatosis, obesity and glucose intolerance, have been associated with conditions of circadian misalignment wherein the feeding schedule has been moved to the resting phase. Here we describe the physiological processes involved in liver lipid accumulation and show how they follow a circadian pattern importantly regulated by both the autonomic nervous system and the feeding-fasting cycle. We propose that an unbalanced activity of the sympathetic-parasympathetic branches between organs induced by circadian misalignment provides the conditions for the development and progression of non-alcoholic fatty liver disease. © 2015 World Obesity.

  7. What is the role of adiponectin in obesity related non-alcoholic fatty liver disease?

    Science.gov (United States)

    Finelli, Carmine; Tarantino, Giovanni

    2013-02-14

    Non-alcoholic fatty liver disease (NAFLD) is recognized as the most common type of chronic liver disease in Western countries. Insulin resistance is a key factor in the pathogenesis of NAFLD, the latter being considered as the hepatic component of insulin resistance or obesity. Adiponectin is the most abundant adipose-specific adipokine. There is evidence that adiponectin decreases hepatic and systematic insulin resistance, and attenuates liver inflammation and fibrosis. Adiponectin generally predicts steatosis grade and the severity of NAFLD; however, to what extent this is a direct effect or related to the presence of more severe insulin resistance or obesity remains to be addressed. Although there is no proven pharmacotherapy for the treatment of NAFLD, recent therapeutic strategies have focused on the indirect upregulation of adiponectin through the administration of various therapeutic agents and/or lifestyle modifications. In this adiponectin-focused review, the pathogenetic role and the potential therapeutic benefits of adiponectin in NAFLD are analyzed systematically.

  8. Gastrointestinal complications of obesity: non-alcoholic fatty liver disease (NAFLD) and its sequelae.

    Science.gov (United States)

    Karlas, Thomas; Wiegand, Johannes; Berg, Thomas

    2013-04-01

    Obesity is a major risk factor for malign and non-malign diseases of the gastrointestinal tract. Non-alcoholic fatty liver disease (NAFLD) is an outstanding example for the complex pathophysiology of the metabolic system and represents both source and consequence of the metabolic syndrome. NAFLD has a growing prevalence and will become the leading cause of advanced liver disease and cirrhosis. Obesity has a negative impact on NAFLD at all aspects and stages of the disease. The growing epidemic will strain health care resources and demands new concepts for prevention, screening and therapeutic approaches. A better understanding of the interplay of liver, gut and hormonal system is necessary for new insights in the underlying mechanisms of NAFLD and the metabolic syndrome including obesity. Identification of patients at risk for progressive liver disease will allow a better adaption of treatment strategies. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Adipose Tissue, Metabolic Syndrome, and Non-Alcoholic Fatty Liver Disease – A Short Review

    Directory of Open Access Journals (Sweden)

    Panayiotis Kouis

    2014-05-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD is the most common chronic liver disease globally, and it is expected to rise even further as a result of the increase in obesity and related risk factors. This short review summarises current evidence on the role of adipose tissue and insulin resistance in NAFLD and the interrelationship between NAFLD and the metabolic syndrome (MetS, considering central adiposity is a major feature of both the MetS and NAFLD, and that NAFLD has been previously described as the hepatic manifestation of the MetS. In addition, genetic studies of NAFLD with relation to adiposity and insulin resistance are reviewed, and up-to-date diagnostic and therapeutic tools are also discussed.

  10. Hepatic fibrosis in nonalcoholic fatty liver disease and its quantitative assessment

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    WANG Yan

    2017-12-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD is becoming a primary etiology underlying the chronic liver injury-related fibrogenesis among general population. Histologic fibrosis has been demonstrated as the most important independent predictor for the major outcomes of NAFLD patients. NAFLD-related fibrosis has distinct characteristics through the disease course, which is largely attributed to its "metabolic" pathophysiology: The progression of fibrosis is correlated to the factors including obesity, metabolic syndrome components, aging, etc.; and the patterns of histologic distribution and evolution as well as the association with the other histological features are remarkably different from those of the other chronic liver diseases. Based on the criteria of current standard histology, accurate quantitative assessment of NAFLD fibrosis could be relevant in terms of research and utilization to stratifying the disease risk, monitoring the therapeutic response, as well as to facilitating the development of new diagnostic tools.

  11. Liver Toxicity of Anabolic Androgenic Steroid Use in an Adolescent with Nonalcoholic Fatty Liver Disease

    Science.gov (United States)

    Awai, Hannah I; Yu, Elizabeth L; Ellis, Linda S; Schwimmer, Jeffrey B

    2013-01-01

    The prevalence of obesity and related morbidities such as nonalcoholic fatty liver disease (NAFLD) is high among adolescents. Current treatment recommendations for NAFLD focus on lifestyle optimization via nutrition and exercise. After encouraging exercise, many adolescents choose to participate in organized sports, which may lead to use of illicit substances such as anabolic androgenic steroids (AAS) to boost athletic performance. Approximately 3,000,000 individuals use non-therapeutic AAS at supra-physiologic doses in the United States.1 In 2012, 5.9% of adolescent boys reported steroid use in the previous year.2 We anticipate adolescents with pre-existing liver disease are at increased risk for AAS induced hepatotoxicity. We present such a case with IRB approval and written individual patient consent. PMID:23568051

  12. Adherence to the Dietary Approaches to Stop Hypertension (DASH) and risk of Nonalcoholic Fatty Liver Disease.

    Science.gov (United States)

    Hekmatdoost, Azita; Shamsipour, Ali; Meibodi, Mohammad; Gheibizadeh, Newsha; Eslamparast, Tannaz; Poustchi, Hossein

    2016-12-01

    This case-control study was conducted to examine the association between adherence to the Dietary Approaches to Stop Hypertension (DASH) diet and risk of Nonalcoholic Fatty Liver Disease (NAFLD) development in 102 patients with newly diagnosed NAFLD and 204 controls. Adherence to DASH-style diet was assessed using a validated food frequency questionnaire, and a DASH diet score based on food and nutrients emphasized or minimized in the DASH diet. Participants in the top quartile of DASH diet score were 30% less likely to have NAFLD (OR: 0.0.70; 95% CI: 0.61, 0.80); however, more adjustment for dyslipidemia and body mass index changed the association to non-significant (OR: 0.92; 95% CI: 0.73, 1.12). In conclusion, we found an inverse relationship between the DASH-style diet and risk of NAFLD. Prospective studies are needed to confirm this association.

  13. Comparison of the Phenotype and Approach to Pediatric Versus Adult Patients with Nonalcoholic Fatty Liver Disease

    Science.gov (United States)

    Nobili, V; Alisi, A; Newton, Kimberly P.; Schwimmer, Jeffrey B.

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) is one of the main chronic non-communicable diseases in westernized societies; its worldwide prevalence has doubled during the last 20 years. NAFLD has serious health implications not only for adults, but also for children. However, pediatric NAFLD is not only an important global problem in itself, but it is likely to be associated with increases in comorbidities such as metabolic syndrome and cardiovascular diseases. There are several differences between NAFLD in children and adults and it is not clear whether the disease observed in children is the initial phase of a process that progresses with age. The increasing prevalence of pediatric NAFLD has serious implications for the future adult population requiring appropriate action. Studies of NAFLD progression, pathogenesis, and management should evaluate disease phenotypes in children and follow these over patient lifetimes. We review the similarities and differences of NAFLD between children and adults. PMID:27003600

  14. Liver fat content, non-alcoholic fatty liver disease, and ischaemic heart disease

    DEFF Research Database (Denmark)

    Lauridsen, Bo Kobberø; Stender, Stefan; Kristensen, Thomas Skårup

    2018-01-01

    Aims: In observational studies, non-alcoholic fatty liver disease (NAFLD) is associated with high risk of ischaemic heart disease (IHD). We tested the hypothesis that a high liver fat content or a diagnosis of NAFLD is a causal risk factor for IHD. Methods and results: In a cohort study...... of the Danish general population (n = 94 708/IHD = 10 897), we first tested whether a high liver fat content or a diagnosis of NAFLD was associated observationally with IHD. Subsequently, using Mendelian randomization, we tested whether a genetic variant in the gene encoding the protein patatin......-like phospholipase domain containing 3 protein (PNPLA3), I148M (rs738409), a strong and specific cause of high liver fat content and NAFLD, was causally associated with the risk of IHD. We found that the risk of IHD increased stepwise with increasing liver fat content (in quartiles) up to an odds ratio (OR) of 2...

  15. Research advances in susceptibility genes and their role in the pathogenesis of nonalcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    XUAN Shiying

    2016-03-01

    Full Text Available Currently the incidence of nonalcoholic fatty liver disease (NAFLD is increasing, and the age of onset is getting younger worldwide, resulting in a heavy economic burden for both individuals and the society. Since NAFLD is closely related to heredity, metabolism, and the environment, genetic factors play an important role in the development and progression of NAFLD. With the development and wide application of the techniques from the genome-wide association studies, new research advances have been achieved in the susceptibility genes of NAFLD. This review summarizes the related research findings at home and abroad, and investigates the pathogenic factors for NAFLD and related mechanisms with a focus on the polymorphisms of susceptibility genes.

  16. Ethnicity and nonalcoholic fatty liver disease in an obesity clinic: the impact of triglycerides.

    Science.gov (United States)

    Kallwitz, Eric R; Kumar, Mrudula; Aggarwal, Radhika; Berger, Reed; Layden-Almer, Jennifer; Gupta, Neil; Cotler, Scott J

    2008-05-01

    Nonalcoholic fatty liver disease (NAFLD) is a growing problem that is associated with the metabolic syndrome. The goal of the present study was to evaluate for ethnic differences in NAFLD and clinical correlates of NAFLD. The study population consisted of 567 patients seen at an urban obesity clinic. Elevated aminotransferase levels were used as a surrogate marker for NAFLD. The prevalence of elevated aminotransferases was highest in Hispanics (39%), followed by Caucasians (28%), and African Americans (12%). In univariate analysis, elevated aminotransferase levels were associated with ethnicity (Hispanic > African American, P African American P = 0.030), hypertriglyceridemia (P < 0.001), and male gender (P < 0.001). The pattern of results was confirmed in multivariate analysis, except that the differences between Caucasians and African Americans was no longer significant. In conclusion, in an obesity clinic population, elevated aminotransferase levels and hypertriglyceridemia were most common in Hispanics and least common in African Americans.

  17. What does irritable bowel syndrome share with non-alcoholic fatty liver disease?

    Science.gov (United States)

    Scalera, Antonella; Di Minno, Matteo Nicola Dario; Tarantino, Giovanni

    2013-09-07

    Non-alcoholic fatty liver disease (NAFLD) and irritable bowel syndrome (IBS) are two very common diseases in the general population. To date, there are no studies that highlight a direct link between NAFLD and IBS, but some recent reports have found an interesting correlation between obesity and IBS. A systematic PubMed database search was conducted highlighting that common mechanisms are involved in many of the local and systemic manifestations of NAFLD, leading to an increased cardiovascular risk, and IBS, leading to microbial dysbiosis, impaired intestinal barrier and altered intestinal motility. It is not known when considering local and systemic inflammation/immune system activation, which one has greater importance in NAFLD and IBS pathogenesis. Also, the nervous system is implicated. In fact, inflammation participates in the development of mood disorders, such as anxiety and depression, characteristics of obesity and consequently of NAFLD and, on the other hand, in intestinal hypersensitivity and dysmotility.

  18. The Impact of Nonalcoholic Fatty Liver Disease on Renal Function in Children with Overweight/Obesity.

    Science.gov (United States)

    Pacifico, Lucia; Bonci, Enea; Andreoli, Gian Marco; Di Martino, Michele; Gallozzi, Alessia; De Luca, Ester; Chiesa, Claudio

    2016-07-27

    The association between nonalcoholic fatty liver disease (NAFLD) and chronic kidney disease has attracted interest and attention over recent years. However, no data are available in children. We determined whether children with NAFLD show signs of renal functional alterations, as determined by estimated glomerular filtration rate (eGFR) and urinary albumin excretion. We studied 596 children with overweight/obesity, 268 with NAFLD (hepatic fat fraction ≥5% on magnetic resonance imaging) and 328 without NAFLD, and 130 healthy normal-weight controls. Decreased GFR was defined as eGFR children with abnormal albuminuria was also higher in the NAFLD group compared to those without NAFLD, and controls (9.3% vs. 4.0% vs. 0; p Children with NAFLD are at risk for early renal dysfunction. Recognition of this abnormality in the young may help to prevent the ongoing development of the disease.

  19. Dietary Composition Independent of Weight Loss in the Management of Non-Alcoholic Fatty Liver Disease.

    Science.gov (United States)

    Eslamparast, Tannaz; Tandon, Puneeta; Raman, Maitreyi

    2017-07-26

    Poor dietary composition is an important factor in the progression of non-alcoholic fatty liver disease (NAFLD). The majority of NAFLD patients follow diets with overconsumption of simple carbohydrates, total and saturated fat, with reduced intake of dietary fiber and omega-3 rich foods. Although lifestyle modifications including weight loss and exercise remain the keystone of NAFLD management, modifying dietary composition with or without a calorie-restricted diet may also be a feasible and sustainable strategy for NAFLD treatment. In the present review article, we highlight the potential therapeutic role of a "high quality healthy diet" to improve hepatic steatosis and metabolic dysfunction in patients with NAFLD, independent of caloric restriction and weight loss. We provide a literature review evaluating the evidence behind dietary components including fiber-, meat- and omega-3-rich diets and, pending further evidence, we concur with the EASL-EASD-EASO Clinical Guidelines recommendation of the Mediterranean diet as the diet of choice in these patients.

  20. Alimentary regimen in non-alcoholic fatty liver disease: Mediterranean diet

    Science.gov (United States)

    Abenavoli, Ludovico; Milic, Natasa; Peta, Valentina; Alfieri, Francesco; De Lorenzo, Antonino; Bellentani, Stefano

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. The mechanisms of the underlying disease development and progression are awaiting clarification. Insulin resistance and obesity-related inflammation status, among other possible genetic, dietary, and lifestyle factors, are thought to play the key role. There is no consensus concerning the pharmacological treatment. However, the dietary nutritional management to achieve weight loss is an essential component of any treatment strategy. On the basis of its components, the literature reports on the effectiveness of the Mediterranean diet in reducing cardiovascular risk and in preventing major chronic diseases, including obesity and diabetes. New evidence supports the idea that the Mediterranean diet, associated with physical activity and cognitive behaviour therapy, may have an important role in the prevention and the treatment of NAFLD. PMID:25492997

  1. Increased circulating zonulin in children with biopsy-proven nonalcoholic fatty liver disease.

    Science.gov (United States)

    Pacifico, Lucia; Bonci, Enea; Marandola, Lidia; Romaggioli, Sara; Bascetta, Stefano; Chiesa, Claudio

    2014-12-07

    To investigate the potential association of circulating zonulin with the stage of liver disease in obese children with biopsy-confirmed nonalcoholic fatty liver disease (NAFLD). A case-control study was performed. Cases were 40 obese children with NAFLD. The diagnosis of NAFLD was based on magnetic resonance imaging (MRI) with high hepatic fat fraction (HFF ≥ 5%), and confirmed by liver biopsy with ≥ 5% of hepatocytes containing macrovesicular fat. Controls were selected from obese children with normal levels of aminotransferases, and without MRI evidence of fatty liver as well as of other causes of chronic liver diseases. Controls were matched (1-to 1) with the cases on age, gender, pubertal stage and as closely as possible on body mass index- standard deviation score. All participants underwent clinical examination, laboratory tests including zonulin, inflammatory and metabolic parameters, and MRI for measurement of HFF and visceral adipose tissue. Zonulin values were significantly greater in obese subjects with NAFLD than in those without NAFLD [median (interquartile range), 4.23 (3.18-5.89) vs 3.31 (2.05-4.63), P zonulin concentrations increased significantly with the severity of steatosis and the Spearman's coefficient revealed a positive correlation between zonulin values and steatosis (r = 0.372, P zonulin and lobular inflammation (P = 0.23), ballooning (P = 0.10), fibrosis score (P = 0.18), or presence of nonalcoholic steatohepatitis (P = 0.17). Within the entire study population, zonulin levels were positively associated with gamma-glutamyl transferase, 2-h insulin, HFF, and negatively associated with whole-body insulin sensitivity index (WBISI), after adjustment for age, gender and pubertal status. When the associations were restricted to the group of NAFLD patients, 2-h insulin, hepatic fat, and WBISI retained statistical significance. Circulating zonulin is increased in children and adolescents with NAFLD and correlates with the severity of

  2. Fish oil alleviated high-fat diet-induced non-alcoholic fatty liver disease via regulating hepatic lipids metabolism and metaflammation: a transcriptomic study.

    Science.gov (United States)

    Yuan, Fahu; Wang, Hualin; Tian, Yu; Li, Qi; He, Lei; Li, Na; Liu, Zhiguo

    2016-02-01

    Intake of fish oil rich in n-3 polyunsaturated fatty acids (PUFAs) is believed to be beneficial against development of non-alcoholic fatty liver disease (NAFLD). However, the underlying mechanisms remain unclear. This study was to gain further understanding of the potential mechanisms of the protective effects of fish oil against NAFLD. Ten male Sprague-Dawley rats were fed a control diet (CON), a Western style high-fat and high-cholesterol diet (WD), or a WD diet containing fish oil (FOH) for 16 weeks respectively. The development of liver steatosis and fibrosis were verified by histological and biochemical examination. Hepatic transcriptome were extracted for RNA-seq analysis, and particular results were confirmed by real-time polymerase chain reaction (PCR). The consumption of fish oil significantly ameliorated WD-induced dyslipidemia, transaminase elevation, hepatic steatosis, inflammatory infiltration, and fibrosis. Hepatic RNA-Seq analysis showed that long-term intake of fish oil restored the expression of circadian clock-related genes per2 and per3, which were reduced in WD fed animals. Fish oil consumption also corrected the expression levels of genes involved in fatty acid and cholesterol metabolism, such as Srebf1, Fasn, Scd1, Insig2, Cd36, Cyp7a1, Abcg5, Abcg8 and Pcsk9. Moreover, the expression levels of pro-inflammation genes Mcp1, Socs2, Sema4a, and Cd44 in the FOH group were lower than that of WD group, implying that fish oil protects the liver against WD-induced hepatic inflammation. The present study demonstrates fish oil protects against WD-induced NALFD via improving lipid metabolism and ameliorating hepatic inflammation. Our findings add to the current understanding on the benefits of n-3 PUFAs against NAFLD.

  3. Prediction of Nonalcoholic Fatty Liver Disease Via a Novel Panel of Serum Adipokines

    Science.gov (United States)

    Jamali, Raika; Arj, Abbas; Razavizade, Mohsen; Aarabi, Mohammad Hossein

    2016-01-01

    Abstract Considering limitations of liver biopsy for diagnosis of nonalcoholic liver disease (NAFLD), biomarkers’ panels were proposed. The aims of this study were to establish models based on serum adipokines for discriminating NAFLD from healthy individuals and nonalcoholic steatohepatitis (NASH) from simple steatosis. This case-control study was conducted in patients with persistent elevated serum aminotransferase levels and fatty liver on ultrasound. Individuals with evidence of alcohol consumption, hepatotoxic medication, viral hepatitis, and known liver disease were excluded. Liver biopsy was performed in the remaining patients to distinguish NAFLD/NASH. Histologic findings were interpreted using “nonalcoholic fatty liver activity score.” Control group consisted of healthy volunteers with normal physical examination, liver function tests, and liver ultrasound. Binary logistic regression analysis was applied to ascertain the effects of independent variables on the likelihood that participants have NAFLD/NASH. Decreased serum adiponectin and elevated serum visfatin, IL-6, TNF-a were associated with an increased likelihood of exhibiting NAFLD. NAFLD discriminant score was developed as the following: [(−0.298 × adiponectin) + (0.022 × TNF-a) + (1.021 × Log visfatin) + (0.709 × Log IL-6) + 1.154]. In NAFLD discriminant score, 86.4% of original grouped cases were correctly classified. Discriminant score threshold value of (−0.29) yielded a sensitivity and specificity of 91% and 83% respectively, for discriminating NAFLD from healthy controls. Decreased serum adiponectin and elevated serum visfatin, IL-8, TNF-a were correlated with an increased probability of NASH. NASH discriminant score was proposed as the following: [(−0.091 × adiponectin) + (0.044 × TNF-a) + (1.017 × Log visfatin) + (0.028 × Log IL-8) − 1.787] In NASH model, 84% of original cases were correctly classified. Discriminant score threshold value of (−0.22) yielded a

  4. Effect and the probable mechanisms of silibinin in regulating insulin resistance in the liver of rats with non-alcoholic fatty liver

    International Nuclear Information System (INIS)

    Yao, Jiayin; Zhi, Min; Gao, Xiang; Hu, Pinjin; Li, Chujun; Yang, Xiaobo

    2013-01-01

    Our previous study has shown that reduced insulin resistance (IR) was one of the possible mechanisms for the therapeutic effect of silibinin on non-alcoholic fatty liver disease (NAFLD) in rats. In the present study, we investigated the pathways of silibinin in regulating hepatic glucose production and IR amelioration. Forty-five 4- to 6-week-old male Sprague Dawley rats were divided into a control group, an HFD group (high-fat diet for 6 weeks) and an HFD + silibinin group (high-fat diet + 0.5 mg kg -1 ·day -1 silibinin, starting at the beginning of the protocol). Both subcutaneous and visceral fat was measured. Homeostasis model assessment-IR index (HOMA-IR), intraperitoneal glucose tolerance test and insulin tolerance test (ITT) were performed. The expression of adipose triglyceride lipase (ATGL) and of genes associated with hepatic gluconeogenesis was evaluated. Silibinin intervention significantly protected liver function, down-regulated serum fat, and improved IR, as shown by decreased HOMA-IR and increased ITT slope. Silibinin markedly prevented visceral obesity by reducing visceral fat, enhanced lipolysis by up-regulating ATGL expression and inhibited gluconeogenesis by down-regulating associated genes such as Forkhead box O1, phosphoenolpyruvate carboxykinase and glucose-6-phosphatase. Silibinin was effective in ameliorating IR in NAFLD rats. Reduction of visceral obesity, enhancement of lipolysis and inhibition of gluconeogenesis might be the underlying mechanisms

  5. Effect and the probable mechanisms of silibinin in regulating insulin resistance in the liver of rats with non-alcoholic fatty liver

    Directory of Open Access Journals (Sweden)

    Jiayin Yao

    Full Text Available Our previous study has shown that reduced insulin resistance (IR was one of the possible mechanisms for the therapeutic effect of silibinin on non-alcoholic fatty liver disease (NAFLD in rats. In the present study, we investigated the pathways of silibinin in regulating hepatic glucose production and IR amelioration. Forty-five 4- to 6-week-old male Sprague Dawley rats were divided into a control group, an HFD group (high-fat diet for 6 weeks and an HFD + silibinin group (high-fat diet + 0.5 mg kg-1·day-1 silibinin, starting at the beginning of the protocol. Both subcutaneous and visceral fat was measured. Homeostasis model assessment-IR index (HOMA-IR, intraperitoneal glucose tolerance test and insulin tolerance test (ITT were performed. The expression of adipose triglyceride lipase (ATGL and of genes associated with hepatic gluconeogenesis was evaluated. Silibinin intervention significantly protected liver function, down-regulated serum fat, and improved IR, as shown by decreased HOMA-IR and increased ITT slope. Silibinin markedly prevented visceral obesity by reducing visceral fat, enhanced lipolysis by up-regulating ATGL expression and inhibited gluconeogenesis by down-regulating associated genes such as Forkhead box O1, phosphoenolpyruvate carboxykinase and glucose-6-phosphatase. Silibinin was effective in ameliorating IR in NAFLD rats. Reduction of visceral obesity, enhancement of lipolysis and inhibition of gluconeogenesis might be the underlying mechanisms.

  6. Effect and the probable mechanisms of silibinin in regulating insulin resistance in the liver of rats with non-alcoholic fatty liver

    Energy Technology Data Exchange (ETDEWEB)

    Yao, Jiayin; Zhi, Min; Gao, Xiang; Hu, Pinjin; Li, Chujun; Yang, Xiaobo [Department of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province (China)

    2013-03-15

    Our previous study has shown that reduced insulin resistance (IR) was one of the possible mechanisms for the therapeutic effect of silibinin on non-alcoholic fatty liver disease (NAFLD) in rats. In the present study, we investigated the pathways of silibinin in regulating hepatic glucose production and IR amelioration. Forty-five 4- to 6-week-old male Sprague Dawley rats were divided into a control group, an HFD group (high-fat diet for 6 weeks) and an HFD + silibinin group (high-fat diet + 0.5 mg kg{sup -1}·day{sup -1} silibinin, starting at the beginning of the protocol). Both subcutaneous and visceral fat was measured. Homeostasis model assessment-IR index (HOMA-IR), intraperitoneal glucose tolerance test and insulin tolerance test (ITT) were performed. The expression of adipose triglyceride lipase (ATGL) and of genes associated with hepatic gluconeogenesis was evaluated. Silibinin intervention significantly protected liver function, down-regulated serum fat, and improved IR, as shown by decreased HOMA-IR and increased ITT slope. Silibinin markedly prevented visceral obesity by reducing visceral fat, enhanced lipolysis by up-regulating ATGL expression and inhibited gluconeogenesis by down-regulating associated genes such as Forkhead box O1, phosphoenolpyruvate carboxykinase and glucose-6-phosphatase. Silibinin was effective in ameliorating IR in NAFLD rats. Reduction of visceral obesity, enhancement of lipolysis and inhibition of gluconeogenesis might be the underlying mechanisms.

  7. Systems biology elucidates common pathogenic mechanisms between nonalcoholic and alcoholic-fatty liver disease.

    Directory of Open Access Journals (Sweden)

    Silvia Sookoian

    Full Text Available The abnormal accumulation of fat in the liver is often related either to metabolic risk factors associated with metabolic syndrome in the absence of alcohol consumption (nonalcoholic fatty liver disease, NAFLD or to chronic alcohol consumption (alcoholic fatty liver disease, AFLD. Clinical and histological studies suggest that NAFLD and AFLD share pathogenic mechanisms. Nevertheless, current data are still inconclusive as to whether the underlying biological process and disease pathways of NAFLD and AFLD are alike. Our primary aim was to integrate omics and physiological data to answer the question of whether NAFLD and AFLD share molecular processes that lead to disease development. We also explored the extent to which insulin resistance (IR is a distinctive feature of NAFLD. To answer these questions, we used systems biology approaches, such as gene enrichment analysis, protein-protein interaction networks, and gene prioritization, based on multi-level data extracted by computational data mining. We observed that the leading disease pathways associated with NAFLD did not significantly differ from those of AFLD. However, systems biology revealed the importance of each molecular process behind each of the two diseases, and dissected distinctive molecular NAFLD and AFLD-signatures. Comparative co-analysis of NAFLD and AFLD clarified the participation of NAFLD, but not AFLD, in cardiovascular disease, and showed that insulin signaling is impaired in fatty liver regardless of the noxa, but the putative regulatory mechanisms associated with NAFLD seem to encompass a complex network of genes and proteins, plausible of epigenetic modifications. Gene prioritization showed a cancer-related functional map that suggests that the fatty transformation of the liver tissue is regardless of the cause, an emerging mechanism of ubiquitous oncogenic activation. In conclusion, similar underlying disease mechanisms lead to NAFLD and AFLD, but specific ones depict a

  8. Pathogenesis and management issues for non-alcoholic fatty liver disease

    Science.gov (United States)

    Duvnjak, Marko; Lerotić, Ivan; Baršić, Neven; Tomašić, Vedran; Jukić, Lucija Virović; Velagić, Vedran

    2007-01-01

    Nonalcoholic fatty liver disease (NAFLD) has, although it is a very common disorder, only relatively recently gained broader interest among physicians and scientists. Fatty liver has been documented in up to 10 to 15 percent of normal individuals and 70 to 80 percent of obese individuals. Although the pathophysiology of NAFLD is still subject to intensive research, several players and mechanisms have been suggested based on the substantial evidence. Excessive hepatocyte triglyceride accumulation resulting from insulin resistance is the first step in the proposed ‘two hit’ model of the pathogenesis of NAFLD. Oxidative stress resulting from mitochondrial fatty acids oxidation, NF-κB-dependent inflammatory cytokine expression and adipocytokines are all considered to be the potential factors causing second hits which lead to hepatocyte injury, inflammation and fibrosis. Although it was initially believed that NAFLD is a completely benign disorder, histologic follow-up studies have showed that fibrosis progression occurs in about a third of patients. A small number of patients with NAFLD eventually ends up with end-stage liver disease and even hepatocellular carcinoma. Although liver biopsy is currently the only way to confirm the NAFLD diagnosis and distinguish between fatty liver alone and NASH, no guidelines or firm recommendations can still be made as for when and in whom it is necessary. Increased physical activity, gradual weight reduction and in selected cases bariatric surgery remain the mainstay of NAFLD therapy. Studies with pharmacologic agents are showing promising results, but available data are still insufficient to make specific recommendations; their use therefore remains highly individual. PMID:17729403

  9. Increased prevalence and risk of non-alcoholic fatty liver disease in overweight and obese patients with Type 2 diabetes in South China.

    Science.gov (United States)

    Yi, M; Chen, R-P; Yang, R; Chen, H

    2017-04-01

    To investigate the prevalence of and risk factors for non-alcoholic fatty liver disease in overweight and obese patients with Type 2 diabetes mellitus. We recruited patients with Type 2 diabetes with a BMI ≥ 24 kg/m 2 , who visited the diabetes clinics of 60 hospitals in 21 cities in Guangdong Province, China from August 2011 to March 2012. Anthropometric measurements, biochemical tests and abdominal ultrasonography were performed for all the patients. The study included 3861 patients (1860 men) with a mean ± sd (range) age of 58.91 ± 13.06 (18-90) years. Non-alcoholic fatty liver disease was found in 1751 patients (45.4%), with a significantly higher prevalence among men than women (48.0 vs 42.9%). The peak of non-alcoholic fatty liver disease prevalence was in patients with a BMI of 34-35 kg/m 2 , those with a triglyceride/HDL cholesterol ratio of 5.5-6.0, men aged non-alcoholic fatty liver disease, while heart rate and female gender were protective factors. The prevalence of non-alcoholic fatty liver disease in overweight and obese patients with Type 2 diabetes in South China is high. Multiple metabolic disorders were significantly associated with non-alcoholic fatty liver disease in overweight and obese patients with Type 2 diabetes. © 2016 Diabetes UK.

  10. Cassia tora (Leguminosae) seed extract alleviates high-fat diet-induced nonalcoholic fatty liver.

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    Tzeng, Thing-Fong; Lu, Hung-Jen; Liou, Shorong-Shii; Chang, Chia Ju; Liu, I-Min

    2013-01-01

    The aim of this study was to examine the effects of Cassia tora seeds on high-fat diet (HFD)-induced hepatic steatosis, and elucidate the molecular mechanisms behind its effects. After being fed a HFD for two weeks, rats were orally dosed with Cassia seed ethanol extract (CSEE) (100, 200, or 300mg/kg) once daily for 8weeks. CSEE induced dose-dependent reductions in plasma lipid levels, as well as decreased the over hepatic lipid accumulation. Furthermore, CSEE treatment improved HFD-induced hepatic histological lesions. CSEE enhanced the phosphorylation of AMP-activated protein kinase (AMPK) and its primary downstream targeting enzyme, acetyl-CoA carboxylase, up-regulated the gene expression of carnitine palmitoyl transferase 1, and down-regulated sterol regulatory element binding protein 1 and fatty acid synthase protein levels in the livers of HFD-fed rats. AMPK inhibition by compound C retarded CSEE-induced reduction in triglyceride accumulation in HepG2 cells stimulated by insulin. Our findings suggest that CSEE may regulate hepatic lipid homeostasis related with an AMPK-dependent signaling pathway. Targeting AMPK activation with CSEE may represent a promising approach for the prevention and treatment of obesity-related non-alcoholic fatty liver disease. Copyright © 2012 Elsevier Ltd. All rights reserved.

