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Sample records for acid-induced fatty liver

  1. Free fatty acids repress small heterodimer partner (SHP) activation and adiponectin counteracts bile acid-induced liver injury in superobese patients with nonalcoholic steatohepatitis

    NARCIS (Netherlands)

    Bechmann, Lars P.; Kocabayoglu, Peri; Sowa, Jan-Peter; Sydor, Svenja; Best, Jan; Schlattjan, Martin; Beilfuss, Anja; Schmitt, Johannes; Hannivoort, Rebekka A.; Kilicarslan, Alpaslan; Rust, Christian; Berr, Frieder; Tschopp, Oliver; Gerken, Guido; Friedman, Scott L.; Geier, Andreas; Canbay, Ali

    2013-01-01

    Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in industrialized countries and may proceed to steatohepatitis (NASH). Apoptosis and free fatty acid (FFA)-induced lipotoxicity are important features of NASH pathogenesis. We have shown a hepatoprotective effect of adiponecti

  2. Docosahexaenoic acid prevents trans-10, cis-12 conjugated linoleic acid-induced non-alcoholic fatty liver disease in mice by altering expression of hepatic genes regulating fatty acid synthesis and oxidation

    Science.gov (United States)

    Background: Concomitant supplementation with docosahexaenoic acid (22:6 n-3; DHA) prevented t10, c12- conjugated linoleic acid (CLA)-induced non-alcoholic fatty liver disease (NAFLD) and insulin resistance. Effective dose of DHA and mechanisms involved are poorly understood. Methods: We examined abi...

  3. Fatty liver in children

    OpenAIRE

    Rafeey, Mandana; Mortazavi, Fakhrossadat; Mogaddasi, Nafiseh; Robabeh, Ghergherehchi; Ghaffari, Shamsi; Hasani, Alka

    2009-01-01

    Aims: The aim of this study is to investigate the clinical and laboratory characteristics of nonalcoholic fatty liver disease (NAFLD) in a referral center of pediatrics in the northwest of Iran. Methods: In this cross-sectional study all subjects aged between six months to 15 years that were referred to the sonography unit, were investigated for fatty liver from March 2005 to August 2006. Patients with fatty liver change underwent detailed clinical and laboratory evaluation. Results: From 150...

  4. Liver cirrhosis and fatty liver

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008447 Identification of gene expression patterns in a rat model of nonalcoholic fatty liver disease. ZHANG Xuequn(张雪群), et al. Dept Gastroenterol, 1st Hosp, Med Coll, Zhejiang Univ, Hangzhou 310003. Chin J Dig 2008;28(5):323-327. Objective To compare and analyze gene expression patterns in a rat model of nonalcoholic fatty liver disease (NAFLD). Methods Twelve male Sprague-Dawley rats were randomly given either general diet (control group) or a high-fat diet (model group) for 4 weeks.

  5. Liver cirrhosis and fatty liver

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008075 Effect of Jiangzhi granules on expression of leptin receptor mRNA, P-JAK2 and P-STAT3 in rats with non-alcoholic fatty liver disease. MA Zansong(马赞颂), et al. Dept Gastroenterol, Instit Spleen and Stomach Dis, Longhua Hosp. Shanghai TCM Univ, Shanghai 200032.World Chin J Digestol 2007;15(32):3360-3366. Objective To study the effect of Jiangzhi granules on non-alcoholic fatty liver disease in rats, and on the expression of

  6. Hypoxia and fatty liver.

    Science.gov (United States)

    Suzuki, Tomohiro; Shinjo, Satoko; Arai, Takatomo; Kanai, Mai; Goda, Nobuhito

    2014-11-07

    The liver is a central organ that metabolizes excessive nutrients for storage in the form of glycogen and lipids and supplies energy-producing substrates to the peripheral tissues to maintain their function, even under starved conditions. These processes require a considerable amount of oxygen, which causes a steep oxygen gradient throughout the hepatic lobules. Alcohol consumption and/or excessive food intake can alter the hepatic metabolic balance drastically, which can precipitate fatty liver disease, a major cause of chronic liver diseases worldwide, ranging from simple steatosis, through steatohepatitis and hepatic fibrosis, to liver cirrhosis. Altered hepatic metabolism and tissue remodeling in fatty liver disease further disrupt hepatic oxygen homeostasis, resulting in severe liver hypoxia. As master regulators of adaptive responses to hypoxic stress, hypoxia-inducible factors (HIFs) modulate various cellular and organ functions, including erythropoiesis, angiogenesis, metabolic demand, and cell survival, by activating their target genes during fetal development and also in many disease conditions such as cancer, heart failure, and diabetes. In the past decade, it has become clear that HIFs serve as key factors in the regulation of lipid metabolism and fatty liver formation. This review discusses the molecular mechanisms by which hypoxia and HIFs regulate lipid metabolism in the development and progression of fatty liver disease.

  7. Fatty liver in children

    OpenAIRE

    Rafeey, Mandana; Mogaddasi,; Hasani, Alka; Ghaffari, Shamsi

    2009-01-01

    Mandana Rafeey1, Fakhrossadat Mortazavi2, Nafiseh Mogaddasi2, Ghergherehchi Robabeh2, Shamsi Ghaffari2, Alka Hasani31Liver and gastrointestinal Research Center; 2Tabriz University (Medical Science) Tabriz, Iran; 3Research Center of Infectious Diseases and Tropical MedicineAims: The aim of this study is to investigate the clinical and laboratory characteristics of nonalcoholic fatty liver disease (NAFLD) in a referral center of pediatrics in the northwest of Iran.Methods: In this cross-section...

  8. Liver regeneration in nonalcoholic fatty liver disease

    OpenAIRE

    Aldo Lagomarsino

    2012-01-01

    Steatosis is the accumulation of fat in hepatocytes, which may be the result of liver regeneration or pathological processes such as alcoholic and nonalcoholic fatty liver disease. Despite its importance, in both cases the exact mechanism that prevails in fatty liver regeneration is poorly understood. Previous studies have shown that patients with fatty liver express dispar regeneration, possibly due to the accumulation of reactive oxygen species generated by inflammatory processes caused by ...

  9. Fatty liver in childhood

    Institute of Scientific and Technical Information of China (English)

    Yesim; Ozturk; Ozlem; Bekem; Soylu

    2014-01-01

    Fatty liver is a growing health problem worldwide. It might evolve to nonalcoholic steatohepatitis, cirrhosis and cause hepatocellular carcinoma. This disease, which has increased because of eating habits, changes in food content and lifestyle, affects people from childhood. The most important risk factors are obesity and insulin resistance. Besides these factors, gender, ethnicity, genetic predisposition and some medical problems are also important. Cirrhosis in children is rare but is reported. Nonalcoholic fatty liver disease(NAFLD) has no specific symptoms or signs but should be considered in obese children. NAFLD does not have a proven treatment. Weight loss with family based treatments is the most acceptable management. Exercise and an applicable diet with low glycemic index and appropriate calorie intake are preferred. Drugs are promising but not sufficient in children for today.

  10. Hypoxia and fatty liver

    OpenAIRE

    Suzuki, Tomohiro; Shinjo, Satoko; Arai, Takatomo; Kanai, Mai; Goda, Nobuhito

    2014-01-01

    The liver is a central organ that metabolizes excessive nutrients for storage in the form of glycogen and lipids and supplies energy-producing substrates to the peripheral tissues to maintain their function, even under starved conditions. These processes require a considerable amount of oxygen, which causes a steep oxygen gradient throughout the hepatic lobules. Alcohol consumption and/or excessive food intake can alter the hepatic metabolic balance drastically, which can precipitate fatty li...

  11. Fatty liver in childhood

    OpenAIRE

    Ozturk,Yesim; Soylu, Ozlem Bekem

    2014-01-01

    Fatty liver is a growing health problem worldwide. It might evolve to nonalcoholic steatohepatitis, cirrhosis and cause hepatocellular carcinoma. This disease, which has increased because of eating habits, changes in food content and lifestyle, affects people from childhood. The most important risk factors are obesity and insulin resistance. Besides these factors, gender, ethnicity, genetic predisposition and some medical problems are also important. Cirrhosis in children is rare but is repor...

  12. Nonalcoholic Fatty Liver Disease

    OpenAIRE

    You, Jie; Huang, Sha; Huang, Gui-Qian; Zhu, Gui-Qi; Ma, Rui-Min; Liu, Wen-yue; Shi, Ke-Qing; Guo, Gui-Long; Chen, Yong-Ping; Braddock, Martin; Zheng, Ming-Hua

    2015-01-01

    Abstract Nonalcoholic fatty liver disease (NAFLD) is known to be associated with an increased risk of colorectal cancer (CRC). However, the relationship between NAFLD and the prognosis of CRC remains unclear. The primary objective of this study was to evaluate the overall survival (OS) and disease-free survival (DFS) rates in patients with CRC and the secondary objective was to compare clinicopathologic variables which were stratified by NAFLD. We performed a large cohort study of 1314 patien...

  13. In Vitro Screening for Antihepatic Steatosis Active Components within Coptidis Rhizoma Alkaloids Extract Using Liver Cell Extraction with HPLC Analysis and a Free Fatty Acid-Induced Hepatic Steatosis HepG2 Cell Assay.

    Science.gov (United States)

    Fan, Hui; Chen, Yuan-Yuan; Bei, Wei-Jian; Wang, Lai-You; Chen, Bao-Tian; Guo, Jiao

    2013-01-01

    A high-throughput method was developed and applied to screen for the active antihepatic steatosis components within Coptidis Rhizoma Alkaloids Extract (CAE). This method was a combination of two previously described assays: HepG2 cell extraction with HPLC analysis and a free fatty acid-induced (FFA) hepatic steatosis HepG2 cell assay. Two alkaloids within CAE, berberine and coptisine, were identified by HepG2 cell extraction with HPLC analysis as high affinity components for HepG2. These alkaloids were also determined to be active and potent compounds capable of lowering triglyceride (TG) accumulation in the FFA-induced hepatic steatosis HepG2 cell assay. This remarkable inhibition of TG accumulation (P components from HepG2 cells and a lower inhibition of TG accumulation. The finding of two potent and active compounds within CAE indicates that the screening method we developed is a feasible, rapid, and useful tool for studying traditional Chinese medicines (TCMs) in treating hepatic steatosis.

  14. Acute fatty liver in pregnancy.

    NARCIS (Netherlands)

    Tan, A.; Krieken, J.H.J.M. van; Peters, W.H.M.; Steegers, E.A.P.

    2002-01-01

    When confronted with liver abnormalities during the third trimester of pregnancy, one should consider acute fatty liver of pregnancy. The differential diagnosis with (pre-)eclampsia and HELLP syndrome is sometimes difficult. In these cases a liver biopsy is helpful though rarely performed during pre

  15. Liver cirrhosis and fatty liver

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008310 Expression of αVβ3 integrin and platelet-endothelial cell adhesion molecule-1 in progressive liver fibrosis: experiment with rats. SONG Zhengji(宋正已), et al. Dept Gastroenterol, Zhongshan Hosp, Fudan Univ, Shanghai 200032. Natl Med J China 2008;88(16):1121-1125.Objective To investigate the expression ofαVβ3 integrin and platelet endothelial cell adhesion molecule-1(CD31)in progressive liver fibrosis of rats.Methods Sixty-four SD rats were randomly divided into 4 equal groups:TAA group,undergoing peritoneal injection of

  16. Liver cirrhosis and fatty liver

    Institute of Scientific and Technical Information of China (English)

    1997-01-01

    970345 An experimental and clinical study on α1-adrenergic receptor of liver plasma membranes in cir-rhosis with portal hypertension. ZHANG Youcheng(张有成), et al. Dept Surg, People’s Hosp, Beijing MedUniv, Beijing, 100044 Chin J Dig 1996; 16(6): 332-335.

  17. Liver cirrhosis and fatty liver

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

    930137 Effects of selective and non-selectiveβ-adrenoreceptor blockers on portal hemody-namics in patients with liver cirrhosis.HUANGTianwei(黄天卫),et al.1st Affili Hosp,DalianMed Coll.Chin J Digest 1992;12(3):145-147.Effects of selective(atenolol)and non-selec-tive(propranolol)β-adrenoreceptor blockerson portal hemodynamics in patients with livercirrhosis were measured by pulsed Doppler du-

  18. Liver cirrhosis and fatty liver

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

    930537 Preliminary report on portal hyperten-tion in liver cirrhosis treated by transjugular in-trahepatic portosystemic stent shunt(analysis of8 cases).XU Ke(徐克),et al.Dept Radiol,lst Hosp,China Med Univ,Shenyang,110001.Chin J Radiol 1993;25(5):294—297.Transjugular intrahepatic portosystemic stentshunt(TIPPS)was performed in 8 cases of livercirrhosis with portal hypertention.Moderate orsevere hemorrhage from gastroesophageal variceshad happened in all patients for 2~5 times beforTIPSS.The average pressure of portal veindropped from 3.80±0.50kPa to 2.58±0.26kPa.The diameter of the shunt established be-tween portal and hepatic veins was 10~12mm.Gastrointestinal bleeding and ascites were effec-

  19. Acute fatty liver of pregnancy

    OpenAIRE

    Ko, Hin Hin; Yoshida, Eric

    2006-01-01

    Acute fatty liver of pregnancy (AFLP) is a rare, potentially fatal complication that occurs in the third trimester or early postpartum period. Although the exact pathogenesis is unknown, this disease has been linked to an abnormality in fetal fatty acid metabolism. Early diagnosis of AFLP sometimes can be difficult because it shares features with other common conditions such as pre-eclampsia, viral hepatitis and cholestasis of pregnancy. However, a careful history and physical examination, in...

  20. Carboxyatractyloside effects on brown-fat mitochondria imply that the adenine nucleotide translocator isoforms ANT1 and ANT2 may be responsible for basal and fatty-acid-induced uncoupling respectively.

    Science.gov (United States)

    Shabalina, Irina G; Kramarova, Tatiana V; Nedergaard, Jan; Cannon, Barbara

    2006-11-01

    In brown-fat mitochondria, fatty acids induce thermogenic uncoupling through activation of UCP1 (uncoupling protein 1). However, even in brown-fat mitochondria from UCP1-/- mice, fatty-acid-induced uncoupling exists. In the present investigation, we used the inhibitor CAtr (carboxyatractyloside) to examine the involvement of the ANT (adenine nucleotide translocator) in the mediation of this UCP1-independent fatty-acid-induced uncoupling in brown-fat mitochondria. We found that the contribution of ANT to fatty-acid-induced uncoupling in UCP1-/- brown-fat mitochondria was minimal (whereas it was responsible for nearly half the fatty-acid-induced uncoupling in liver mitochondria). As compared with liver mitochondria, brown-fat mitochondria exhibit a relatively high (UCP1-independent) basal respiration ('proton leak'). Unexpectedly, a large fraction of this high basal respiration was sensitive to CAtr, whereas in liver mitochondria, basal respiration was CAtr-insensitive. Total ANT protein levels were similar in brown-fat mitochondria from wild-type mice and in liver mitochondria, but the level was increased in brown-fat mitochondria from UCP1-/- mice. However, in liver, only Ant2 mRNA was found, whereas in brown adipose tissue, Ant1 and Ant2 mRNA levels were equal. The data are therefore compatible with a tentative model in which the ANT2 isoform mediates fatty-acid-induced uncoupling, whereas the ANT1 isoform may mediate a significant part of the high basal proton leak in brown-fat mitochondria.

  1. Nonalcoholic fatty liver disease

    DEFF Research Database (Denmark)

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

    2009-01-01

    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...

  2. Unsaturated fatty acids induce mesenchymal stem cells to increase secretion of angiogenic mediators.

    Science.gov (United States)

    Smith, Andria N; Muffley, Lara A; Bell, Austin N; Numhom, Surawej; Hocking, Anne M

    2012-09-01

    Mesenchymal stem cells (MSC) represent emerging cell-based therapies for diabetes and associated complications. Ongoing clinical trials are using exogenous MSC to treat type 1 and 2 diabetes, cardiovascular disease and non-healing wounds due to diabetes. The majority of these trials are aimed at exploiting the ability of these multipotent mesenchymal stromal cells to release soluble mediators that reduce inflammation and promote both angiogenesis and cell survival at sites of tissue damage. Growing evidence suggests that MSC secretion of soluble factors is dependent on tissue microenvironment. Despite the contribution of fatty acids to the metabolic environment of type 2 diabetes, almost nothing is known about their effects on MSC secretion of growth factors and cytokines. In this study, human bone marrow-derived MSC were exposed to linoleic acid, an omega-6 polyunsaturated fatty acid, or oleic acid, a monounsaturated fatty acid, for seven days in the presence of 5.38 mM glucose. Outcomes measured included MSC proliferation, gene expression, protein secretion and chemotaxis. Linoleic and oleic acids inhibited MSC proliferation and altered MSC expression and secretion of known mediators of angiogenesis. Both unsaturated fatty acids induced MSC to increase secretion of interleukin-6, VEGF and nitric oxide. In addition, linoleic acid but not oleic acid induced MSC to increase production of interleukin-8. Collectively these data suggest that exposure to fatty acids may have functional consequences for MSC therapy. Fatty acids may affect MSC engraftment to injured tissue and MSC secretion of cytokines and growth factors that regulate local cellular responses to injury.

  3. Pathophysiology of Non Alcoholic Fatty Liver Disease

    Science.gov (United States)

    Petta, Salvatore; Gastaldelli, Amalia; Rebelos, Eleni; Bugianesi, Elisabetta; Messa, Piergiorgio; Miele, Luca; Svegliati-Baroni, Gianluca; Valenti, Luca; Bonino, Ferruccio

    2016-01-01

    The physiopathology of fatty liver and metabolic syndrome are influenced by diet, life style and inflammation, which have a major impact on the severity of the clinicopathologic outcome of non-alcoholic fatty liver disease. A short comprehensive review is provided on current knowledge of the pathophysiological interplay among major circulating effectors/mediators of fatty liver, such as circulating lipids, mediators released by adipose, muscle and liver tissues and pancreatic and gut hormones in relation to diet, exercise and inflammation. PMID:27973438

  4. Nonalcoholic Fatty Liver Disease Treatment

    Directory of Open Access Journals (Sweden)

    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

  5. Role of bioactive fatty acids in nonalcoholic fatty liver disease.

    Science.gov (United States)

    Juárez-Hernández, Eva; Chávez-Tapia, Norberto C; Uribe, Misael; Barbero-Becerra, Varenka J

    2016-08-02

    Nonalcoholic fatty liver disease (NAFLD) is characterized by fat deposition in hepatocytes, and a strong association with nutritional factors. Dietary fatty acids are classified according to their biochemical properties, which confer their bioactive roles. Monounsaturated fatty acids have a dual role in various human and murine models. In contrast, polyunsaturated fatty acids exhibit antiobesity, anti steatosic and anti-inflammatory effects. The combination of these forms of fatty acids-according to dietary type, daily intake and the proportion of n-6 to n-3 fats-can compromise hepatic lipid metabolism. A chemosensory rather than a nutritional role makes bioactive fatty acids possible biomarkers for NAFLD. Bioactive fatty acids provide health benefits through modification of fatty acid composition and modulating the activity of liver cells during liver fibrosis. More and better evidence is necessary to elucidate the role of bioactive fatty acids in nutritional and clinical treatment strategies for patients with NAFLD.

  6. Amelioration by chicory seed extract of diabetes- and oleic acid-induced non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) via modulation of PPARα and SREBP-1.

    Science.gov (United States)

    Ziamajidi, Nasrin; Khaghani, Shahnaz; Hassanzadeh, Gholamreza; Vardasbi, Safura; Ahmadian, Shahram; Nowrouzi, Azin; Ghaffari, Seyed Mahmood; Abdirad, Afshin

    2013-08-01

    We evaluated the effect of chicory (Cichorium intybus L.) seed extract (CI) on hepatic steatosis caused by early and late stage diabetes in rats (in vivo), and induced in HepG2 cells (in vitro) by BSA-oleic acid complex (OA). Different dosages of CI (1.25, 2.5 and 5 mg/ml) were applied along with OA (1 mM) to HepG2 cells, simultaneously and non-simultaneously; and without OA to ordinary non-steatotic cells. Cellular lipid accumulation and glycerol release, and hepatic triglyceride (TG) content were measured. The expression levels of sterol regulatory element-binding protein-1c (SREBP-1c) and peroxisome proliferator-activated receptor alpha (PPARα) were determined. Liver samples were stained with hematoxylin and eosin (H&E). Significant histological damage (steatosis-inflammation-fibrosis) to the cells and tissues and down-regulation of SREBP-1c and PPARα genes that followed steatosis induction were prevented by CI in simultaneous treatment. In non-simultaneous treatment, CI up-regulated the expression of both genes and restored the normal levels of the corresponding proteins; with a greater stimulating effect on PPARα, CI acted as a PPARα agonist. CI released glycerol from HepG2 cells, and targeted the first and the second hit phases of hepatic steatosis. A preliminary attempt to characterize CI showed caffeic acid, chlorogenic acid, and chicoric acid, among the constituents.

  7. Sida rhomboidea.Roxb extract alleviates pathophysiological changes in experimental in vivo and in vitro models of high fat diet/fatty acid induced non-alcoholic steatohepatitis.

    Science.gov (United States)

    Thounaojam, Menaka C; Jadeja, Ravirajsinh N; Dandekar, Deven S; Devkar, Ranjitsinh V; Ramachandran, A V

    2012-03-01

    The present study was aim to evaluate protective role of Sida rhomboidea.Roxb (SR) extract against high fat diet/fatty acid induced pathophysiological alterations in experimental model of non-alcoholic steatohepatitis (NASH). Effect of SR extract on plasma levels of markers of hepatic damage, plasma and hepatic lipids, mitochondrial oxidative stress, status of enzymatic and non-enzymatic antioxidants and histopathological changes in liver tissue were evaluated in high fat diet fed C57BL/6J mice. Also, the effect of SR supplementation on lipid accumulation, lipid peroxidation, cytotoxicity and cell viability were evaluated in oleic acid treated HepG2 cells. Supplementation of NASH mice with SR extract prevented high fat diet induced elevation in plasma marker enzymes of liver damage, plasma and hepatic lipids, mitochondrial oxidative stress and compromised enzymatic and non-enzymatic antioxidant status. Further, addition of SR extract to in vitro HepG2 cells minimized oleic acid induced lipid accumulation, higher lipid peroxidation, cytotoxicity and reduced cell viability. These in vivo and in vitro studies suggest that SR extract has the potential of preventing high fat/fatty acid induced NASH mainly due to its hypolipidemic and antioxidant activities.