  11. Hepatocellular carcinoma in nonalcoholic fatty liver: role of environmental and genetic factors.

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    Dongiovanni, Paola; Romeo, Stefano; Valenti, Luca

    2014-09-28

    Hepatocellular carcinoma (HCC) is the fourth cause of cancer related mortality, and its incidence is rapidly increasing. Viral hepatitis, alcohol abuse, and exposure to hepatotoxins are major risk factors, but nonalcoholic fatty liver disease (NAFLD) associated with obesity, insulin resistance, and type 2 diabetes, is an increasingly recognized trigger, especially in developed countries. Older age, severity of insulin resistance and diabetes, and iron overload have been reported to predispose to HCC in this context. Remarkably, HCCs have been reported in non-cirrhotic livers in a higher proportion of cases in NAFLD patients than in other etiologies. Inherited factors have also been implicated to explain the different individual susceptibility to develop HCC, and their role seems magnified in fatty liver, where only a minority of affected subjects progresses to cancer. In particular, the common I148M variant of the PNPLA3 gene influencing hepatic lipid metabolism influences HCC risk independently of its effect on the progression of liver fibrosis. Recently, rare loss-of-function mutations in Apolipoprotein B resulting in very low density lipoproteins hepatic retention and in Telomerase reverse transcriptase influencing cellular senescence have also been linked to HCC in NAFLD. Indeed, hepatic stellate cells senescence has been suggested to bridge tissue aging with alterations of the intestinal microbiota in the pathogenesis of obesity-related HCC. A deeper understanding of the mechanisms mediating hepatic carcinogenesis during insulin resistance, and the identification of its genetic determinants will hopefully provide new diagnostic and therapeutic tools.

  12. Pathogenesis, diagnosis and treatment of non-alcoholic fatty liver disease

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    Verónica Martín-Domínguez

    2013-08-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD includes a broad spectrum of alterations that go from simple steatosis to steatohepatitis and cirrhosis. Type 2 diabetes mellitus (DM-2 and obesity are the principle factors associated to NAFLD. A 20-30 % prevalence in general population has been described. The survival of this type of patient is lower than the general population's, showing a higher incidence of hepatic and cardiovascular complications. The aetiopathogenesis is still unclear, but we know the intervention of different factors that produce fatty-acid accumulation in hepatic parenchyma, causing oxidative stress, oxygen-free radicals and the synthesis of an inflammatory cascade, that determine the progression of this disease from steatosis up to advanced fibrosis. The diagnostic gold-standard is still the liver biopsy, even though the development of newer non-invasive techniques, like serological and imaging (radiology, have opened a new field for research that allows bloodless testing of these patients and better study of the natural history of this disease. Nowadays, there is still no specific treatment for NAFLD. The development of healthy life habits and moderate exercise continue to be the pillars of treatment. Different pharmacological approaches have been studied and applied, such as the control of insulin resistance, lowering cholesterol levels, antioxidants, and other alternatives in experimental trials.

  13. Biochemical Profile of Nonalcoholic Fatty Liver Disease Patients in Eastern India with Histopathological Correlation.

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    Swain, Manorama; Nath, Preetam; Parida, Prasant Kumar; Narayan, Jimmy; Padhi, Pradeep Kumar; Pati, Girish Kumar; Singh, Ayaskanta; Misra, Bijay; Misra, Debasis; Kar, Sanjib Kumar; Panigrahi, Manas Kumar; Meher, Chudamani; Agrawal, Omprakash; Rout, Niranjan; Pattnaik, Kaumudee; Bhuyan, Pallavi; Mishra, Pramila Kumari; Singh, Shivaram Prasad

    2017-07-01

    Aminotransferase assay is often used as a screening test as well as an endpoint for resolution of disease in nonalcoholic fatty liver disease (NAFLD). Aim of the study was to evaluate the relationship of transaminase level with metabolic variables and histology in NAFLD. Single center observational study was conducted in a gastroenterology clinic at Cuttack in coastal Odisha. Subjects were consecutive patients presenting with functional bowel disease and undergoing abdominal sonography. All participants were evaluated for the presence of metabolic syndrome (MS), insulin resistance, liver function test and lipid profile. Various parameters were compared between NAFLD subjects and controls. 53.5 % of NAFLD had normal serum transaminases, whereas 20.8 % of healthy controls had transaminitis. NAFLD patients had significantly higher BMI, fasting plasma glucose, serum transaminases, serum triglycerides, serum insulin and homeostatic model assessment (HOMA) IR than controls. NAFLD patients who had transaminitis had significantly higher incidence of MS and higher mean HOMA IR than those without. There was no significant difference in histopathological features between NAFLD with and without transaminitis. To conclude, over half of NAFLD subjects do not have transaminitis while transaminitis is present in a fifth of healthy people without fatty liver. Hence serum transaminase should not be used as screening test for NAFLD. NAFLD patients with transaminitis had a higher incidence of MS and insulin resistance than those without. However, there was no significant difference in histopathological features between these two groups.

  14. Activation of CDK4 Triggers Development of Non-alcoholic Fatty Liver Disease.

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    Jin, Jingling; Valanejad, Leila; Nguyen, Thuy Phuong; Lewis, Kyle; Wright, Mary; Cast, Ashley; Stock, Lauren; Timchenko, Lubov; Timchenko, Nikolai A

    2016-07-19

    The development of non-alcoholic fatty liver disease (NAFLD) is a multiple step process. Here, we show that activation of cdk4 triggers the development of NAFLD. We found that cdk4 protein levels are elevated in mouse models of NAFLD and in patients with fatty livers. This increase leads to C/EBPα phosphorylation on Ser193 and formation of C/EBPα-p300 complexes, resulting in hepatic steatosis, fibrosis, and hepatocellular carcinoma (HCC). The disruption of this pathway in cdk4-resistant C/EBPα-S193A mice dramatically reduces development of high-fat diet (HFD)-mediated NAFLD. In addition, inhibition of cdk4 by flavopiridol or PD-0332991 significantly reduces development of hepatic steatosis, the first step of NAFLD. Thus, this study reveals that activation of cdk4 triggers NAFLD and that inhibitors of cdk4 may be used for the prevention/treatment of NAFLD. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  15. GRADING SCALE OF VISCERAL ADIPOSE TISSUE THICKNESS AND THEIR RELATION TO THE NONALCOHOLIC FATTY LIVER DISEASE

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    Luís Jesuino de Oliveira ANDRADE

    2014-04-01

    Full Text Available Context The mesenteric fat is drained by the portal system, being related to the metabolic syndrome which is an impor­tant risk factor for non-alcoholic fatty liver disease (NAFLD. Objectives Graduate of visceral fat thickness and correlate with the NAFLD degree through ultrasonography method. Methods We studied 352 subjects for age, gender, measures of subcutaneous fat thickness and visceral fat thickness as well as the presence and degree of liver fatty. Was analyzed the independent relationship between visceral fat thickness and NAFLD, and linear regression analysis was used in order to predict the visceral fat thickness from subcutaneous fat thickness. Results The mean age of 225 women (63.9% and 127 men (36.1% was 47.5 ± 14.0 (18-77 years, 255 subjects had normal examinations, 97 had NAFLD thus distributed, 37 grade 1, 32 grade 2, and 28 grade 3. The subcutaneous fat thickness ranged from 0.26 to 3.50 cm with a mean of 1.3 ± 0.6 cm and visceral fat thickness ranged from 0.83 to 8.86 cm with a mean of 3.6 ± 1.7 cm. Linear regression showed that for every increase of 1 cm in subcutaneous fat thickness the visceral fat thickness will increase 0.9 cm. Conclusions The visceral fat thickness measured by ultrasonography is a useful and seems to be able to help estimate the risk of NAFLD.

  16. Hypoxia-regulated mechanisms in the pathogenesis of obesity and non-alcoholic fatty liver disease.

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    Lefere, Sander; Van Steenkiste, Christophe; Verhelst, Xavier; Van Vlierberghe, Hans; Devisscher, Lindsey; Geerts, Anja

    2016-09-01

    The pandemic rise in obesity has resulted in an increased incidence of metabolic complications. Non-alcoholic fatty liver disease is the hepatic manifestation of the metabolic syndrome and has become the most common chronic liver disease in large parts of the world. The adipose tissue expansion and hepatic fat accumulation characteristics of these disorders compromise local oxygen homeostasis. The resultant tissue hypoxia induces adaptive responses to restore oxygenation and tissue metabolism and cell survival. Hypoxia-inducible factors (HIFs) function as master regulators of this hypoxia adaptive response, and are in turn hydroxylated by prolyl hydroxylases (PHDs). PHDs are the main cellular oxygen sensors and regulate HIF proteasomal degradation in an oxygen-dependent manner. HIFs and PHDs are implicated in numerous physiological and pathological conditions. Extensive research using genetic models has revealed that hypoxia signaling is also a key mechanism in adipose tissue dysfunction, leading to adipose tissue fibrosis, inflammation and insulin resistance. Moreover, hypoxia affects liver lipid metabolism and deranges hepatic lipid accumulation. This review summarizes the molecular mechanisms through which the hypoxia adaptive response affects adipocyte and hepatic metabolism, and the therapeutic possibilities of modulating HIFs and PHDs in obesity and fatty liver disease.

  17. Gut-liver axis, nutrition, and non-alcoholic fatty liver disease.

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    Kirpich, Irina A; Marsano, Luis S; McClain, Craig J

    2015-09-01

    Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of diseases involving hepatic fat accumulation, inflammation with the potential progression to fibrosis and cirrhosis over time. NAFLD is often associated with obesity, insulin resistance, and diabetes. The interactions between the liver and the gut, the so-called "gut-liver axis", play a critical role in NAFLD onset and progression. Compelling evidence links the gut microbiome, intestinal barrier integrity, and NAFLD. The dietary factors may alter the gut microbiota and intestinal barrier function, favoring the occurrence of metabolic endotoxemia and low grade inflammation, thereby contributing to the development of obesity and obesity-associated fatty liver disease. Therapeutic manipulations with prebiotics and probiotics to modulate the gut microbiota and maintain intestinal barrier integrity are potential agents for NAFLD management. This review summarizes the current knowledge regarding the complex interplay between the gut microbiota, intestinal barrier, and dietary factors in NAFLD pathogenesis. The concepts addressed in this review have important clinical implications, although more work needs to be done to understand how dietary factors affect the gut barrier and microbiota, and to comprehend how microbe-derived components may interfere with the host's metabolism contributing to NAFLD development. Copyright © 2015 The Canadian Society of Clinical Chemists. All rights reserved.

  18. Antioxidant vitamins in the context of nonalcoholic fatty liver disease in obese children and adolescents

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    Fábio da Veiga Ued

    2013-12-01

    Full Text Available OBJECTIVE: To review the literature on the importance of antioxidant vitamins, analyzed in the context of dietary intake, its plasma levels, and its current use as a supplementation treatment in obese children and adolescents with nonalcoholic fatty liver disease. DATA SOURCES: The articles were identified in Lilacs, Ibecs, SciELO, PubMed/Medline, and Scopus databases. To conduct the survey, the "fatty liver" descriptor was associated to the following words: "children", "antioxidants" and "vitamins". The search was limited to articles written in Portuguese, Spanish and English, with publication date until December, 2012. DATA SYNTHESIS: Six studies were selected. The survey revealed a low dietary intake and low antioxidant vitamins serum levels in this population. The changes in lifestyle, with adequate dietary intake of vitamins, and the increase in physical activity were associated with a significant improvement in liver histology and in laboratory tests. Vitamin supplementation also improved the disease progression markers, as the alanine aminotransferase serum levels and the histological characteristics of lobular inflammation and hepatocellular damage. However, these improvements were not statistically significant in all studies. CONCLUSIONS: There is insufficient evidence to recommend or to refute antioxidant supplementation in patients with simple steatosis or steatohepatitis. The changes in lifestyle seem to be, at the present time, the more advisable therapy.

  19. Nonalcoholic Fatty Liver Disease: Pathogenesis and Therapeutics from a Mitochondria-Centric Perspective

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    Aaron M. Gusdon

    2014-01-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD describes a spectrum of disorders characterized by the accumulation of triglycerides within the liver. The global prevalence of NAFLD has been increasing as the obesity epidemic shows no sign of relenting. Mitochondria play a central role in hepatic lipid metabolism and also are affected by upstream signaling pathways involved in hepatic metabolism. This review will focus on the role of mitochondria in the pathophysiology of NAFLD and touch on some of the therapeutic approaches targeting mitochondria as well as metabolically important signaling pathways. Mitochondria are able to adapt to lipid accumulation in hepatocytes by increasing rates of beta-oxidation; however increased substrate delivery to the mitochondrial electron transport chain (ETC leads to increased reactive oxygen species (ROS production and eventually ETC dysfunction. Decreased ETC function combined with increased rates of fatty acid beta-oxidation leads to the accumulation of incomplete products of beta-oxidation, which combined with increased levels of ROS contribute to insulin resistance. Several related signaling pathways, nuclear receptors, and transcription factors also regulate hepatic lipid metabolism, many of which are redox sensitive and regulated by ROS.

  20. Protective effects of glycyrrhizic acid against non-alcoholic fatty liver disease in mice.

    Science.gov (United States)

    Sun, Xue; Duan, Xingping; Wang, Changyuan; Liu, Zhihao; Sun, Pengyuan; Huo, Xiaokui; Ma, Xiaodong; Sun, Huijun; Liu, Kexin; Meng, Qiang

    2017-07-05

    Non-alcoholic fatty liver disease (NAFLD) has become a predictive factor of death from many diseases. The purpose of the present study is to investigate the protective effect of glycyrrhizic acid (GA), a natural triterpene glycoside, on NAFLD induced by a high-fat diet (HFD) in mice, and further to elucidate the mechanisms underlying GA protection. GA treatment significantly reduced the relative liver weight, serum ALT, AST activities, levels of serum lipid, blood glucose and insulin. GA suppressed lipid accumulation in liver. Further mechanism investigation indicated that GA reduced hepatic lipogenesis via downregulating SREBP-1c, FAS and SCD1 expression, increased fatty acids β-oxidation via an increase in PPARα, CPT1α and ACADS, and promoted triglyceride metabolism through inducing LPL activity. Furthermore, GA reduced gluconeogenesis through repressing PEPCK and G6Pase, and increased glycogen synthesis through an induction in gene expression of PDase and GSK3β. In addition, GA increased insulin sensitivity through upregulating phosphorylation of IRS-1 and IRS-2. In conclusion, GA produces protective effect against NAFLD, due to regulation of genes involved in lipid, glucose homeostasis and insulin sensitivity. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Protective Effects and Mechanism of Meretrix meretrix Oligopeptides against Nonalcoholic Fatty Liver Disease

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    Fangfang Huang

    2017-02-01

    Full Text Available Meretrix meretrix oligopeptides (MMO derived from shellfish have important medicinal properties. We previously obtained MMO from alcalase by hydrolysis processes. Here we examine the protective effects of MMO against nonalcoholic fatty liver disease (NAFLD and explored the underlying mechanism. Human Chang liver cells were used in our experiments after exposure to palmitic acid at a final concentration of 15 μg/mL for 48 h to induce an overload of fatty acid as NAFLD model cells. Treatment with MMO for 24 h increased the viability of the NAFLD model cells by inhibiting apoptosis. MMO alleviated oxidative stress in the NAFLD model cells by preserving reactive oxygen species activity and increasing malondialdehyde and superoxide dismutase activity. MMO improved mitochondrial dysfunction by decreasing the mitochondrial membrane potential and increasing the activities of Na+/K+-ATPase and Ca2+/Mg2+-ATPase. In addition, MMO inhibited the activation of cell death-related pathways, based on reduced p-JNK, Bax expression, tumor necrosis factor-α, caspase-9, and caspase-3 activity in the NAFLD model cells, and Bcl-2 expression was enhanced in the NAFLD model cells compared with the control group. These findings indicate that MMO have antioxidant and anti-apoptotic effects on NAFLD model cells and may thus exert protective effects against NAFLD.

  2. Cordyceps militaris alleviates non-alcoholic fatty liver disease in ob/ob mice.

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    Choi, Ha-Neul; Jang, Yang-Hee; Kim, Min-Joo; Seo, Min Jeong; Kang, Byoung Won; Jeong, Yong Kee; Kim, Jung-In

    2014-04-01

    Non-alcoholic fatty liver disease (NAFLD) is becoming an important public health problem as metabolic syndrome and type 2 diabetes have become epidemic. In this study we investigated the protective effect of Cordyceps militaris (C. militaris) against NAFLD in an obese mouse model. Four-week-old male ob/ob mice were fed an AIN-93G diet or a diet containing 1% C. militaris water extract for 10 weeks after 1 week of adaptation. Serum glucose, insulin, free fatty acid (FFA), alanine transaminase (ALT), and proinflammatory cytokines were measured. Hepatic levels of lipids, glutathione (GSH), and lipid peroxide were determined. Consumption of C. militaris significantly decreased serum glucose, as well as homeostasis model assessment for insulin resistance (HOMA-IR), in ob/ob mice. In addition to lowering serum FFA levels, C. militaris also significantly decreased hepatic total lipids and triglyceride contents. Serum ALT activities and tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels were reduced by C. militaris. Consumption of C. militaris increased hepatic GSH and reduced lipid peroxide levels. These results indicate that C. militaris can exert protective effects against development of NAFLD, partly by reducing inflammatory cytokines and improving hepatic antioxidant status in ob/ob mice.

  3. Accuracy of prediction scores and novel biomarkers for predicting nonalcoholic fatty liver disease in obese children.

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    Koot, Bart G P; van der Baan-Slootweg, Olga H; Bohte, Anneloes E; Nederveen, Aart J; van Werven, Jochem R; Tamminga-Smeulders, Christine L J; Merkus, Maruschka P; Schaap, Frank G; Jansen, Peter L M; Stoker, Jaap; Benninga, Marc A

    2013-03-01

    Accurate prediction scores for liver steatosis are demanded to enable clinicians to noninvasively screen for nonalcoholic fatty liver disease (NAFLD). Several prediction scores have been developed, however external validation is lacking. The aim was to determine the diagnostic accuracy of four existing prediction scores in severely obese children, to develop a new prediction score using novel biomarkers and to compare these results to the performance of ultrasonography. Liver steatosis was measured using proton magnetic resonance spectroscopy in 119 severely obese children (mean age 14.3 ± 2.1 years, BMI z-score 3.35 ± 0.35). Prevalence of steatosis was 47%. The four existing predictions scores ("NAFLD liver fat score," "fatty liver index," "hepatic steatosis index," and the pediatric prediction score) had only moderate diagnostic accuracy in this cohort (positive predictive value (PPV): 70, 61, 61, 69% and negative predictive value (NPV) 77, 69, 68, 75%, respectively). A new prediction score was built using anthropometry, routine biochemistry and novel biomarkers (leptin, adiponectin, TNF-alpha, IL-6, CK-18, FGF-21, and adiponutrin polymorphisms). The final model included ALT, HOMA, sex, and leptin. This equation (PPV 79% and NPV 80%) did not perform substantially better than the four other equations and did not outperform ultrasonography for excluding NAFLD (NPV 82%). The conclusion is in severely obese children and adolescents existing prediction scores and the tested novel biomarkers have insufficient diagnostic accuracy for diagnosing or excluding NAFLD. Copyright © 2012 The Obesity Society.

  4. Gut-liver axis and probiotics: Their role in non-alcoholic fatty liver disease

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    Paolella, Giulia; Mandato, Claudia; Pierri, Luca; Poeta, Marco; Di Stasi, Martina; Vajro, Pietro

    2014-01-01

    The incidence of obesity and its related conditions, including non-alcoholic fatty liver disease (NAFLD), has dramatically increased in all age groups worldwide. Given the health consequences of these conditions, and the subsequent economic burden on healthcare systems, their prevention and treatment have become major priorities. Because standard dietary and lifestyle changes and pathogenically-oriented therapies (e.g., antioxidants, oral hypoglycemic agents, and lipid-lowering agents) often fail due to poor compliance and/or lack of efficacy, novel approaches directed toward other pathomechanisms are needed. Here we present several lines of evidence indicating that, by increasing energy extraction in some dysbiosis conditions or small intestinal bacterial overgrowth, specific gut microbiota and/or a “low bacterial richness” may play a role in obesity, metabolic syndrome, and fatty liver. Under conditions involving a damaged intestinal barrier (“leaky gut”), the gut-liver axis may enhance the natural interactions between intestinal bacteria/bacterial products and hepatic receptors (e.g., toll-like receptors), thus promoting the following cascade of events: oxidative stress, insulin-resistance, hepatic inflammation, and fibrosis. We also discuss the possible modulation of gut microbiota by probiotics, as attempted in NAFLD animal model studies and in several pilot pediatric and adult human studies. Globally, this approach appears to be a promising and innovative add-on therapeutic tool for NAFLD in the context of multi-target therapy. PMID:25400436

  5. Managing the Combination of Nonalcoholic Fatty Liver Disease and Metabolic Syndrome with Chinese Herbal Extracts in High-Fat-Diet Fed Rats

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    Yi Tan

    2013-01-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD is the hepatic manifestation of metabolic syndrome (MetS. The aim of the study was to evaluate the effects of Chinese herbal extracts from Salvia miltiorrhiza and Gardenia jasminoides (SGE on the combination of NAFLD and MetS induced by a high-fat diet (HFD in rats. After 6 weeks of HFD feeding, rats (n=10 each group were treated with saline, rosiglitazone (RSG, and SGE for 4 weeks. HFD rats were obese, hyperinsulinemic, hyperlipidemic and increased hepatic enzymes with the histological images of NAFLD. Treatment with SGE significantly reduced serum triglycerides (TG, nonesterified fatty acids and enhanced insulin sensitivity, and ameliorated the elevated serum hepatic enzymes compared with HFD-saline group. SGE treatment also attenuated hepatic TG by 18.5% (P<0.05. Histological stains showed SGE decreased lipids droplets in hepatocytes (P<0.05 and normalized macrovesicular steatosis in HFD rats. Significant reduction of TNF-α and IL6 in adipose tissue was detected in SGE treated rats. The anti-inflammatory action may be, at least in part, the mechanism of SGE on MetS associated with NAFLD. This study discovered that SGE is capable of managing metabolic and histological abnormalities of NAFLD and MetS. SGE may be an optimal treatment for the combination of NAFLD and MetS.

  6. Molecular pathways involved in the improvement of non-alcoholic fatty liver disease.

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    Paz-Filho, Gilberto; Mastronardi, Claudio Alberto; Parker, Brian J; Khan, Ainy; Inserra, Antonio; Matthaei, Klaus I; Ehrhart-Bornstein, Monika; Bornstein, Stefan; Wong, Ma-Li; Licinio, Julio

    2013-01-01

    Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis are components of the metabolic syndrome. Serum leptin levels are elevated in obesity, but the role of leptin in the pathophysiology of the liver involvement is still unclear. To identify the effects and mechanisms by which leptin influences the pathogenesis of NAFLD, we performed epididymal white adipose tissue (eWAT) transplantation from congenic wild-type mice into the subcutaneous dorsal area of Lep(ob/ob) recipient mice and compared the results with those of the Lep(ob/ob) sham-operated mice. The mice were followed for 102-216 days. During killing, the transplanted mice had significantly lost body weight and exhibited significantly higher leptin levels, improved glucose tolerance, and lower liver injury scores than the sham-operated mice. Liver microarray analysis showed that novel pathways related to GA-binding protein (GABP) transcription factor targets, pheromone binding, and olfactory signaling were differentially expressed in the transplanted mice. Our data also replicate pathways known to be involved in NAFLD, such as those involved in the regulation of microRNAs, lipid, glucose, and glutathione metabolism, peroxisome proliferator-activated receptor signaling, cellular regulation, carboxylic acid processes, iron, heme, and tetrapyrrole binding, immunity and inflammation, insulin signaling, cytochrome P450 function, and cancer. wild-type eWAT transplantation into Lep(ob/ob) mice led to improvements in metabolism, body weight, and liver injury, possibly attributed to the production of leptin by the transplanted eWAT. These improvements were accompanied by the differential expression of novel pathways. The causal relationship between GABP downregulation and NAFLD improvement remains to be determined.

  7. Patients with Nonalcoholic Fatty Liver Disease Have a Low Response Rate to Vitamin D Supplementation.

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    Dasarathy, Jaividhya; Varghese, Rony; Feldman, Abram; Khiyami, Amer; McCullough, Arthur J; Dasarathy, Srinivasan

    2017-10-01

    Background: Hypovitaminosis D is associated with an increased severity of nonalcoholic fatty liver disease (NAFLD), but reports on the response to cholecalciferol (vitamin D 3 ) supplementation are conflicting. Objective: The objective of this study was to determine if standard vitamin D 3 supplementation is effective in NAFLD with hypovitaminosis D. Methods: Sixty-five well-characterized adults [age (mean ± SD): 51.6 ± 12.3 y] with biopsy-proven NAFLD were screened. Forty-two patients (the ratio of men to women was 13:29) had hypovitaminosis D (plasma 25-hydroxyvitamin D [25(OH)D] D treated with 2000 IU cholecalciferol (vitamin D 3 ) daily for 6 mo per clinical practice. Plasma 25(OH)D, hepatic and metabolic panels, and metabolic syndrome components were assessed before and after cholecalciferol supplementation. Body composition was measured by using bioelectrical impedance analysis. The primary outcome measure was plasma 25(OH)D ≥30 ng/mL at the end of the study. Secondary outcomes included change in serum transaminases, fasting plasma glucose, and insulin and homeostasis model assessment of insulin resistance (HOMA-IR). Chi-square, Student's t tests, correlation coefficient, and multivariate analysis were performed. Results: Twenty-six (61.9%) patients had nonalcoholic steatohepatitis (NASH), and 16 (38.1%) had hepatic steatosis. After 6 mo of cholecalciferol supplementation, plasma 25(OH)D ≥30 ng/mL was observed in 16 subjects (38.1%; responders) whereas the remaining 26 patients (61.9%) were nonresponders with plasma 25(OH)D D in the majority of patients with NASH. Further studies are needed to determine if higher doses are effective. This trial was registered at clinicaltrials.gov as 13-00153. © 2017 American Society for Nutrition.

  8. Gallbladder Function and Hepatic Structural Changes in Children with Nonalcoholic Fatty Liver Disease

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    N.Yu. Zavgorodnya

    2016-04-01

    Full Text Available During the last decade, pediatric nonalcoholic liver disease has reached epidemic proportions, becoming one of the most frequent chronic liver diseases in the global child population. Purpose: to study the relationship of the functional state of the gallbladder with structural changes in the liver in children with nonalcoholic fatty liver disease. Materials and methods. We examined 34 children aged from 8 to 17 years old. Hepatic steatosis was determined using the FibroScan® 502 touch with controlled attenuation parameter (CAP. According to the results of transient elastometry and ultrasound of the abdomen with the gallbladder function study, patients were divided into 4 groups: the 1st group consisted of 7 patients with steatosis and hypofunction of gallbladder (20.5 %, group 2 included 6 patients with steatosis and gallbladder normofunction (17.65 %, group 3 consisted of 11 patients without hepatic steatosis with hypofunction of gallbladder (32.35 %, group 4 included 10 patients without hepatic steatosis with gallbladder normofunction (29.4 %. Results. The sonographic studies demonstrated children of the 1st group (steatosis with gallbladder hypokinesia to have significantly larger sizes of liver lobes compared to group 4 (children without steatosis with gallbladder normofunction. Also, the stiffness of the liver parenchyma was highest in patients with hepatic steatosis and gallbladder hypokinesia. Discussion. The combination of hepatic steatosis and hypokinesia of the gallbladder in children is accompanied by a significant increase in liver size, increased stiffness of the liver parenchyma and increasing degree of steatosis. The data indicate the relationship of the gallbladder function and the liver structural changes.

  9. Enhanced expression of BMP6 inhibits hepatic fibrosis in non-alcoholic fatty liver disease.

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    Arndt, Stephanie; Wacker, Eva; Dorn, Christoph; Koch, Andreas; Saugspier, Michael; Thasler, Wolfgang E; Hartmann, Arndt; Bosserhoff, Anja Katrin; Hellerbrand, Claus

    2015-06-01

    Bone morphogenetic protein 6 (BMP6) has been identified as crucial regulator of iron homeostasis. However, its further role in liver pathology including non-alcoholic fatty liver disease (NAFLD) and its advanced form non-alcoholic steatohepatitis (NASH) is elusive. The aim of this study was to investigate the expression and function of BMP6 in chronic liver disease. BMP6 was analysed in hepatic samples from murine models of chronic liver injury and patients with chronic liver diseases. Furthermore, a tissue microarray comprising 110 human liver tissues with different degree of steatosis and inflammation was assessed. BMP6-deficient (BMP6(-/-)) and wild-type mice were compared in two dietary NASH-models, that is, methionine choline-deficient (MCD) and high-fat (HF) diets. BMP6 was solely upregulated in NAFLD but not in other murine liver injury models or diseased human livers. In NAFLD, BMP6 expression correlated with hepatic steatosis but not with inflammation or hepatocellular damage. Also, in vitro cellular lipid accumulation in primary human hepatocytes induced increased BMP6 expression. MCD and HF diets caused more hepatic inflammation and fibrosis in BMP6(-/-) compared with wild-type mice. However, only in the MCD and not in the HF diet model BMP6(-/-) mice developed marked hepatic iron overload, suggesting that further mechanisms are responsible for protective BMP6 effect. In vitro analysis revealed that recombinant BMP6 inhibited the activation of hepatic stellate cells (HSCs) and reduced proinflammatory and profibrogenic gene expression in already activated HSCs. Steatosis-induced upregulation of BMP6 in NAFLD is hepatoprotective. Induction of BMP6-signalling may be a promising antifibrogenic strategy. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  10. Pediatric non-alcoholic fatty liver disease: Recent solutions, unresolved issues, and future research directions.

    Science.gov (United States)

    Clemente, Maria Grazia; Mandato, Claudia; Poeta, Marco; Vajro, Pietro

    2016-09-28

    Non-alcoholic fatty liver disease (NAFLD) in children is becoming a major health concern. A "multiple-hit" pathogenetic model has been suggested to explain the progressive liver damage that occurs among children with NAFLD. In addition to the accumulation of fat in the liver, insulin resistance (IR) and oxidative stress due to genetic/epigenetic background, unfavorable lifestyles, gut microbiota and gut-liver axis dysfunction, and perturbations of trace element homeostasis have been shown to be critical for disease progression and the development of more severe inflammatory and fibrotic stages [non-alcoholic steatohepatitis (NASH)]. Simple clinical and laboratory parameters, such as age, history, anthropometrical data (BMI and waist circumference percentiles), blood pressure, surrogate clinical markers of IR (acanthosis nigricans), abdominal ultrasounds, and serum transaminases, lipids and glucose/insulin profiles, allow a clinician to identify children with obesity and obesity-related conditions, including NAFLD and cardiovascular and metabolic risks. A liver biopsy (the "imperfect" gold standard) is required for a definitive NAFLD/NASH diagnosis, particularly to exclude other treatable conditions or when advanced liver disease is expected on clinical and laboratory grounds and preferably prior to any controlled trial of pharmacological/surgical treatments. However, a biopsy clearly cannot represent a screening procedure. Advancements in diagnostic serum and imaging tools, especially for the non-invasive differentiation between NAFLD and NASH, have shown promising results, e.g., magnetic resonance elastography. Weight loss and physical activity should be the first option of intervention. Effective pharmacological treatments are still under development; however, drugs targeting IR, oxidative stress, proinflammatory pathways, dyslipidemia, gut microbiota and gut liver axis dysfunction are an option for patients who are unable to comply with the recommended lifestyle

  11. Association between noninvasive fibrosis markers and chronic kidney disease among adults with nonalcoholic fatty liver disease.

    Directory of Open Access Journals (Sweden)

    Giorgio Sesti

    Full Text Available Evidence suggests that nonalcoholic fatty liver disease (NAFLD and non-alcoholic steatohepatitis (NASH are associated with an increased risk of chronic kidney disease (CKD. In this study we aimed to evaluate whether the severity of liver fibrosis estimated by NAFLD fibrosis score is associated with higher prevalence of CKD in individuals with NAFLD. To this end NAFLD fibrosis score and estimated glomerular filtration rate (eGFR were assessed in 570 White individuals with ultrasonography-diagnosed NAFLD. As compared with subjects at low probability of liver fibrosis, individuals at high and intermediate probability showed an unfavorable cardio-metabolic risk profile having significantly higher values of waist circumference, insulin resistance, high sensitivity C-reactive protein, fibrinogen, uric acid and lower insulin-like growth factor-1 levels. Individuals at high and intermediate probability of liver fibrosis have lower eGFR after adjustment for gender, smoking, glucose tolerance status, homeostasis model assessment index of insulin resistance (HOMA-IR index, diagnosis of metabolic syndrome, statin therapy, anti-diabetes and anti-hypertensive treatments (P = 0.001. Individuals at high probability of liver fibrosis had a 5.1-fold increased risk of having CKD (OR 5.13, 95%CI 1.13-23.28; P = 0.03 as compared with individuals at low probability after adjustment for age, gender, and BMI. After adjustment for glucose tolerance status, statin therapy, and anti-hypertensive treatment in addition to gender, individuals at high probability of liver fibrosis had a 3.9-fold increased risk of CKD (OR 3.94, 95%CI 1.11-14.05; P = 0.03 as compared with individuals at low probability. In conclusion, advanced liver fibrosis, determined by noninvasive fibrosis markers, is associated with CKD independently from other known factors.