  8. CKD and nonalcoholic fatty liver disease.

    Science.gov (United States)

    Targher, Giovanni; Chonchol, Michel B; Byrne, Christopher D

    2014-10-01

    The possible link between nonalcoholic fatty liver disease and chronic kidney disease (CKD) recently has attracted considerable scientific interest. Accumulating clinical evidence indicates that the presence and severity of nonalcoholic fatty liver disease is associated significantly with CKD (defined as decreased estimated glomerular filtration rate and/or proteinuria) and that nonalcoholic fatty liver disease predicts the development and progression of CKD, independently of traditional cardiorenal risk factors. Experimental evidence also suggests that nonalcoholic fatty liver disease itself may exacerbate systemic and hepatic insulin resistance, cause atherogenic dyslipidemia, and release a variety of proinflammatory, procoagulant, pro-oxidant, and profibrogenic mediators that play important roles in the development and progression of CKD. However, despite the growing evidence linking nonalcoholic fatty liver disease with CKD, it has not been definitively established whether a causal association exists. The clinical implication for these findings is that patients with nonalcoholic fatty liver disease may benefit from more intensive surveillance or early treatment interventions to decrease the risk of CKD. In this review, we discuss the evidence linking nonalcoholic fatty liver disease with CKD and the putative mechanisms by which nonalcoholic fatty liver disease contributes to kidney damage. We also briefly discuss current treatment options for this increasingly prevalent disease that is likely to have an important future impact on the global burden of disease.

  9. Elevated body mass index and fatty liver

    Directory of Open Access Journals (Sweden)

    Marović Dragana

    2008-01-01

    Full Text Available Introduction Obesity and overweight, expressed by elevated Body Mass Index (BMI, result from excessive consumption of fatty food and carbohydrates above the body needs. The fat from the blood, through free fatty acids, is taken directly into the liver. Objective The aim of this study was to examine correlation among the accepted ultrasonography findings of the fatty liver and the normal ultrasonography findings and the elevated average level of BMI and those with normal BMI in examinees in one investigation. All was done aimed at proving that the BMI is one of the direct factors of the increased occurence of fatty liver. METHOD The method of the investigation consisted of anthropometric measuring of height and weight on the basis of which there were established BMI values. Consequently, the examinees were divided in two groups: one with normal BMI (under 24.9 kg/m2 and the other with increased BMI (over 25 kg/m2. Fatty liver was diagnosed when the liver of the examinees was observed by ultrasonography. Thus there were given subgroups of the examinees, one with the findings of fatty liver and the second with a normal finding, without changes. After that, the obtained results were statistically analysed. Results It was found that the average level of BMI in the examinees was by two units higher in the subgroup with ultrasonography findings of fatty liver than the average value of BMI in the subgroup with the normal ultrasonography findings of the liver. The difference was tested by the Student's t-test and a significant difference was found. The difference in frequencies of the appearance of the finding of fatty liver in the subgroups was tested by χ2-test. A statistically significant difference was found in frequencies of the appearance of fatty liver in the subgroup with the increased value of BMI. Conclusion The increased BMI, which is represented by overweight and obesity, is one of the direct risk factors which cause fatty liver, checked by

  10. Uridine prevents fenofibrate-induced fatty liver.

    Directory of Open Access Journals (Sweden)

    Thuc T Le

    Full Text Available Uridine, a pyrimidine nucleoside, can modulate liver lipid metabolism although its specific acting targets have not been identified. Using mice with fenofibrate-induced fatty liver as a model system, the effects of uridine on liver lipid metabolism are examined. At a daily dosage of 400 mg/kg, fenofibrate treatment causes reduction of liver NAD(+/NADH ratio, induces hyper-acetylation of peroxisomal bifunctional enzyme (ECHD and acyl-CoA oxidase 1 (ACOX1, and induces excessive accumulation of long chain fatty acids (LCFA and very long chain fatty acids (VLCFA. Uridine co-administration at a daily dosage of 400 mg/kg raises NAD(+/NADH ratio, inhibits fenofibrate-induced hyper-acetylation of ECHD, ACOX1, and reduces accumulation of LCFA and VLCFA. Our data indicates a therapeutic potential for uridine co-administration to prevent fenofibrate-induced fatty liver.

  11. Update on fatty liver disease and steatohepatitis.

    Science.gov (United States)

    Aly, Fatima Zahra; Kleiner, David E

    2011-07-01

    Non-alcoholic fatty liver disease (NAFLD) is a broad term that includes liver diseases characterized by abnormal hepatocellular accumulations of lipid that cannot be related to alcohol abuse. It may be found in both adults and children, particularly those who are obese or have insulin resistance. Steatohepatitis is a specific pattern of injury within the spectrum of NAFLD and this pattern is associated with fibrotic progression and cirrhosis. In addition to steatohepatitis, a distinct form of fibrotic fatty liver disease exists in children. There have been a number of recent advances in the characterization of histologic changes in NAFLD. In light of these recent reports, this study will: (1) review the histologic features of steatosis and nonalcoholic steatohepatitis in adults; (2) review the variation of histologic patterns of pediatric fatty liver disease; and (3) discuss the validity and use of the nonalcoholic fatty liver disease Activity Score.

  12. Ameliorative effects of polyunsaturated fatty acids against palmitic acid-induced insulin resistance in L6 skeletal muscle cells

    Directory of Open Access Journals (Sweden)

    Sawada Keisuke

    2012-03-01

    Full Text Available Abstract Background Fatty acid-induced insulin resistance and impaired glucose uptake activity in muscle cells are fundamental events in the development of type 2 diabetes and hyperglycemia. There is an increasing demand for compounds including drugs and functional foods that can prevent myocellular insulin resistance. Methods In this study, we established a high-throughput assay to screen for compounds that can improve myocellular insulin resistance, which was based on a previously reported non-radioisotope 2-deoxyglucose (2DG uptake assay. Insulin-resistant muscle cells were prepared by treating rat L6 skeletal muscle cells with 750 μM palmitic acid for 14 h. Using the established assay, the impacts of several fatty acids on myocellular insulin resistance were determined. Results In normal L6 cells, treatment with saturated palmitic or stearic acid alone decreased 2DG uptake, whereas unsaturated fatty acids did not. Moreover, co-treatment with oleic acid canceled the palmitic acid-induced decrease in 2DG uptake activity. Using the developed assay with palmitic acid-induced insulin-resistant L6 cells, we determined the effects of other unsaturated fatty acids. We found that arachidonic, eicosapentaenoic and docosahexaenoic acids improved palmitic acid-decreased 2DG uptake at lower concentrations than the other unsaturated fatty acids, including oleic acid, as 10 μM arachidonic acid showed similar effects to 750 μM oleic acid. Conclusions We have found that polyunsaturated fatty acids, in particular arachidonic and eicosapentaenoic acids prevent palmitic acid-induced myocellular insulin resistance.

  13. Palmitic acid-induced apoptosis in pancreatic β-cells is increased by liver X receptor agonist and attenuated by eicosapentaenoate.

    Science.gov (United States)

    Liang, Huasheng; Zhong, Yuhua; Zhou, Shaobi; Li, Qingdi Quentin

    2011-01-01

    Saturated fatty acids are implicated in the development of diabetes via the impairment of pancreatic islet β-cell viability and function. Liver X receptors (LXRs) and eicosapentaenoate (EPA) are known regulators of fatty acid metabolism. However, their roles in the pathogenesis of diabetes remain incompletely understood. The aim of this study was to determine the effects of EPA and the LXR agonist T0901317 on saturated fatty acid (palmitic acid)-induced apoptosis in the insulinoma β-cell line INS-1, a model for insulin-secreting β-cells. T0901317 significantly promoted palmitic acid-induced apoptotic cell death in the INS-1 cells. Consistent with these results, caspase-3 activity and BAX and sterol regulatory element binding protein-1c (SREBP-1c) mRNA levels were markedly increased in INS-1 cells co-administered palmitic acid and T0901317. The production of reactive oxygen species was considerably higher in the cells cultured concurrently with T0901317 and palmitic acid than in the cells incubated with either agent alone. EPA treatment attenuated the cellular death promoted by palmitic acid and T0901317 in the INS-1 cells, disclosing a possible mediating mechanism involving the inhibition of SREBP-1c. Finally, T0901317 up-regulated the palmitic acid-induced expression of p27(KIP1), transforming growth factor beta 1, and SMAD3 proteins in INS-1 cells. These results demonstrate that palmitic acid-induced apoptosis in β-cells is enhanced by T0901317 via the activation of LXRs and is blocked by EPA via the inhibition of SREBP-1c, suggesting that the regulation of lipogenesis and lipotoxicity affecting pancreatic β-cell viability and insulin production may be a unique strategy for diabetes therapy.

  14. Nonalcoholic fatty liver disease after liver transplantation for cryptogenic cirrhosis or nonalcoholic fatty liver disease.

    Science.gov (United States)

    Yalamanchili, Kanthi; Saadeh, Sherif; Klintmalm, Göran B; Jennings, Linda W; Davis, Gary L

    2010-04-01

    Nonalcoholic steatohepatitis (NASH) may account for many cases of cryptogenic cirrhosis. If so, then steatosis might recur after liver transplantation. Two thousand fifty-two patients underwent primary liver transplantation for chronic liver disease between 1986 and 2004. Serial liver biopsy samples were assessed for steatosis and fibrosis. Two hundred fifty-seven patients (12%) had a pretransplant diagnosis of cryptogenic cirrhosis (239) or NASH (18). Fatty liver developed in 31% and was more common when the pretransplant diagnosis was NASH (45% at 5 years versus 23% for cryptogenic cirrhosis, P = 0.007). NASH developed in only 4% and occurred exclusively when steatosis had already occurred. Steatosis after liver transplantation was associated with the baseline body weight and body mass index by univariate analyses, but no pretransplant or posttransplant characteristic independently predicted steatosis after liver transplantation because obesity was so common in all groups. Five percent and 10% developed bridging fibrosis or cirrhosis after 5 and 10 years, respectively, and this was more common after NASH (31%) than in those who developed steatosis alone (6%) or had no fat (3%, P = 0.002). One-, 5-, and 10-year survival was the same in patients who underwent transplantation for cryptogenic cirrhosis or NASH (86%, 71%, and 56%) and in patients who underwent transplantation for other indications (86%, 71%, and 53%; not significant), but death was more often due to cardiovascular disease and less likely from recurrent liver disease. In conclusion, fatty liver is common after liver transplantation for cryptogenic cirrhosis or NASH but is twice as common in the latter group; this suggests that some cryptogenic cirrhosis, but perhaps not all, is caused by NASH. Posttransplant NASH is unusual, and steatosis appears to be a prerequisite. Advanced fibrosis is uncommon, and survival is the same as that of patients who undergo transplantation for other causes.