  12. Decreased hepatotoxic bile acid composition and altered synthesis in progressive human nonalcoholic fatty liver disease

    Energy Technology Data Exchange (ETDEWEB)

    Lake, April D. [University of Arizona, Department of Pharmacology and Toxicology, Tucson, AZ 85721 (United States); Novak, Petr [Biology Centre ASCR, Institute of Plant Molecular Biology, Ceske Budejovice 37001 (Czech Republic); Shipkova, Petia; Aranibar, Nelly; Robertson, Donald; Reily, Michael D. [Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Co., Princeton, NJ 08543 (United States); Lu, Zhenqiang [The Arizona Statistical Consulting Laboratory, University of Arizona, Tucson, AZ 85721 (United States); Lehman-McKeeman, Lois D. [Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Co., Princeton, NJ 08543 (United States); Cherrington, Nathan J., E-mail: cherrington@pharmacy.arizona.edu [University of Arizona, Department of Pharmacology and Toxicology, Tucson, AZ 85721 (United States)

    2013-04-15

    Bile acids (BAs) have many physiological roles and exhibit both toxic and protective influences within the liver. Alterations in the BA profile may be the result of disease induced liver injury. Nonalcoholic fatty liver disease (NAFLD) is a prevalent form of chronic liver disease characterized by the pathophysiological progression from simple steatosis to nonalcoholic steatohepatitis (NASH). The hypothesis of this study is that the ‘classical’ (neutral) and ‘alternative’ (acidic) BA synthesis pathways are altered together with hepatic BA composition during progression of human NAFLD. This study employed the use of transcriptomic and metabolomic assays to study the hepatic toxicologic BA profile in progressive human NAFLD. Individual human liver samples diagnosed as normal, steatosis, and NASH were utilized in the assays. The transcriptomic analysis of 70 BA genes revealed an enrichment of downregulated BA metabolism and transcription factor/receptor genes in livers diagnosed as NASH. Increased mRNA expression of BAAT and CYP7B1 was observed in contrast to decreased CYP8B1 expression in NASH samples. The BA metabolomic profile of NASH livers exhibited an increase in taurine together with elevated levels of conjugated BA species, taurocholic acid (TCA) and taurodeoxycholic acid (TDCA). Conversely, cholic acid (CA) and glycodeoxycholic acid (GDCA) were decreased in NASH liver. These findings reveal a potential shift toward the alternative pathway of BA synthesis during NASH, mediated by increased mRNA and protein expression of CYP7B1. Overall, the transcriptomic changes of BA synthesis pathway enzymes together with altered hepatic BA composition signify an attempt by the liver to reduce hepatotoxicity during disease progression to NASH. - Highlights: ► Altered hepatic bile acid composition is observed in progressive NAFLD. ► Bile acid synthesis enzymes are transcriptionally altered in NASH livers. ► Increased levels of taurine and conjugated bile acids

  13. Nonalcoholic fatty liver disease and vascular disease: State-of-the-art

    Science.gov (United States)

    Fargion, Silvia; Porzio, Marianna; Fracanzani, Anna Ludovica

    2014-01-01

    Nonalcoholic fatty liver disease (NAFLD), the most common of chronic liver disease in Western Country, is closely related to insulin resistance and oxidative stress and includes a wide spectrum of liver diseases ranging from steatosis alone, usually a benign and non-progressive condition, to nonalcoholic steatohepatitis (NASH), which may progress to liver fibrosis and cirrhosis. NAFLD is considered the hepatic manifestation of the metabolic syndrome with which shares several characteristics, however recent data suggest that NAFLD is linked to increased cardiovascular risk independently of the broad spectrum of risk factors of metabolic syndrome. Accumulating evidence suggests that the clinical burden of NAFLD is not restricted to liver-related morbidity and mortality, with the majority of deaths in NAFLD patients related to cardiovascular disease and cancer and not to the progression of liver disease. Retrospective and prospective studies provide evidence of a strong association between NAFLD and subclinical manifestation of atherosclerosis (increased intima-media thickness, endothelial dysfunction, arterial stiffness, impaired left ventricular function and coronary calcification). A general agreement emerging from these studies indicates that patients with NASH are at higher risk of cardiovascular diseases than those with simple steatosis, emphasizing the role of chronic inflammation in the pathogenesis of atherosclerosis of these patients. It is very likely that the different mechanisms involved in the pathogenesis of atherosclerosis in patients with NAFLD have a different relevance in the patients according to individual genetic background. In conclusion, in the presence of NAFLD patients should undergo a complete cardiovascular evaluation to prevent future atherosclerotic complications. Specific life-style modification and aggressive pharmaceutical modification will not only reduce the progression of liver disease, but also reduce morbidity for cardiovascular

  14. Pediatric non-alcoholic fatty liver disease: Recent solutions, unresolved issues, and future research directions

    Science.gov (United States)

    Clemente, Maria Grazia; Mandato, Claudia; Poeta, Marco; Vajro, Pietro

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD) in children is becoming a major health concern. A “multiple-hit” pathogenetic model has been suggested to explain the progressive liver damage that occurs among children with NAFLD. In addition to the accumulation of fat in the liver, insulin resistance (IR) and oxidative stress due to genetic/epigenetic background, unfavorable lifestyles, gut microbiota and gut-liver axis dysfunction, and perturbations of trace element homeostasis have been shown to be critical for disease progression and the development of more severe inflammatory and fibrotic stages [non-alcoholic steatohepatitis (NASH)]. Simple clinical and laboratory parameters, such as age, history, anthropometrical data (BMI and waist circumference percentiles), blood pressure, surrogate clinical markers of IR (acanthosis nigricans), abdominal ultrasounds, and serum transaminases, lipids and glucose/insulin profiles, allow a clinician to identify children with obesity and obesity-related conditions, including NAFLD and cardiovascular and metabolic risks. A liver biopsy (the “imperfect” gold standard) is required for a definitive NAFLD/NASH diagnosis, particularly to exclude other treatable conditions or when advanced liver disease is expected on clinical and laboratory grounds and preferably prior to any controlled trial of pharmacological/surgical treatments. However, a biopsy clearly cannot represent a screening procedure. Advancements in diagnostic serum and imaging tools, especially for the non-invasive differentiation between NAFLD and NASH, have shown promising results, e.g., magnetic resonance elastography. Weight loss and physical activity should be the first option of intervention. Effective pharmacological treatments are still under development; however, drugs targeting IR, oxidative stress, proinflammatory pathways, dyslipidemia, gut microbiota and gut liver axis dysfunction are an option for patients who are unable to comply with the recommended

  15. Effect of dietary fat to produce non-alcoholic fatty liver in the rat.

    Science.gov (United States)

    Ahmed, Umbreen; Redgrave, Trevor G; Oates, Phillip S

    2009-08-01

    Non-alcoholic steatohepatitis (NASH) belongs to a spectrum of non-alcoholic fatty liver disease (NAFLD). Oxidative stress is hypothesized to play an important role in the progression of the disease. We used the Lieber/DeCarli model for NASH to investigate the mechanisms involved in its progression. Male Sprague-Dawley rats were fed standard (35% of energy from fat) or high fat (71% of energy from fat) liquid diets, ad libitum or two-thirds of the amount consumed ad libitum initially for 3 weeks and then extended to 5 weeks. Steatosis was absent in rats at 3 weeks feeding, but by 5 weeks, the high fat/ad lib group showed microvesicular steatosis and foci of macrovesicular steatosis without inflammation. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were not different. By 5 weeks feeding, hepatic triglycerides were highest in the high fat ad lib group and the ad lib groups were higher compared with their restricted groups. The oxidative stress marker, hydroxyalkenal (HAE) was decreased in the standard ad lib compared with the high fat ad lib group. Liver mRNA of interleukin-6, haem oxygenase-1, and markers of endoplasmic stress: C/EBP homologous protein (CHOP), glucose responsive protein-78 (GRP78) and spliced X-box DNA binding protein (spliced XBP1) were similar in the ad lib groups. Extending the feeding period of the high fat/ad lib diet for 5 weeks placed our rats with Type I to II NAFLD compared to the more progressed Type III state previously obtained after 3 weeks feeding. The milder condition obtained raised the prospect of genetic modifiers present in our rats that resist disease progression.

  16. The expanding role of fish models in understanding non-alcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    Yoichi Asaoka

    2013-07-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD is a condition in which excessive fat accumulates in the liver of an individual who has not consumed excessive alcohol. Non-alcoholic steatohepatitis (NASH, a severe form of NAFLD, can progress to hepatic cirrhosis and/or hepatocellular carcinoma (HCC. NAFLD is considered to be a hepatic manifestation of metabolic syndrome, and its incidence has risen worldwide in lockstep with the increased global prevalence of obesity. Over the last decade, rodent studies have yielded an impressive list of molecules associated with NAFLD and NASH pathogenesis. However, the identification of currently unknown metabolic factors using mammalian model organisms is inefficient and expensive compared with studies using fish models such as zebrafish (Danio rerio and medaka (Oryzias latipes. Substantial advances in unraveling the molecular pathogenesis of NAFLD have recently been achieved through unbiased forward genetic screens using small fish models. Furthermore, these easily manipulated organisms have been used to great advantage to evaluate the therapeutic effectiveness of various chemical compounds for the treatment of NAFLD. In this Review, we summarize aspects of NAFLD (specifically focusing on NASH pathogenesis that have been previously revealed by rodent models, and discuss how small fish are increasingly being used to uncover factors that contribute to normal hepatic lipid metabolism. We describe the various types of fish models in use for this purpose, including those generated by mutation, transgenesis, or dietary or chemical treatment, and contrast them with rodent models. The use of small fish in identifying novel potential therapeutic agents for the treatment of NAFLD and NASH is also addressed.

  17. High Prevalence of Nonalcoholic Fatty Liver Disease in Adolescents Undergoing Bariatric Surgery.

    Science.gov (United States)

    Xanthakos, Stavra A; Jenkins, Todd M; Kleiner, David E; Boyce, Tawny W; Mourya, Reena; Karns, Rebekah; Brandt, Mary L; Harmon, Carroll M; Helmrath, Michael A; Michalsky, Marc P; Courcoulas, Anita P; Zeller, Meg H; Inge, Thomas H

    2015-09-01

    Little is known about the prevalence of nonalcoholic fatty liver disease (NAFLD) among severely obese adolescents or factors that determine its development. We investigated the prevalence of NAFLD in a multicenter cohort of adolescents undergoing bariatric surgery and the factors associated with it. We enrolled 242 adolescents undergoing bariatric surgery between March 2007 and February 2012 at 5 tertiary care centers into a multicenter, prospective observational cohort study. Intraoperative core liver biopsies were collected from 165 subjects; 17 were excluded because of insufficient liver tissue or use of hepatotoxic medications, so 148 remained in the study (mean age, 16.8 ± 1.6 years; median body mass index = 52 kg/m(2)). Liver tissues were analyzed by histology using validated criteria. Hepatic gene expression was analyzed in 67 samples. NAFLD was present in 59% of this predominantly female (72%), white (68%), non-Hispanic (91%) cohort. Of subjects with NAFLD, 24% had borderline and 10% had definite nonalcoholic steatohepatitis (NASH). Mild fibrosis (stage 2 or lower) was observed in 18% of liver biopsies and stage 3 was observed in 0.7%, but cirrhosis was not detected. Dyslipidemia was present in 78% of subjects, hypertension in 44%, and diabetes in 14%. More severe NAFLD was associated with increasing levels of alanine aminotransferase, fasting glucose level, hypertension (each P adolescents undergoing bariatric surgery in this cohort had NAFLD, yet the prevalence of severe or fibrotic NASH was low. Increasing severity of NAFLD was associated with level of alanine aminotransferase and cardiometabolic risk factors, but not body mass index. Based on gene expression analysis, borderline and definite NASH were associated with abnormal immune function, intestinal cholesterol absorption, and lipid metabolism. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

  18. Decreased hepatotoxic bile acid composition and altered synthesis in progressive human nonalcoholic fatty liver disease

    International Nuclear Information System (INIS)

    Lake, April D.; Novak, Petr; Shipkova, Petia; Aranibar, Nelly; Robertson, Donald; Reily, Michael D.; Lu, Zhenqiang; Lehman-McKeeman, Lois D.; Cherrington, Nathan J.

    2013-01-01

    Bile acids (BAs) have many physiological roles and exhibit both toxic and protective influences within the liver. Alterations in the BA profile may be the result of disease induced liver injury. Nonalcoholic fatty liver disease (NAFLD) is a prevalent form of chronic liver disease characterized by the pathophysiological progression from simple steatosis to nonalcoholic steatohepatitis (NASH). The hypothesis of this study is that the ‘classical’ (neutral) and ‘alternative’ (acidic) BA synthesis pathways are altered together with hepatic BA composition during progression of human NAFLD. This study employed the use of transcriptomic and metabolomic assays to study the hepatic toxicologic BA profile in progressive human NAFLD. Individual human liver samples diagnosed as normal, steatosis, and NASH were utilized in the assays. The transcriptomic analysis of 70 BA genes revealed an enrichment of downregulated BA metabolism and transcription factor/receptor genes in livers diagnosed as NASH. Increased mRNA expression of BAAT and CYP7B1 was observed in contrast to decreased CYP8B1 expression in NASH samples. The BA metabolomic profile of NASH livers exhibited an increase in taurine together with elevated levels of conjugated BA species, taurocholic acid (TCA) and taurodeoxycholic acid (TDCA). Conversely, cholic acid (CA) and glycodeoxycholic acid (GDCA) were decreased in NASH liver. These findings reveal a potential shift toward the alternative pathway of BA synthesis during NASH, mediated by increased mRNA and protein expression of CYP7B1. Overall, the transcriptomic changes of BA synthesis pathway enzymes together with altered hepatic BA composition signify an attempt by the liver to reduce hepatotoxicity during disease progression to NASH. - Highlights: ► Altered hepatic bile acid composition is observed in progressive NAFLD. ► Bile acid synthesis enzymes are transcriptionally altered in NASH livers. ► Increased levels of taurine and conjugated bile acids

  19. Characterization of nonalcoholic fatty liver disease unrelated to the metabolic syndrome.

    Science.gov (United States)

    Yilmaz, Yusuf; Senates, Ebubekir; Ayyildiz, Talat; Colak, Yasar; Tuncer, Ilyas; Ovunc, Ayse Oya Kurdas; Dolar, Enver; Kalayci, Cem

    2012-04-01

    Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome (MS). However, not all patients with the MS will develop NAFLD and not all patients with NAFLD have the MS. We sought to investigate the differences between patients with biopsy-proven NAFLD with and without the MS. A total of 357 consecutive patients with biopsy-proven NAFLD were analysed. Of them, 216 patients had nonalcoholic steatohepatitis (NASH) and 96 a fibrosis score ≥ 2. The MS was defined as ≥ 3 of the ATP III criteria. A total of 214 patients with NAFLD met the criteria for the MS, while the remaining 143 did not. In NAFLD patients with the MS, homeostasis model of insulin resistance (P = 0·03; OR, 1·06; 95% CI, 1·023-1·25 per unit increase) and diabetes (P = 0·01; OR, 1·2; 95% CI, 1·1-2·4) were independent predictors of NASH. In NAFLD patients without the MS, the only variable independently associated with NASH was haemoglobin (P = 0·007; OR, 1·9; 95% CI, 1·4-3·6 per 50 g/L increase). Alanine aminotransferase (P = 0·03; OR, 1·04; 95% CI, 1·006-1·11 per 10 U/L increase) was an independent predictor of fibrosis ≥ 2 in NAFLD patients with the MS, while haemoglobin (P = 0·02; OR, 1·4; 95% CI, 1·2-1·9 per 50 g/L increase) was the only variable significantly associated with fibrosis ≥ 2 in NAFLD patients without the MS. Increased haemoglobin in NAFLD subjects without MS should be considered in the selection of cases for histological assessment. © 2011 The Authors. European Journal of Clinical Investigation © 2011 Stichting European Society for Clinical Investigation Journal Foundation.

  20. Genetic ancestry analysis in non-alcoholic fatty liver disease patients from Brazil and Portugal.

    Science.gov (United States)

    Cavalcante, Lourianne Nascimento; Stefano, Jose Tadeu; Machado, Mariana V; Mazo, Daniel F; Rabelo, Fabiola; Sandes, Kiyoko Abe; Carrilho, Flair José; Cortez-Pinto, Helena; Lyra, Andre Castro; de Oliveira, Claudia P

    2015-06-08

    To study the association between genetic ancestry, non-alcoholic fatty liver disease (NAFLD) metabolic characteristics in two cohorts of patients, from Brazil and Portugal. We included 131 subjects from Brazil [(n = 45 with simple steatosis (S. Steatosis) and n = 86 with nonalcoholic steatohepatitis (NASH)] and 90 patients from Portugal (n = 66, S. Steatosis; n = 24, NASH). All patients had biopsy-proven NAFLD. In histologic evaluation NAFLD activity score was used to assess histology and more than 5 points defined NASH in this study. Patients were divided into two groups according to histology diagnosis: simple steatosis or non-alcoholic statohepatitis. Genetic ancestry was assessed using real-time polymerase chain reaction. Seven ancestry informative markers (AT3-I/D, LPL, Sb19.3, APO, FY-Null, PV92, and CKMM) with the greatest ethnic-geographical differential frequencies (≥ 48%) were used to define genetic ancestry. Data were analyzed using R PROJECTS software. Ancestry allele frequencies between groups were analyzed by GENEPOP online and the estimation of genetic ancestry contribution was evaluated by ADMIX-95 software. The 5% alpha-error was considered as significant (P 2.5 [NASH 5.3 (70.8%) vs S. Steatosis 4.6 (29.2%) P = 0.04]. In the Portuguese study population, dyslipidemia was present in all patients with NASH (P = 0.03) and hypertension was present in a larger percentage of subjects in the S. Steatosis group (P = 0.003, respectively). The genetic ancestry contribution among Brazilian and Portuguese individuals with NASH was similar to those with S. Steatosis from each cohort (Brazilian cohort: P = 0.75; Portuguese cohort: P = 0.97). Nonetheless, the genetic ancestry contribution of the Brazilian and Portuguese population were different, and a greater European and Amerindian ancestry contribution was detected in the Portuguese population while a higher African genetic ancestry contribution was observed in Brazilian population of both NASH and S

  1. Genetic ancestry analysis in non-alcoholic fatty liver disease patients from Brazil and Portugal

    Science.gov (United States)

    Cavalcante, Lourianne Nascimento; Stefano, Jose Tadeu; Machado, Mariana V; Mazo, Daniel F; Rabelo, Fabiola; Sandes, Kiyoko Abe; Carrilho, Flair José; Cortez-Pinto, Helena; Lyra, Andre Castro; de Oliveira, Claudia P

    2015-01-01

    AIM: To study the association between genetic ancestry, non-alcoholic fatty liver disease (NAFLD) metabolic characteristics in two cohorts of patients, from Brazil and Portugal. METHODS: We included 131 subjects from Brazil [(n = 45 with simple steatosis (S. Steatosis) and n = 86 with nonalcoholic steatohepatitis (NASH)] and 90 patients from Portugal (n = 66, S. Steatosis; n = 24, NASH). All patients had biopsy-proven NAFLD. In histologic evaluation NAFLD activity score was used to assess histology and more than 5 points defined NASH in this study. Patients were divided into two groups according to histology diagnosis: simple steatosis or non-alcoholic statohepatitis. Genetic ancestry was assessed using real-time polymerase chain reaction. Seven ancestry informative markers (AT3-I/D, LPL, Sb19.3, APO, FY-Null, PV92, and CKMM) with the greatest ethnic-geographical differential frequencies (≥ 48%) were used to define genetic ancestry. Data were analyzed using R PROJECTS software. Ancestry allele frequencies between groups were analyzed by GENEPOP online and the estimation of genetic ancestry contribution was evaluated by ADMIX-95 software. The 5% alpha-error was considered as significant (P 2.5 [NASH 5.3 (70.8%) vs S. Steatosis 4.6 (29.2%) P = 0.04]. In the Portuguese study population, dyslipidemia was present in all patients with NASH (P = 0.03) and hypertension was present in a larger percentage of subjects in the S. Steatosis group (P = 0.003, respectively). The genetic ancestry contribution among Brazilian and Portuguese individuals with NASH was similar to those with S. Steatosis from each cohort (Brazilian cohort: P = 0.75; Portuguese cohort: P = 0.97). Nonetheless, the genetic ancestry contribution of the Brazilian and Portuguese population were different, and a greater European and Amerindian ancestry contribution was detected in the Portuguese population while a higher African genetic ancestry contribution was observed in Brazilian population of both NASH

  2. The Relationship between Nonalcoholic Fatty Liver Disease and Colorectal Cancer: The Future Challenges and Outcomes of the Metabolic Syndrome

    OpenAIRE

    Muhidin, Said O.; Magan, Ahmed A.; Osman, Khalid A.; Syed, Shareef; Ahmed, Mohamed H.

    2012-01-01

    Nonalcoholic fatty liver disease (NAFLD) is closely related to insulin resistance, metabolic syndrome, obesity, type 2 diabetes, and dyslipidaemia. Obesity and metabolic syndrome are associated with an increased cancer risk, and recent evidence demonstrated an association between NAFLD and colorectal cancer (CRC). The mechanism of how NAFLD can be associated with increased risk of CRC is not fully understood; however, NAFLD represents a condition of profound insulin resistance and a proinflam...

  3. Editor’s Pick: Non-Alcoholic Fatty Liver Disease – Changing the Prevalence of Liver Cancer?

    OpenAIRE

    Benedetta Campana; David Semela; Markus Heim; Christine Bernsmeier

    2015-01-01

    Due to its increasing prevalence, exceeding 25% of the Western population, non-alcoholic fatty liver disease (NAFLD) merits recognition as one of the most frequent chronic liver diseases (CLD) and requires consideration of the associated disease-related complications and their consequences for the surveillance and treatment of patients and the socio-economy worldwide. Along with the increasing incidence of NAFLD-related cirrhosis and end-stage liver disease, the frequency of NAFLD-related he...

  4. Circulating microRNAs as Potential Biomarkers in Non-Alcoholic Fatty Liver Disease and Hepatocellular Carcinoma

    OpenAIRE

    Afonso, Marta B.; Rodrigues, Pedro M.; Sim?o, Andr? L.; Castro, Rui E.

    2016-01-01

    Obesity and metabolic syndrome are growing epidemics worldwide and greatly responsible for many liver diseases, including nonalcoholic fatty liver disease (NAFLD). NAFLD often progresses to cirrhosis, end-stage liver failure and hepatocellular carcinoma (HCC), the most common primary liver cancer and one of the leading causes for cancer-related deaths globally. Currently available tools for the diagnosis of NAFLD staging and progression towards HCC are largely invasive and of limited accuracy...

  5. Obesity in children and adolescents: the relation between metabolic syndrome and non-alcoholic fatty-liver disease

    OpenAIRE

    Duarte,Maria Amélia Soares de Melo; Silva,Giselia Alves Pontes da

    2010-01-01

    This article aims to review clinical and diagnostic aspects of non-alcoholic fatty liver disease associated with obesity and its relation to metabolic syndrome in children and adolescents. An on-line search was carried out of original articles in the Medical Literature Analysis and Retrieval System Online (MEDLINE), Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS) and Scientific Eletronic Library Online (SciELO) databases, using the following key words: "hepatic steatosis...

  6. Quality of Life of Patients with Stable Coronary Artery Disease Combined with Non-Alcoholic Fatty Liver Disease

    OpenAIRE

    Vakalyuk, Iryna; Virstyuk, Nataliya; Petryna, Vitaliy

    2016-01-01

    Quality of life assessment is an integral part of a comprehensive treatment in modern medical practice. Analysis of quality of life of patients with comorbidities is an interesting and poorly understood issue.  The objective of the research was to evaluate the quality of life of patients with postinfarction cardiosclerosis depending on the presence and progression of non-alcoholic fatty liver disease (NAFLD). Material and methods. The research included 300 patients with stable coronary ...

  7. Bariatric Surgery as Potential Treatment for Nonalcoholic Fatty Liver Disease: A Future Treatment by Choice or by Chance?

    OpenAIRE

    Hafeez, Shuja; Ahmed, Mohamed H.

    2013-01-01

    Morbid obesity is strongly associated with nonalcoholic fatty liver disease (NAFLD) which is one of the most common causes of chronic liver disease worldwide. The current best treatment of NAFLD and NASH is weight reduction through life style modifications, antiobesity medication, and bariatric surgery. Importantly, bariatric surgery is the best alternative option for weight reduction if lifestyle modifications and pharmacological therapy have not yielded long-term success. Bariatric surgery ...

  8. Intake of nutrients, fiber, and sugar in patients with nonalcoholic fatty liver disease in comparison to healthy individuals

    OpenAIRE

    Hamid Zolfaghari; Gholamreza Askari; Fereydoun Siassi; Awat Feizi; Gity Sotoudeh

    2016-01-01

    Background: Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the world. Although some studies have been conducted about dietary intakes of these patients, but the results are inconsistent. The aim of this study was to survey all macronutrients and micronutrients included in dietary intake of these patients for better understanding the factors influencing this disease. Methods: The present study is a case-control conducted in Isfahan city, Iran....

  9. Prevalence of Nonalcoholic Fatty Liver Disease in Normal-weight and Overweight Preadolescent Children in Haryana, India.

    Science.gov (United States)

    Das, Manoja Kumar; Bhatia, Vidyut; Sibal, Anupam; Gupta, Abha; Gopalan, Sarath; Sardana, Raman; Sahni, Reeti; Roy, Ankur; Arora, Narendra K

    2017-12-15

    To document the prevalence of non-alcoholic fatty liver disease (NAFLD) and metabolic parameters among normal-weight and overweight schoolchildren. Cross-sectional study. Thirteen private schools in urban Faridabad, Haryana. 961 school children aged 5-10 years. Ultrasound testing was done, and 215 with fatty liver on ultrasound underwent further clinical, biochemical and virological testing. Prevalence of fatty liver on ultrasound, and NAFLD and its association with biochemical abnormalities and demographic risk factors. On ultrasound, 215 (22.4%) children had fatty liver; 18.9% in normal-weight and 45.6% in overweight category. Presence and severity of fatty liver disease increased with body mass index (BMI) and age. Among the children with NAFLD, elevated SGOT and SGPT was observed in 21.5% and 10.4% children, respectively. Liver enzyme derangement was significantly higher in overweight children (27% vs 19.4% in normal-weight) and severity of fatty liver (28% vs 20% in mild fatty liver cases). Eleven (8.1%) children with NAFLD had metabolic syndrome. Higher BMI (OR 35.9), severe fatty liver disease (OR 1.7) and female sex (OR 1.9) had strong association with metabolic syndrome. 22.4% of normal-weight and overweight children aged 5-10 years had fatty liver. A high proportion (18.9%) of normal-weight children with fatty liver on ultrasound indicates the silent burden in the population.

  10. Limitations of liver biopsy and non-invasive diagnostic tests for the diagnosis of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis

    Science.gov (United States)

    Sumida, Yoshio; Nakajima, Atsushi; Itoh, Yoshito

    2014-01-01

    It is estimated that 30% of the adult population in Japan is affected by nonalcoholic fatty liver disease (NAFLD). Fatty changes of the liver are generally diagnosed using imaging methods such as abdominal ultrasonography (US) and computed tomography (CT), but the sensitivity of these imaging techniques is low in cases of mild steatosis. Alanine aminotransferase levels may be normal in some of these patients, warranting the necessity to establish a set of parameters useful for detecting NAFLD, and the more severe form of the disease, nonalcoholic steatohepatitis (NASH). Although liver biopsy is currently the gold standard for diagnosing progressive NASH, it has many drawbacks, such as sampling error, cost, and risk of complications. Furthermore, it is not realistic to perform liver biopsies on all NAFLD patients. Diagnosis of NASH using various biomarkers, scoring systems and imaging methods, such as elastography, has recently been attempted. The NAFIC score, calculated from the levels of ferritin, fasting insulin, and type IV collagen 7S, is useful for the diagnosis of NASH, while the NAFLD fibrosis score and the FIB-4 index are useful for excluding NASH in cases of advanced fibrosis. This article reviews the limitations and merits of liver biopsy and noninvasive diagnostic tests in the diagnosis of NAFLD/NASH. PMID:24574716

  11. Does propolis have any effect on non-alcoholic fatty liver disease?

    Science.gov (United States)

    Kismet, Kemal; Ozcan, Cigdem; Kuru, Serdar; Gencay Celemli, Omur; Celepli, Pinar; Senes, Mehmet; Guclu, Tuncay; Sorkun, Kadriye; Hucumenoglu, Sema; Besler, Tanju

    2017-06-01

    The aim of this study was to evaluate the therapeutic effect of propolis on non-alcoholic fatty liver disease (NAFLD) in rats. The rats were randomly divided into 3 groups of 10 as the NAFLD, NAFLD+100 and NAFLD+200 groups. The rats were fed with a fatty diet (25g/kg/day) to provoke NAFLD. Then after the formation of fatty liver, a standard diet (SD) (25g/kg/day) was given to the NAFLD group and the other two groups were fed with SD and 100mg/kg (NAFLD+100 Group) or 200mg/kg propolis (NAFLD+200 Group) for two weeks. At the end of two weeks the animals were sacrificed. Blood and tissue samples were taken for biochemical and histopathological evaluations. The propolis-treated groups had better results in serum lipids (total cholesterol, non-HDL cholesterol, triglyceride), ALT, and ALP values. When compared with the NAFLD group, IL-6 and TNF-α values decreased in the NAFLD+100 and NAFLD+200 groups. The administration of propolis to the rats significantly reduced serum and tissue MDA and GPX values and increased SH in serum when compared with the NAFLD group. No difference was determined between the groups treated with two different doses of propolis in respect of biochemical values. When the mean histological scores of the groups were compared, statistically significant differences were found between the NAFLD group and the propolis-treated groups. No difference was determined between the groups treated with the two different doses of propolis in respect of histopathological results. Propolis had positive effects on histopathological and biochemical parameters of NAFLD and these effects were related to the anti-oxidant and anti-inflammatory effects of propolis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  12. Prevalence and determinants of non-alcoholic fatty liver disease in lifelines: A large Dutch population cohort.

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    Eline H van den Berg

    Full Text Available Non-alcoholic fatty liver disease is an increasing health issue that develops rather unnoticed with obesity, type 2 diabetes mellitus and metabolic syndrome. We investigated prevalence, determinants and associated metabolic abnormalities of non-alcoholic fatty liver disease in the largest population-based cohort to date.Biochemical characteristics, type 2 diabetes mellitus and metabolic syndrome were determined in the Lifelines Cohort Study (N = 167,729, a population-based cohort in the North of the Netherlands. Non-alcoholic fatty liver disease was defined as Fatty Liver Index (FLI≥60. Exclusion criteria were age <18 years, immigrants, missing data to assess FLI and metabolic syndrome, excessive alcohol use, previous-diagnosed hepatitis or cirrhosis and non-fasting blood sampling.Out of 37,496 included participants (median age 44 years, 62.1% female, 8,259 (22.0% had a FLI≥60. Individuals with a FLI≥60 were more often male, older, obese, had higher levels of hemoglobinA1c, fasting glucose, liver enzymes, total cholesterol, low-density lipoprotein cholesterol, triglycerides, c-reactive protein and leucocytes and lower high-density lipoprotein cholesterol (all P<0.0001. Participants with a FLI≥60 showed higher prevalence of type 2 diabetes mellitus (9.3% vs. 1.4%, metabolic syndrome (54.2% vs. 6.2%, impaired renal function (20.1% vs. 8.7% and cardiovascular disease (4.6% vs. 1.6% (all P<0.0001. Multivariable logistic analysis showed that smoking, hemoglobin, leucocytes, c-reactive protein, platelets, alanine aminotransferase, alkaline phosphatase, albumin, impaired renal function (OR 1.27, 95%CI 1.15-1.41, metabolic syndrome (OR 11.89, 95%CI 11.03-12.82 and its individual components hyperglycemia (OR 2.53, 95%CI 2.34-2.72, hypertension (OR 1.89, 95%CI 1.77-2.01 and reduced high-density lipoprotein cholesterol (OR 3.44, 95%CI 3.22-3.68 were independently associated with suspected non-alcoholic fatty liver disease (all P<0.0001.Twenty

  13. Probiotics as a Novel Treatment for Non-Alcoholic Fatty Liver Disease; A Systematic Review on the Current Evidences

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    Kelishadi, Roya; Farajian, Sanam; Mirlohi, Maryam

    2013-01-01

    Context Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease, with 5-10% of liver having extra fat. Increase in its prevalence in all age groups is linked with obesity and Type II diabetes. The treatment of NAFLD remains controversial. A growing body of evidence suggests a relation between overgrowth of gut microbiota with NAFLD and non-alcoholic steatohepatitis (NASH). The objective of this review is to provide an overview on experimental and clinical studies assessing all positive and negative effects of probiotics. Evidence Acquisition We made a critical appraisal on various types of documents published from 1999 to March 2012 in journals, electronic books, seminars, and symposium contexts including Medline, PubMed, and Cochrane Central Register of Controlled Trials databases. We used the key words: “non-alcoholic fatty liver disease, probiotics, non-alcoholic steatohepatitis, liver disease, and fatty liver”. Results Probiotics, as biological factors, control the gut microbiota and result in its progression. It is in this sense that they are suggestive of a new and a natural way of promoting liver function. Correspondingly, limited evidence suggests that probiotics could be considered as a new way of treatment for NAFLD. Conclusions Various experimental studies and clinical trials revealed promising effects of probiotics in improving NAFLD; however given the limited experience in this field, generalization of probiotics as treatment of NAFLD needs substantiation through more trials with a larger sample sizes and with longer-term follow up. PMID:23885277

  14. Effect of resveratrol on experimental non-alcoholic fatty liver disease depends on severity of pathology and timing of treatment.

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    Heebøll, Sara; El-Houri, Rime Bahij; Hellberg, Ylva Erika Kristina; Haldrup, David; Pedersen, Steen Bønløkke; Jessen, Niels; Christensen, Lars Porskjaer; Grønbaek, Henning

    2016-03-01

    Non-alcoholic steatohepatitis (NASH) is a leading cause of chronic liver disease with few therapeutic options. Resveratrol (RSV) prevents the development of steatosis in a number of experimental fatty liver (non-alcoholic fatty liver [NAFL]) models, but the preventive or therapeutic effects on experimental NASH are not yet clarified, and clinical results on non-alcoholic fatty liver disease are ambiguous. Thus, we aimed to compare the RSV-mediated preventive and therapeutic effects on experimental NAFL and NASH. We used a high-fat (HF) diet to generate a rat NAFL model and a high-fat, high-cholesterol (HFC) diet to generate a rat NASH model. The preventive and therapeutic potential of RSV was tested by adding RSV to the HF and HFC diet from study start or after 1 week of the diets. Animals were sacrificed after 8 weeks with appropriate controls. Blood and liver were harvested for analysis, including measurement of RSV metabolites. Resveratrol reduced the development of histological steatosis (P = 0.03) and partly triglyceride accumulation (fold change reduced from 3.6 to 2.4, P = 0.08) in the male NAFL model, although effects were moderate. In NASH prevention, RSV reduced the accumulation of triglyceride in hepatic tissue (P hepatic benefit of RSV treatment is seen in prevention of steatosis only. © 2015 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  15. Association of Serum Adipocyte-Specific Fatty Acid Binding Protein with Fatty Liver Index as a Predictive Indicator of Nonalcoholic Fatty Liver Disease

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    Won Seon Jeon

    2013-12-01

    Full Text Available BackgroundAdipocyte-specific fatty acid-binding protein (A-FABP is a cytoplasmic protein expressed in macrophages and adipocytes and it plays a role in insulin resistance and metabolic syndrome. Recently, the fatty liver index (FLI was introduced as an indicator of nonalcoholic fatty liver disease (NAFLD. In this study, we aimed to investigate the relationship between baseline serum A-FABP levels and FLI after 4 years in apparently healthy subjects.MethodsA total of 238 subjects without a past history of alcoholism or hepatitis were recruited from a medical check-up program. The NAFLD state was evaluated 4 years later in the same subjects using FLI. Fatty liver disease was diagnosed as diffusely increased echogenicity of the hepatic parenchyma compared to the kidneys, vascular blurring, and deep-echo attenuation. NAFLD was defined as subjects with fatty liver and no history of alcohol consumption (>20 g/day.ResultsBaseline serum A-FABP levels were significantly associated with FLI after adjustment for age and sex (P<0.001. The subjects with higher A-FABP levels had a higher mean FLI (P for trend=0.006. After adjusting for age and sex, serum A-FABP levels at baseline were shown to be significantly associated with FLI as a marker of development of NAFLD after 4 years (odds ratio, 2.68; 95% confidence interval, 1.24 to 5.80 for highest tertile vs. lowest tertile; P=0.012.ConclusionThis study demonstrated that higher baseline serum A-FABP levels were associated with FLI as a predictive indicator of NAFLD after 4 years of follow-up in healthy Korean adults.

  16. Clinical correlation of nonalcoholic fatty liver disease in a Chinese taxi drivers population in Taiwan: Experience at a teaching hospital

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    2011-01-01

    Background To explore any gender-related differences in the prevalence of conditions-associated with non-alcoholic fatty liver disease (NAFLD) among Taiwanese taxi drivers in Taipei, Taiwan. Methods We studied 1635 healthy taxi drivers (1541 males and 94 females) who volunteered for physical check-ups in 2006. Blood samples and ultrasound fatty liver sonography results were collected. Results The prevalence of NAFLD was 66.4% and revealed no statistically significant decrease with increasing age (p = 0.58). Males exhibited a greater prevalence of NAFLD than did females (67.5% vs 47.9%, p taxi drivers. PMID:21878129

  17. Transient Elastography Role in the Diagnosis of Nonalcoholic Fatty Liver Disease

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    Yu.M. Stepanov

    2016-04-01

    Full Text Available Non-alcoholic fatty liver disease includes hepatic steatosis, steatohepatitis and fibrosis, which can progress to cirrhosis. In view of the prevalence of this disease, the deterioration of the quality of life of patients, mortality from complications, the development of methods for accurate and timely assessment of the severity of fatty liver and progression of fibrosis are becoming of greater interest. Purpose. The study of diagnostic potential of transient elastography in patients with idiopathic transaminase elevations. Methods. In 52 patients (20 men and 32 women with idiopathic increased transaminases without signs of hepatic steatosis according to sonographic study, controlled attenuation parameter (CAP and liver stiffness measurements (LSM were performed using FibroScan with M probe. Exclusion criteria from the study were the presence of chronic viral, autoimmune hepatitis and alcohol abuse. Results. Forty one patients (78.8 % had fatty liver disease according to CAP. The analysis of the data of transient elastography demonstrated that 63.4 % had fibrosis F0–F1, 29.3 % — F1–F2 and in 7.3 % — F3. In terms of the CAP there were significant differences between the group with severe fibrosis (F3 and groups with minimal fibrosis (F0–F1 ((203.0 ± 5.1 vs. (243.0 ± 10.1, p < 0.05. The analysis of biochemical parameters demonstrated significant differences in terms of gamma-glutamyltransferase in the groups with severe fibrosis (F3 and minimal fibrosis ((40.2 ± 5.7 vs. (26.4 ± 3.7, p < 0.05. Thus, the results obtained in the study indicate that a significant proportion of patients with idiopathic transaminase elevations inflammation factor is fatty liver disease, which is not detected at routine ultrasound examination. In the group with more expressed fibrosis reduction of fat in the liver and increased activity gamma glutamyltransferase were determined, that indicated the cholestasis deterioration in the liver in these patients

  18. Fatty acids in non-alcoholic steatohepatitis: Focus on pentadecanoic acid.

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    Wonbeak Yoo

    Full Text Available Non-alcoholic fatty liver disease (NAFLD is the most common form of liver disease and ranges from isolated steatosis to NASH. To determine whether circulating fatty acids could serve as diagnostic markers of NAFLD severity and whether specific fatty acids could contribute to the pathogenesis of NASH, we analyzed two independent NAFLD patient cohorts and used the methionine- and choline-deficient diet (MCD NASH mouse model. We identified six fatty acids that could serve as non-invasive markers of NASH in patients with NAFLD. Serum levels of 15:0, 17:0 and 16:1n7t negatively correlated with NAFLD activity scores and hepatocyte ballooning scores, while 18:1n7c serum levels strongly correlated with fibrosis stage and liver inflammation. Serum levels of 15:0 and 17:0 also negatively correlated with fasting glucose and AST, while 16:1n7c and 18:1n7c levels positively correlated with AST and ferritin, respectively. Inclusion of demographic and clinical parameters improved the performance of the fatty acid panels in detecting NASH in NAFLD patients. The panel [15:0, 16:1n7t, 18:1n7c, 22:5n3, age, ferritin and APRI] predicted intermediate or advanced fibrosis in NAFLD patients, with 82% sensitivity at 90% specificity [AUROC = 0.92]. 15:0 and 18:1n7c were further selected for functional studies in vivo. Mice treated with 15:0-supplemented MCD diet showed reduced AST levels and hepatic infiltration of ceroid-laden macrophages compared to MCD-treated mice, suggesting that 15:0 deficiency contributes to liver injury in NASH. In contrast, 18:1n7c-supplemented MCD diet didn't affect liver pathology. In conclusion, 15:0 may serve as a promising biomarker or therapeutic target in NASH, opening avenues for the integration of diagnosis and treatment.

  19. Aerobic vs. resistance exercise in non-alcoholic fatty liver disease: A systematic review.

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    Hashida, Ryuki; Kawaguchi, Takumi; Bekki, Masafumi; Omoto, Masayuki; Matsuse, Hiroo; Nago, Takeshi; Takano, Yoshio; Ueno, Takato; Koga, Hironori; George, Jacob; Shiba, Naoto; Torimura, Takuji

    2017-01-01

    Exercise is a first-line therapy for patients with non-alcoholic fatty liver disease (NAFLD). We sought to: 1) summarize effective aerobic and resistance exercise protocols for NAFLD; and 2) compare the effects and energy consumption of aerobic and resistance exercises. A literature search was performed using PubMed, Web of Science, and Scopas to January 28, 2016. From a total of 95 articles, 23 studies including 24 aerobic and 7 resistance exercise protocols were selected for the summary of exercise protocols. Twelve articles including 13 aerobic and 4 resistance exercise protocols were selected for the comparative analysis. For aerobic exercise, the median effective protocol was 4.8 metabolic equivalents (METs) for 40min/session, 3times/week for 12weeks. For resistance exercise, the median effective protocol was 3.5 METs for 45min/session, 3times/week for 12weeks. Aerobic and resistance exercise improved hepatic steatosis. No significant difference was seen in the duration, frequency, or period of exercise between the two exercise groups; however, %VO 2 max and energy consumption were significantly lower in the resistance than in the aerobic group (50% [45-98] vs. 28% [28-28], p=0.0034; 11,064 [6394-21,087] vs. 6470 [4104-12,310] kcal/total period, p=0.0475). Resistance exercise improves NAFLD with less energy consumption. Thus, resistance exercise may be more feasible than aerobic exercise for NAFLD patients with poor cardiorespiratory fitness or for those who cannot tolerate or participate in aerobic exercise. These data may indicate a possible link between resistance exercise and lipid metabolism in the liver. Both aerobic and resistance exercise reduce hepatic steatosis in non-alcoholic fatty liver disease (NAFLD) with similar frequency, duration, and period of exercise (40-45min/session 3times/week for 12weeks); however, the two forms of exercise have different characteristics. Intensity and energy consumption were significantly lower for resistance than for

  20. Pharmacological promotion of autophagy alleviates steatosis and injury in alcoholic and non-alcoholic fatty liver conditions in mice.

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    Lin, Chih-Wen; Zhang, Hao; Li, Min; Xiong, Xiwen; Chen, Xi; Chen, Xiaoyun; Dong, Xiaocheng C; Yin, Xiao-Ming

    2013-05-01

    Pharmacological approaches can potentially improve fatty liver condition in alcoholic and non-alcoholic fatty liver diseases. The salutary effects of reducing lipid synthesis or promoting lipid oxidation have been well reported, but the benefits of increasing lipid degradation have yet to be well explored. Macroautophagy is a cellular degradation process that can remove subcellular organelles including lipid droplets. We thus investigated whether pharmacological modulation of macroautophagy could be an effective approach to alleviate fatty liver condition and liver injury. C57BL/6 mice were given ethanol via intraperitoneal injection (acute) or by a 4-week oral feeding regime (chronic), or high fat diet for 12 weeks. An autophagy enhancer, carbamazepine or rapamycin, or an autophagy inhibitor, chloroquine, was given before sacrifice. Activation of autophagy, level of hepatic steatosis, and blood levels of triglycerides, liver enzyme, glucose and insulin were measured. In both acute and chronic ethanol condition, macroautophagy was activated. Carbamazepine, as well as rapamycin, enhanced ethanol-induced macroautophagy in hepatocytes in vitro and in vivo. Hepatic steatosis and liver injury were exacerbated by chloroquine, but alleviated by carbamazepine. The protective effects of carbamazepine and rapamycin in reducing steatosis and in improving insulin sensitivity were also demonstrated in high fat diet-induced non-alcoholic fatty liver condition. These findings indicate that pharmacological modulation of macroautophagy in the liver can be an effective strategy for reducing fatty liver condition and liver injury. Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  1. An Overview of Dietary Interventions and Strategies to Optimize the Management of Non-Alcoholic Fatty Liver Disease

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    Brandon J. Perumpail

    2017-10-01

    Full Text Available Aim: To investigate the efficacy of lifestyle adjustment strategies as a preventive measure and/or treatment of obesity-related non-alcoholic fatty liver disease in adults. Method: A systematic review of literature through 1 July 2017 on the PubMed Database was performed. A comprehensive search was conducted using key terms, such as non-alcoholic fatty liver disease (NAFLD, combined with lifestyle intervention, diet, and exercise. All of the articles and studies obtained from the search were reviewed. Redundant literature was excluded. Results: Several types of dietary compositions and exercise techniques were identified. Most studies concluded and recommended reduction in the intake of saturated and trans fatty acids, carbohydrates, and animal-based protein, and increased intake of polyunsaturated fatty acids (PUFAs, monounsaturated fatty acids (MUFAs, plant-based proteins, antioxidants, and other nutrients was recommended. The Mediterranean and Paleo diet both seem to be promising schemes for NAFLD patients to follow. Exercise was also encouraged, but the type of exercise did not affect its efficacy as a NAFLD treatment when the duration is consistent. Conclusions: Although these different dietary strategies and exercise regimens can be adopted to treat NAFLD, current literature on the topic is limited in scope. Further research should be conducted to truly elucidate which lifestyle adjustments individually, and in combination, may facilitate patients with obesity-related NAFLD.

  2. Association between serum irisin levels and non-alcoholic fatty liver disease in health screen examinees.

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    Eun Sung Choi

    Full Text Available Irisin is a recently found myokine that aids obesity control and improves glucose homeostasis by acting on white adipose tissue cells and increases total energy consumption. The aim of this study was to evaluate serum irisin levels in patients with non-alcoholic fatty liver disease (NAFLD and to compare these levels with those of normal controls. Among 595 health screen examinees who had visited our institute between January 2013 to March 2013, 355 patients (84 NAFLD patients and 271 normal controls were enrolled depending on whether they gave written informed consents and their history of alcohol intake, blood tests, and abdominal ultrasonographic findings. Age; sex; laboratory test parameters; homeostasis model assessment-insulin resistance; and levels of leptin, adiponectin, and irisin were assessed. Serum irisin levels (ng/ml were significantly higher in the NAFLD group than in normal controls (63.4 ± 32.6 vs. 43.0 ± 29.7, p<0.001 and higher in the mild fatty liver group than in the moderate-to-severe fatty liver group (68.3 ± 38.2 vs. 56.6 ± 21.2, p<0.001. Additionally, serum irisin levels were not different between the non-obese and obese groups (48.4 ± 34.2 vs. 45.8 ± 22.9, p = 0.492; however, the levels were significantly lowest in normal controls and highest in the mild fatty liver group in the non-obese (44.9 ± 31.7 vs. 73.1 ± 48.5 vs 59.7 ± 18.0, p<0.001 and obese groups (35.0 ± 17.0 vs. 62.9 ± 21.2 vs. 54.6 ± 23.3, p<0.001. Serum irisin levels were significantly higher in NAFLD patients, which is not consistent with the results of previously published studies. Therefore, more studies are needed to confirm the role of irisin in NAFLD.

  3. Effects of nigella sativa on various parameters in Patients of non-alcoholic fatty liver disease.

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    Hussain, Mazhar; Tunio, Ali Gul; Akhtar, Lubna; Shaikh, Ghulam Serwar

    2017-01-01

    Non-alcoholic Fatty Liver disease (NAFLD) is the most common cause of progressive liver disorders worldwide. Drug options are limited with varying results. Nigella sativa in the form of herbal medicine could be another option because of its strong historical background. The objective of the study was to evaluate the effect Nigella sativa on various parameters in patients of NAFLD. A randomized controlled trial was conducted at outpatient clinic of medical unit-1 of Sheikh Zayed Medical College/Hospital, Rahim Yar Khan, in which seventy patients of NAFLD were divided in to interventional and non-interventional groups. The interventional group was given cap Nigella sativa 1g twice a day while noninterventional group was given cap placebo in a same way for three months. Body weight, BMI, liver enzymes and ultrasound finding of fatty liver were assayed before and after treatment. After 12 weeks treatment with Nigella sativa body weight decreased significantly from 86±13.8 to76±12.6 kg vs placebo (p=0.041). BMI also reduced significantly from 29.06±4.6 to 26.25±6.2kg/m2 vs placebo (p=0.012). There is remarkable reduction in aminotransferases level after treatment with Nigella sativa vs placebo (ALT: 78.05±5.52 to 52.6±5.65 IU/L vs 76.48±4.95-74.32±5.58 IU/L (p=0.036). AST: 65.54±4.56-44.56±5.52 IU/L vs 63.25±5.43- 59.43±3.39 IU/L (p=0.021). There was overall 57.14 % patient had normal fatty liver grading on ultrasound after 12 weeks treatment with Nigella sativa as compared to placebo (p=0.002). Nigella sativa improves bio chemical and fatty liver changes in NAFLD patients. Its use in early stages of NAFLD is recommended in order to prevent its life-threatening complication.

  4. Effects of nigella sativa on various parameters in patients of non-alcoholic fatty liver disease

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    Hussain, M.; Shaikh, G.S.

    2017-01-01

    Background: Non-alcoholic Fatty Liver disease (NAFLD) is the most common cause of progressive liver disorders worldwide. Drug options are limited with varying results. Nigella sativa in the form of herbal medicine could be another option because of its strong historical background. The objective of the study was to evaluate the effect Nigella sativa on various parameters in patients of NAFLD. Methods: A randomized controlled trial was conducted at outpatient clinic of medical unit-1 of Sheikh Zayed Medical College/Hospital, Rahim Yar Khan, in which seventy patients of NAFLD were divided in to interventional and non-interventional groups. The interventional group was given cap Nigella sativa 1g twice a day while non-interventional group was given cap placebo in a same way for three months. Body weight, BMI, liver enzymes and ultrasound finding of fatty liver were assayed before and after treatment. Results: After 12 weeks treatment with Nigella sativa body weight decreased significantly from 86±13.8 to76±12.6 kg vs placebo (p=0.041). BMI also reduced significantly from 29.06±4.6 to 26.25±6.2kg/m2 vs placebo(p=0.012). There is remarkable reduction in aminotransferases level after treatment with Nigella sativa vs placebo (ALT: 78.05±5.52 to 52.6±5.65 IU/L vs 76.48±4.95-74.32±5.58 IU/L (p=0.036). AST: 65.54±4.56-44.56±5.52 IU/L vs 63.25±5.43-59.43±3.39 IU/L (p=0.021). There was overall 57.14 % patient had normal fatty liver grading on ultrasound after 12 weeks treatment with Nigella sativa as compared to placebo (p=0.002). Conclusion: Nigella sativa improves bio chemical and fatty liver changes in NAFLD patients. Its use in early stages of NAFLD is recommended in order to prevent its life-threatening complication. (author)

  5. Association between Helicobacter pylori Infection and Nonalcoholic Fatty Liver Disease: A Single-Center Clinical Study

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    Ou Cai

    2018-01-01

    Full Text Available Objective. To investigate the association between Helicobacter pylori (H. pylori infection and nonalcoholic fatty liver disease (NAFLD. Methods. Data from 2051 participants who underwent 13C urea breath test and abdominal ultrasound examinations was collected. Participants were allocated to NAFLD risk group and NAFLD nonrisk group based on definite risk factors for NAFLD. The relationship between H. pylori infection and NAFLD was analyzed. Results. No significant difference was found between rates of H. pylori infection and NAFLD using the chi-square test (P=0.30 or regression analysis (P=0.70. There was no significant difference between rates of H. pylori infection with and without NAFLD (P=0.47 in the NAFLD risk group or in the NAFLD nonrisk group (P=0.59. There was no significant difference between rates of H. pylori infection in men (P=0.69 and in women (P=0.27 or in participants aged 18–40 years (P=0.43, 41–65 years (P=0.14, and ≥66 years (P=0.66 with and without NAFLD in the NAFLD risk group or between the same sex or age groups (P=0.82, P=0.66, P=0.24, P=0.53, and P=1.00, resp. in the NAFLD nonrisk group. Conclusions. H. pylori infection does not appear to increase the NAFLD prevalence rate or to be associated with, or a risk factor for, NAFLD.

  6. Hepatocellular carcinoma in non-alcoholic fatty liver disease: an emerging menace.

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    Baffy, György; Brunt, Elizabeth M; Caldwell, Stephen H

    2012-06-01

    Hepatocellular carcinoma (HCC) is a common cancer worldwide that primarily develops in cirrhosis resulting from chronic infection by hepatitis B virus and hepatitis C virus, alcoholic injury, and to a lesser extent from genetically determined disorders such as hemochromatosis. HCC has recently been linked to non-alcoholic fatty liver disease (NAFLD), the hepatic manifestation of obesity and related metabolic disorders such as diabetes. This association is alarming due to the globally high prevalence of these conditions and may contribute to the rising incidence of HCC witnessed in many industrialized countries. There is also evidence that NAFLD acts synergistically with other risk factors of HCC such as chronic hepatitis C and alcoholic liver injury. Moreover, HCC may complicate non-cirrhotic NAFLD with mild or absent fibrosis, greatly expanding the population potentially at higher risk. Major systemic and liver-specific molecular mechanisms involved include insulin resistance and hyperinsulinemia, increased TNF signaling pathways, and alterations in cellular lipid metabolism. These provide new targets for prevention, early recognition, and effective treatment of HCC associated with NAFLD. Indeed, both metformin and PPAR gamma agonists have been associated with lower risk and improved prognosis of HCC. This review summarizes current evidence as it pertains to the epidemiology, pathogenesis, and prevention of NAFLD-associated HCC. Published by Elsevier B.V.

  7. Extracellular Vesicles: A New Frontier in Biomarker Discovery for Non-Alcoholic Fatty Liver Disease

    Science.gov (United States)

    Ban, Linda A.; Shackel, Nicholas A.; McLennan, Susan V.

    2016-01-01

    In recent years, the global burden of obesity and diabetes has seen a parallel rise in other metabolic complications, such as non-alcoholic fatty liver disease (NAFLD). This condition, once thought to be a benign accumulation of hepatic fat, is now recognized as a serious and prevalent disorder that is conducive to inflammation and fibrosis. Despite the rising incidence of NAFLD, there is currently no reliable method for its diagnosis or staging besides the highly invasive tissue biopsy. This limitation has resulted in the study of novel circulating markers as potential candidates, one of the most popular being extracellular vesicles (EVs). These submicron membrane-bound structures are secreted from stressed and activated cells, or are formed during apoptosis, and are known to be involved in intercellular communication. The cargo of EVs depends upon the parent cell and has been shown to be changed in disease, as is their abundance in the circulation. The role of EVs in immunity and epigenetic regulation is widely attested, and studies showing a correlation with disease severity have made these structures a favorable target for diagnostic as well as therapeutic purposes. This review will highlight the research that is available on EVs in the context of NAFLD, the current limitations, and projections for their future utility in a clinical setting. PMID:26985892

  8. Extracellular Vesicles: A New Frontier in Biomarker Discovery for Non-Alcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Linda A. Ban

    2016-03-01

    Full Text Available In recent years, the global burden of obesity and diabetes has seen a parallel rise in other metabolic complications, such as non-alcoholic fatty liver disease (NAFLD. This condition, once thought to be a benign accumulation of hepatic fat, is now recognized as a serious and prevalent disorder that is conducive to inflammation and fibrosis. Despite the rising incidence of NAFLD, there is currently no reliable method for its diagnosis or staging besides the highly invasive tissue biopsy. This limitation has resulted in the study of novel circulating markers as potential candidates, one of the most popular being extracellular vesicles (EVs. These submicron membrane-bound structures are secreted from stressed and activated cells, or are formed during apoptosis, and are known to be involved in intercellular communication. The cargo of EVs depends upon the parent cell and has been shown to be changed in disease, as is their abundance in the circulation. The role of EVs in immunity and epigenetic regulation is widely attested, and studies showing a correlation with disease severity have made these structures a favorable target for diagnostic as well as therapeutic purposes. This review will highlight the research that is available on EVs in the context of NAFLD, the current limitations, and projections for their future utility in a clinical setting.

  9. Nonalcoholic Fatty Liver Disease-Related Hepatocellular Carcinoma: A Problem of Growing Magnitude.

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    Pocha, Christine; Kolly, Philippe; Dufour, Jean-Francois

    2015-08-01

    Hepatocellular carcinoma (HCC) is a cancer with globally rising incidence. Growing evidence supports associations between metabolic syndrome and diabetes as well as obesity and HCC arising in patients with nonalcoholic fatty liver disease (NAFLD). This constitutes a problem of alarming magnitude given the rising epidemic of these conditions. The role of diabetes seems to be particularly important when associated with obesity or cirrhosis. Excess hepatic iron may be another potential risk factor for the development of NAFLD-associated HCC. In the context of NAFLD, HCC frequently develops in a not-yet cirrhotic liver. As there are no surveillance programs for these patients, diagnosis often occurs at a tumor stage beyond curative options. Clinical, tumor, and patient characteristics in NAFLD-associated HCC differ from other etiologies. Older age and cardiovascular comorbidities may limit treatment options further. The outcome in patients with NAFLD-associated early HCC is excellent and therefore aggressive treatment should be pursued in appropriate patients. Population-based prevention to reduce the culprit-NAFLD-early recognition through targeted surveillance programs in risk-stratified patients and effective treatment of HCC associated with NAFLD are urgently needed. In this review, the authors summarize the epidemiology, risk factors, features, and prevention of NAFLD-associated HCC. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  10. Non-alcoholic fatty liver disease and its associated risk factors in Brazilian postmenopausal women.

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    Bruno, A de Souza; Rodrigues, M H; Alvares, M C B; Nahas-Neto, J; Nahas, E A Petri

    2014-08-01

    To evaluate the prevalence and risk factors of non-alcoholic fatty liver disease (NAFLD) in postmenopausal women. A cross-sectional study was carried involving 188 women (age ≥ 45 years and amenorrhea ≥ 12 months) attending the outpatient unit in south-eastern Brazil. Exclusion criteria were liver disease (hepatitis B and C, cholestatic disease, liver insufficiency), use of drugs that affect liver metabolism; alcoholics; AIDS or cancer history; and morbid obesity. NAFLD was diagnosed by abdominal ultrasound. Clinical, anthropometric (body mass index, waist circumference) and biochemical variables were measured. Of the 188 women, 73 (38.8%) had NAFLD. Blood pressure, waist circumference, body mass index, LDL cholesterol, triglycerides and glucose were significantly higher in NAFLD patients when compared with women without NAFLD (control group) (p NAFLD group (6.1 ± 4.6 vs. 2.4 ± 1.4 in control group, p NAFLD, and 46.1% of the control group (p NAFLD, were: high waist circumference (odds ratio (OR) 1.07, 95% confidence interval (CI) 1.01-1.13), insulin resistance (OR 3.81, 95% CI 2.01-7.13), and presence of metabolic syndrome (OR 8.68, 95% CI 3.3-24.1). NAFLD showed a high prevalence among postmenopausal women. The presence of metabolic syndrome, abdominal obesity and IR were indicators of risk for the development of NAFLD.

  11. Epigenetic regulation of hepatocellular carcinoma in non-alcoholic fatty liver disease.

    Science.gov (United States)

    Tian, Yuan; Wong, Vincent Wai-Sun; Chan, Henry Lik-Yuen; Cheng, Alfred Sze-Lok

    2013-12-01

    Emerging evidence that epigenetics converts alterations in nutrient and metabolism into heritable pattern of gene expression has profound implications in understanding human physiology and diseases. Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome including obesity and diabetes which elevate the risk of hepatocellular carcinoma (HCC) especially in male. This review focuses on the molecular connections between metabolic dysfunction and aberrant epigenetic alterations in the development of HCC in NAFLD. The metabolites derived from excessive insulin, glucose and lipid may perturb epigenetic gene regulation through DNA methylation, histone modifications, and RNA interference, leading to activation of pro-inflammatory signaling and deregulation of metabolic pathways. The interplay and crosstalk of chromatin-modifying enzymes, microRNAs, signaling pathways and the downstream transcription factors result in epigenomic reprogramming that drives hepatocellular transformation. The interactions between sex hormone pathways and the epigenetic machineries that influence chromatin states in NAFLD provide potential molecular mechanisms of gender disparity in HCC. A deeper understanding of these connections and comprehensive molecular catalog of hepatocarcinogenesis may shed light in the identification of druggable epigenetic targets for the prevention and treatment of HCC in obese or diabetic patients. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Association between Serum Uric Acid and Non-Alcoholic Fatty Liver Disease: A Meta-Analysis.

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    Darmawan, Guntur; Hamijoyo, Laniyati; Hasan, Irsan

    2017-04-01

    non-alcoholic fatty liver disease (NAFLD) is known to be associated with some metabolic disorders. Recent studies suggested the role of uric acid in NAFLD through oxidative stress and inflammatory process. This study is aimed to evaluate the association between serum uric acid and NAFLD. a systematic literature review was conducted using Pubmed and Cochrane library. The quality of all studies was assessed using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE). All data were analyzed using REVIEW MANAGER 5.3. eleven studies from America and Asia involving 100,275 subjects were included. The pooled adjusted OR for NAFLD was 1.92 (95% CI: 1.66-2.23; puric acid levels and severity of NAFLD. No publication bias was observed. our study demonstrated association between serum uric acid level and NAFLD. This finding brings a new insight of uric acid in clinical practice. Increased in serum uric acid levels might serve as a trigger for physician to screen for NAFLD.

  13. In Vitro and in Vivo Models of Non-Alcoholic Fatty Liver Disease (NAFLD

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    Ina Bergheim

    2013-06-01

    Full Text Available By now, non-alcoholic fatty liver disease (NAFLD is considered to be among the most common liver diseases world-wide. NAFLD encompasses a broad spectrum of pathological conditions ranging from simple steatosis to steatohepatitis, fibrosis and finally even cirrhosis; however, only a minority of patients progress to end-stages of the disease, and the course of the disease progression to the later stages seems to be slow, developing progressively over several years. Key risk factors including overweight, insulin resistance, a sedentary life-style and an altered dietary pattern, as well as genetic factors and disturbances of the intestinal barrier function have been identified in recent years. Despite intense research efforts that lead to the identification of these risk factors, knowledge about disease initiation and molecular mechanisms involved in progression is still limited. This review summarizes diet-induced and genetic animal models, as well as cell culture models commonly used in recent years to add to the understanding of the mechanisms involved in NAFLD, also referring to their advantages and disadvantages.