  15. Saturated Fatty Acid Induces Insulin Resistance Partially Through Nucleotide-binding Oligomerization Domain 1 Signaling Pathway in Adipocytes

    Institute of Scientific and Technical Information of China (English)

    Yi-jun Zhou; Yin-si Tang; Yu-ling Song; Ai Li; Hui Zhou; Yan Li

    2013-01-01

    Objective To investigate the potential role of nucleotide-binding oligomerization domain 1 (NOD1), a component of the innate immune system, in mediating lipid-induced insulin resistance in adipocytes. Methods Adipocytes from Toll-like receptor 4 deficiency mice were used for stimulation experiments. The effect of oleate/palmitate mixture on nuclear factor-κB (NF-κB) activation was analyzed by reporter plasmid assay. The release of proinflammatory chemokine/cytokines production was determined by using real-time PCR. Insulin-stimulated glucose uptake was measured by 2-deoxy-D-[3H] glucose uptake assay. Chemokine/cytokine expression and glucose uptake in adipocytes transfected with small interfering RNA (siRNA) targeting NOD1 upon fatty acids treatment were analyzed. Results Oleate/palmitate mixture activated the NF-κB pathway and induced interleukin-6, tumor necrosis factor-α, and monocyte chemoattractant protein-1 mRNA expressions in adipocytes from mice deficient in Toll-like receptor 4, and these effects were blocked by siRNA targeting NOD1. Furthermore, saturated fatty acids decreased the ability of insulin-stimulated glucose uptake. Importantly, siRNA targeting NOD1 partially reversed saturated fatty acid-induced suppression of insulin-induced glucose uptake. Conclusion NOD1 might play an important role in saturated fatty acid-induced insulin resistance in adipocytes, suggesting a mechanism by which reduced NOD1 activity confers beneficial effects on insulin action.

  16. Reversible fatty infiltration of the liver

    Energy Technology Data Exchange (ETDEWEB)

    Bostel, F.; Hauger, W.

    1987-11-01

    Case studies show that acute pancreatitis occurring independently or combined with a preceding abuse of alcohol may be the cause of fatty infiltration of the liver. These fat areas can evolve in a very short time and provoke in the case of focal incidence diagnostic problems of differentiation against abscesses of metastases. Due to this fact and because of the rapid reversibility of the fatty infiltration under therapy, the safest method to clarify the situation consists of short-term CT controls.

  17. Fatty Liver Disease (Nonalcoholic Steatohepatitis)

    Science.gov (United States)

    ... Liver Disease & NASH Definition & Facts Symptoms & Causes Diagnosis Treatment Eating, Diet, & Nutrition Clinical Trials Biliary Atresia Cirrhosis Hemochromatosis Hepatitis A through E (Viral Hepatitis) Hepatitis ...

  18. [Non-alcoholic fatty liver disease (NAFLD)].

    Science.gov (United States)

    Rau, Monika; Weiss, Johannes; Geier, Andreas

    2015-07-01

    Non-alcoholic fatty liver disease is the most common chronic liver disease in Europe and in the USA with rising prevalence. Patients with a metabolic syndrome (diabetes mellitus, obesity, dyslipidemia) are patients at risk with the highest prevalence for NAFLD. Progression from a non-alcoholic fatty liver (NAFL) to a non-alcoholic steatohepatitis (NASH) occurs in 5-20% of patients with the potential to develop a liver fibrosis/cirrhosis. NASH patients and NAFLD patients with higher fibrosis should be identified because they are at risk of a higher mortality. A specific treatment for NASH is not available at the moment. Therefore, the treatment of risk factors and metabolic syndrome has high priority.

  19. 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.

  20. Histopathology of nonalcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    Elizabeth; M; Brunt; Dina; G; Tiniakos

    2010-01-01

    Histological analysis of liver biopsies remains a standard against which other methods of assessment for the presence and amount of hepatic injury due to nonalcoholic fatty liver disease(NAFLD) are measured.Histological evaluation remains the sole method of distinguishing steatosis from advanced forms of NAFLD,i.e.nonalcoholic steatohepatitis(NASH) and fibrosis.Included in the lesions of NAFLD are steatosis,lobular and portal inflammation,hepatocyte injury in the forms of ballooning and apoptosis,and fibros...

  1. Managing non-alcoholic fatty liver disease

    Science.gov (United States)

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

    2016-01-01

    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. PMID:27439352

  2. Expression of fatty acid synthase in nonalcoholic fatty liver disease.

    Science.gov (United States)

    Dorn, Christoph; Riener, Marc-Oliver; Kirovski, Georgi; Saugspier, Michael; Steib, Kathrin; Weiss, Thomas S; Gäbele, Erwin; Kristiansen, Glen; Hartmann, Arndt; Hellerbrand, Claus

    2010-03-25

    Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic lipid accumulation which starts with simple hepatic steatosis and may progress toward inflammation (nonalcoholic steatohepatitis [NASH]). Fatty acid synthase (FASN) catalyzes the last step in fatty acid biosynthesis, and thus, it is believed to be a major determinant of the maximal hepatic capacity to generate fatty acids by de novo lipogenesis. The aim of this study was to analyze the correlation between hepatic steatosis and inflammation with FASN expression. In vitro incubation of primary human hepatocytes with fatty acids dose-dependently induced cellular lipid-accumulation and FASN expression, while stimulation with TNF did not affect FASN levels. Further, hepatic FASN expression was significantly increased in vivo in a murine model of hepatic steatosis without significant inflammation but not in a murine NASH model as compared to control mice. Also, FASN expression was not increased in mice subjected to bile duct ligation, an experimental model characterized by severe hepatocellular damage and inflammation. Furthermore, FASN expression was analyzed in 102 human control or NAFLD livers applying tissue micro array technology and immunohistochemistry, and correlated significantly with the degree of hepatic steatosis, but not with inflammation or ballooning of hepatocytes. Quantification of FASN mRNA expression in human liver samples confirmed significantly higher FASN levels in hepatic steatosis but not in NASH, and expression of SREBP1, which is the main transcriptional regulator of FASN, paralleled FASN expression levels in human and experimental NAFLD. In conclusion, the transcriptional induction of FASN expression in hepatic steatosis is impaired in NASH, while hepatic inflammation in the absence of steatosis does not affect FASN expression, suggesting that FASN may serve as a new diagnostic marker or therapeutic target for the progression of NAFLD.

  3. Inhibitory effect of schisandrin B on free fatty acid-induced steatosis in L-02 cells

    Institute of Scientific and Technical Information of China (English)

    Jian-Hong Chu; Hui Wang; Yan Ye; Ping-Kei Chan; Si-Yuan Pan; Wang-Fun Fong; Zhi-Ling Yu

    2011-01-01

    AIM: To investigate the effects of schisandrin B (Sch B) on free fatty acid (FFA)-induced steatosis in L-02 cells. METHODS: Cellular steatosis was induced by incubating L-02 cells with a FFA mixture (oleate and palmitate at the ratio of 2:1) for 24 h. Cytotoxicity and apoptosis were evaluated by 3-(4, 5-dmethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide assay and Annexin V/propidium iodide staining, respectively. Cellular total lipid was determined using a photocolorimetric method after Nile red staining, and triglyceride content was measured using an enzymatic kit. To study the effects of Sch B on steatosis, L-02 cells were treated with Sch B (1-100 μmol/L) in the absence or presence of 1 mmol/L FFA for 24 h, and cellular total lipid and triglyceride levels were measured. To explore the mechanisms of action of Sch B in the steatotic L-02 cells, mRNA levels of several regulators of hepatic lipid metabolism including adipose differentiation related protein (ADRP), sterol regulatory element binding protein 1 (SREBP-1), peroxisome proliferator-activated receptor (PPAR)-α and PPAR-γ were measured by quantitative real-time polymerase chain reaction (PCR), and protein levels of ADRP and SREBP-1 were measured by immunoblotting. RESULTS: Treatment with 1 mmol/L FFA for 24 h induced intracellular lipid accumulation in L-02 cells comparable to that in human steatotic livers without causing apparent apoptosis and cytotoxicity. Sch B mitigated cellular total lipid and triglyceride accumulations in the steatotic L-02 cells in a dose-dependent manner. Quantitative real-time PCR and Western blot analyses revealed that treatment of L-02 cells with 100 μmol/L Sch B reverted the FFA-stimulated up-regulation of ADRP and SREBP-1.

  4. Nonalcoholic Fatty Liver Disease in Pediatrics.

    Science.gov (United States)

    Duncan, Martin; Zong, Wenjing; Biank, Vincent F; Hageman, Joseph R

    2016-02-01

    A 16-year-old Hispanic girl with an elevated body mass index in an otherwise normal state of health presented for her well-child examination. She had signs of metabolic syndrome and insulin resistance including increased waist circumference and acanthosis nigricans. Laboratory results revealed elevated transaminases with otherwise normal hepatic function. Based on the physical examination and laboratory results, she was diagnosed with nonalcoholic fatty liver disease (NAFLD). After further evaluation, she eventually underwent a liver biopsy. The biopsy revealed nonalcoholic steatohepatitis (NASH) with stage 2 fibrosis. This article reviews the definition of NAFLD and NASH, an increasingly prevalent cause of pediatric chronic liver disease associated with obesity and metabolic syndrome. The article also outlines the epidemiology, risk factors, and natural history of NAFLD, which may help identify and prevent high-risk pediatric patients from progressing to irreversible liver disease. Understanding the diagnostic and treatment options offers the best chance at preventing and reversing the early stages of this disease.

  5. Micronutrient Antioxidants and Nonalcoholic Fatty Liver Disease

    Science.gov (United States)

    Chen, Guanliang; Ni, Yinhua; Nagata, Naoto; Xu, Liang; Ota, Tsuguhito

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) is one of the most important chronic liver diseases worldwide and has garnered increasing attention in recent decades. NAFLD is characterized by a wide range of liver changes, from simple steatosis to nonalcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma. The blurred pathogenesis of NAFLD is very complicated and involves lipid accumulation, insulin resistance, inflammation, and fibrogenesis. NAFLD is closely associated with complications such as obesity, diabetes, steatohepatitis, and liver fibrosis. During the progression of NAFLD, reactive oxygen species (ROS) are activated and induce oxidative stress. Recent attempts at establishing effective NAFLD therapy have identified potential micronutrient antioxidants that may reduce the accumulation of ROS and finally ameliorate the disease. In this review, we present the molecular mechanisms involved in the pathogenesis of NAFLD and introduce some dietary antioxidants that may be used to prevent or cure NAFLD, such as vitamin D, E, and astaxanthin. PMID:27563875

  6. Nonalcoholic fatty liver disease in developing countries

    Institute of Scientific and Technical Information of China (English)

    Hossein Bahrami

    2005-01-01

    @@ TO THE EDITOR Nonalcoholic fatty liver disease (NAFLD) is an increasingly known medical entity with high prevalence, about 1 0 to 24 percent in general population and up to 74% in obese population[1]. The prevalence of the disease is expected to increase worldwide, as we are encountering the global obesity epidemic and the trend in developing countries toward the Western lifestyles. However, it looks that there are some differences between the demographic and epidemiologic features of NAFLD in developing and developed countries.