  14. Healthy dietary pattern is inversely associated with non-alcoholic fatty liver disease in elderly.

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    Adriano, Lia Silveira; Sampaio, Helena Alves de Carvalho; Arruda, Soraia Pinheiro Machado; Portela, Clarissa Lima de Melo; de Melo, Maria Luisa Pereira; Carioca, Antônio Augusto Ferreira; Soares, Nadia Tavares

    2016-06-01

    The prevalence of non-alcoholic fatty liver disease (NAFLD) is rising, an increase that may be associated with changes in lifestyle such as unhealthy dietary patterns. Although advanced age is a risk factor for NAFLD, no studies reporting this association in the elderly population were found. In the present study, the association between dietary patterns and NAFLD in the elderly was assessed. A study including 229 older adults was conducted. NAFLD diagnosis was defined as individuals whose ultrasound examination disclosed hepatic steatosis at any stage, in the absence of excess intake of alcoholic beverages. Dietary patterns were obtained by principal components analysis. Mean scores and standard errors of each dietary pattern were calculated for the groups with and without NAFLD, and mean scores of the two groups were compared using the Mann-Whitney U test. The prevalence ratios and 95 % CI were estimated for each tertile of the dietary pattern adherence scores using Poisson multiple regression models with robust variance. A total of 103 (45 %) elderly with NAFLD and four dietary patterns were identified: traditional, regional snacks, energy dense and healthy. Mean scores for adherence to the healthy pattern in the groups with and without NAFLD differed. NAFLD was inversely associated with greater adherence to the healthy pattern and directly associated with the regional snacks, after adjustment for confounders. In conclusion, healthy dietary pattern is inversely associated with NAFLD in elderly.

  15. Metabolic pathway of non-alcoholic fatty liver disease: Network properties and robustness

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    WenJun Zhang

    2017-03-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD is a systematic and complex disease involving various cytokines/metabolites. In present article, we use methodology of network biology to analyze network properties of NAFLD metabolic pathway. It is found that the metabolic pathway of NAFLD is not a typical complex network with power-law degree distribution, p(x=x^(-4.4275, x>=5. There is only one connected component in the metabolic pathway. The calculated cut cytokines/metabolites of the metabolic pathway are SREBP-1c, ChREBP, ObR, AMPK, IRE1alpha, ROS, PERK, elF2alpha, ATF4, CHOP, Bim, CASP8, Bid, CxII, Lipogenic enzymes, XBP1, and FFAs. The most important cytokine/metabolite for possible network robustness is FFAs, seconded by TNF-alpha. It is concluded that FFAs is the most important cytokine/metabolite in the metabolic pathway, seconded by ROS. FFAs, LEP, ACDC, CYP2E1, and Glucose are the only cytokines/metabolites that affect others without influences from other cytokines/metabolites. Finally, the IDs matrix for identifying possible sub-networks/modules is given. However, jointly combining the results of connectedness analysis and sub-networks/modules identification, we hold that there are not significant sub-networks/modules in the pathway.

  16. Expression of resistin in the liver of patients with non-alcoholic fatty liver disease

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    Piotr Gierej

    2017-11-01

    Full Text Available Adipokines are cytokines that presumably connect the pathologies of metabolic syndrome. One of the adipokines is resistin, the role of which in insulin resistance, obesity, and non-alcoholic fatty liver disease (NAFLD needs to be determined. Liver biopsy specimens were obtained intraoperatively from 214 obese patients. Histological assessment was based on NAFLD activity score according to Kleiner. Statistical analysis involved semi-quantitive immunohistochemistry assessment of resistin staining and: NAFLD status in obese patients compared with a non-obese control group, selected clinical data (age, sex, body mass index – BMI, selected biochemical data, comorbidities (hypertension, type 2 diabetes mellitus, dyslipidaemia, and metformin treatment in patients with type 2 diabetes mellitus. Resistin expression was observed in the histiocytes of inflammatory infiltrate, Kupffer cells, and histiocytes surrounding the hepatocytes with steatosis. There was a positive correlation between the total expression of resistin and: (1 NAFLD advancement (NAFLD Activity Score- NAS, (2 AST, ALT, BMI, glucose, insulin, Homeostasis Model Assessment (HOMA, LDH, GGT, triglycerides (TG, and glycated haemoglobin (HbA1c. Resistin expression was more intense in patients with type 2 diabetes mellitus and dyslipidaemia and less intense in the control group. Resistin probably plays a role in the pathogenesis of hepatic insulin resistance and aggravates pathologic changes in the liver of patients with NAFLD.

  17. Relationship between diverticulosis and nonalcoholic fatty liver disease in elderly patients.

    Science.gov (United States)

    Sahin, Abdurrahman; Tunc, Nurettin; Demirel, Ulvi; Kursat Poyrazoglu, Orhan; Yalniz, Mehmet; Halil Bahcecioglu, Ibrahim

    2018-04-01

    Objective To compare clinical and laboratory features of elderly patients with and without diverticulosis and assess factors related to hepatosteatosis. Method This retrospective case-control study analysed the clinical and laboratory data, colonoscopy and abdominal ultrasonography records of patients >65 years who underwent colonoscopies. Subjects were categorized according to the presence and absence of colonic diverticulosis. Univariate/multivariate logistic regression analyses were performed to evaluate the independent predictive factors of hepatosteatosis. Results A total of 355 patients were enrolled in the study: 169 had colonic diverticulosis; and 186 without colonic diverticulosis formed the control group. Age, sex and chronic disorders associated with the metabolic syndrome did not differ between the diverticulosis and control groups. The rate of hepatosteatosis was lower in patients with diverticulosis compared with the control group (27% versus 42%, respectively). Diabetes mellitus, hyperlipidaemia and hepatosteatosis were more common among patients aged diverticulosis remained an independent predictor of hepatosteatosis (odds ratio 0.529; 95% confidence interval 0.323, 0.866). Other independent predictive factors in the multivariate analysis were triglyceride and albumin. Conclusion Diverticulosis in the elderly was found to be a negative predictor of hepatosteatosis. Higher values of albumin and triglyceride in conjunction with the absence of diverticulosis may be suggestive of nonalcoholic fatty liver disease in the elderly.

  18. Peroxisome Proliferator-Activated Receptors Associated with Nonalcoholic Fatty Liver Disease

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    Nan Wang

    2017-01-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD is rapidly becoming a major cause of chronic liver disease worldwide. Concurrent to an increase in NAFLD prevalence, there is an increase in the obesity epidemic and the correlated insulin-resistant state. It is a challenge to diagnose NAFLD because many patients are asymptomatic until the later stages of disease. The most common symptoms include fatigue, malaise, and discomfort in the right upper quadrant. The major and most accurate tool to clinically diagnose NAFLD is a liver biopsy, followed by histological analysis. However, this procedure is invasive and often carries a high risk of complications. Currently, there are no officially approved medications for the treatment of NAFLD. Although lifestyle modifications with proper diet and exercise have been shown to be beneficial, this has been difficult to achieve and sustain for many patients. Effective pharmacological treatments are still lacking; therefore, additional research to identify novel drugs is clearly warranted. PPARs are promising drug targets for the management of NAFLD and its related conditions of type 2 diabetes mellitus and cardiovascular disease. In this review, we provide an overview of recent studies on the association of PPARs and NAFLD.

  19. A Guide to Non-Alcoholic Fatty Liver Disease in Childhood and Adolescence

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    Jonathan L. Temple

    2016-06-01

    Full Text Available Non-Alcoholic Fatty Liver Disease (NAFLD is now the most prevalent form of chronic liver disease, affecting 10%–20% of the general paediatric population. Within the next 10 years it is expected to become the leading cause of liver pathology, liver failure and indication for liver transplantation in childhood and adolescence in the Western world. While our understanding of the pathophysiological mechanisms underlying this disease remains limited, it is thought to be the hepatic manifestation of more widespread metabolic dysfunction and is strongly associated with a number of metabolic risk factors, including insulin resistance, dyslipidaemia, cardiovascular disease and, most significantly, obesity. Despite this, ”paediatric” NAFLD remains under-studied, under-recognised and, potentially, undermanaged. This article will explore and evaluate our current understanding of NAFLD in childhood and adolescence and how it differs from adult NAFLD, in terms of its epidemiology, pathophysiology, natural history, diagnosis and clinical management. Given the current absence of definitive radiological and histopathological diagnostic tests, maintenance of a high clinical suspicion by all members of the multidisciplinary team in primary and specialist care settings remains the most potent of diagnostic tools, enabling early diagnosis and appropriate therapeutic intervention.

  20. Relationship between Nonalcoholic Fatty Liver Disease and Vitamin D Nutritional Status in Extreme Obesity

    Science.gov (United States)

    Pereira, Silvia; Saboya, Carlos José; Ramalho, Andrea

    2017-01-01

    Aim To evaluate the relationship of nonalcoholic fatty liver disease (NAFLD) with nutritional status of vitamin D in extreme obesity. Methods Descriptive cross-sectional study in individuals with class III obesity (BMI ≥ 40 kg/m2), aged ≥ 20 years to deficiency and 20–29.9 ng/ml for insufficiency. NAFLD gradation was conducted through histological evaluation by liver biopsy. Results The sample is comprised of 50 individuals (86% female). BMI and average weight were 44.1 ± 3.8 kg/m2 and 121.4 ± 21.4 kg, respectively. Sample distribution according to serum 25(OH)D levels showed 42% of deficiency and 48% of insufficiency. The diagnosis of NAFLD was confirmed in 100% of the individuals, of which 70% had steatosis and 30% had steatohepatitis. The highest percentage of 25(OH)D insufficiency was seen in individuals with steatosis (66%/n = 21) and steatohepatitis (93%/n = 16). All individuals with steatohepatitis presented VDD (p prevalence of serum 25(OH)D inadequacy in individuals with class III obesity, which worsens as the stage of liver disease progresses. PMID:28685131

  1. Relationship between Nonalcoholic Fatty Liver Disease and Vitamin D Nutritional Status in Extreme Obesity

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    Adryana Cordeiro

    2017-01-01

    Full Text Available Aim. To evaluate the relationship of nonalcoholic fatty liver disease (NAFLD with nutritional status of vitamin D in extreme obesity. Methods. Descriptive cross-sectional study in individuals with class III obesity (BMI ≥ 40 kg/m2, aged ≥ 20 years to < 60 years. Data were obtained for weight, height, waist circumference (WC, and serum 25-hydroxyvitamin D (25(OHD levels. Vitamin D analysis was performed by high performance liquid chromatography (HPLC and the cutoff points used for its classification were < 20 ng/mL for deficiency and 20–29.9 ng/ml for insufficiency. NAFLD gradation was conducted through histological evaluation by liver biopsy. Results. The sample is comprised of 50 individuals (86% female. BMI and average weight were 44.1 ± 3.8 kg/m2 and 121.4 ± 21.4 kg, respectively. Sample distribution according to serum 25(OHD levels showed 42% of deficiency and 48% of insufficiency. The diagnosis of NAFLD was confirmed in 100% of the individuals, of which 70% had steatosis and 30% had steatohepatitis. The highest percentage of 25(OHD insufficiency was seen in individuals with steatosis (66%/n=21 and steatohepatitis (93%/n=16. All individuals with steatohepatitis presented VDD (p<0.01. Conclusion. The results of this study showed high prevalence of serum 25(OHD inadequacy in individuals with class III obesity, which worsens as the stage of liver disease progresses.

  2. Associations of Fatty Liver Disease with Hypertension, Diabetes, and Dyslipidemia: Comparison between Alcoholic and Nonalcoholic Steatohepatitis

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    Nobuyuki Toshikuni

    2017-01-01

    Full Text Available Alcoholic steatohepatitis (ASH and nonalcoholic steatohepatitis (NASH are representative types of fatty liver disease (FLD and have similar histologic features. In this study, we aimed to compare the associations of the two FLD types with hypertension (HT, diabetes mellitus (DM, and dyslipidemia (DL. A nationwide survey investigating FLD status included 753 Japanese subjects (median age 55 years; male 440, female 313 with biopsy-proven ASH (n=172 or NASH (n=581. We performed a multiple logistic regression analysis to identify the factors associated with HT, DM, or DL. Older age and a higher body mass index were significant factors associated with HT. Older age, female sex, a higher body mass index, advanced liver fibrosis, and the NASH type of FLD (odds ratio 2.77; 95% confidence interval 1.78–4.31; P<0.0001 were significant factors associated with DM. Finally, the NASH type of FLD (odds ratio 4.05; 95% confidence interval 2.63–6.24; P<0.0001 was the only significant factor associated with DL. Thus, the associations of NASH with DM and DL were stronger than those of ASH with DM and DL. In the management of FLD subjects, controlling DM and DL is particularly important for NASH subjects.

  3. Imaging evaluation of non-alcoholic fatty liver disease: focused on quantification

    Science.gov (United States)

    2017-01-01

    Non-alcoholic fatty liver disease (NAFLD) has been an emerging major health problem, and the most common cause of chronic liver disease in Western countries. Traditionally, liver biopsy has been gold standard method for quantification of hepatic steatosis. However, its invasive nature with potential complication as well as measurement variability are major problem. Thus, various imaging studies have been used for evaluation of hepatic steatosis. Ultrasonography provides fairly good accuracy to detect moderate-to-severe degree hepatic steatosis, but limited accuracy for mild steatosis. Operator-dependency and subjective/qualitative nature of examination are another major drawbacks of ultrasonography. Computed tomography can be considered as an unsuitable imaging modality for evaluation of NAFLD due to potential risk of radiation exposure and limited accuracy in detecting mild steatosis. Both magnetic resonance spectroscopy and magnetic resonance imaging using chemical shift technique provide highly accurate and reproducible diagnostic performance for evaluating NAFLD, and therefore, have been used in many clinical trials as a non-invasive reference of standard method. PMID:28994271

  4. Effects of probiotic yogurt consumption on metabolic factors in individuals with nonalcoholic fatty liver disease.

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    Nabavi, S; Rafraf, M; Somi, M H; Homayouni-Rad, A; Asghari-Jafarabadi, M

    2014-12-01

    The aim of this study was to investigate the effects of probiotic yogurt consumption on some metabolic factors in nonalcoholic fatty liver disease (NAFLD) patients. This double-blind, randomized, controlled clinical trial was conducted on 72 patients with NAFLD (33 males and 39 females) aged 23 to 63 yr. Subjects in the intervention group (n=36) consumed 300 g/d of probiotic yogurt containing Lactobacillus acidophilus La5 and Bifidobacterium lactis Bb12 and those in the control group (n=36) consumed 300 g/d of conventional yogurt for 8 wk. Fasting blood samples, anthropometric measurements, and dietary records (24h/d for 3 d) were collected at baseline and at the end of the trial. Probiotic yogurt consumption resulted in reductions of 4.67, 5.42, 4.1, and 6.92% in serum levels of alanine aminotransferase, aspartate aminotransferase, total cholesterol, and low-density lipoprotein cholesterol, respectively, compared with control group. No significant changes were observed in levels of serum glucose, triglycerides, or high-density lipoprotein cholesterol in either group. Probiotic yogurt consumption improved hepatic enzymes, serum total cholesterol, and low-density lipoprotein cholesterol levels in studied subjects and might be useful in management of NAFLD risk factors. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  5. [Efficacy of probiotics on the treatment of non-alcoholic fatty liver disease].

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    Wang, W; Shi, L P; Shi, L; Xu, L

    2018-02-01

    Objective: To study the clinical effect of probiotics in the treatment of non-alcoholic fatty liver disease (NAFLD). Methods: A total of 200 patients with NAFLD were randomly divided into 4 groups: control group (routine treatment group) and combined treatment group A, B and C. Each group had equal patients. The control group received orally polyene phosphatidylcholine capsules; whereas combined group A, B and C were given orally the live "combined Bifidobacterium Lactobacillus and Enterococcus powder" , "two live combined Bacillus subtilis and Enterococcus " , and the both probiotics respectively. The duration of treatment was 1 month. Laboratory parameters were evaluated before treatment and thirtieth day after treatment, including cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol(LDL-C), alanine aminotransferase(ALT), aspartate aminotransferase (AST), fasting blood glucose (FPG), serum high molecular weight adiponectin (HMW-APN) and serum TNFα. Meanwhile the faece sample was collected for routine test and bacterial culture. Liver ultrasound scan was done in all patients. Results: In terms of blood lipids and blood glucose, each group improved after treatment with significant differences ( PProbiotics improve intestinal microecological system in NAFLD patients via inhibiting TNFα and enhancing adiponectin, possibly resulting in regulating blood glucose, lipid metabolism, and protecting liver injury from NAFLD.

  6. Association between Serum Uric Acid and Non-Alcoholic Fatty Liver Disease: A Meta-Analysis

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    Guntur Darmawan

    2017-04-01

    Full Text Available Background: non-alcoholic fatty liver disease (NAFLD is known to be associated with some metabolic disorders. Recent studies suggested the role of uric acid in NAFLD through oxidative stress and inflammatory process. This study is aimed to evaluate the association between serum uric acid and NAFLD. Methods: a systematic literature review was conducted using Pubmed and Cochrane library. The quality of all studies was assessed using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE. All data were analyzed using REVIEW MANAGER 5.3. Results: eleven studies from America and Asia involving 100,275 subjects were included. The pooled adjusted OR for NAFLD was 1.92 (95% CI: 1.66-2.23; p<0.00001. Subgroup analyses were done based on study design, gender, non-diabetic subjects, non-obese subjects. All subgroup analyses showed statistically significant adjusted OR and most of which having low to moderate heterogeneity. Two studies revealed relationship between increased serum uric acid levels and severity of NAFLD. No publication bias was observed. Conclusion: our study demonstrated association between serum uric acid level and NAFLD. This finding brings a new insight of uric acid in clinical practice. Increased in serum uric acid levels might serve as a trigger for physician to screen for NAFLD.

  7. Dietary Composition Independent of Weight Loss in the Management of Non-Alcoholic Fatty Liver Disease

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    Tannaz Eslamparast

    2017-07-01

    Full Text Available Poor dietary composition is an important factor in the progression of non-alcoholic fatty liver disease (NAFLD. The majority of NAFLD patients follow diets with overconsumption of simple carbohydrates, total and saturated fat, with reduced intake of dietary fiber and omega-3 rich foods. Although lifestyle modifications including weight loss and exercise remain the keystone of NAFLD management, modifying dietary composition with or without a calorie-restricted diet may also be a feasible and sustainable strategy for NAFLD treatment. In the present review article, we highlight the potential therapeutic role of a “high quality healthy diet” to improve hepatic steatosis and metabolic dysfunction in patients with NAFLD, independent of caloric restriction and weight loss. We provide a literature review evaluating the evidence behind dietary components including fiber-, meat- and omega-3-rich diets and, pending further evidence, we concur with the EASL-EASD-EASO Clinical Guidelines recommendation of the Mediterranean diet as the diet of choice in these patients.

  8. Effects of Probiotics on Nonalcoholic Fatty Liver Disease in Obese Children and Adolescents.

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    Famouri, Fatemeh; Shariat, Zainab; Hashemipour, Mahin; Keikha, Mojtaba; Kelishadi, Roya

    2017-03-01

    This study aims to evaluate the effects of some probiotics on sonographic and biochemical nonalcoholic fatty liver disease (NAFLD). This randomized triple-blind trial was conducted among 64 obese children with sonographic NAFLD. They were randomly allocated to receive probiotic capsule (containing Lactobacillus acidophilus ATCC B3208, 3 × 10 colony forming units [CFU]; Bifidobacterium lactis DSMZ 32269, 6 × 10 CFU; Bifidobacterium bifidum ATCC SD6576, 2 × 10 CFU; Lactobacillus rhamnosus DSMZ 21690, 2 × 10 CFU) or placebo for 12 weeks. After intervention, in the probiotic group the mean levels of alanine aminotransferase decreased from 32.8 (19.6) to 23.1 (9.9) U/L (P = 0.02) and mean aspartate aminotransferase decreased from 32.2 (15.7) to 24.3 (7.7) U/L (P = 0.02). Likewise the mean cholesterol, low-density lipoprotein-C, and triglycerides as well as waist circumference decreased in the intervention group, without significant change in weight, body mass index, and body mass index z score. After the trial, normal liver sonography was reported in 17 (53.1%) and 5 (16.5%) of patients in the intervention and placebo groups, respectively. The present findings suggest that a course of the abovementioned probiotic compound can be effective in improving pediatric NAFLD.

  9. Exploration of a symptoms experience in people with obesity-related nonalcoholic fatty liver disease.

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    Houghton-Rahrig, Lori D; Schutte, Debra L; von Eye, Alexander; Fenton, Jenifer I; Given, Barbara A; Hord, Norman G

    2013-01-01

    Nonalcoholic fatty liver disease (NAFLD) is a highly prevalent condition strongly associated with obesity that can result in premature death. Little is known about the symptoms experience in this progressive disease, preventing health care providers from intervening in the early stages. This study explicated symptoms in persons with NAFLD at higher risk of disease progression defined as the presence of one or two copies of the PNPLA3 (rs738409)-G allele. Guided by the Symptoms Experience Model, 42 persons older than 21 years of age with diagnosed NAFLD were recruited from Western Michigan specialty offices in this cross-sectional descriptive study design. The Memorial Symptom Assessment Scale was used to measure the symptoms experience. Participants (97%) experienced 1 or more symptoms (average number of symptoms 12.02, standard deviation = 8.817). There was no statistically significant relationship between symptoms and the PNPLA3 (rs738409) variants. Significant predictors of mean frequency, severity, and distress of symptoms (the Total Memorial Symptom Scale) (F[15, 25] = 2.609, p = .016) were identified. People with NAFLD experience an average of 12 symptoms. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Intracellular role of exchangeable apolipoproteins in energy homeostasis, obesity and non-alcoholic fatty liver disease.

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    Wu, Chen-Lu; Zhao, Shui-Ping; Yu, Bi-Lian

    2015-05-01

    Exchangeable apolipoproteins play an important role in systemic lipid metabolism, especially for lipoproteins with which they are associated. Recently, emerging evidence has suggested that exchangeable apolipoproteins, such as apolipoprotein A4 (apoA4), apolipoprotein A5 (apoA5), apolipoprotein C3 (apoC3) and apolipoprotein E (apoE), also exert important effects on intracellular lipid homeostasis. There is a close link between lipid metabolism in adipose tissue and liver because the latter behaves as the metabolic sensor of dysfunctional adipose tissue and is a main target of lipotoxicity. Given that the energy balance between these two major lipogenic organs is intimately involved in the pathogenesis of obesity and non-alcoholic fatty liver disease (NAFLD), we here review recent findings concerning the intracellular function of exchangeable apolipoproteins in triglyceride metabolism in adipocytes and hepatocytes. These apolipoproteins may act as mediators of crosstalk between adipose tissue and liver, thus influencing development of obesity and hepatosteatosis. This review provides new insights into the physiological role of exchangeable apolipoproteins and identifies latent targets for therapeutic intervention of obesity and its related disorders. © 2014 The Authors. Biological Reviews © 2014 Cambridge Philosophical Society.

  11. IL-17 Axis Driven Inflammation in Non-Alcoholic Fatty Liver Disease Progression

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    Giles, Daniel A.; Moreno-Fernandez, Maria E; Divanovic, Senad

    2016-01-01

    Obesity is a primary risk factor for the development of non-alcoholic fatty liver disease (NAFLD). NAFLD, the most common chronic liver disease in the world, represents a spectrum of disorders that range from steatosis (NAFL) to steatohepatitis (NASH) to cirrhosis. It is anticipated that NAFLD will soon surpass chronic hepatitis C infection as the leading cause for needing liver transplantation. Despite its clinical and public health significance no specific therapies are available. Although the etiology of NAFLD is multifactorial and remains largely enigmatic, it is well accepted that inflammation is a central component of NAFLD pathogenesis. Despite the significance, critical immune mediators, loci of immune activation, the immune signaling pathways and the mechanism(s) underlying disease progression remain incompletely understood. Recent findings have focused on the role of Interleukin 17 (IL-17) family of proinflammatory cytokines in obesity and pathogenesis of obesity-associated sequelae. Notably, obesity favors a Th17 bias and is associated with increased IL-17A expression in both humans and mice. Further, in mice, IL-17 axis has been implicated in regulation of both obesity and NAFLD pathogenesis. However, despite these recent advances several important questions require further evaluation including: the relevant cellular source of IL-17A production; the critical IL-17RA-expressing cell type; the critical liver infiltrating immune cells; and the underlying cellular effector mechanisms. Addressing these questions may aid in the identification and development of novel therapeutic targets for prevention of inflammation-driven NAFLD progression. PMID:26028039

  12. Hepatic energy metabolism in human diabetes mellitus, obesity and non-alcoholic fatty liver disease.

    Science.gov (United States)

    Koliaki, Chrysi; Roden, Michael

    2013-10-15

    Alterations of hepatic mitochondrial function have been observed in states of insulin resistance and non-alcoholic fatty liver disease (NAFLD). Patients with overt type 2 diabetes mellitus (T2DM) can exhibit reduction in hepatic adenosine triphosphate (ATP) synthesis and impaired repletion of their hepatic ATP stores upon ATP depletion by fructose. Obesity and NAFLD may also associate with impaired ATP recovery after ATP-depleting challenges and augmented oxidative stress in the liver. On the other hand, patients with obesity or NAFLD can present with upregulated hepatic anaplerotic and oxidative fluxes, including β-oxidation and tricarboxylic cycle activity. The present review focuses on the methods and data on hepatic energy metabolism in various states of human insulin resistance. We propose that the liver can adapt to increased lipid exposition by greater lipid storing and oxidative capacity, resulting in increased oxidative stress, which in turn could deteriorate hepatic mitochondrial function in chronic insulin resistance and NAFLD. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  13. Histopathologic Evaluation of Nonalcoholic Fatty Liver Disease in Hypothyroidism-Induced Rats

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    Demir, Şule; Ünübol, Mustafa; Aypak, Serap Ünübol; İpek, Emrah; Aktaş, Serdar; Ekren, Gamze Sevri; Yılmaz, Murat; Tunca, Recai; Güney, Engin

    2016-01-01

    It is speculated that thyroid hormones may be involved in nonalcoholic fatty liver disease (NAFLD) pathogenesis. A literature scan, however, demonstrated conflicting results from studies investigating the relationship between hypothyroidism and NAFLD. Therefore, our study aims to evaluate NAFLD, from the histopathologic perspective, in hypothyroidism-induced rats. Wistar rats were divided into 2 groups: the experimental group consumed water containing methimazole 0.025% (MMI, Sigma, USA) for 12 weeks and the control group consumed tap water. At the end of week 12, serum glucose, ALT, AST, triglyceride, HDL, LDL, TSH, fT4, fT3, visfatin, and insulin assays were performed. Sections were stained with hematoxylin-eosin and “Oil Red-O” for histopathologic examination of the livers. In our study, we detected mild hepatosteatosis in all hypothyroidism-induced rats. There was statistically significant difference with respect to obesity between the two groups (p hypothyroidism-induced group and 102.63 ± 15.51 mg/dL in the control group, with a statistically significant difference between the groups (p = 0.032). The two groups did not differ statistically significantly with respect to visfatin levels (p > 0.05). In conclusion, we found that hypothyroidism-induced rats had mild hepatosteatosis as opposed to the control group histopathologically. Our study indicates that hypothyroidism can cause NAFLD. PMID:27143968

  14. [Waist circumference as a marker for screening nonalcoholic fatty liver disease in obese adolescents].

    Science.gov (United States)

    Clemente, Ana Paula Grotti; Netto, Bárbara Dal Molin; de Carvalho-Ferreira, Joana Pereira; da Silveira Campos, Raquel Munhoz; de Piano Ganen, Aline; Tock, Lian; de Mello, Marco Túlio; Dâmaso, Ana Raimunda

    2016-01-01

    To assess the relationship between the degree of waist circumference (WC) and nonalcoholic fatty liver disease (NAFLD) in obese adolescents of both genders, analyzed according to quartiles of WC. Cross-sectional study that involved 247 obese adolescents aged 12-19 years. Mean values of the nutritional parameters and serum analyses were compared with the groups using the independent t-test. Pearson correlation coefficient was used to determine the relationship of the parameters studied. Chi-square test for trend was used to determine the relationship between the prevalence of the NAFLD and WC quartile by gender. NAFLD were presented in 60% of the study participants. Obese adolescents in the 3rd and 4th quartiles of WC presented higher prevalence of NAFLD when compared with that in the 1st quartile in both genders. The NAFLD patients had significantly higher values for body weight, BMI (body mass index), BAZ-score (BMI-for-age z-scores), total fat (% and kg), WC, visceral fat, insulin, insulin resistance index (HOMA-IR), aspartate aminotransferase and alanine aminotransferase, when compared with non-NAFLD obese adolescents. The results presented here suggest that an increase in WC can reliably predict the risk of NAFLD in obese adolescents. This is a low cost and easy-to-use tool that can help in screening in adolescents. Copyright © 2015 Sociedade de Pediatria de São Paulo. Publicado por Elsevier Editora Ltda. All rights reserved.

  15. Oral Fructose Absorption in Obese Children with Non-Alcoholic Fatty Liver Disease

    Science.gov (United States)

    Sullivan, Jillian S; Le, MyPhuong T; Pan, Zhaoxing; Rivard, Christopher; Love-Osborne, Kathryn; Robbins, Kristen; Johnson, Richard J; Sokol, Ronald J; Sundaram, Shikha S

    2014-01-01

    Background Fructose intake is associated with NAFLD (Non-Alcoholic Fatty Liver Disease) development. Objective To measure fructose absorption/metabolism in pediatric NAFLD compared to obese and lean controls. Methods Children with histologically proven NAFLD, and obese and lean controls received oral fructose (1 gm/kg ideal body weight). Serum glucose, insulin, uric acid, and fructose, urine uric acid, urine fructose, and breath hydrogen levels were measured at baseline and multiple points until 360 minutes after fructose ingestion. Results Nine NAFLD (89% Hispanic, mean age 14.3 years, mean BMI 35.3 kg/m2), 6 Obese Controls (67% Hispanic, mean age 12.7 years, mean BMI 31.0 kg/m2), and 9 Lean Controls (44% Hispanic, mean age 14.3 years, mean BMI 19.4 kg/m2) were enrolled. Following fructose ingestion, NAFLD vs. Lean Controls had elevated serum glucose, insulin, and uric acid (pfructose excretion (p=0.002) and lower breath hydrogen 180-min AUC (p=0.04). NAFLD vs. Obese Controls had similar post-fructose serum glucose, insulin, urine uric acid, and breath hydrogen, but elevated serum uric acid (pfructose excretion (p=0.02). Conclusions Children with NAFLD absorb and metabolize fructose more effectively than lean subjects, associated with an exacerbated metabolic profile following fructose ingestion. PMID:24961681

  16. Effect of metformin treatment on circulating osteoprotegerin in patients with nonalcoholic fatty liver disease.

    Science.gov (United States)

    Sofer, Elena; Shargorodsky, Marina

    2016-01-01

    Growing evidence suggests complex interplay between nonalcoholic fatty liver disease (NAFLD) and bone health. The present study's aim was to examine the impact of metformin treatment on circulating osteoprotegerin (OPG) in patients with NAFLD, a population in which this relationship has not yet been studied. In a randomized, placebo-controlled study, 63 patients with NAFLD were assigned to one of two groups: Group 1 received daily metformin; Group 2 received a placebo. Metabolic parameters, insulin resistance markers and OPG levels were examined at baseline and at the end of the study. In the placebo group, liver function and OPG levels did not change during the study. Among metformin-treated patients, significant declines in OPG and alkaline phosphatase were observed. CRP and ALT decreased marginally during the 4-month treatment period. While at baseline circulating OPG levels did not differ significantly between the groups, by the end of the study OPG was significantly lower in patients treated with metformin than in the placebo group (p < 0.0001). Delta OPG was significantly greater in the metformin group than the placebo group (p = 0.001). In the general linear model, metformin treatment was the only significant independent predictor of endpoint and delta OPG. Metformin treatment was associated with a significant decrease in OPG levels in patients with NAFLD. The effect on OPG was associated with exposure to metformin per se. NCT01084486.

  17. Characteristics of hepatocellular carcinoma in cirrhotic and non-cirrhotic non-alcoholic fatty liver disease.

    Science.gov (United States)

    Leung, Christopher; Yeoh, Sern Wei; Patrick, Desmond; Ket, Shara; Marion, Kaye; Gow, Paul; Angus, Peter W

    2015-01-28

    To determine characteristics and prognostic predictors of patients with hepatocellular carcinoma (HCC) in association with non-alcoholic fatty liver disease (NAFLD). We reviewed the records of all patients with NAFLD associated HCC between 2000 and 2012. Data collected included demographics; histology; presence or absence of cirrhosis, size and number of HCC, alpha-fetoprotein, body mass index (BMI), and the presence of diabetes, hypertension, or dyslipidaemia. Fifty-four patients with NAFLD associated HCC were identified. Mean age was 64 years with 87% male. Fifteen percent (8/54) were not cirrhotic. 11%, 24% and 50% had a BMI of <25 kg/m2, 25-29 kg/m2 and ≥30 kg/m2 respectively. Fifty-nine percent were diabetic, 44% hypertensive and 26% hyperlipidaemic. Thirty-four percent of the patients had ≤1 of these risk factors. Non-cirrhotics had a significantly larger mean tumour diameter at diagnosis than cirrhotics (P=0.041). Multivariate analysis did not identify any other patient characteristics that predicted the size or number of HCC. HCC can develop in NAFLD without cirrhosis. At diagnosis such tumours are larger than those in cirrhotics, conferring a poorer prognosis.

  18. In Children With Nonalcoholic Fatty Liver Disease, Zone 1 Steatosis Is Associated With Advanced Fibrosis.

    Science.gov (United States)

    Africa, Jonathan A; Behling, Cynthia A; Brunt, Elizabeth M; Zhang, Nan; Luo, Yunjun; Wells, Alan; Hou, Jiayi; Belt, Patricia H; Kohil, Rohit; Lavine, Joel E; Molleston, Jean P; Newton, Kimberly P; Whitington, Peter F; Schwimmer, Jeffrey B

    2018-03-01

    Focal zone 1 steatosis, although rare in adults with nonalcoholic fatty liver disease (NAFLD), does occur in children with NAFLD. We investigated whether focal zone 1 steatosis and focal zone 3 steatosis are distinct subphenotypes of pediatric NAFLD. We aimed to determine associations between the zonality of steatosis and demographic, clinical, and histologic features in children with NAFLD. We performed a cross-sectional study of baseline data from 813 children (age Zone 1 steatosis was present in 18% of children with NAFLD (n = 146) and zone 3 steatosis was present in 32% (n = 244). Children with zone 1 steatosis were significantly younger (10 vs 14 years; P 51%; P zone 3 steatosis. In contrast, children with zone 3 steatosis were significantly more likely to have steatohepatitis (30% vs 6% in children with zone 1 steatosis; P zone 1 or zone 3 distribution of steatosis have an important subphenotype of pediatric NAFLD. Children with zone 1 steatosis are more likely to have advanced fibrosis and children with zone 3 steatosis are more likely to have steatohepatitis. To achieve a comprehensive understanding of pediatric NAFLD, studies of pathophysiology, natural history, and response to treatment should account for the zonality of steatosis. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

  19. Risk of cardiovascular, cardiac and arrhythmic complications in patients with non-alcoholic fatty liver disease

    Science.gov (United States)

    Ballestri, Stefano; Lonardo, Amedeo; Bonapace, Stefano; Byrne, Christopher D; Loria, Paola; Targher, Giovanni

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) has emerged as a public health problem of epidemic proportions worldwide. Accumulating clinical and epidemiological evidence indicates that NAFLD is not only associated with liver-related morbidity and mortality but also with an increased risk of coronary heart disease (CHD), abnormalities of cardiac function and structure (e.g., left ventricular dysfunction and hypertrophy, and heart failure), valvular heart disease (e.g., aortic valve sclerosis) and arrhythmias (e.g., atrial fibrillation). Experimental evidence suggests that NAFLD itself, especially in its more severe forms, exacerbates systemic/hepatic insulin resistance, causes atherogenic dyslipidemia, and releases a variety of pro-inflammatory, pro-coagulant and pro-fibrogenic mediators that may play important roles in the pathophysiology of cardiac and arrhythmic complications. Collectively, these findings suggest that patients with NAFLD may benefit from more intensive surveillance and early treatment interventions to decrease the risk for CHD and other cardiac/arrhythmic complications. The purpose of this clinical review is to summarize the rapidly expanding body of evidence that supports a strong association between NAFLD and cardiovascular, cardiac and arrhythmic complications, to briefly examine the putative biological mechanisms underlying this association, and to discuss some of the current treatment options that may influence both NAFLD and its related cardiac and arrhythmic complications. PMID:24587651

  20. Relationship between Non-Alcoholic Fatty Liver Disease and Psoriasis: A Novel Hepato-Dermal Axis?

    Science.gov (United States)

    Mantovani, Alessandro; Gisondi, Paolo; Lonardo, Amedeo; Targher, Giovanni

    2016-02-05

    Over the past 10 years, it has become increasingly evident that nonalcoholic fatty liver disease (NAFLD) is a multisystem disease that affects multiple extra-hepatic organ systems and interacts with the regulation of several metabolic and immunological pathways. In this review we discuss the rapidly expanding body of clinical and epidemiological evidence supporting a strong association between NAFLD and chronic plaque psoriasis. We also briefly discuss the possible biological mechanisms underlying this association, and discuss treatment options for psoriasis that may influence NAFLD development and progression. Recent observational studies have shown that the prevalence of NAFLD (as diagnosed either by imaging or by histology) is remarkably higher in psoriatic patients (occurring in up to 50% of these patients) than in matched control subjects. Notably, psoriasis is associated with NAFLD even after adjusting for metabolic syndrome traits and other potential confounding factors. Some studies have also suggested that psoriatic patients are more likely to have the more advanced forms of NAFLD than non-psoriatic controls, and that psoriatic patients with NAFLD have more severe psoriasis than those without NAFLD. In conclusion, the published evidence argues for more careful evaluation and surveillance of NAFLD among patients with psoriasis.

  1. Adrenic acid as an inflammation enhancer in non-alcoholic fatty liver disease.

    Science.gov (United States)

    Horas H Nababan, Saut; Nishiumi, Shin; Kawano, Yuki; Kobayashi, Takashi; Yoshida, Masaru; Azuma, Takeshi

    2017-06-01

    This study was designed to identify novel links between lipid species and disease progression in non-alcoholic fatty liver disease (NAFLD). We analyzed lipid species in the liver and plasma of db/db mice fed a choline-deficient l-amino acid-defined, high-fat diet (CDAHFD) using liquid chromatography/mass spectrometry (LC/MS). An in vitro experiment was performed using HepG2 cells stimulated with recombinant human TNFα or IL1β. The expression of steatosis-, inflammation-, and fibrosis-related genes were analyzed. Plasma samples from NAFLD patients were also analyzed by LC/MS. The CDAHFD-fed db/db mice with hepatic steatosis, inflammation, mild fibrosis, obesity, and hypercholesterolemia displayed significantly higher hepatic and plasma levels of free adrenic acid (p < 0.05). The accumulated adrenic acid in the CDAHFD-fed db/db mice was associated with increased expression of ELOVL2 and 5, and the suppression of the acyl-CoA oxidase 1 gene during peroxisomal β-oxidation. The pretreatment of HepG2 cells with adrenic acid enhanced their cytokine-induced cytokines and chemokines mRNA expression. In NAFLD patients, the group with the highest ALT levels exhibited higher plasma adrenic acid concentrations than the other ALT groups (p-value for trend <0.001). Data obtained demonstrated that adrenic acid accumulation contributes to disease progression in NAFLD. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. A Guide to Non-Alcoholic Fatty Liver Disease in Childhood and Adolescence

    Science.gov (United States)

    Temple, Jonathan L.; Cordero, Paul; Li, Jiawei; Nguyen, Vi; Oben, Jude A.

    2016-01-01

    Non-Alcoholic Fatty Liver Disease (NAFLD) is now the most prevalent form of chronic liver disease, affecting 10%–20% of the general paediatric population. Within the next 10 years it is expected to become the leading cause of liver pathology, liver failure and indication for liver transplantation in childhood and adolescence in the Western world. While our understanding of the pathophysiological mechanisms underlying this disease remains limited, it is thought to be the hepatic manifestation of more widespread metabolic dysfunction and is strongly associated with a number of metabolic risk factors, including insulin resistance, dyslipidaemia, cardiovascular disease and, most significantly, obesity. Despite this, ”paediatric” NAFLD remains under-studied, under-recognised and, potentially, undermanaged. This article will explore and evaluate our current understanding of NAFLD in childhood and adolescence and how it differs from adult NAFLD, in terms of its epidemiology, pathophysiology, natural history, diagnosis and clinical management. Given the current absence of definitive radiological and histopathological diagnostic tests, maintenance of a high clinical suspicion by all members of the multidisciplinary team in primary and specialist care settings remains the most potent of diagnostic tools, enabling early diagnosis and appropriate therapeutic intervention. PMID:27314342

  3. Non-alcoholic fatty liver disease severity, central fat mass and adinopectin: a close relationship.

    Science.gov (United States)

    Abenavoli, Ludovico; DI Renzo, Laura; Guzzi, Pietro Hiram; Pellicano, Rinaldo; Milic, Natasa; DE Lorenzo, Antonino

    2015-01-01

    Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the general population. Overweight is a common condition in patients with NAFLD, and body composition (BC) assessment is useful to evaluate nutritional status and the efficacy of nutritional strategies. A valid tool for assessing BC is dual-energy X-ray absorptiometry (DXA). Adiponectin has been shown to be relevant to the pathogenesis of NAFLD. The aim of this observational study is to define the relationship between the severity of NAFLD, the central fat mass evaluated by DXA, and the circulating levels of adiponectin. The study was carried out in 31 overweight patients. The degree of liver steatosis was evaluated by ultrasound (US) examination. Anthropometric parameters were measured according to standard methods. Fasting glucose and insulin level were used also to calculate insulin resistance (IR), according to the homeostasis model assessment-insulin resistance (HOMA-IR). The enzyme-linked immunosorbent assay technique was performed to dose fasting serum levels of adiponectin. NAFLD progression was significantly associated with increased central fat (ppractice, can improve the nutritional strategies and follow-up. In the clinical setting adiponectin may represent a potential marker for the staging of NAFLD.

  4. Does nonalcoholic fatty liver disease predispose patients to hepatocellular carcinoma in the absence of cirrhosis?

    Science.gov (United States)

    Guzman, Grace; Brunt, Elizabeth M; Petrovic, Lydia M; Chejfec, Gregorio; Layden, Thomas J; Cotler, Scott J

    2008-11-01

    Hepatocellular carcinoma (HCC) is recognized as a complication of cirrhosis related to nonalcoholic fatty liver disease (NAFLD). Diabetes and the metabolic syndrome are also associated with HCC. However, it is not clear whether NAFLD predisposes patients to HCC in the absence of cirrhosis. To seek evidence that HCC can develop in NAFLD unaccompanied by cirrhosis. Retrospective case study was performed on cases from 2004 to 2007 at the University of Illinois at Chicago Medical Center, using the key words hepatocellular carcinoma, liver explant, and liver resection. The diagnosis of HCC was identified and confirmed by hematoxylin-eosin-stained slides in 50 cases. Cause of liver disease was determined by review of liver histology, clinical history, and laboratory data. Three patients presented with advanced HCC with features of metabolic syndrome, including an elevated body mass index. Each patient had bland steatosis on liver biopsy, without fibrosis or cirrhosis. None of the 3 patients had evidence of any cause for liver disease other than NAFLD. The cases presented here suggest that NAFLD may predispose patients to HCC in the absence of cirrhosis. Further studies are needed to confirm this potentially important observation.

  5. Association of non-alcoholic fatty liver disease with renal stone disease detected on computed tomography

    International Nuclear Information System (INIS)

    Nam, In Chul

    2016-01-01

    To evaluate the association between Non-alcoholic fatty liver disease (NAFLD) with renal stone disease detected on computed tomography (CT). A total 1812 patients who underwent abdomen-pelvis CT in July 2015 were included in this study. The inclusion criteria for NAFLD were as follows: (i) lower average Hounsfield unit (HU) of hepatic right lobe, left medial and lateral segment when compared with that of spleen, (ii) patients who having urolithiasis in kidneys, ureters and urinary bladder, and (iii) patients underwent abdomen-pelvis CT including noncontrast image. The statistical significance of the association between NAFLD and renal stone disease was assessed using Chi Square Test. The Odds ratios and 95% CI were calculated to assess the propensity of renal stones disease for NAFLD by using Logistic Regression analysis. The frequency of renal stone disease in patients with NAFLD was higher approximately 19% than those who having renal stone disease without NAFLD. In addition, the presence of NAFLD was linked with renal stone disease showing that detection rate of renal stone disease in patients with NAFLD was markedly high (odds ratio: 5, 95% CI, 3–8.2) (p < 0.05) in multivariate analysis. The presence of significant association between NAFLD with renal stone disease and NAFLD may be considered to be an independent variable as a risk factor for renal stone disease

  6. Turmeric Supplementation Improves Serum Glucose Indices and Leptin Levels in Patients with Nonalcoholic Fatty Liver Diseases.

    Science.gov (United States)

    Navekar, Roya; Rafraf, Maryam; Ghaffari, Aida; Asghari-Jafarabadi, Mohammad; Khoshbaten, Manouchehr

    2017-01-01

    Insulin and leptin resistance are important risk factors for non-alcoholic fatty liver disease (NAFLD). There is limited evidence regarding the effects of turmeric on NAFLD. The aim of this study was to investigate the effects of turmeric supplementation on glycemic status and serum leptin levels in patients with NAFLD. This double-blind randomized controlled clinical trial was conducted on 46 patients with NAFLD (21males and 25 females) aged 20-60 years old and body mass index (BMI) between 24.9 and 40 kg/m2. The turmeric group (n = 23) was given six turmeric capsules daily for 12 weeks. Each capsule contained 500 mg turmeric powder (6×500 mg). The placebo group (n = 23) was given six placebo capsules daily for the same period. Fasting blood samples, anthropometric measurements, and physical activity levels were collected at the baseline and at the end of the study. Daily dietary intakes also were obtained throughout the study. Data were analyzed by independent t test, paired t test and analysis of covariance. Turmeric consumption decreased serum levels of glucose, insulin, HOMA-IR and leptin (by 1.22, 17.69, 19.48 and 21.33% respectively, p Turmeric supplementation improved glucose indexes and serum leptin levels and may be useful in the control of NAFLD complications.

  7. The effect of the Spanish Ketogenic Mediterranean Diet on nonalcoholic fatty liver disease: a pilot study.

    Science.gov (United States)

    Pérez-Guisado, Joaquín; Muñoz-Serrano, Andrés

    2011-01-01

    The "Spanish Ketogenic Mediterranean Diet" (SKMD) has been shown to be an effective and safe way to cure patients suffering from metabolic syndrome (MS). Keeping in mind that nonalcoholic fatty liver disease (NAFLD) is closely associated with MS, the purpose of this study was to evaluate the potential therapeutic properties under free living conditions of the SKMD in patients with MS (following the International Diabetes Federation [IDF] consensus guidelines) and NAFLD (suspected by using a cutoff value of alanine aminotransferase [ALT] levels of >40 U/L and confirmed by abdominal ultrasonography) over a 12-week period. A prospective study was carried out in 14 obese men meeting the inclusion criteria and whose body mass index (BMI) and age were 36.58±0.54 kg/m² and 41.18±2.28 years, respectively. Statistical differences between the parameters studied before and after administration of the SKMD (week 0 and 12) were analyzed by paired Student's t test (continuous variables) and the χ² test (discontinuous variables). Pdiet all the subjects were free of MS according to the IDF definition, and 100% of them had normal triacylglycerols and HDLc levels, in spite of the fact that 100% of them still had a BMI of >30 kg/m². We conclude that the SKMD could be an effective and safe way to treat patients suffering from MS and the associated NAFLD.

  8. The Role of Dietary Sugars and De novo Lipogenesis in Non-Alcoholic Fatty Liver Disease

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    J. Bernadette Moore

    2014-12-01

    Full Text Available Dietary sugar consumption, in particular sugar-sweetened beverages and the monosaccharide fructose, has been linked to the incidence and severity of non-alcoholic fatty liver disease (NAFLD. Intervention studies in both animals and humans have shown large doses of fructose to be particularly lipogenic. While fructose does stimulate de novo lipogenesis (DNL, stable isotope tracer studies in humans demonstrate quantitatively that the lipogenic effect of fructose is not mediated exclusively by its provision of excess substrates for DNL. The deleterious metabolic effects of high fructose loads appear to be a consequence of altered transcriptional regulatory networks impacting intracellular macronutrient metabolism and altering signaling and inflammatory processes. Uric acid generated by fructose metabolism may also contribute to or exacerbate these effects. Here we review data from human and animal intervention and stable isotope tracer studies relevant to the role of dietary sugars on NAFLD development and progression, in the context of typical sugar consumption patterns and dietary recommendations worldwide. We conclude that the use of hypercaloric, supra-physiological doses in intervention trials has been a major confounding factor and whether or not dietary sugars, including fructose, at typically consumed population levels, effect hepatic lipogenesis and NAFLD pathogenesis in humans independently of excess energy remains unresolved.

  9. The Role of Dendritic Cells in Fibrosis Progression in Nonalcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Paloma Almeda-Valdes

    2015-01-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD is the most frequent cause of chronic liver disease. NAFLD encompasses a wide range of pathologies, from simple steatosis to steatosis with inflammation to fibrosis. The pathogenesis of NAFLD progression has not been completely elucidated, and different liver cells could be implicated. This review focuses on the current evidence of the role of liver dendritic cells (DCs in the progression from NAFLD to fibrosis. Liver DCs are a heterogeneous population of hepatic antigen-presenting cells; their main function is to induce T-cell mediated immunity by antigen processing and presentation to T cells. During the steady state liver DCs are immature and tolerogenic. However, in an environment of chronic inflammation, DCs are transformed to potent inducers of immune responses. There is evidence about the role of DC in liver fibrosis, but it is not clearly understood. Interestingly, there might be a link between lipid metabolism and DC function, suggesting that immunogenic DCs are associated with liver lipid storage, representing a possible pathophysiological mechanism in NAFLD development. A better understanding of the interaction between inflammatory pathways and the different cell types and the effect on the progression of NAFLD is of great relevance.

  10. Histopathologic Evaluation of Nonalcoholic Fatty Liver Disease in Hypothyroidism-Induced Rats

    Directory of Open Access Journals (Sweden)

    Şule Demir

    2016-01-01

    Full Text Available It is speculated that thyroid hormones may be involved in nonalcoholic fatty liver disease (NAFLD pathogenesis. A literature scan, however, demonstrated conflicting results from studies investigating the relationship between hypothyroidism and NAFLD. Therefore, our study aims to evaluate NAFLD, from the histopathologic perspective, in hypothyroidism-induced rats. Wistar rats were divided into 2 groups: the experimental group consumed water containing methimazole 0.025% (MMI, Sigma, USA for 12 weeks and the control group consumed tap water. At the end of week 12, serum glucose, ALT, AST, triglyceride, HDL, LDL, TSH, fT4, fT3, visfatin, and insulin assays were performed. Sections were stained with hematoxylin-eosin and “Oil Red-O” for histopathologic examination of the livers. In our study, we detected mild hepatosteatosis in all hypothyroidism-induced rats. There was statistically significant difference with respect to obesity between the two groups (p0.05. In conclusion, we found that hypothyroidism-induced rats had mild hepatosteatosis as opposed to the control group histopathologically. Our study indicates that hypothyroidism can cause NAFLD.

  11. Non-alcoholic Fatty Liver Disease in Lean Subjects: Characteristics and Implications.

    Science.gov (United States)

    Kumar, Ramesh; Mohan, Shantam

    2017-09-28

    Non-alcoholic fatty liver disease (NAFLD) is commonly diagnosed in obese subjects; however, it is not rare among lean individuals. Given the absence of traditional risk factors, it tends to remain under-recognised. The metabolic profiles of lean NAFLD patients are frequently comparable to those of obese NAFLD patients. Though results from several studies have been mixed, it has been generally revealed that lean subjects with NAFLD have minor insulin resistance compared to that in obese NAFLD. Several genetic variants are associated with NAFLD without insulin resistance. Some data suggest that the prevalence of steatohepatitis and advanced fibrosis do not differ significantly between lean and obese NAFLD; however, the former tend to have less severe disease at presentation. The underlying pathophysiology of lean NAFLD may be quite different. Genetic predispositions, fructose- and cholesterol-rich diet, visceral adiposity and dyslipidaemia have potential roles in the pathogenic underpinnings. Lean NAFLD may pose a risk for metabolic disturbances, cardiovascular morbidity or overall mortality. Secondary causes of hepatic steatosis are also needed to be ruled out in lean subjects with NAFLD. The effectiveness of various treatment modalities, such as exercise and pharmacotherapy, on lean NAFLD is not known. Weight loss is expected to help lean NAFLD patients who have visceral obesity. Further investigation is needed for many aspects of lean NAFLD, including mechanistic pathogenesis, risk assessment, natural history and therapeutic approach.

  12. ASSOCIATION OF INTESTINAL AMOEBIASIS WITH NONALCOHOLIC FATTY LIVER DISEASE (NAFLD- A CASE-CONTROL STUDY

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    Amarendra Narayan Choudhary

    2017-07-01

    Full Text Available Little work has been done to show the association of intestinal amoebiasis with the nonalcoholic fatty liver disease. There are so many factors, which are related with the causation of NAFLD as for example obesity, diabetes mellitus, hypertension, hypercholesteraemia and sedentary living. Besides these, there are many unknown or little known factors, which should be studied. Amoebiasis is very common infection in North India including Gangetic plain of Bihar. These two conditions are very frequently observed together in a same person; therefore, a case-control study was done to confirm the association between these two conditions. MATERIALS AND METHODS In the present study, 120 cases of diagnosed NAFLD were taken of the age group between 30 years to 60 years, both male and female. 130 persons who were not suffering from NAFLD were taken as a control group in the same age and sex composition in the same community. Stool examination of all these 250 persons were done and cases of amoebiasis were diagnosed after getting at least two positive findings out of three examinations. RESULTS Prevalence of amoebiasis was clearly in excess in the NAFLD group in comparison to control group. This difference was tested statistically by calculating standard error of difference between two proportions and Chi-square test. The result showed a positive, strong and statistically significant association between NAFLD and intestinal amoebiasis. CONCLUSION There is a strong association between NAFLD and intestinal amoebiasis and further study is needed to show the biological plausibility to establish the causation.

  13. Benign Prostatic Hyperplasia, Metabolic Syndrome and Non-Alcoholic Fatty Liver Disease: Is Metaflammation the Link?

    Science.gov (United States)

    Russo, Giorgio Ivan; Cimino, Sebastiano; Castelli, Tommaso; Favilla, Vincenzo; Gacci, Mauro; Carini, Marco; Condorelli, Rosita A; La Vignera, Sandro; Calogero, Aldo E; Motta, Fabio; Puzzo, Lidia; Caltabiano, Rosario; Morgia, Giuseppe

    2016-12-01

    The prevalence of prostatic inflammation (PI) is very frequent in patients affected by benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS). To investigate the relationship between prostatic inflammation (PI) and the presence of MetS and non-alcoholic fatty liver disease (NAFLD) in a cohort of patients affected by BPH/LUTS. We conducted a prospective study from January 2012 to June 2014 on 264 consecutive patients, who underwent transurethral resection of the prostate for bladder outlet obstruction. Metabolic syndrome (MetS) has been defined according to the International Diabetes Federation (IDF). Prior to surgery, each patient has been evaluated for the presence of MetS and NAFLD. All surgical specimens were investigated for the presence of an inflammatory infiltrate, according to the Irani score. The prevalence of patients affected by MetS alone was 13.8% (32/232), 13.8% (32/232) by NAFLD alone, and 42.7% (99/232) by both diseases. The rate of subjects affected by MetS + NAFLD and severe PI was significantly greater than those with only one metabolic alteration (75.8% vs. 24.2%, P prostate gland by increasing severity of inflammation. Prostate 76:1528-1535, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  14. Modulation of hepatic lipid metabolism by olive oil and its phenols in nonalcoholic fatty liver disease.

    Science.gov (United States)

    Priore, Paola; Cavallo, Alessandro; Gnoni, Antonio; Damiano, Fabrizio; Gnoni, Gabriele V; Siculella, Luisa

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) represents the most common chronic liver disease in western countries, being considered the hepatic manifestation of metabolic syndrome. Cumulative lines of evidence suggest that olive oil, used as primary source of fat by Mediterranean populations, may play a key role in the observed health benefits on NAFLD. In this review, we summarize the state of the art of the knowledge on the protective role of both major and minor components of olive oil on lipid metabolism during NAFLD. In particular, the biochemical mechanisms responsible for the increase or decrease in hepatic lipid content are critically analyzed, taking into account that several studies have often provided different and/or conflicting results in animal models fed on olive oil-enriched diet. In addition, new findings that highlight the hypolipidemic and the antisteatotic actions of olive oil phenols are presented. As mitochondrial dysfunction plays a key role in the pathogenesis of NAFLD, the targeting of these organelles with olive oil phenols as a powerful therapeutic approach is also discussed. © 2015 International Union of Biochemistry and Molecular Biology.

  15. Nonalcoholic Fatty Liver Disease and Cardiovascular Disease: Has the Time Come for Cardiologists to Be Hepatologists?

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    Mohamed H. Ahmed

    2012-01-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD is prevalent in people with the metabolic syndrome and type 2 diabetes and is present in up to one-third of the general population. Evidence is now accumulating that NAFLD is associated with obesity and diabetes and may serve as a predictor of cardiovascular disease (CVD. The possible mechanisms linking NAFLD and CVD include inflammation and oxidative stress, hyperlipidaemia, insulin resistance, and direct impact of NAFLD on coronary arteries and left ventricular dysfunction. In addition, several studies suggest that NAFLD is associated with high risk of CVD and atherosclerosis such as carotid artery wall thickness and lower endothelial flow-mediated vasodilation independently of classical risk factors and components of the metabolic syndrome. It is not yet clear how treatment of NAFLD will modulate the risk of CVD. Furthermore, studies are urgently needed to establish (i the pathophysiology of CVD with NAFLD and (ii the benefit of early diagnosis and treatment of CVD in patients with NAFLD. In the absence of biochemical markers, it is crucial that screening and surveillance strategies are adopted in clinical practice in the growing number of patients with NAFLD and at risk of developing CVD. Importantly, the current evidence suggest that statins are safe and effective treatment for CVD in individuals with NAFLD.

  16. [Early identification of impaired renal function in obese children with non-alcoholic fatty liver disease].

    Science.gov (United States)

    Lin, Hu; Fu, Junfen; Chen, Xuefeng; Huang, Ke; Wu, Wei; Liang, Li

    2013-07-01

    To early assess the impaired renal function in the obese children with non-alcoholic fatty liver disease (NAFLD) and to identify the relationship between NAFLD and impairment of renal function. Three hundred and eighty-six obese children were enrolled and divided into NAFLD group and simple obesity group (control) according to the diagnostic criteria. Clinical biochemical parameters and early impaired renal functions were evaluated and compared. Among all patients 234 obese children aged over 10 y were subdivided into 3 groups: NAFLD combined with metabolic syndrome (NAFLD+MS) group, NAFLD group and simple obesity group (control), and the above indexes were compared among 3 groups. The urinary microalbumin levels in NAFLD, NAFLD+MS (>10y) and NAFLD groups (>10y) were significantly higher than those in controls. Additionally, the positive correlations of urinary microalbumin with systolic pressure, triglyceride and 2h-postprandial blood glucose were found. There is early renal dysfunction in children with NAFLD and those accompanied with MS, which may be associated with hypertension and glucose-lipid metabolic disorder. The results indicate that NAFLD is not only an early sign of early impaired renal function but also an early stage of chronic kidney disease (CKD) in obese children.

  17. Bioinformatics-driven identification and examination of candidate genes for non-alcoholic fatty liver disease.

    Directory of Open Access Journals (Sweden)

    Karina Banasik

    2011-01-01

    Full Text Available Candidate genes for non-alcoholic fatty liver disease (NAFLD identified by a bioinformatics approach were examined for variant associations to quantitative traits of NAFLD-related phenotypes.By integrating public database text mining, trans-organism protein-protein interaction transferal, and information on liver protein expression a protein-protein interaction network was constructed and from this a smaller isolated interactome was identified. Five genes from this interactome were selected for genetic analysis. Twenty-one tag single-nucleotide polymorphisms (SNPs which captured all common variation in these genes were genotyped in 10,196 Danes, and analyzed for association with NAFLD-related quantitative traits, type 2 diabetes (T2D, central obesity, and WHO-defined metabolic syndrome (MetS.273 genes were included in the protein-protein interaction analysis and EHHADH, ECHS1, HADHA, HADHB, and ACADL were selected for further examination. A total of 10 nominal statistical significant associations (P<0.05 to quantitative metabolic traits were identified. Also, the case-control study showed associations between variation in the five genes and T2D, central obesity, and MetS, respectively. Bonferroni adjustments for multiple testing negated all associations.Using a bioinformatics approach we identified five candidate genes for NAFLD. However, we failed to provide evidence of associations with major effects between SNPs in these five genes and NAFLD-related quantitative traits, T2D, central obesity, and MetS.

  18. Health benefits of blue-green algae: prevention of cardiovascular disease and nonalcoholic fatty liver disease.

    Science.gov (United States)

    Ku, Chai Siah; Yang, Yue; Park, Youngki; Lee, Jiyoung

    2013-02-01

    Blue-green algae (BGA) are among the most primitive life forms on earth and have been consumed as food or medicine by humans for centuries. BGA contain various bioactive components, such as phycocyanin, carotenoids, γ-linolenic acid, fibers, and plant sterols, which can promote optimal health in humans. Studies have demonstrated that several BGA species or their active components have plasma total cholesterol and triglyceride-lowering properties due to their modulation of intestinal cholesterol absorption and hepatic lipogenic gene expression. BGA can also reduce inflammation by inhibiting the nuclear factor κ B activity, consequently reducing the production of proinflammatory cytokines. Furthermore, BGA inhibit lipid peroxidation and have free radical scavenging activity, which can be beneficial for the protection against oxidative stress. The aforementioned effects of BGA can contribute to the prevention of metabolic and inflammatory diseases. This review provides an overview of the current knowledge of the health-promoting functions of BGA against cardiovascular disease and nonalcoholic fatty liver disease, which are major health threats in the developed countries.

  19. Mediterranean diet and non-alcoholic fatty liver disease: New therapeutic option around the corner?

    Science.gov (United States)

    Sofi, Francesco; Casini, Alessandro

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) represents the most common chronic liver disease in Western countries, being considered as the hepatic manifestation of metabolic syndrome. NAFLD has a common pathogenic background to that of metabolic syndrome, and shares many risk factors such as obesity, hypertension, insulin resistance and dyslipidemia. Although there is no currently available evidence-based established treatment for NAFLD, all the recommendations from the medical associations indicate that the most effective treatment is to reduce weight through lifestyle modifications. Diet, indeed, plays a key role in the management of NAFLD patients, as both the quantity and quality of the diet have been reported to have a beneficial role in the onset and severity of the liver disease. Among all the diets that have been proposed, a Mediterranean diet was the most effective dietary option for inducing weight loss together with beneficial effects on all the risk factors associated with metabolic syndrome and NAFLD. Over the last few years, research has demonstrated a beneficial effect of a Mediterranean diet in NAFLD. In this review, we will examine all the available data on the association between diet, nutrients and the Mediterranean diet in association with onset and severity of NAFLD. PMID:24966604

  20. Prevalence of Nonalcoholic Fatty Liver Disease and its Related Metabolic Risk Factors in Isfahan, Iran

    Science.gov (United States)

    Adibi, Atoosa; Maleki, Shahab; Adibi, Peyman; Etminani, Reza; Hovsepian, Silva

    2017-01-01

    Background: This study aimed to determine the prevalence of nonalcoholic fatty liver disease (NAFLD) and its related risk factors among the general population of Isfahan city located in the central part of Iran. Materials and Methods: In this cross-sectional study, the prevalence of NAFLD among 483 general adult populations was determined using ultrasonography. Anthropometric and biochemical variables were compared in groups with and without NAFLD and their predictive value for occurrence of NAFLD was investigated also. Results: Prevalence of NAFLD was 39.3%. Frequency of focal fatty infiltration (FFI), Grade I, Grade II, and Grade III of NAFLD was 9.5%, 21.1%, 7.2%, 1.4%, respectively. Prevalence of different types of NAFLD and FFI, was not different between female and male participants (P = 0.238). Ordinal regression was determined that all of the studied variables have significant predictive value for NAFLD (P < 0.001, γ = 0.615). Spearman correlation indicated that there was a significant relationship between NAFLD and BMI (r = 0.37, P < 0.001), age (r = 0.15, P = 0.001), FBS (r = 0.20, P < 0.001), cholesterol (r = 0.19, P < 0.001), triglyceride (r = 0.20, P < 0.001), LDL (r = 0.16, P < 0.001), AST (r = 0.17, P < 0.001), and ALT (r = 0.31, P < 0.001). Conclusions: Considering the high prevalence of NAFLD specially its lower grades among Isfahani adult general population and their association with studied variables, it seems that interventional studies which target-related mentioned risk factors could reduce the overall occurrence of NAFLD. PMID:28503502

  1. Prevalence of Nonalcoholic Fatty Liver Disease and its Related Metabolic Risk Factors in Isfahan, Iran

    Directory of Open Access Journals (Sweden)

    Atoosa Adibi

    2017-01-01

    Full Text Available Background: This study aimed to determine the prevalence of nonalcoholic fatty liver disease (NAFLD and its related risk factors among the general population of Isfahan city located in the central part of Iran. Materials and Methods: In this cross-sectional study, the prevalence of NAFLD among 483 general adult populations was determined using ultrasonography. Anthropometric and biochemical variables were compared in groups with and without NAFLD and their predictive value for occurrence of NAFLD was investigated also. Results: Prevalence of NAFLD was 39.3%. Frequency of focal fatty infiltration (FFI, Grade I, Grade II, and Grade III of NAFLD was 9.5%, 21.1%, 7.2%, 1.4%, respectively. Prevalence of different types of NAFLD and FFI, was not different between female and male participants (P = 0.238. Ordinal regression was determined that all of the studied variables have significant predictive value for NAFLD (P < 0.001, γ = 0.615. Spearman correlation indicated that there was a significant relationship between NAFLD and BMI (r = 0.37, P< 0.001, age (r = 0.15, P = 0.001, FBS (r = 0.20, P< 0.001, cholesterol (r = 0.19, P< 0.001, triglyceride (r = 0.20, P< 0.001, LDL (r = 0.16, P< 0.001, AST (r = 0.17, P< 0.001, and ALT (r = 0.31, P< 0.001. Conclusions: Considering the high prevalence of NAFLD specially its lower grades among Isfahani adult general population and their association with studied variables, it seems that interventional studies which target-related mentioned risk factors could reduce the overall occurrence of NAFLD.