  7. Loss of n-6 fatty acid induced pediatric obesity protects against acute murine colitis

    Science.gov (United States)

    Dietary influences may affect microbiome composition and host immune responses, thereby modulating propensity toward inflammatory bowel diseases: Crohn disease and ulcerative colitis. Dietary n-6 fatty acids have been associated with ulcetative colitis in prospective studies. However, the critical d...

  8. Nonalcoholic fatty liver disease and mitochondrial dysfunction

    Institute of Scientific and Technical Information of China (English)

    Yongzhong Wei; R Scott Rector; John P Thyfault; Jamal A Ibdah

    2008-01-01

    Nonalcoholic fatty liver disease (NAFLD) includes hepatic steatosis, nonalcoholic steatohepatitis (NASH), fibrosis,and cirrhosis. NAFLD is the most common liver disorder in the United States and worldwide. Due to the rapid rise of the metabolic syndrome, the prevalence of NAFLD has recently dramatically increased and will continue to increase. NAFLD has also the potential to progress to hepatocellular carcinoma (HCC) or liver failure. NAFLD is strongly linked to caloric overconsumption, physical inactivity, insulin resistance and genetic factors. Although significant progress in understanding the pathogenesis of NAFLD has been achieved in years, the primary metabolic abnormalities leading to lipid accumulation within hepatocytes has remained poorly understood.Mitochondria are critical metabolic organelles serving as "cellular power plants". Accumulating evidence indicate that hepatic mitochondrial dysfunction is crucial to the pathogenesis of NAFLD. This review is focused on the significant role of mitochondria in the development of NAFLD.

  9. Treatment of nonalcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    Juergen Siebler; Peter R Galle

    2006-01-01

    Nonalcoholic fatty liver disease (NAFLD) is the most common cause for elevated liver enzymes in the developed nations. Beyond prevention programs which are of particular interest because of the increasing number of overweight children, treatment should be focussed on the most important risk factors, obesity and insulin resistance. As a consequence of elucidating the pathomechanisms of NAFLD, the number of potential therapeutic options increased. However, many studies investigating the therapeutic effect show shortcomings in at least one of the following points: lack of a serial liver biopsy, short term of treatment and limited number of included patients. The second generation insulin sensitizer pioglitazone and rosiglitazone show the most promising improvements in NAFLD, but weight gain and potential hepatotoxicity calls for attention. In conclusion,a general recommendation for the application of specific drugs cannot be given. Besides controlled clinical trials,weight reduction and physical activity to improve insulin sensitivity in obese patients should be the priority objective.

  10. Role of liver biopsy in nonalcoholic fatty liver disease.

    Science.gov (United States)

    Nalbantoglu, I L Ke; Brunt, Elizabeth M

    2014-07-21

    Nonalcoholic fatty liver disease (NAFLD), defined as abnormal accumulation (> 5%) of hepatic triglyceride without excess alcohol intake, is the most common form of chronic liver disease in adults and children in the United States. NAFLD encompasses a spectrum of histologic findings including uncomplicated steatosis, steatosis with inflammation and steatohepatitis [nonalcoholic steatohepatitis (NASH)]; the latter can advance to cirrhosis and hepatocellular carcinoma. NASH is currently accepted as the hepatic manifestation of the set of cardiovascular risk factors collectively known as metabolic syndrome. In 1999 a system for histologic grading and staging for NASH was proposed; this was revised by the NASH Clinical Research Network in 2005 for the entire spectrum of lesions in NAFLD, including the lesions and patterns of pediatric NAFLD, and for application in clinical research trials. Diagnosis remains distinct from grade and stage. A recent European proposal separates steatosis from activity to derive a numeric diagnosis of NASH. Even though there have been promising advancements in non-invasive testing, these tests are not yet detailed enough to replace the full range of findings provided by liver biopsy evaluation. Limitations of biopsy are acknowledged, but liver biopsy remains the "gold standard" for diagnosis and determination of amounts of necroinflammatory activity, and location of fibrosis, as well as remodeling of the parenchyma in NASH. This review focuses on the specific histologic lesions of NAFLD and NASH, grading and staging, differential diagnoses to be considered, and the continuing role of the liver biopsy in this important liver disease.

  11. Soft drinks consumption and nonalcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    William; Nseir; Fares; Nassar; Nimer; Assy

    2010-01-01

    Nonalcoholic fatty liver disease(NAFLD) is a common clinical condition which is associated with metabolic syndrome in 70% of cases.Inappropriate dietary fat intake,excessive intake of soft drinks,insulin resistance and increased oxidative stress combine to increase free fatty acid delivery to the liver,and increased hepatic triglyceride accumulation contributes to fatty liver.Regular soft drinks have high fructose corn syrup which contains basic sugar building blocks,fructose 55% and glucose 45%.Soft drinks...

  12. Obesity, fatty liver disease and intestinal microbiota.

    Science.gov (United States)

    Arslan, Nur

    2014-11-28

    Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disorder that is increasing in prevalence with the worldwide epidemic of obesity. NAFLD is the hepatic manifestation of the metabolic syndrome. The term NAFLD describes a spectrum of liver pathology ranges from simple steatosis to steatosis with inflammation nonalcoholic steatohepatitis and even cirrhosis. Metabolic syndrome and NAFLD also predict hepatocellular carcinoma. Many genetic and environmental factors have been suggested to contribute to the development of obesity and NAFLD, but the exact mechanisms are not known. Intestinal ecosystem contains trillions of microorganisms including bacteria, Archaea, yeasts and viruses. Several studies support the relationship between the intestinal microbial changes and obesity and also its complications, including insulin resistance and NAFLD. Given that the gut and liver are connected by the portal venous system, it makes the liver more vulnerable to translocation of bacteria, bacterial products, endotoxins or secreted cytokines. Altered intestinal microbiota (dysbiosis) may stimulate hepatic fat deposition through several mechanisms: regulation of gut permeability, increasing low-grade inflammation, modulation of dietary choline metabolism, regulation of bile acid metabolism and producing endogenous ethanol. Regulation of intestinal microbial ecosystem by diet modifications or by using probiotics and prebiotics as a treatment for obesity and its complications might be the issue of further investigations.

  13. Within brown-fat cells, UCP1-mediated fatty acid-induced uncoupling is independent of fatty acid metabolism.

    Science.gov (United States)

    Shabalina, Irina G; Backlund, Emma C; Bar-Tana, Jacob; Cannon, Barbara; Nedergaard, Jan

    2008-01-01

    In the present investigation, we have utilized the availability of UCP1(-/-) mice to examine a wide range of previously proposed lipid activators of Uncoupling Protein 1 (UCP1) in its native environment, i.e. in the brown-fat cells. A non-metabolizable fatty acid analogue, beta,beta cent-methyl-substituted hexadecane alpha,omega-dicarboxylic acid (Medica-16) is a potent UCP1 (re)activator in brown-fat cells, despite its bipolar structure. All-trans-retinoic acid activates UCP1 within cells, whereas beta-carotene only does so after metabolism. The UCP1-dependent effects of fatty acids are positively correlated with their chain length. Medium-chain fatty acids are potent UCP1 activators in cells, despite their lack of protonophoric properties in mitochondrial membranes. Thus, neither the ability to be metabolized nor an innate uncoupling/protonophoric ability is a necessary property of UCP1 activators within brown-fat cells.

  14. Fatty acids induce leukotriene C4 synthesis in macrophages in a fatty acid binding protein-dependent manner.

    Science.gov (United States)

    Long, Eric K a; Hellberg, Kristina; Foncea, Rocio; Hertzel, Ann V; Suttles, Jill; Bernlohr, David A

    2013-07-01

    Obesity results in increased macrophage recruitment to adipose tissue that promotes a chronic low-grade inflammatory state linked to increased fatty acid efflux from adipocytes. Activated macrophages produce a variety of pro-inflammatory lipids such as leukotriene C4 (LTC4) and 5-, 12-, and 15-hydroxyeicosatetraenoic acid (HETE) suggesting the hypothesis that fatty acids may stimulate eicosanoid synthesis. To assess if eicosanoid production increases with obesity, adipose tissue of leptin deficient ob/ob mice was analyzed. In ob/ob mice, LTC4 and 12-HETE levels increased in the visceral (but not subcutaneous) adipose depot while the 5-HETE levels decreased and 15-HETE abundance was unchanged. Since macrophages produce the majority of inflammatory molecules in adipose tissue, treatment of RAW264.7 or primary peritoneal macrophages with free fatty acids led to increased secretion of LTC4 and 5-HETE, but not 12- or 15-HETE. Fatty acid binding proteins (FABPs) facilitate the intracellular trafficking of fatty acids and other hydrophobic ligands and in vitro stabilize the LTC4 precursor leukotriene A4 (LTA4) from non-enzymatic hydrolysis. Consistent with a role for FABPs in LTC4 synthesis, treatment of macrophages with HTS01037, a specific FABP inhibitor, resulted in a marked decrease in both basal and fatty acid-stimulated LTC4 secretion but no change in 5-HETE production or 5-lipoxygenase expression. These results indicate that the products of adipocyte lipolysis may stimulate the 5-lipoxygenase pathway leading to FABP-dependent production of LTC4 and contribute to the insulin resistant state.

  15. Omega-9 Oleic Acid Induces Fatty Acid Oxidation and Decreases Organ Dysfunction and Mortality in Experimental Sepsis

    Science.gov (United States)

    Oliveira, Flora Magno de Jesus; Burth, Patrícia; Bozza, Patrícia Torres; Castro Faria, Mauro Velho; Silva, Adriana Ribeiro; de Castro-Faria-Neto, Hugo Caire

    2016-01-01

    Sepsis is characterized by inflammatory and metabolic alterations, which lead to massive cytokine production, oxidative stress and organ dysfunction. In severe systemic inflammatory response syndrome, plasma non-esterified fatty acids (NEFA) are increased. Several NEFA are deleterious to cells, activate Toll-like receptors and inhibit Na+/K+-ATPase, causing lung injury. A Mediterranean diet rich in olive oil is beneficial. The main component of olive oil is omega-9 oleic acid (OA), a monounsaturated fatty acid (MUFA). We analyzed the effect of OA supplementation on sepsis. OA ameliorated clinical symptoms, increased the survival rate, prevented liver and kidney injury and decreased NEFA plasma levels in mice subjected to cecal ligation and puncture (CLP). OA did not alter food intake and weight gain but diminished reactive oxygen species (ROS) production and NEFA plasma levels. Carnitine palmitoyltransferase IA (CPT1A) mRNA levels were increased, while uncoupling protein 2 (UCP2) liver expression was enhanced in mice treated with OA. OA also inhibited the decrease in 5' AMP-activated protein kinase (AMPK) expression and increased the enzyme expression in the liver of OA-treated mice compared to septic animals. We showed that OA pretreatment decreased NEFA concentration and increased CPT1A and UCP2 and AMPK levels, decreasing ROS production. We suggest that OA has a beneficial role in sepsis by decreasing metabolic dysfunction, supporting the benefits of diets high in monounsaturated fatty acids (MUFA). PMID:27078880

  16. Induction of CYP2E1 in non-alcoholic fatty liver diseases.

    Science.gov (United States)

    Aljomah, Ghanim; Baker, Susan S; Liu, Wensheng; Kozielski, Rafal; Oluwole, Janet; Lupu, Benita; Baker, Robert D; Zhu, Lixin

    2015-12-01

    Mounting evidence supports a contribution of endogenous alcohol metabolism in the pathogenesis of non-alcoholic steatohepatitis (NASH). However, it is not known whether the expression of alcohol metabolism genes is altered in the livers of simple steatosis. There is also a current debate on whether fatty acids induce CYP2E1 in fatty livers. In this study, expression of alcohol metabolizing genes in the liver biopsies of simple steatosis patients was examined by quantitative real-time PCR (qRT-PCR), in comparison to biopsies of NASH livers and normal controls. Induction of alcohol metabolizing genes was also examined in cultured HepG2 cells treated with ethanol or oleic acid, by qRT-PCR and Western blots. We found that the mRNA expression of alcohol metabolizing genes including ADH1C, ADH4, ADH6, catalase and CYP2E1 was elevated in the livers of simple steatosis, to similar levels found in NASH livers. In cultured HepG2 cells, ethanol induced the expression of CYP2E1 mRNA and protein, but not ADH4 or ADH6; oleic acid did not induce any of these genes. These results suggest that elevated alcohol metabolism may contribute to the pathogenesis of NAFLD at the stage of simple steatosis as well as more severe stages. Our in vitro data support that CYP2E1 is induced by endogenous alcohol but not by fatty acids.