  2. Effect of dietary monosodium glutamate on trans fat-induced nonalcoholic fatty liver disease

    Science.gov (United States)

    Collison, Kate S.; Maqbool, Zakia; Saleh, Soad M.; Inglis, Angela; Makhoul, Nadine J.; Bakheet, Razan; Al-Johi, Mohammed; Al-Rabiah, Rana; Zaidi, Marya Z.; Al-Mohanna, Futwan A.

    2009-01-01

    The effects of dietary monosodium glutamate (MSG) on trans-fatty acid (TFA)-induced nonalcoholic fatty liver disease (NAFLD) are addressed in an animal model. We used Affymetrix microarray analysis to investigate hepatic gene expression and the contribution of visceral white adipose tissue (WAT) to diet-induced NAFLD. Trans-fat feeding increased serum leptin, FFA, HDL-cholesterol (HDL-C), and total cholesterol (T-CHOL) levels, while robustly elevating the expression of genes involved in hepatic lipogenesis, including the transcription factor sterol-regulatory element binding protein 1c. Histological examination revealed hepatic macrosteatosis in TFA-fed animals. Conversely, dietary MSG at doses similar to human average daily intake caused hepatic microsteatosis and the expression of β-oxidative genes. Serum triglyceride, FFA, and insulin levels were elevated in MSG-treated animals. The abdominal cavities of TFA- or MSG-treated animals had increased WAT deposition compared with controls. Microarray analysis of WAT gene expression revealed increased lipid biosynthetic gene expression, together with a 50% decrease in the key transcription factor Ppargc1a. A combination of TFA+MSG resulted in the highest levels of serum HDL-C, T-CHOL, and leptin. Microarray analysis of TFA+MSG-treated livers showed elevated expression of markers of hepatic inflammation, lipid storage, cell damage, and cell cycle impairment. TFA+MSG mice also had a high degree of WAT deposition and lipogenic gene expression. Levels of Ppargc1a were further reduced to 25% by TFA+MSG treatment. MSG exacerbates TFA-induced NAFLD. PMID:19001666

  3. Obstructive Sleep Apnea and Non-alcoholic Fatty Liver Disease: Is the Liver Another Target?

    Directory of Open Access Journals (Sweden)

    Aibek eMirrakhimov

    2012-10-01

    Full Text Available Obstructive sleep apnea (OSA is recurrent obstruction of the upper airway during sleep leading to intermittent hypoxia (IH. OSA has been associated with all components of the metabolic syndrome as well as with non-alcoholic fatty liver disease (NAFLD. NAFLD is a common condition ranging in severity from uncomplicated hepatic steatosis to steatohepatitis (NASH, liver fibrosis and cirrhosis. The gold standard for the diagnosis and staging of NAFLD is liver biopsy. Obesity and insulin resistance lead to liver steatosis, but the causes of the progression to NASH are not known. Emerging evidence suggests that OSA may play a role in the progression of hepatic steatosis and the development of NASH. Several cross-sectional studies showed that the severity of IH in patients with OSA predicted the severity of NAFLD on liver biopsy. However, neither prospective nor interventional studies with continuous positive airway pressure (CPAP treatment have been performed. Studies in a mouse model showed that IH causes triglyceride accumulation in the liver and liver injury as well as hepatic inflammation. The mouse model provided insight in the pathogenesis of liver injury showing that (1 IH accelerates the progression of hepatic steatosis by inducing adipose tissue lipolysis and increasing free fatty acids (FFA flux into the liver; (2 IH up-regulates lipid biosynthetic pathways in the liver; (3 IH induces oxidative stress in the liver; (4 IH up-regulates hypoxia inducible factor 1 alpha and possibly HIF-2 alpha, which may increase hepatic steatosis and induce liver inflammation and fibrosis. However, the role of FFA and different transcription factors in the pathogenesis of IH-induced NAFLD is yet to be established. Thus, multiple lines of evidence suggest that IH of OSA may contribute to the progression of NAFLD but definitive clinical studies and experiments in the mouse model have yet to be done.

  4. Metabolic and histological implications of intrahepatic triglyceride content in nonalcoholic fatty liver disease.

    Science.gov (United States)

    Bril, Fernando; Barb, Diana; Portillo-Sanchez, Paola; Biernacki, Diane; Lomonaco, Romina; Suman, Amitabh; Weber, Michelle H; Budd, Jeffrey T; Lupi, Maria E; Cusi, Kenneth

    2017-04-01

    The cut-off point of intrahepatic triglyceride (IHTG) content to define nonalcoholic fatty liver disease (NAFLD) by proton magnetic resonance spectroscopy ( 1 H-MRS) was established based on the 95th percentile in a group of healthy individuals (i.e., ≥5.56%). Whether this threshold correlates with metabolic and histological changes and whether a further accumulation of IHTG is associated with worsening of these parameters has not been properly assessed in a large cohort of patients. In this cross-sectional study, 352 subjects were carefully characterized with the following studies: liver 1 H-MRS; euglycemic insulin clamp with measurement of glucose turnover; oral glucose tolerance test; and a liver biopsy. Hepatic insulin sensitivity (suppression of endogenous glucose production by insulin) was affected early on after IHTG content was ∼1.5% and remained uniformly impaired (∼40%-45%), regardless of further IHTG accumulation. Skeletal muscle insulin sensitivity showed a gradual impairment at low degrees of IHTG accumulation, but remained unchanged after IHTG content reached the ∼6 ± 2% threshold. A similar pattern was observed for metabolic changes typically associated with NAFLD, such as hypertriglyceridemia and low high-density lipoprotein cholesterol (HDL-C). In contrast, adipose tissue insulin sensitivity (suppression of free fatty acids by insulin) showed a continuous worsening across the spectrum of IHTG accumulation in NAFLD (r = -0.38; P liver disease (inflammation, ballooning, and fibrosis) was not associated with the amount of IHTG content. IHTG accumulation is strongly associated with adipose tissue insulin resistance (IR), supporting the current theory of lipotoxicity as a driver of IHTG accumulation. Once IHTG accumulation reaches ∼6 ± 2%, skeletal muscle IR, hypertriglyceridemia, and low HDL-C become fully established. Histological activity appears to have an early threshold and is not significantly influenced by increasing amounts of IHTG

  5. Guidelines for the diagnosis and treatment of nonalcoholic fatty liver disease in children and adults in China and foreign countries: comparison and analysis

    Directory of Open Access Journals (Sweden)

    WANG Qin

    2017-12-01

    Full Text Available This article makes a comparative analysis of the key recommendations in Guidelines for the diagnosis and management of nonalcoholic fatty liver disease published by American Association for the Study of Liver Diseases in 2017, Clinical practice guidelines for nonalcoholic fatty liver disease jointly published by European Association for the Study of the Liver, European Association for the Study of Diabetes, and European Association for the Study of Obesity in 2016, Guidelines for the diagnosis and treatment of nonalcoholic fatty liver disease published by Chinese Society of Hepatology, Chinese Medical Association in 2010, and Diagnosis and treatment of fatty liver disease in children published by North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition, from the following five aspects: basic concepts and typing, risk factors and screening, diagnosis and evaluation, treatment, and monitoring and follow-up, in order to provide a reference for clinical practice.

  6. Nonalcoholic Fatty Liver Disease Is Exacerbated in High-Fat Diet-Fed Gnotobiotic Mice by Colonization with the Gut Microbiota from Patients with Nonalcoholic Steatohepatitis

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    Chien-Chao Chiu

    2017-11-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD is a serious liver disorder associated with the accumulation of fat and inflammation. The objective of this study was to determine the gut microbiota composition that might influence the progression of NAFLD. Germ-free mice were inoculated with feces from patients with nonalcoholic steatohepatitis (NASH or from healthy persons (HL and then fed a standard diet (STD or high-fat diet (HFD. We found that the epididymal fat weight, hepatic steatosis, multifocal necrosis, and inflammatory cell infiltration significantly increased in the NASH-HFD group. These findings were consistent with markedly elevated serum levels of alanine transaminase, aspartate transaminase, endotoxin, interleukin 6 (IL-6, monocyte chemotactic protein 1 (Mcp1, and hepatic triglycerides. In addition, the mRNA expression levels of Toll-like receptor 2 (Tlr2, Toll-like receptor 4 (Tlr4, tumor necrosis factor alpha (Tnf-α, Mcp1, and peroxisome proliferator-activated receptor gamma (Ppar-γ significantly increased. Only abundant lipid accumulation and a few inflammatory reactions were observed in group HL-HFD. Relative abundance of Bacteroidetes and Firmicutes shifted in the HFD-fed mice. Furthermore, the relative abundance of Streptococcaceae was the highest in group NASH-HFD. Nevertheless, obesity-related Lactobacillaceae were significantly upregulated in HL-HFD mice. Our results revealed that the gut microbiota from NASH Patients aggravated hepatic steatosis and inflammation. These findings might partially explain the NAFLD progress distinctly was related to different compositions of gut microbiota.

  7. Disturbed Vitamin A Metabolism in Non-Alcoholic Fatty Liver Disease (NAFLD

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    Ali Saeed

    2017-12-01

    Full Text Available Vitamin A is required for important physiological processes, including embryogenesis, vision, cell proliferation and differentiation, immune regulation, and glucose and lipid metabolism. Many of vitamin A’s functions are executed through retinoic acids that activate transcriptional networks controlled by retinoic acid receptors (RARs and retinoid X receptors (RXRs.The liver plays a central role in vitamin A metabolism: (1 it produces bile supporting efficient intestinal absorption of fat-soluble nutrients like vitamin A; (2 it produces retinol binding protein 4 (RBP4 that distributes vitamin A, as retinol, to peripheral tissues; and (3 it harbors the largest body supply of vitamin A, mostly as retinyl esters, in hepatic stellate cells (HSCs. In times of inadequate dietary intake, the liver maintains stable circulating retinol levels of approximately 2 μmol/L, sufficient to provide the body with this vitamin for months. Liver diseases, in particular those leading to fibrosis and cirrhosis, are associated with impaired vitamin A homeostasis and may lead to vitamin A deficiency. Liver injury triggers HSCs to transdifferentiate to myofibroblasts that produce excessive amounts of extracellular matrix, leading to fibrosis. HSCs lose the retinyl ester stores in this process, ultimately leading to vitamin A deficiency. Non-alcoholic fatty liver disease (NAFLD is the hepatic manifestation of metabolic syndrome and is a spectrum of conditions ranging from benign hepatic steatosis to non-alcoholic steatohepatitis (NASH; it may progress to cirrhosis and liver cancer. NASH is projected to be the main cause of liver failure in the near future. Retinoic acids are key regulators of glucose and lipid metabolism in the liver and adipose tissue, but it is unknown whether impaired vitamin A homeostasis contributes to or suppresses the development of NAFLD. A genetic variant of patatin-like phospholipase domain-containing 3 (PNPLA3-I148M is the most prominent

  8. Modeling the epidemic of nonalcoholic fatty liver disease demonstrates an exponential increase in burden of disease.

    Science.gov (United States)

    Estes, Chris; Razavi, Homie; Loomba, Rohit; Younossi, Zobair; Sanyal, Arun J

    2018-01-01

    Nonalcoholic fatty liver disease (NAFLD) and resulting nonalcoholic steatohepatitis (NASH) are highly prevalent in the United States, where they are a growing cause of cirrhosis and hepatocellular carcinoma (HCC) and increasingly an indicator for liver transplantation. A Markov model was used to forecast NAFLD disease progression. Incidence of NAFLD was based on historical and projected changes in adult prevalence of obesity and type 2 diabetes mellitus (DM). Assumptions were derived from published literature where available and validated using national surveillance data for incidence of NAFLD-related HCC. Projected changes in NAFLD-related cirrhosis, advanced liver disease, and liver-related mortality were quantified through 2030. Prevalent NAFLD cases are forecasted to increase 21%, from 83.1 million (2015) to 100.9 million (2030), while prevalent NASH cases will increase 63% from 16.52 million to 27.00 million cases. Overall NAFLD prevalence among the adult population (aged ≥15 years) is projected at 33.5% in 2030, and the median age of the NAFLD population will increase from 50 to 55 years during 2015-2030. In 2015, approximately 20% of NAFLD cases were classified as NASH, increasing to 27% by 2030, a reflection of both disease progression and an aging population. Incidence of decompensated cirrhosis will increase 168% to 105,430 cases by 2030, while incidence of HCC will increase by 137% to 12,240 cases. Liver deaths will increase 178% to an estimated 78,300 deaths in 2030. During 2015-2030, there are projected to be nearly 800,000 excess liver deaths. With continued high rates of adult obesity and DM along with an aging population, NAFLD-related liver disease and mortality will increase in the United States. Strategies to slow the growth of NAFLD cases and therapeutic options are necessary to mitigate disease burden. (Hepatology 2018;67:123-133). © 2017 The Authors. Hepatology published by Wiley Periodicals, Inc., on behalf of the American Association for

  9. Systems-level organization of non-alcoholic fatty liver disease progression network

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    K. Shubham

    2017-10-01

    Full Text Available Non-Alcoholic Fatty Liver Disease (NAFLD is a hepatic metabolic disorder that is commonly associated with sedentary lifestyle and high fat diets. NAFLD is prevalent in individuals with obesity, insulin resistance and Type 2 Diabetes (T2D. The clinical spectrum of NAFLD ranges from simple steatosis to Non-Alcoholic Steatohepatitis (NASH with fibrosis, which can progress to cirrhosis and hepatocellular carcinoma.The pathogenesis of NAFLD is complex, involving crosstalk between multiple organs, cell-types, and environmental and genetic factors. Dysfunction of White Adipose Tissue (WAT plays a central role in the development of NAFLD and other metabolic disorders. WAT is an active endocrine organ that regulates whole-body energy homeostasis, lipid metabolism, insulin sensitivity and food intake by secreting biologically active molecules (lipokines, adipokines and cytokines. WAT dynamically reacts to nutrient excess or deprivation by remodelling the number (called hyperplasia and/or size (called hypertrophy of adipocytes to store fat or supply nutrients to other tissues by lipolysis, respectively. Adipose tissue remodelling is also accompanied by changes in the composition or function of stromal vascular cells and ECM. The major objective of our study was to identify and characterize the metabolic and signaling modules associated with the progression of NAFLD in the VAT. We performed Weighted Gene Co-expression Network Analysis (WGCNA to organize microarray data obtained from the VAT of patients at different stages of NAFLD into functional modules. In order to obtain insights into the metabolism and its regulation at the genome scale, a co-expression network of metabolic genes in the Human Metabolic Network (HMR2 was constructed and compared with the co-expression network constructed based on all the varying genes. We also used the prior network information on adipocyte metabolism (GEM to verify and extract reporter metabolites. Our analysis revealed

  10. A new noninvasive technique for estimating hepatic triglyceride: will liver biopsy become redundant in diagnosing non-alcoholic fatty liver disease?

    OpenAIRE

    Betzel, Bark; Drenth, Joost PH

    2014-01-01

    Obesity and metabolic syndrome are healthcare problems that continue to rise in frequency worldwide. Both phenotypes are a strong predictor for development of liver steatosis in the context of non-alcoholic fatty liver disease or non-alcoholic steatohepatitis. Ultrasound may detect steatosis, but its sensitivity is limited and liver biopsy is still considered to be the gold standard. Less invasive techniques that accurately quantify liver steatosis are warranted. Jimenez-Aguero and colleagues...

  11. Spontaneous nonalcoholic fatty liver disease and ER stress in Sidt2 deficiency mice

    International Nuclear Information System (INIS)

    Gao, Jialin; Zhang, Yao; Yu, Cui; Tan, Fengbiao; Wang, Lizhuo

    2016-01-01

    Sidt2 is a newly discovered lysosomal membrane protein that is closely related to glucose metabolism. In the present study, we found that Sidt2 is also closely related to lipid metabolism. Gradual increases in serum triglyceride (TG) and free fatty acid, as well as elevated aspartate transaminase and alanine transaminase levels were observed in Sidt2 −/− mice fed a normal diet from the age of 3 months, suggesting the presence of lipid metabolism disorders and impaired liver function in these mice. In the liver slices of 6-month-old Sidt2 −/− mice, there were obvious fat degeneration and inflammatory changes. Almost all of the liver cells demonstrated different levels of lipid droplet accumulation and cell swelling, and some of the cells demonstrated balloon-like changes. Infiltration of inflammatory cells was observed in the portal area and hepatic lobule. Electron microscopy showed that macrophages tended to be attached to the endothelial cells, and a large number of lipid droplets were present in the liver cells. Oil red O staining showed that there were significantly increased number of deep straining particles in the liver cells of Sidt2 −/− mice, and the TG content in liver tissue was also significantly increased. Detection of key genes and proteins related to fat synthesis showed that mRNA and protein levels of the SREBP1c in the liver of Sidt2 −/− mice were significantly elevated, and the downstream genes acetyl-CoA carboxylase, fatty acid synthase, and mitochondrial glycerol 3-phosphate acyltransferase were significantly upregulated. In addition, there was severe endoplasmic reticulum stress (ERS) in the liver of Sidt2 −/− mice, which had significantly increased levels of markers specific for unfolded protein response activation, Grp78 and CHOP, as well as significant elevation of downstream p-PERK, p-eIF2a, p-IRE1a, along with ER damage. These results suggest that Sidt2 −/− mice had spontaneous nonalcoholic fatty liver disease

  12. Spontaneous nonalcoholic fatty liver disease and ER stress in Sidt2 deficiency mice

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Jialin [Department of Endocrinology and Genetic Metabolism, Yijishan Hospital of Wannan Medical College, Wuhu, 241002 (China); Anhui Province Key Laboratory of Biological Macro-molecules Research, Wannan Medical College, Wuhu, 241001 (China); Zhang, Yao [Anhui Province Key Laboratory of Biological Macro-molecules Research, Wannan Medical College, Wuhu, 241001 (China); Department of Biochemistry and Molecular Biology, Wannan Medical Collage, Wuhu, 241002 (China); Yu, Cui [Department of Endocrinology and Genetic Metabolism, Yijishan Hospital of Wannan Medical College, Wuhu, 241002 (China); Anhui Province Key Laboratory of Biological Macro-molecules Research, Wannan Medical College, Wuhu, 241001 (China); Tan, Fengbiao [Anhui Province Key Laboratory of Biological Macro-molecules Research, Wannan Medical College, Wuhu, 241001 (China); Department of Biochemistry and Molecular Biology, Wannan Medical Collage, Wuhu, 241002 (China); Wang, Lizhuo, E-mail: 19277924@qq.com [Anhui Province Key Laboratory of Biological Macro-molecules Research, Wannan Medical College, Wuhu, 241001 (China); Department of Biochemistry and Molecular Biology, Wannan Medical Collage, Wuhu, 241002 (China)

    2016-08-05

    nonalcoholic fatty liver disease (NAFLD) accompanied by ERS. In summary, as a lysosomal membrane protein, Sidt2 plays an important role in the pathogenesis of NAFLD, and ERS may mediate the occurrence and development of this disease in Sdit2 deficiency mice.

  13. Candidate proteomic biomarkers for non-alcoholic fatty liver disease (steatosis and non-alcoholic steatohepatitis) discovered with mass-spectrometry: a systematic review.

    Science.gov (United States)

    Lădaru, Anca; Bălănescu, Paul; Stan, Mihaela; Codreanu, Ioana; Anca, Ioana Alina

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD) is characterized by lipid accumulation in the liver which is accompanied by a series of metabolic deregulations. There are sustained research efforts focusing upon biomarker discovery for NAFLD diagnosis and its prognosis in order investigate and follow-up patients as minimally invasive as possible. The objective of this study is to critically review proteomic studies that used mass spectrometry techniques and summarize relevant proteomic NAFLD candidate biomarkers. Medline and Embase databases were searched from inception to December 2014. A final number of 22 records were included that identified 251 candidate proteomic biomarkers. Thirty-three biomarkers were confirmed - 14 were found in liver samples, 21 in serum samples, and two from both serum and liver samples. Some of the biomarkers identified have already been extensively studied regarding their diagnostic and prognostic capacity. However, there are also more potential biomarkers that still need to be addressed in future studies.

  14. Circulating sCD36 levels in patients with non-alcoholic fatty liver disease and controls

    DEFF Research Database (Denmark)

    Heebøll, S; Poulsen, M K; Ornstrup, M J

    2017-01-01

    BACKGROUND AND OBJECTIVE: CD36 is implicated in fatty acid uptake in multiple tissues, including hepatocytes and adipocytes. Circulating CD36 (sCD36) is increased in non-alcoholic fatty liver disease (NAFLD).We explored this association further by investigating correlations between sCD36 levels....... An unhealthy and unbalanced CD36 expression in adipose and hepatic tissue may shift the fatty acid load to the liver.Clinical Trials.gov (NCT01464801, NCT01412645, NCT01446276).International Journal of Obesity accepted article preview online, 05 December 2016. doi:10.1038/ijo.2016.223....... resonance imaging (n=94, subcutaneous and visceral adipose tissue) and liver biopsy (n=28 NAFLD patients) performed. Plasma sCD36 was assessed by ELISA. RESULTS: NAFLD patients had elevated sCD36 levels compared to controls (0.68 (0.12-2.27) versus 0.43 (0.10-1.18), P

  15. Effects of Stigmasterol and β-Sitosterol on Nonalcoholic Fatty Liver Disease in a Mouse Model: A Lipidomic Analysis.

    Science.gov (United States)

    Feng, Simin; Gan, Ling; Yang, Chung S; Liu, Anna B; Lu, Wenyun; Shao, Ping; Dai, Zhuqing; Sun, Peilong; Luo, Zisheng

    2018-04-04

    To study the effects of stigmasterol and β-sitosterol on high-fat Western diet (HFWD)-induced nonalcoholic fatty liver disease (NAFLD), lipidomic analyses were conducted in liver samples collected after 33 weeks of the treatment. Principal component analysis showed these phytosterols were effective in protecting against HFWD-induced NAFLD. Orthogonal projections to latent structures-discriminate analysis (OPLS-DA) and S-plots showed that triacylglycerols (TGs), phosphatidylcholines, cholesteryl esters, diacylglycerols, and free fatty acids (FFAs) were the major lipid species contributing to these discriminations. The alleviation of NAFLD is mainly associated with decreases in hepatic cholesterol, TGs with polyunsaturated fatty acids, and alterations of free hepatic FFA. In conclusion, phytosterols, at a dose comparable to that suggested for humans by the FDA for the reduction of plasma cholesterol levels, are shown to protect against NAFLD in this long-term (33-week) study.

  16. Non-alcoholic fatty liver disease and type 2 diabetes mellitus: the liver disease of our age?

    Science.gov (United States)

    Firneisz, Gábor

    2014-07-21

    Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease that might affect up to one-third of the adult population in industrialised countries. NAFLD incorporates histologically and clinically different non-alcoholic entities; fatty liver (NAFL, steatosis hepatis) and steatohepatitis (NASH-characterised by hepatocyte ballooning and lobular inflammation ± fibrosis) might progress to cirrhosis and rarely to hepatocellular cancer. NAFL increasingly affects children (paediatric prevalence is 4.2%-9.6%). Type 2 diabetes mellitus (T2DM), insulin resistance (IR), obesity, metabolic syndrome and NAFLD are particularly closely related. Increased hepatic lipid storage is an early abnormality in insulin resistant women with a history of gestational diabetes mellitus. The accumulation of triacylglycerols in hepatocytes is predominantly derived from the plasma nonesterified fatty acid pool supplied largely by the adipose tissue. A few NAFLD susceptibility gene variants are associated with progressive liver disease, IR, T2DM and a higher risk for hepatocellular carcinoma. Although not approved, pharmacological approaches might be considered in NASH patients.

  17. Non-alcoholic fatty liver disease and type 2 diabetes mellitus: The liver disease of our age?

    Science.gov (United States)

    Firneisz, Gábor

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease that might affect up to one-third of the adult population in industrialised countries. NAFLD incorporates histologically and clinically different non-alcoholic entities; fatty liver (NAFL, steatosis hepatis) and steatohepatitis (NASH-characterised by hepatocyte ballooning and lobular inflammation ± fibrosis) might progress to cirrhosis and rarely to hepatocellular cancer. NAFL increasingly affects children (paediatric prevalence is 4.2%-9.6%). Type 2 diabetes mellitus (T2DM), insulin resistance (IR), obesity, metabolic syndrome and NAFLD are particularly closely related. Increased hepatic lipid storage is an early abnormality in insulin resistant women with a history of gestational diabetes mellitus. The accumulation of triacylglycerols in hepatocytes is predominantly derived from the plasma nonesterified fatty acid pool supplied largely by the adipose tissue. A few NAFLD susceptibility gene variants are associated with progressive liver disease, IR, T2DM and a higher risk for hepatocellular carcinoma. Although not approved, pharmacological approaches might be considered in NASH patients. PMID:25083080

  18. Longitudinal assessment of high blood pressure in children with nonalcoholic fatty liver disease.

    Directory of Open Access Journals (Sweden)

    Jeffrey B Schwimmer

    Full Text Available Nonalcoholic fatty liver disease (NAFLD affects 9.6% of children and may put these children at elevated risk of high blood pressure and subsequent cardiovascular morbidity and mortality. Therefore, we sought to determine the prevalence of and risk factors for high blood pressure in children with NAFLD.Cohort study performed by the NIDDK NASH Clinical Research Network. There were 484 children with NAFLD ages 2 to 17 at enrollment; 382 children were assessed both at enrollment and 48 weeks afterwards. The main outcomes were high blood pressure at baseline and persistent high blood pressure at both baseline and 48 weeks.Prevalence of high blood pressure at baseline was 35.8% and prevalence of persistent high blood pressure was 21.4%. Children with high blood pressure were significantly more likely to have worse steatosis than children without high blood pressure (mild 19.8% vs. 34.2%, moderate 35.0% vs. 30.7%, severe 45.2% vs. 35.1%; P = 0.003. Higher body mass index, low-density lipoprotein, and uric acid were independent risk factors for high blood pressure (Odds Ratios: 1.10 per kg/m2, 1.09 per 10 mg/dL, 1.25 per mg/dL, respectively. Compared to boys, girls with NAFLD were significantly more likely to have persistent high blood pressure (28.4% vs.18.9%; P = 0.05.In conclusion, NAFLD is a common clinical problem that places children at substantial risk for high blood pressure, which may often go undiagnosed. Thus blood pressure evaluation, control, and monitoring should be an integral component of the clinical management of children with NAFLD.

  19. Lower fructose intake may help protect against development of nonalcoholic fatty liver in adolescents with obesity.

    Science.gov (United States)

    OʼSullivan, Therese A; Oddy, Wendy H; Bremner, Alexandra P; Sherriff, Jill L; Ayonrinde, Oyekoya T; Olynyk, John K; Beilin, Lawrence J; Mori, Trevor A; Adams, Leon A

    2014-05-01

    Although obesity is a major risk factor for nonalcoholic fatty liver (NAFL), not all individuals with obesity develop the condition, suggesting that other factors such as diet may also contribute to NAFL development. We evaluated associations between fructose and total sugar intake and subsequent diagnosis of NAFL in adolescents with obesity and without obesity in a population-based cohort. Adolescents participating in the Western Australian Pregnancy Cohort (Raine) Study completed 3-day food records and body mass index measurement at age 14 years. At age 17 years, participants underwent abdominal ultrasound to determine NAFL status. Multivariable logistic regression models were used to analyse associations between energy-adjusted fructose and total sugar intake and NAFL status. Food diaries and liver assessments were completed for 592 adolescents. The prevalence of NAFL at age 17 was 12.8% for the total group and 50% for adolescents with obesity. Fructose intake did not significantly differ between adolescents with or without NAFL in our cohort as a whole. Among adolescents with obesity, those without NAFL had significantly lower energy-adjusted fructose intake at age 14 years compared with those with NAFL (mean ± standard deviation [SD] 38.8 ± 19.8 g/day, vs 55.7 ± 14.4 g/day, P = 0.02). Energy-adjusted fructose intake was independently associated with NAFL in adolescents with obesity (OR [odds ratio] 1.09, 95% CI 1.01-1.19, P = 0.03) after the adjustment for confounding factors. Energy-adjusted total sugar intake showed less significance (OR 1.03, 95% CI 0.999-1.07, P = 0.06). No significant associations were observed in other body mass index categories. Lower fructose consumption in adolescents with obesity at 14 years is associated with a decreased risk of NAFL at 17 years. Fructose rather than overall sugar intake may be more physiologically relevant in this association.

  20. Non-alcohol fatty liver disease in Asia: Prevention and planning.

    Science.gov (United States)

    Ashtari, Sara; Pourhoseingholi, Mohamad Amin; Zali, Mohamad Reza

    2015-07-08

    To review all of epidemiological aspects of non-alcoholic fatty liver disease (NAFLD) and also prevent this disease is examined. We conducted a systematic review according to the PRISMA guidelines. All searches for writing this review is based on the papers was found in PubMed (MEDLINE), Cochrane database and Scopus in August and September 2014 for topic of NAFLD in Asia and the way of prevention of this disease, with no language limitations. All relevant articles were accessed in full text and all relevant materials was evaluated and reviewed. NAFLD is the most common liver disorder in worldwide, with an estimated with 20%-30% prevalence in Western countries and 2%-4% worldwide. The prevalence of NAFLD in Asia, depending on location (urban vs rural), gender, ethnicity, and age is variable between 15%-20%. According to the many studies in the world, the relationship between NAFLD, obesity, diabetes mellitus, and metabolic syndrome (MS) is quiet obvious. Prevalence of NAFLD in Asian countries seems to be lower than the Western countries but, it has increased recently due to the rise of obesity, type 2 diabetes and MS in this region. One of the main reasons for the increase in obesity, diabetes and MS in Asia is a lifestyle change and industrialization. Today, NAFLD is recognized as a major chronic liver disease in Asia. Therefore, prevention of this disease in Asian countries is very important and the best strategy for prevention and control of NAFLD is lifestyle modifications. Lifestyle modification programs are typically designed to change bad eating habits and increase physical activity that is associated with clinically significant improvements in obesity, type 2 diabetes and MS. Prevention of NAFLD is very important in Asian countries particularly in Arab countries because of high prevalence of obesity, diabetes and MS.