  17. Nutraceutical with Resveratrol and Omega-3 Fatty Acids Induces Autophagy in ARPE-19 Cells.

    Science.gov (United States)

    Koskela, Ali; Reinisalo, Mika; Petrovski, Goran; Sinha, Debasish; Olmiere, Céline; Karjalainen, Reijo; Kaarniranta, Kai

    2016-05-11

    Impaired autophagic and proteasomal cleansing have been documented in aged retinal pigment epithelial (RPE) cells and age-related macular degeneration (AMD). Omega-3 fatty acids and resveratrol have many positive homeostatic effects in RPE cells. In this work, ARPE-19 cells were treated with 288 ng of Resvega, containing 30 mg of trans resveratrol and 665 mg of omega-3 fatty acids, among other nutrients, with proteasome inhibitor MG-132 or autophagy inhibitor bafilomycin A1 up to 48 h. Autophagy markers p62/SQSTM1 (p62) and LC3 (microtubule-associated protein 1A/1B-light chain 3) were analyzed by Western blotting. Fluorescence microscopy with mCherry-GFP-LC3 plasmid was applied to study the autophagy flux, and cytoprotective effects were investigated with colorimetric MTT and LDH assays. Resvega induced autophagy by showing increased autolysosome formation and autophagy flux, and the change in the p62 and LC3 protein levels further confirmed the fluorescent microscopy results. Moreover, Resvega provided a clear cytoprotection under proteasome inhibition. These findings highlight the potential of the nutraceuticals containing resveratrol, omega-3 fatty acids and other nutrients in the prevention of ARPE-19 cell damage.

  18. Analysis of fatty liver by CT values in obese children

    Energy Technology Data Exchange (ETDEWEB)

    Naganuma, Yoshihiro; Tomizawa, Shuichi; Ikarashi, Kozo; Tohyama, Jun; Ozawa, Kanzi [Niigata Hospital National Sanatorium, Kashiwazaki (Japan); Uchiyama, Makoto

    1996-06-01

    Liver attenuation values were measured by CT in 97 (183 times) obese children with ages 3 to 18 years and a diagnosis of fatty liver was made in 42 subjects. Liver/spleen ration from CT measurements showed a significant negative correlation with the percentage of standard body weight, and with the systolic pressure. In children with fatty liver, systolic pressure and serum GOT, GPT, ChE, TC, TG, ApoB and insulin were significantly higher than those in children without fatty liver. After a low-calorie dietary regimen and exercise therapy, the liver/spleen ratio and GPT improved in all children. The diagnosis of fatty infiltration (fatty liver) was made with a liver/spleen ratio of less than 1.0 as determined by the number of measurements taken, a reasonable criterion for the diagnosis of fatty liver by CT in children. There were some children with elevated GPT who showed normal CT findings. This may be caused by overnutrition which was associated with fatty infiltration, since GPT decreased in all these children after treatment. The present study suggests that CT is a useful procedure in diagnosing fatty liver, and in monitoring and determining efficacy of treatment in obese children. (author)

  19. Herbal medicines and nonalcoholic fatty liver disease.

    Science.gov (United States)

    Yao, Hong; Qiao, Yu-Jie; Zhao, Ya-Li; Tao, Xu-Feng; Xu, Li-Na; Yin, Lian-Hong; Qi, Yan; Peng, Jin-Yong

    2016-08-14

    Nonalcoholic fatty liver disease (NAFLD), which is characterized by excessive fat accumulation in the liver of patients who consume little or no alcohol, becomes increasingly common with rapid economic development. Long-term excess fat accumulation leads to NAFLD and represents a global health problem with no effective therapeutic approach. NAFLD is considered to be a series of complex, multifaceted pathological processes involving oxidative stress, inflammation, apoptosis, and metabolism. Over the past decades, herbal medicines have garnered growing attention as potential therapeutic agents to prevent and treat NAFLD, due to their high efficacy and low risk of side effects. In this review, we evaluate the use of herbal medicines (including traditional Chinese herbal formulas, crude extracts from medicinal plants, and pure natural products) to treat NAFLD. These herbal medicines are natural resources that can inform innovative drug research and the development of treatments for NAFLD in the future.

  20. Herbal medicines and nonalcoholic fatty liver disease

    Science.gov (United States)

    Yao, Hong; Qiao, Yu-Jie; Zhao, Ya-Li; Tao, Xu-Feng; Xu, Li-Na; Yin, Lian-Hong; Qi, Yan; Peng, Jin-Yong

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD), which is characterized by excessive fat accumulation in the liver of patients who consume little or no alcohol, becomes increasingly common with rapid economic development. Long-term excess fat accumulation leads to NAFLD and represents a global health problem with no effective therapeutic approach. NAFLD is considered to be a series of complex, multifaceted pathological processes involving oxidative stress, inflammation, apoptosis, and metabolism. Over the past decades, herbal medicines have garnered growing attention as potential therapeutic agents to prevent and treat NAFLD, due to their high efficacy and low risk of side effects. In this review, we evaluate the use of herbal medicines (including traditional Chinese herbal formulas, crude extracts from medicinal plants, and pure natural products) to treat NAFLD. These herbal medicines are natural resources that can inform innovative drug research and the development of treatments for NAFLD in the future. PMID:27570425

  1. Association of nonalcoholic fatty liver disease and liver cancer

    Science.gov (United States)

    Schulz, Perla Oliveira; Ferreira, Fabio Gonçalves; Nascimento, Maria de Fátima Araújo; Vieira, Andrea; Ribeiro, Mauricio Alves; David, André Ibrahim; Szutan, Luiz Arnaldo

    2015-01-01

    AIM: To investigate the association between nonalcoholic fatty liver disease (NAFLD) and liver cancer, and NAFLD prevalence in different liver tumors. METHODS: This is a retrospective study of the clinical, laboratory and histological data of 120 patients diagnosed with primary or secondary hepatic neoplasms and treated at a tertiary center where they underwent hepatic resection and/or liver transplantation, with subsequent evaluation of the explant or liver biopsy. The following criteria were used to exclude patients from the study: a history of alcohol abuse, hepatitis B or C infection, no tumor detected in the liver tissue examined by histological analysis, and the presence of chronic autoimmune hepatitis, hemochromatosis, Wilson’s disease, or hepatoblastoma. The occurrence of NAFLD and the association with its known risk factors were studied. The risk factors considered were diabetes mellitus, impaired glucose tolerance, impaired fasting glucose, body mass index, dyslipidemia, and arterial hypertension. Presence of reticulin fibers in the hepatic neoplasms was assessed by histological analysis using slide-mounted specimens stained with either hematoxylin and eosin or Masson’s trichrome and silver impregnation. Analysis of tumor-free liver parenchyma was carried out to determine the association between NAFLD and its histological grade. RESULTS: No difference was found in the association of NAFLD with the general population (34.2% and 30.0% respectively, 95%CI: 25.8-43.4). Evaluation by cancer type showed that NAFLD was more prevalent in patients with liver metastasis of colorectal cancer than in patients with hepatocellular carcinoma and intrahepatic cholangiocarcinoma (OR = 3.99, 95%CI: 1.78-8.94, P < 0.001 vs OR = 0.60, 95%CI: 0.18-2.01, P = 0.406 and OR = 0.70, 95%CI: 0.18-2.80, P = 0.613, respectively). There was a higher prevalence of liver fibrosis in patients with hepatocellular carcinoma (OR = 3.50, 95%CI: 1.06-11.57, P = 0.032). Evaluation of the

  2. Arachidonic acid, an omega-6 fatty acid, induces cytoplasmic phospholipase A2 in prostate carcinoma cells.

    Science.gov (United States)

    Hughes-Fulford, Millie; Tjandrawinata, Raymond R; Li, Chai-Fei; Sayyah, Sina

    2005-09-01

    For the past 60 years, dietary intake of essential fatty acids has increased. Moreover, the omega-6 fatty acids have recently been found to play an important role in regulation of gene expression. Proliferation of human prostate cells was significantly increased 48 h after arachidonic acid (AA) addition. We have analyzed initial uptake using nile red fluorescence and we found that the albumin conjugated AA is endocytosed into the cells followed by the induction of RNA within minutes, protein and PGE2 synthesis within hours. Here we describe that AA induces expression of cytosolic phospholipase A2 (cPLA2) in a dose-dependent manner and that this upregulation is dependent upon downstream synthesis of PGE2. The upregulation of cox-2 and cPLA2 was inhibited by flurbiprofen, a cyclooxygenase (COX) inhibitor, making this a second feed-forward enzyme in the eicosanoid pathway. Cox-2 specific inhibitors are known to inhibit colon and prostate cancer growth in humans; however, recent findings show that some of these have cardiovascular complications. Since cPLA2 is upstream in the eicosanoid pathway, it may be a good alternative for a pharmaceutical target for the treatment of cancer.

  3. Solution Structure and Backbone Dynamics of Human Liver Fatty Acid Binding Protein: Fatty Acid Binding Revisited

    OpenAIRE

    Cai, Jun; Lücke, Christian; Chen, Zhongjing; Qiao, Ye; Klimtchuk, Elena; Hamilton, James A.

    2012-01-01

    Liver fatty acid binding protein (L-FABP), a cytosolic protein most abundant in liver, is associated with intracellular transport of fatty acids, nuclear signaling, and regulation of intracellular lipolysis. Among the members of the intracellular lipid binding protein family, L-FABP is of particular interest as it can i), bind two fatty acid molecules simultaneously and ii), accommodate a variety of bulkier physiological ligands such as bilirubin and fatty acyl CoA. To better understand the p...

  4. PGC-1β suppresses saturated fatty acid-induced macrophage inflammation by inhibiting TAK1 activation.

    Science.gov (United States)

    Chen, Hongen; Liu, Yan; Li, Di; Song, Jiayi; Xia, Min

    2016-02-01

    Inflammation of infiltrated macrophages in adipose tissue is a key contributor to the initiation of adipose insulin resistance. These macrophages are exposed to high local concentrations of free fatty acids (FFAs) and can be proinflammatory activated by saturated fatty acids (SFAs). However, the regulatory mechanisms on SFA-induced macrophage inflammation are still elusive. Peroxisome proliferator-activated receptor γ coactivator-1β (PGC-1β) is a member of the PGC-1 family of transcriptional coactivators and has been reported to play a key role in SFAs metabolism and in the regulation of inflammatory signaling. However, it remains unclear whether PGC-1β is involved in SFA-induced macrophage inflammation. In this study, we found that PGC-1β expression was significantly decreased in response to palmitic acid (PA) in macrophages in a dose dependent manner. PGC-1β inhibited PA induced TNFα, MCP-1, and IL-1β mRNA and protein expressions. Furthermore, PGC-1β significantly antagonized PA induced macrophage nuclear factor-κB (NF-κB) p65 and JUN N-terminal kinase activation. Mechanistically, we revealed that TGF-β-activated kinase 1 (TAK1) and its adaptor protein TAK1 binding protein 1 (TAB1) played a dominant role in the regulatory effects of PGC-1β. We confirmed that PGC-1β inhibited downstream inflammatory signals via binding with TAB1 and thus preventing TAB1/TAK1 binding and TAK1 activation. Finally, we showed that PGC-1β overexpression in PA treated macrophages improved adipocytes PI3K-Akt insulin signaling in a paracrine fashion. Collectively, our results uncovered a novel mechanism on how macrophage inflammation induced by SFAs was regulated and suggest a potential target in the treatment of obesity induced insulin resistance.

  5. Is nonalcoholic fatty liver disease an endogenous alcoholic fatty liver disease? - A mechanistic hypothesis.

    Science.gov (United States)

    de Medeiros, Ivanildo Coutinho; de Lima, Josivan Gomes

    2015-08-01

    Nonalcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (AFLD) are so similar that only a detailed history of alcohol intake can distinguish one from the other. Because subjects with NAFLD produce significantly more endogenous ethanol (EE) than controls, some researchers suspected that these similarities are not merely coincidental. For this reason, it was attempted to show that NAFLD is actually an endogenous alcoholic fatty liver disease (EAFLD). However, negligible blood-alcohol concentration (BAC) and the inability of gut microbiota to produce hepatotoxic concentrations of EE rejected this hypothesis. To clarify these conflicting results, we provide a mechanistic framework explaining how NAFLD may be an EAFLD. First of all, the key finding is that ethanol is a prodrug, enabling the idea that AFLD may develop with negligible/absent BAC. Second, extrahepatic acetaldehyde (ACD) alone recapitulates AFLD and is about 330-fold more hepatotoxic than that generated inside the liver. Third, gut microbiota can even produce much larger amounts of EE than those currently considered cirrhotogenic for man. Fourth, an extensive gut-liver axis first-pass metabolism of ethanol prevents the development of significant BAC in NAFLD. Fifth, all genes involved in EE metabolism are upregulated in the livers of patients with nonalcoholic steatohepatitis (NASH). Last, overexpression of the gene encoding alcohol dehydrogenase (ADH) 4 implicates liver exposure to high concentrations of EE. In conclusion, this work provides mechanistic explanation supporting the assumption that NAFLD may indeed be an EAFLD. If validated by further testing, the hypothesis may help develop novel therapeutic and preventive strategies against this ubiquitous condition.

  6. Nuclear receptors and nonalcoholic fatty liver disease.

    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

    2016-09-01

    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. Nonalcoholic 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

  7. Clinical Experience in TCM Differential Treatment of Fatty Liver

    Institute of Scientific and Technical Information of China (English)

    Cai Min; Yang Yonghe

    2007-01-01

    @@ In recent years, with improvement of living standard,changes in dietary structure and technical progress in medical tests, the rate of detecting fatty liver has been rising, hence constant increase in its incidence. Based on the TCM principle for differentiating syndromes,the authors have achieved remarkable curative effects in treating fatty liver.

  8. Docosahexaenoic acid and other fatty acids induce a decrease in pHi in Jurkat T-cells

    Science.gov (United States)

    Aires, Virginie; Hichami, Aziz; Moutairou, Kabirou; Khan, Naim Akhtar

    2003-01-01

    Docosahexaenoic acid (DHA) induced rapid (t1/2=33 s) and dose-dependent decreases in pHi in BCECF-loaded human (Jurkat) T-cells. Addition of 5-(N,N-dimethyl)-amiloride, an inhibitor of Na+/H+ exchanger, prolonged DHA-induced acidification as a function of time, indicating that the exchanger is implicated in pHi recovery. Other fatty acids like oleic acid, arachidonic acid, eicosapentaenoic acid, but not palmitic acid, also induced a fall in pHi in these cells. To assess the role of calcium in the DHA-induced acidification, we conducted experiments in Ca2+-free (0% Ca2+) and Ca2+-containing (100% Ca2+) buffer. We observed that there was no difference in the degree of DHA-induced transient acidification in both the experimental conditions, though pHi recovery was faster in 0% Ca2+ medium than that in 100% Ca2+ medium. In the presence of BAPTA, a calcium chelator, a rapid recovery of DHA-induced acidosis was observed. Furthermore, addition of CaCl2 into 0% Ca2+ medium curtailed DHA-evoked rapid pHi recovery. In 0% Ca2+ medium, containing BAPTA, DHA did not evoke increases in [Ca2+]i, though this fatty acid still induced a rapid acidification in these cells. These observations suggest that calcium is implicated in the long-lasting DHA-induced acidosis. DHA-induced rapid acidification may be due to its deprotonation in the plasma membrane (flip-flop model), as suggested by the following observations: (1) DHA with a –COOH group induced intracellular acidification, but this fatty acid with a –COOCH3 group failed to do so, and (2) DHA, but not propionic acid, -induced acidification was completely reversed by addition of fatty acid-free bovine serum albumin in these cells. These results suggest that DHA induces acidosis via deprotonation and Ca2+ mobilization in human T-cells. PMID:14645139

  9. Dietary omega-3 polyunsaturated fatty acids induce plasminogen activator activity and DNA damage in rabbit spermatozoa.

    Science.gov (United States)

    Kokoli, A N; Lavrentiadou, S N; Zervos, I A; Tsantarliotou, M P; Georgiadis, M P; Nikolaidis, E A; Botsoglou, N; Boscos, C M; Taitzoglou, I A

    2017-02-20

    The aim of this study was to determine the effect(s) of dietary omega-3 polyunsaturated fatty acids (ω-3 PUFA) on rabbit semen. Adult rabbit bucks were assigned to two groups that were given two diets, a standard diet (control) and a diet supplemented with ω-3 PUFA. Sperm samples were collected from all bucks with the use of an artificial vagina in 20-day intervals, for a total period of 120 days. The enrichment of membranes in ω-3 PUFA was manifested by the elevation of the 22:5 ω-3 (docosapentaenoic acid [DPA]) levels within 40 days. This increase in DPA content did not affect semen characteristics (i.e., concentration, motility and viability). However, it was associated with the induction of lipid peroxidation in spermatozoa, as determined on the basis of the malondialdehyde content. Lipid peroxidation was associated with DNA fragmentation in ω-3 PUFA-enriched spermatozoa and a concomitant increase in plasminogen activator (PA) activity. The effects of ω-3 PUFA on sperm cells were evident within 40 days of ω-3 PUFA dietary intake and exhibited peack values on day 120. Our findings suggest that an ω-3 PUFA-rich diet may not affect semen characteristics; however, it may have a negative impact on the oxidative status and DNA integrity of the spermatozoa, which was associated with an induction of PAs activity.

  10. Fatty acid-induced changes in vascular reactivity in healthy adult rats.

    Science.gov (United States)

    Christon, Raymond; Marette, André; Badeau, Mylène; Bourgoin, Frédéric; Mélançon, Sébastien; Bachelard, Hélène

    2005-12-01

    Dietary fatty acids (FAs) are known to modulate endothelial dysfunction, which is the first stage of atherosclerosis. However, their exact role in this initial phase is still unclear. The effects of isolated or combined (by 2) purified FAs from the main FA families were studied on the vascular response of isolated thoracic aorta in healthy rats to get a better understanding of the mechanisms of action of dietary FAs in regulating vascular endothelial function. Cumulative contraction curves to phenylephrine and relaxation curves to carbachol and then to sodium nitroprusside were obtained in the absence or presence of the FAs studied allowing endothelium-dependent and endothelium-independent ability of the smooth muscle to relax to be assessed in each experimental group. The endothelium-dependent vasodilator response to carbachol was lowered by eicosapentaenoic acid, whereas it was not altered either by docosahexaenoic acid alone or by combined eicosapentaenoic acid-docosahexaenoic acid, oleic acid, or stearic acid, and it was increased by linoleic acid (LA). A decreased phenylephrine-induced contraction was observed after incubation with arachidonic acid and with stearic acid. On the other hand, the endothelium-dependent relaxation was reduced by the addition of combined LA-arachidonic acid and LA-oleic acid. In conclusion, these data point out the differential effects of different types of FAs and of FAs alone vs combined on vascular reactivity. The complex nature of these effects could be partially linked to metabolic specificities of endothelial cells and to interactions between some FAs.

  11. Berberine reverses free-fatty-acid-induced insulin resistance in 3T3-L1 adipocytes through targeting IKKβ

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    AIM:To investigate the effects and molecular mechanisms of berberine on improving insulin resistance induced by free fatty acids (FFAs) in 3T3-LI adipocytes.METHODS:The model of insulin resistance in 3T3-L1 adipocytes was established by adding palmic acid (0.5 mmol/L) to the culture medium.Berberine treatment was performed at the same time.Glucose uptake rate was determined by the 2-deoxy-[3H]-Dglucose method.The levels of IkB kinase beta (IKKβ)Ser181 phosphorylation,insulin receptor substrate1(IRS-1) Ser307 phosphorylation,expression of IKKβ,IRS-1,nuclear transcription factor kappaB p65 (NF-κB p65),phosphatidylinositol-3-kinase p85(PI-3K p85) and glucose transporter 4 (GLUT4) proteins were detected by Western blotting.The distribution of NF-κB p65 proteins inside the adipocytes was observed through confocal laser scanning microscopy(CLSM).RESULTS:After the intervention of palmic acid for 24 h,the insulin-stimulated glucose transport in 3T3-L1 adipocytes was inhibited by 67%.Meanwhile,the expression of IRS-1 and PI-3K p85 protein was reduced,while the levels of IKKβ Ser181 and IRS-1 Ser307 phosphorylation,and nuclear translocation of NF-κB p65 protein were increased.However,the above indexes,which indicated the existence of insulin resistance,were reversed by berberine although the expression of GLUT4,IKKβ and total NF-κB p65 protein were not changed during this study.CONCLUSION:Insulin resistance induced by FFAs in 3T3-L1 adipocytes can be improved by berberine.Berberine reversed free-fatty-acid-induced insulin resistance in 3T3-L1 adipocytes through targeting IKKβ.