  1. Periodontitis is associated with significant hepatic fibrosis in patients with non-alcoholic fatty liver disease.

    Science.gov (United States)

    Alazawi, William; Bernabe, Eduardo; Tai, David; Janicki, Tomasz; Kemos, Polychronis; Samsuddin, Salma; Syn, Wing-Kin; Gillam, David; Turner, Wendy

    2017-01-01

    Non-alcoholic fatty liver disease (NAFLD) has a bidirectional association with metabolic syndrome. It affects up to 30% of the general population, 70% of individuals with diabetes and 90% with obesity. The main histological hallmark of progressive NAFLD is fibrosis. There is a bidirectional epidemiological link between periodontitis and metabolic syndrome. NAFLD, periodontitis and diabetes share common risk factors, are characterised by inflammation and associated with changes in commensal bacteria. Therefore we tested the hypothesis that periodontitis is associated with NAFLD and with significant fibrosis in two study groups. We analyzed data from a population-based survey and a patient-based study. NHANES III participants with abdominal ultrasound and sociodemographic, clinical, and oral examination data were extracted and appropriate weighting applied. In a separate patient-based study, consenting patients with biopsy-proved NAFLD (or with liver indices too mild to justify biopsy) underwent dental examination. Basic Periodontal Examination score was recorded. In NHANES, periodontitis was significantly associated with steatosis in 8172 adults even after adjusting for sociodemographic factors. However, associations were fully explained after accounting for features of metabolic syndrome. In the patient-based study, periodontitis was significantly more common in patients with biopsy-proven NASH and any fibrosis (F0-F4) than without NASH (p = 0.009). Periodontitis was more common in patients with NASH and significant fibrosis (F2-4) than mild or no fibrosis (F0-1, p = 0.04). Complementary evidence from an epidemiological survey and a clinical study show that NAFLD is associated with periodontitis and that the association is stronger with significant liver fibrosis.

  2. Relation of physical activity to prevalence of nonalcoholic Fatty liver disease independent of cardiometabolic risk.

    Science.gov (United States)

    Oni, Ebenezer T; Kalathiya, Rohan; Aneni, Ehimen C; Martin, Seth S; Blaha, Michael J; Feldman, Theodore; Agatston, Arthur S; Blumenthal, Roger S; Conceiçao, Raquel D; Carvalho, Jose A M; Santos, Raul D; Nasir, Khurram

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) is associated with obesity and insulin resistance and has been linked with increased cardiovascular risk. Although physical activity (PA) and lifestyle modification are often recommended in patients at cardiovascular risk, the benefit across the cardiometabolic risk spectrum is unclear. We aimed to evaluate the relation of PA and NAFLD independent of metabolic syndrome (MS) or obesity. We evaluated 5,743 healthy Brazilian subjects (43 ± 10 years, 79% men) without clinical coronary heart disease from December 2008 to December 2010. NAFLD was diagnosed using ultrasounds, and self-reported PA was assessed using the International Physical Activity Questionnaire scale. In a multivariate logistic regression adjusted for cardiometabolic risk factors, we evaluated for an independent association of NAFLD and PA. In the total study population, NAFLD prevalence was 36% (n = 2,075), obesity 23% (1,300), and MS 20% (1,152). NAFLD was more prevalent in subjects with MS (74%) than those without (26%) and in those obese (73%) than in those nonobese (25%). Overall, 1,305 (23%) subjects reported low activity, 1,990 (35%) moderate activity, and 2,448 (42%) high activity. NAFLD prevalence was lower at higher levels of reported PA (low 45%, moderate 38%, and high 30%, p activity had lower odds of having NAFLD. The favorable association was independent of obesity or MS. In conclusion, PA presents a dose-response association with NAFLD independent of the MS or obesity. Our results are compatible with the idea that benefits of PA are relevant to everyone regardless of cardiometabolic risk. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Therapeutic effects of globular adiponectin in diabetic rats with nonalcoholic fatty liver disease

    Science.gov (United States)

    Ma, Hong; Cui, Fan; Dong, Jing-Jing; You, Guo-Ping; Yang, Xiang-Jiu; Lu, Hua-Dong; Huang, Yan-Ling

    2014-01-01

    AIM: To explore the therapeutic role of globular adiponectin (gAd) in high-fat diet/streptozotocin (STZ)-induced type 2 diabetic rats with nonalcoholic fatty liver disease (NAFLD). METHODS: Seven rats were fed a basic diet (normal control group; NC) during the experiment. Experimental rats (14 rats) were given a high-fat diet for 4 wk and were then injected with STZ to induce type 2 diabetes mellitus (T2DM) and NAFLD. Half of the T2DM/NAFLD rats were randomly injected intraperitoneally with gAd for 7 d (gAd-treated group), while the other 7 rats (T2DM/NAFLD group) received 0.9% saline. Plasma biochemical parameters and insulin concentrations were measured. Liver histopathology was examined by hematoxylin-eosin staining. Insulin receptor expression in the liver was analyzed by immunohistochemical staining, Western blot and quantitative real-time reverse transcription polymerase chain reaction analysis. RESULTS: Compared to the control group, the T2DM/NAFLD group had increased levels of glucolipid and decreased levels of insulin. Plasma glucose and lipid levels were decreased in the gAd-treated group, while serum insulin levels increased. The expression of insulin receptor in the T2DM/NAFLD group increased compared with the NC group, and gAd downregulated insulin receptor expression in the livers of T2DM/NAFLD rats. Steatosis of the liver was alleviated in the gAd-treated group compared to the T2DM/NAFLD group (NAS 1.39 ± 0.51 vs 1.92 ± 0.51, P T2DM rats with NAFLD by promoting insulin secretion, mediating glucolipid metabolism, regulating insulin receptor expression and alleviating hepatic steatosis. PMID:25356056

  4. Periodontitis is associated with significant hepatic fibrosis in patients with non-alcoholic fatty liver disease.

    Directory of Open Access Journals (Sweden)

    William Alazawi

    Full Text Available Non-alcoholic fatty liver disease (NAFLD has a bidirectional association with metabolic syndrome. It affects up to 30% of the general population, 70% of individuals with diabetes and 90% with obesity. The main histological hallmark of progressive NAFLD is fibrosis. There is a bidirectional epidemiological link between periodontitis and metabolic syndrome. NAFLD, periodontitis and diabetes share common risk factors, are characterised by inflammation and associated with changes in commensal bacteria. Therefore we tested the hypothesis that periodontitis is associated with NAFLD and with significant fibrosis in two study groups.We analyzed data from a population-based survey and a patient-based study. NHANES III participants with abdominal ultrasound and sociodemographic, clinical, and oral examination data were extracted and appropriate weighting applied. In a separate patient-based study, consenting patients with biopsy-proved NAFLD (or with liver indices too mild to justify biopsy underwent dental examination. Basic Periodontal Examination score was recorded.In NHANES, periodontitis was significantly associated with steatosis in 8172 adults even after adjusting for sociodemographic factors. However, associations were fully explained after accounting for features of metabolic syndrome. In the patient-based study, periodontitis was significantly more common in patients with biopsy-proven NASH and any fibrosis (F0-F4 than without NASH (p = 0.009. Periodontitis was more common in patients with NASH and significant fibrosis (F2-4 than mild or no fibrosis (F0-1, p = 0.04.Complementary evidence from an epidemiological survey and a clinical study show that NAFLD is associated with periodontitis and that the association is stronger with significant liver fibrosis.

  5. Hepatic lipase activity is increased in non-alcoholic fatty liver disease beyond insulin resistance.

    Science.gov (United States)

    Miksztowicz, V; Lucero, D; Zago, V; Cacciagiú, L; Lopez, G; Gonzalez Ballerga, E; Sordá, J; Fassio, E; Schreier, L; Berg, G

    2012-09-01

    Hepatic lipase is a lipolytic enzyme mostly synthesized and localized at the surface of liver sinusoidal capillaries, which hydrolyses triglycerides and phospholipids of intermediate density, large low density (LDL) and high density lipoproteins. Hepatic lipase activity is increased in insulin resistant states. Non-alcoholic fatty liver disease (NAFLD) is characterized by insulin resistance. However, at present, no data are available regarding the behaviour of hepatic lipase with regard to the degree of hepatic steatosis. Our aim was to evaluate hepatic lipase activity in NAFLD patients and its relationship to the severity of hepatic steatosis. We studied 48 patients with NAFLD (diagnosed by ultrasonography and confirmed by liver biopsy) and 30 controls. Steatosis was semi-quantitatively assessed and considered as mild or grade 1, moderate or grade 2 and severe or grade 3. hepatic lipase activity, lipid and lipoprotein profile (including intermediate density lipoproteins and dense LDL), adiponectin, insulin, glucose and high sensitivity C-reactive protein were measured. Homeostasis model assessment for insulin resistance (HOMA) index was calculated. Patients with hepatic steatosis presented with higher hepatic lipase activity, HOMA and dense LDL and lower levels of adiponectin, high density lipoproteins, cholesterol and apoA-I. Hepatic lipase activity positively correlated significantly with the severity of hepatic steatosis. Hepatic lipase correlated with a more atherogenic profile and persisted higher in patients even after corrected for age, gender, body mass index, HOMA and adiponectin. The higher hepatic lipase activity in NAFLD patients contributes to a more atherogenic profile linked to increased cardiovascular risk, beyond the insulin resistance and the reduction in adiponectin. Copyright © 2012 John Wiley & Sons, Ltd.

  6. MiR-181b regulates steatosis in nonalcoholic fatty liver disease via targeting SIRT1.

    Science.gov (United States)

    Wang, Yunxia; Zhu, Kongxi; Yu, Weihua; Wang, Hongjuan; Liu, Lan; Wu, Qiong; Li, Shuai; Guo, Jianqiang

    2017-11-04

    Non-alcoholic fatty liver diseases (NAFLD) is one of the leading cause of chronic liver diseases in the world. However, the pathogenesis of NAFLD is still unclear. Emerging studies have demonstrated that microRNAs (miRs) are profoundly involved in NAFLD and related metabolic diseases. Here, we investigated the mechanisms by which miR-181b influences NAFLD via direct targeting SIRT1. The expression of miR181b was up-regulated while SIRT1 was down-regulated in both human NAFLD patients and high fat diet (HFD) induced NAFDL mice model. And palmitic acid (PA) treatment increased the miR-181b expression while decreased SIRT1 expression in HepG2 cells. Further, we identified that SIRT1 is a direct downstream target of miR-181b. Ectopic expression of miR-181b significantly repressed the 3'-UTR reporter activities of SIRT1 in a dose-dependent manner, while the effect of miR-181b was interrupted when the binding site of miR-181b within the SIRT1 3'-UTR was mutated. And overexpression of miR-181b reduced both the mRNA and protein levels of SIRT1 in HepG2 cells. We also found that inhibition of miR-181b expression alleviates hepatic steatosis both in vitro and in vivo. And the effect of miR-181b on steatosis was blocked by SIRT1 overexpression. Taken together, our data indicated that increased expression of miR-181b potentially contributes to altered lipid metabolism in NAFLD. Downregulation of miR-34a may be a therapeutic strategy against NAFLD by regulating its target SIRT1. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Hepatic NAD(+) deficiency as a therapeutic target for non-alcoholic fatty liver disease in ageing.

    Science.gov (United States)

    Zhou, Can-Can; Yang, Xi; Hua, Xia; Liu, Jian; Fan, Mao-Bing; Li, Guo-Qiang; Song, Jie; Xu, Tian-Ying; Li, Zhi-Yong; Guan, Yun-Feng; Wang, Pei; Miao, Chao-Yu

    2016-08-01

    Ageing is an important risk factor of non-alcoholic fatty liver disease (NAFLD). Here, we investigated whether the deficiency of nicotinamide adenine dinucleotide (NAD(+) ), a ubiquitous coenzyme, links ageing with NAFLD. Hepatic concentrations of NAD(+) , protein levels of nicotinamide phosphoribosyltransferase (NAMPT) and several other critical enzymes regulating NAD(+) biosynthesis, were compared in middle-aged and aged mice or patients. The influences of NAD(+) decline on the steatosis and steatohepatitis were evaluated in wild-type and H247A dominant-negative, enzymically-inactive NAMPT transgenic mice (DN-NAMPT) given normal or high-fat diet (HFD). Hepatic NAD(+) level decreased in aged mice and humans. NAMPT-controlled NAD(+) salvage, but not de novo biosynthesis pathway, was compromised in liver of elderly mice and humans. Given normal chow, middle-age DN-NAMPT mice displayed systemic NAD(+) reduction and had moderate NAFLD phenotypes, including lipid accumulation, enhanced oxidative stress, triggered inflammation and impaired insulin sensitivity in liver. All these NAFLD phenotypes, especially release of pro-inflammatory factors, Kupffer cell accumulation, monocytes infiltration, NLRP3 inflammasome pathway and hepatic fibrosis (Masson's staining and α-SMA staining), deteriorated further under HFD challenge. Oral administration of nicotinamide riboside, a natural NAD(+) precursor, completely corrected these NAFLD phenotypes induced by NAD(+) deficiency alone or HFD, whereas adenovirus-mediated SIRT1 overexpression only partially rescued these phenotypes. These results provide the first evidence that ageing-associated NAD(+) deficiency is a critical risk factor for NAFLD, and suggest that supplementation with NAD(+) substrates may be a promising therapeutic strategy to prevent and treat NAFLD. © 2016 The British Pharmacological Society.

  8. Association of Nonalcoholic Fatty Liver Disease and Venous Thromboembolism in Women With Endometrial Cancer.

    Science.gov (United States)

    Moeini, Aida; Machida, Hiroko; Takiuchi, Tsuyoshi; Blake, Erin A; Hom, Marianne S; Miki, Toshio; Matsuo, Osamu; Matsuo, Koji

    2017-11-01

    Recent studies have demonstrated that surgical menopause results in a significantly increased risk of nonalcoholic fatty liver disease (NAFLD) in women with endometrial cancer. In addition, venous thromboembolism (VTE) is known to be one of the major prognostic factors for decreased survival in endometrial cancer. Given the fact that coagulation factors are produced in the liver, the correlation between NAFLD and VTE was examined in endometrial cancer. A retrospective study was conducted to examine patients with endometrial cancer who underwent surgical staging including oophorectomy between 2000 and 2013 (n = 714). Cumulative risk of VTE was examined based on the NAFLD status. A Cox proportional hazard regression model was used to determine the independent risk predictors of VTE. Venous thromboembolism and NAFLD were seen in 57 (8.0%) and 181 (25.4%) cases, respectively. Two-year cumulative risks of VTE and NAFLD were 7.9% and 19.3%, respectively. In univariate analysis, VTE was significantly associated with decreased disease-free survival (2-year rate, 43.6% vs 91.4%, P controlling for clinicopathological factors, NAFLD remained an independent predictor of decreased risk of VTE (hazard ratio [HR]: 0.24, 95% confidence interval [CI]: 0.07-0.79, P = .02). Thrombocytosis (HR: 2.30, 95% CI: 1.22-4.35, P = .01), cancer antigen 125 ≥ 35 (HR: 3.81, 95% CI: 1.78-8.17, P HR: 4.57, 95% CI: 1.97-10.6, P < .001) remained as independent predictors of increased risk of VTE. Our results suggest that NAFLD may be associated with decreased VTE risk in women with endometrial cancer.

  9. Non-alcoholic fatty liver disease in mice with heterozygous mutation in TMED2.

    Science.gov (United States)

    Hou, Wenyang; Gupta, Swati; Beauchamp, Marie-Claude; Yuan, Libin; Jerome-Majewska, Loydie A

    2017-01-01

    The transmembrane emp24 domain/p24 (TMED) family are essential components of the vesicular transport machinery. Members of the TMED family serve as cargo receptors implicated in selection and packaging of endoplasmic reticulum (ER) luminal proteins into coatomer (COP) II coated vesicles for anterograde transport to the Golgi. Deletion or mutations of Tmed genes in yeast and Drosophila results in ER-stress and activation of the unfolded protein response (UPR). The UPR leads to expression of genes and proteins important for expanding the folding capacity of the ER, degrading misfolded proteins, and reducing the load of new proteins entering the ER. The UPR is activated in non-alcoholic fatty liver disease (NAFLD) in human and mouse and may contribute to the development and the progression of NAFLD. Tmed2, the sole member of the vertebrate Tmed β subfamily, exhibits tissue and temporal specific patterns of expression in embryos and developing placenta but is ubiquitously expressed in all adult organs. We previously identified a single point mutation, the 99J mutation, in the signal sequence of Tmed2 in an N-ethyl-N-nitrosourea (ENU) mutagenesis screen. Histological and molecular analysis of livers from heterozygous mice carrying the 99J mutation, Tmed299J/+, revealed a requirement for TMED2 in liver health. We show that Tmed299J/+ mice had decreased levels of TMED2 and TMED10, dilated endoplasmic reticulum membrane, and increased phosphorylation of eIF2α, indicating ER-stress and activation of the UPR. Increased expression of Srebp1a and 2 at the newborn stage and increased incidence of NAFLD were also found in Tmed299J/+ mice. Our data establishes Tmed299J/+ mice as a novel mouse model for NAFLD and supports a role for TMED2 in liver health.

  10. Non-alcoholic fatty liver disease in mice with heterozygous mutation in TMED2.

    Directory of Open Access Journals (Sweden)

    Wenyang Hou

    Full Text Available The transmembrane emp24 domain/p24 (TMED family are essential components of the vesicular transport machinery. Members of the TMED family serve as cargo receptors implicated in selection and packaging of endoplasmic reticulum (ER luminal proteins into coatomer (COP II coated vesicles for anterograde transport to the Golgi. Deletion or mutations of Tmed genes in yeast and Drosophila results in ER-stress and activation of the unfolded protein response (UPR. The UPR leads to expression of genes and proteins important for expanding the folding capacity of the ER, degrading misfolded proteins, and reducing the load of new proteins entering the ER. The UPR is activated in non-alcoholic fatty liver disease (NAFLD in human and mouse and may contribute to the development and the progression of NAFLD. Tmed2, the sole member of the vertebrate Tmed β subfamily, exhibits tissue and temporal specific patterns of expression in embryos and developing placenta but is ubiquitously expressed in all adult organs. We previously identified a single point mutation, the 99J mutation, in the signal sequence of Tmed2 in an N-ethyl-N-nitrosourea (ENU mutagenesis screen. Histological and molecular analysis of livers from heterozygous mice carrying the 99J mutation, Tmed299J/+, revealed a requirement for TMED2 in liver health. We show that Tmed299J/+ mice had decreased levels of TMED2 and TMED10, dilated endoplasmic reticulum membrane, and increased phosphorylation of eIF2α, indicating ER-stress and activation of the UPR. Increased expression of Srebp1a and 2 at the newborn stage and increased incidence of NAFLD were also found in Tmed299J/+ mice. Our data establishes Tmed299J/+ mice as a novel mouse model for NAFLD and supports a role for TMED2 in liver health.

  11. NHE1 deficiency in liver: Implications for non-alcoholic fatty liver disease

    International Nuclear Information System (INIS)

    Prasad, Vikram; Chirra, Shivani; Kohli, Rohit; Shull, Gary E.

    2014-01-01

    Highlights: • FXR, PGC1α and PPARγ levels are upregulated in NHE1 deficient livers. • NHE1 deficiency downregulates expression of pro-lipogenic genes in liver. • Chronic exposure to high-fat diet upregulates hepatic NHE1 expression. • Loss of NHE1 better preserves hepatic insulin signaling in high-fat diet-fed mice. - Abstract: Non-alcoholic fatty liver disease NAFLD is closely associated with the dysregulation of lipid homeostasis. Diet-induced hepatic steatosis, which can initiate NAFLD progression, has been shown to be dramatically reduced in mice lacking the electroneutral Na + /H + exchanger NHE1 (Slc9a1). In this study, we investigated if NHE1 deficiency had effects in liver that could contribute to the apparent protection against aberrant lipid accumulation. RT-PCR and immunoblot analyses of wild-type and NHE1-null livers revealed an expression profile that strongly suggested attenuation of both de novo lipogenesis and hepatic stellate cell activation, which is implicated in liver fibrosis. This included upregulation of the farnesoid X receptor FXR, peroxisome proliferator-activated receptor PPARγ, its co-activator PGC1α, and sestrin 2, an antioxidant protein involved in hepatic metabolic homeostasis. Furthermore, expression levels of the pro-lipogenic liver X receptor LXRα, and acetyl CoA carboxylases 1 and 2 were downregulated. These changes were associated with evidence of reduced cellular stress, which persisted even upon exposure to a high-fat diet, and the better preservation of insulin signaling, as evidenced by protein kinase B/Akt phosphorylation (Ser473). These results indicate that NHE1 deficiency may protect against NAFLD pathogenesis, which is significant given the availability of highly specific NHE1 inhibitors

  12. Risk factors of non-alcoholic fatty liver disease in patients with inflammatory bowel disease.

    Science.gov (United States)

    Sourianarayanane, Achuthan; Garg, Gaurav; Smith, Thomas H; Butt, Mujtaba I; McCullough, Arthur J; Shen, Bo

    2013-09-01

    Metabolic risk factors are associated with non-alcoholic fatty liver disease (NAFLD), but they are less frequent in inflammatory bowel disease (IBD). This study evaluates the frequency of NAFLD and its risk factors among IBD patients including anti-TNF-α therapy. IBD patients who underwent abdominal imaging from January, 2009 to December, 2010 were analyzed in this nested, case-controlled study. IBD patients with NAFLD by imaging were compared with those who had no evidence of NAFLD (control). Among 928 IBD patients, 76 (8.2%) had evidence of NAFLD by imaging, and were compared to 141 patients without NAFLD evaluated (study: control ratio=~1:2). NAFLD patients were older (46.0 ± 13.3 vs. 42.0 ±14.1 years; p=0.018) and had a later onset of IBD compared to the control group (37.2 ± 15.3 vs. 28.7 ± 23.8 years; p=0.002). Metabolic syndrome was present in 29.0% of NAFLD patients, with a median Adult Treatment Panel risk factor of 2 [Interquartile range 1,3]. Patients not receiving anti-TNF-α therapy had a higher occurrence of NAFLD (p=0.048). In multivariate analysis, hypertension (OR=3.5), obesity (OR=2.1), small bowel surgeries (OR=3.7), and use of steroids at the time of imaging (OR=3.7) were independent factors associated with NAFLD. NAFLD occurred in 8.2% of the IBD population. NAFLD patients were older and had a later onset of IBD disease. IBD patients develop NAFLD with fewer metabolic risk factors than non-IBD NAFLD patients. It is also less common among patients who received anti-TNF-α therapy. Copyright © 2012 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

  13. Nonalcoholic Fatty Liver Disease Relationship with Metabolic Syndrome in Class III Obesity Individuals

    Directory of Open Access Journals (Sweden)

    A. Cordeiro

    2015-01-01

    Full Text Available Introduction. Obesity is represented mainly by abdominal obesity and insulin resistance (IR, both present in most individuals diagnosed with metabolic syndrome (MS. IR is the key risk factor in the pathogenesis of nonalcoholic fatty liver disease (NAFLD. Objective. To relate NAFLD to MS in class III obese individuals. Methodology. A descriptive cross-sectional study with class III obese individuals, aged ≥ 20–60 years. Blood pressure measurement, weight, height, body mass index (BMI, waist circumference (WC and blood glucose, insulin, high-density lipoprotein cholesterol (HDL-c, and triglycerides data were obtained. HOMA-IR (homeostatic model assessment insulin resistance calculation was carried out with a cutoff value of 2.71 for IR evaluation. The diagnosis of NAFLD was performed by liver biopsy and the diagnosis of MS was performed in accordance with the National Cholesterol Education Program/Adult Treatment Panel III (NCEPATP III. Results. Of the 50 individuals evaluated, 86% were women and BMI means were 45.4 ± 3.6 Kg/m2. The overall individuals had NAFLD, 70% steatosis, and 30% steatohepatitis. The diagnosis of MS occurred in 56% but showed no significant association with NAFLD (P=0.254. Triglycerides (178 ± 65.5 mg/dL and insulin (28.2 ± 22.6 mcU/mL mean values were significantly higher in steatohepatitis (P=0.002 and P=0.042, resp. compared to individuals with steatosis. IR was confirmed in 76% and showed a relationship with NAFLD severity. Conclusion. NAFLD was not related to MS; however, MS components, evaluated in isolation, as well as IR, were related to the presence and severity of NAFLD.

  14. Cost-effectiveness analysis of ultrasonography screening for nonalcoholic fatty liver disease in metabolic syndrome patients.

    Science.gov (United States)

    Phisalprapa, Pochamana; Supakankunti, Siripen; Charatcharoenwitthaya, Phunchai; Apisarnthanarak, Piyaporn; Charoensak, Aphinya; Washirasaksiri, Chaiwat; Srivanichakorn, Weerachai; Chaiyakunapruk, Nathorn

    2017-04-01

    Nonalcoholic fatty liver disease (NAFLD) can be diagnosed early by noninvasive ultrasonography; however, the cost-effectiveness of ultrasonography screening with intensive weight reduction program in metabolic syndrome patients is not clear. This study aims to estimate economic and clinical outcomes of ultrasonography in Thailand. Cost-effectiveness analysis used decision tree and Markov models to estimate lifetime costs and health benefits from societal perspective, based on a cohort of 509 metabolic syndrome patients in Thailand. Data were obtained from published literatures and Thai database. Results were reported as incremental cost-effectiveness ratios (ICERs) in 2014 US dollars (USD) per quality-adjusted life year (QALY) gained with discount rate of 3%. Sensitivity analyses were performed to assess the influence of parameter uncertainty on the results. The ICER of ultrasonography screening of 50-year-old metabolic syndrome patients with intensive weight reduction program was 958 USD/QALY gained when compared with no screening. The probability of being cost-effective was 67% using willingness-to-pay threshold in Thailand (4848 USD/QALY gained). Screening before 45 years was cost saving while screening at 45 to 64 years was cost-effective. For patients with metabolic syndromes, ultrasonography screening for NAFLD with intensive weight reduction program is a cost-effective program in Thailand. Study can be used as part of evidence-informed decision making. Findings could contribute to changes of NAFLD diagnosis practice in settings where economic evidence is used as part of decision-making process. Furthermore, study design, model structure, and input parameters could also be used for future research addressing similar questions.

  15. Activation of proteinase 3 contributes to Non-alcoholic Fatty Liver Disease (NAFLD) and insulin resistance.

    Science.gov (United States)

    Toonen, Erik J M; Mirea, Andreea-Manuela; Tack, Cees J; Stienstra, Rinke; Ballak, Dov B; van Diepen, Janna A; Hijmans, Anneke; Chavakis, Triantafyllos; Dokter, Wim H; Pham, Christine T N; Netea, Mihai G; Dinarello, Charles A; Joosten, Leo A B

    2016-05-24

    Activation of inflammatory pathways is known to accompany development of obesity-induced non-alcoholic fatty liver disease (NAFLD), insulin resistance and type 2 diabetes. In addition to caspase-1, the neutrophil serine proteases proteinase 3, neutrophil elastase and cathepsin G are able to process the inactive pro-inflammatory mediators IL-1β and IL-18 to their bioactive forms, thereby regulating inflammatory responses. In the present study, we investigated whether proteinase 3 is involved in obesity-induced development of insulin resistance and NAFLD. We investigated the development of NAFLD and insulin resistance in mice deficient for neutrophil elastase/proteinase 3 and neutrophil elastase/cathepsin G and in wild-type mice treated with the neutrophil serine proteinase inhibitor human alpha-1 antitrypsin. Expression profiling of metabolically relevant tissues obtained from insulin resistant mice showed that expression of proteinase 3 was specifically upregulated in the liver, whereas neutrophil elastase, cathepsin G and caspase-1 were not. Neutrophil elastase/proteinase 3 deficient mice showed strongly reduced levels of lipids in the liver after fed a high fat diet. Moreover, these mice were resistant to high fat diet-induced weight gain, inflammation and insulin resistance. Injection of proteinase 3 exacerbated insulin resistance in caspase-1(-/-) mice, indicating that proteinase 3 acts independently of caspase-1. Treatment with alpha-1 antitrypsin during the last 10 days of a 16 week high fat diet reduced hepatic lipid content and decreased fasting glucose levels. We conclude that proteinase 3 is involved in NAFLD and insulin resistance and that inhibition of proteinase 3 may have therapeutic potential.

  16. Fatty acid metabolism is altered in non-alcoholic steatohepatitis independent of obesity.

    Science.gov (United States)

    Walle, Paula; Takkunen, Markus; Männistö, Ville; Vaittinen, Maija; Lankinen, Maria; Kärjä, Vesa; Käkelä, Pirjo; Ågren, Jyrki; Tiainen, Mika; Schwab, Ursula; Kuusisto, Johanna; Laakso, Markku; Pihlajamäki, Jussi

    2016-05-01

    Non-alcoholic steatohepatitis (NASH) is associated with changes in fatty acid (FA) metabolism. However, specific changes in metabolism and hepatic mRNA expression related to NASH independent of simple steatosis, obesity and diet are unknown. Liver histology, serum and liver FA composition and estimated enzyme activities based on the FA ratios in cholesteryl esters and triglycerides were assessed in 92 obese participants of the Kuopio Obesity Surgery Study (KOBS) divided to those with normal liver, steatosis or NASH (30 men and 62 women, age 46.8±9.5years (mean±SD), BMI 44.2±6.2kg/m(2)). Plasma FA composition was also investigated in the Metabolic Syndrome in Men (METSIM) Study (n=769), in which serum alanine aminotransferase (ALT) was used as a marker of liver disease. Obese individuals with NASH had higher activity of estimated activities of delta-6 desaturase (D6D, pliver. Estimated activities of D5D, D6D and SCD1 correlated positively between liver and serum indicating that serum estimates reflected liver metabolism. Accordingly, NASH was associated with higher hepatic mRNA expression of corresponding genes FADS1, FADS2 and SCD. Finally, differences in FA metabolism that associated with NASH in obese individuals were also associated with high ALT in the METSIM Study. We demonstrated alterations in FA metabolism and endogenous desaturase activities that associate with NASH, independent of obesity and diet. This suggests that changes in endogenous FA metabolism are related to NASH and that they may contribute to the progression of the disease. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Practical Dietary Recommendations for the Prevention and Management of Nonalcoholic Fatty Liver Disease in Adults.

    Science.gov (United States)

    George, Elena S; Forsyth, Adrienne; Itsiopoulos, Catherine; Nicoll, Amanda J; Ryan, Marno; Sood, Siddharth; Roberts, Stuart K; Tierney, Audrey C

    2018-01-01

    Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. In the absence of effective pharmacotherapies, clinical guidelines focus primarily on weight loss to treat this condition. Established consensus, evidence-based, and clinical dietary recommendations for NAFLD are currently lacking. The aim of this paper is to provide evidence-based practical dietary recommendations for the prevention and management of NAFLD in adults. A literature review focusing on established principles for the development of clinical practice recommendations was employed using the following criteria: based on substantial evidence, ensures risk minimization, is flexible for an individual patient approach, and is open to further modification as evidence emerges. The Practice-based Evidence in Nutrition classification system was used to grade these principles. Five key dietary recommendations were developed: 1) follow traditional dietary patterns, such as the Mediterranean diet; 2) limit excess fructose consumption and avoid processed foods and beverages with added fructose; 3) PUFAs, especially long-chain omega-3 rich foods and MUFAs, should replace SFAs in the diet; 4) replace processed food, fast food, commercial bakery goods, and sweets with unprocessed foods high in fiber, including whole grains, vegetables, fruits, legumes, nuts, and seeds; and 5) avoid excess alcohol consumption. Improving diet quality may reduce the incidence and progression of NAFLD and associated risk factors. Many of the benefits are likely to result from the collective effect of dietary patterns. High-quality research-in particular, randomized clinical trials assessing dietary interventions that focus on liver-specific endpoints-are needed as a priority. © 2018 American Society for Nutrition. All rights reserved.

  18. Serum levels of endocannabinoids are independently associated with nonalcoholic fatty liver disease.

    Science.gov (United States)

    Zelber-Sagi, Shira; Azar, Shahar; Nemirovski, Alina; Webb, Muriel; Halpern, Zamir; Shibolet, Oren; Tam, Joseph

    2017-01-01

    To evaluate the association between circulating levels of endocannabinoids (eCBs) and non-alcoholic fatty liver disease (NAFLD). The serum levels of the main eCBs, anandamide (AEA) and 2-arachidonoylglycerol (2-AG), and their endogenous precursor and breakdown product, arachidonic acid (AA), were analyzed by liquid chromatography/tandem mass spectrometry in 105 volunteers screened for NAFLD. Hepatic ultrasound, fasting blood tests, and anthropometrics were assessed. Liver fat was quantified by the hepato-renal-ultrasound index representing the ratio between the brightness level of the liver and the kidney. Patients with NAFLD had higher levels (pmol/mL) of AA (2,721 ± 1,112 vs. 2,248 ± 977, P = 0.022) and 2-AG (46.5 ± 25.8 vs. 33.5 ± 13.6, P = 0.003), but not AEA. The trend for higher levels of AA and 2-AG in the presence of NAFLD was observed in both genders and within subgroups of overweight and obesity. The association of AA and 2-AG with NAFLD was maintained with adjustment for age, gender, and BMI (OR = 1.001, 1.000-1.001 95% CI, P = 0.008 and OR = 1.05, 1.01-1.09, P = 0.006, respectively) or waist circumference. This study is th