  12. Mechanism of fatty acids induced suppression of cardiovascular reflexes in rats.

    Science.gov (United States)

    Shaltout, Hossam A; Abdel-Rahman, Abdel A

    2005-09-01

    A blunted baroreflex sensitivity (BRS), impaired heart rate variability (HRV), and high plasma nonesterified fatty acids (NEFA) are predictors of adverse cardiovascular outcomes. We tested the hypothesis that elevation of NEFA negatively impacts the cardiac baroreflex response and undertook spectral analyses and molecular studies to delineate the mechanism of action. We used two interventions to elevate serum NEFA: 1) overnight fasting (n = 7) and 2) i.v. infusion of 1.2 ml/kg intralipid 20% + heparin (I/H) over 10 min (n = 9) in conscious unrestrained male rats. Elevated NEFA caused by fasting complemented by I/H infusion were associated with a concentration-dependent reduction in spontaneous BRS measured by spectral analysis [low-frequency alpha and high-frequency alpha (HFalpha) indices] and sequence method and HRV measured by frequency domain as power of RR interval (RRI) spectra (low-frequency RRI and high-frequency RRI) and by time domain as standard deviation of beat-to-beat interval and root mean square of successive differences along with increase in blood pressure variability measured as standard deviation of mean arterial pressure and power of systolic arterial pressure spectra (low-frequency systolic arterial pressure). Because elevated NEFA suppressed the vagal component of the baroreflex response (HFalpha), we tested the hypothesis that NEFA-evoked sequestration of myocardial muscarinic receptor (M2-mAChR) contributes to the reduced BRS. High NEFA level was accompanied by increased caveolar sequestration of cardiac M2-mAChRs without changing M2-mAChR protein expression. We report the first detailed analyses of NEFA's effect on the cardiac baroreflex and show that increased caveolar sequestration of cardiac M2-mAChRs constitutes a cellular mechanism for elevated NEFA-related deleterious cardiovascular outcomes.

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

    Directory of Open Access Journals (Sweden)

    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. The Riddle of Nonalcoholic Fatty Liver Disease: Progression From Nonalcoholic Fatty Liver to Nonalcoholic Steatohepatitis.

    Science.gov (United States)

    Sharma, Mithun; Mitnala, Shasikala; Vishnubhotla, Ravi K; Mukherjee, Rathin; Reddy, Duvvur N; Rao, Padaki N

    2015-06-01

    Nonalcoholic fatty liver (NAFL) is an emerging global epidemic which progresses to nonalcoholic steatohepatitis (NASH) and cirrhosis in a subset of subjects. Various reviews have focused on the etiology, epidemiology, pathogenesis and treatment of NAFLD. This review highlights specifically the triggers implicated in disease progression from NAFL to NASH. The integrating role of genes, dietary factors, innate immunity, cytokines and gut microbiome have been discussed.

  15. Cholic acid induces a Cftr dependent biliary secretion and liver growth response in mice

    NARCIS (Netherlands)

    Bodewes, Frank A. J. A.; Bijvelds, Marcel J.; de Vries, Willemien; Baller, Juul F. W.; Gouw, Annette S. H.; de Jonge, Hugo R.; Verkade, Henkjan J.

    2015-01-01

    The cause of Cystic fibrosis liver disease (CFLD), is unknown. It is well recognized that hepatic exposure to hydrophobic bile salts is associated with the development of liver disease. For this reason, we hypothesize that, CFTR dependent variations, in the hepatic handling of hydrophobic bile salts

  16. Cholic acid induces a Cftr dependent biliary secretion and liver growth response in mice

    NARCIS (Netherlands)

    F.A.J.A. Bodewes (Frank); M.J.C. Bijvelds (Marcel); De Vries, W. (Willemien); Baller, J.F.W. (Juul F. W.); A.S.H. Gouw (Annette); H.R. de Jonge (Hugo); H.J. Verkade (Henkjan)

    2015-01-01

    textabstractThe cause of Cystic fibrosis liver disease (CFLD), is unknown. It is well recognized that hepatic exposure to hydrophobic bile salts is associated with the development of liver disease. For this reason, we hypothesize that, CFTR dependent variations, in the hepatic handling of hydrophobi

  17. Protective effects of ursodeoxycholic acid on chenodeoxycholic acid-induced liver injury in hamsters

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To investigate the effects of ursodeoxycholic acid (UDCA) on chenodeoxycholic acid (CDCA)-induced liver injury in hamsters, and to elucidate a correlation between liver injury and bile acid profiles in the liver.METHODS: Liver injury was induced in hamsters by administration of 0.5% (w/w) CDCA in their feed for 7 d.UDCA (50 mg/kg and 150 mg/kg) was administered for the last 3 d of the experiment.RESULTS: At the end of the experiment, serum alanine aminotransferase (ALT) increased more than 10 times and the presence of liver injury was confirmed histologically. Marked increase in bile acids was observed in the liver. The amount of total bile acids increased approximately three-fold and was accompanied by the increase in hydrophobic bile acids, CDCA and lithocholic acid (LCA). UDCA (50 mg/kg and 150 mg/kg) improved liver histology, with a significant decrease (679.3 ±77.5 U/L vs 333.6 ± 50.4 U/L and 254.3 ± 35.5 U/L, respectively, P < 0.01) in serum ALT level. UDCA decreased the concentrations of the hydrophobic bile acids, and as a result, a decrease in the total bile acid level in the liver was achieved.CONCLUSION: The results show that UDCA improves oral CDCA-induced liver damage in hamsters. The protective effects of UDCA appear to result from a decrease in the concentration of hydrophobic bile acids, CDCA and LCA, which accumulate and show the cytotoxicity in the liver.

  18. The epidemiology, pathogenesis and histopathology of fatty liver disease.

    Science.gov (United States)

    Levene, Adam P; Goldin, Robert D

    2012-08-01

    Fatty liver disease includes non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD), each of which is increasing in prevalence. Each represents a histological spectrum that extends from isolated steatosis to steatohepatitis and cirrhosis. NAFLD is associated with obesity, diabetes, and insulin resistance, and is considered to be the liver manifestation of the metabolic syndrome. The pathogenesis of NAFLD and ALD involves cytokines, adipokines, oxidative stress, and apoptosis. Histopathology is the gold standard for assessing the severity of liver damage in NAFLD and ALD. We have reviewed the literature, and described and compared the epidemiology, natural disease history, pathogenesis and histopathology of NAFLD and ALD.

  19. Mercaptoacetate blocks fatty acid-induced GLP-1 secretion in male rats by directly antagonizing GPR40 fatty acid receptors.

    Science.gov (United States)

    Li, Ai-Jun; Wang, Qing; Dinh, Thu T; Simasko, Steve M; Ritter, Sue

    2016-04-15

    Mercaptoacetate (MA) is an orexigenic agent reported to block fatty acid (FA) oxidation. Recently, however, we reported evidence from isolated nodose ganglion neurons that MA antagonizes the G protein-coupled long- and medium-chain FA receptor GPR40. GPR40 mediates FA-induced secretion of the satietogenic incretin peptide glucagon-like peptide 1 (GLP-1), by enteroendocrine L cells, as well as FA-induced enhancement of glucose-stimulated insulin secretion. Our results in cultured nodose neurons suggest that MA would also block GPR40 in enteroendocrine cells controlling GLP-1 secretion. If so, this would suggest an alternative mechanism by which MA increases food intake. We tested the hypothesis that MA blocks FA-induced GLP-1 secretion in vitro using cultured STC-1 cells (a murine enteroendocrine cell line) and in vivo in adult male rats. In vitro, MA blocked the increase in both cytosolic Ca(2+)and GLP-1 release stimulated by FAs and also reduced (but less effectively) the response of STC-1 cells to grifolic acid, a partial agonist of the GPR120 FA receptor. In vivo, MA reduced GLP-1 secretion following olive oil gavage while also increasing glucose and decreasing insulin levels. The carnitine palmatoyltransferase 1 antagonist etomoxir did not alter these responses. Results indicate that MA's actions, including its orexigenic effect, are mediated by GPR40 (and possibly GPR120) receptor antagonism and not by blockade of fat oxidation, as previously believed. Analysis of MA's interaction with GPR40 may facilitate understanding of the multiple functions of this receptor and the manner in which FAs participate in the control of hunger and satiety.

  20. Cholic acid induces a Cftr dependent biliary secretion and liver growth response in mice.

    Directory of Open Access Journals (Sweden)

    Frank A J A Bodewes

    Full Text Available The cause of Cystic fibrosis liver disease (CFLD, is unknown. It is well recognized that hepatic exposure to hydrophobic bile salts is associated with the development of liver disease. For this reason, we hypothesize that, CFTR dependent variations, in the hepatic handling of hydrophobic bile salts, are related to the development CFLD. To test our hypothesis we studied, in Cftr-/- and control mice, bile production, bile composition and liver pathology, in normal feeding condition and during cholate exposure, either acute (intravenous or chronic (three weeks via the diet. In Cftr-/- and control mice the basal bile production was comparable. Intravenous taurocholate increased bile production to the same extent in Cftr-/- and control mice. However, chronic cholate exposure increased the bile flow significantly less in Cftr-/- mice than in controls, together with significantly higher biliary bile salt concentration in Cftr-/- mice. Prolonged cholate exposure, however, did not induce CFLD like pathology in Cftr-/- mice. Chronic cholate exposure did induce a significant increase in liver mass in controls that was absent in Cftr-/- mice. Chronic cholate administration induces a cystic fibrosis-specific hepatobiliary phenotype, including changes in bile composition. These changes could not be associated with CFLD like pathological changes in CF mouse livers. However, chronic cholate administration induces liver growth in controls that is absent in Cftr-/- mice. Our findings point to an impaired adaptive homeotrophic liver response to prolonged hydrophobic bile salt exposure in CF conditions.

  1. Long term prognosis of fatty liver: risk of chronic liver disease and death

    DEFF Research Database (Denmark)

    Dam-Larsen, S; Franzmann, M; Andersen, I B;

    2004-01-01

    BACKGROUND AND AIMS: Fatty liver is a common histological finding in human liver biopsy specimens. It affects 10-24% of the general population and is believed to be a marker of risk of later chronic liver disease. The present study examined the risk of development of cirrhotic liver disease...... and the risk of death in a cohort diagnosed with pure fatty liver without inflammation. METHODS: A total of 215 patients who had a liver biopsy performed during the period 1976-1987 were included in the study. The population consisted of 109 non-alcoholic and 106 alcoholic fatty liver patients. Median follow...... of Patients and the nationwide Registry of Causes of Death, and all admissions, discharge diagnoses, and causes of death were obtained. RESULTS: In the non-alcoholic fatty liver group, one patient developed cirrhosis during the follow up period compared with 22 patients in the alcoholic group. Survival...

  2. Hepatic lipogranulomas in patients with chronic liver disease: Association with hepatitis C and fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    Henry; C; Bodenheimer; David; J; Clain; Albert; D; Min; Neil; D; Theise

    2010-01-01

    AIM: To study the significance and clinical implication of hepatic lipogranuloma in chronic liver diseases, including fatty liver disease and hepatitis C. METHODS: A total of 376 sequential, archival liver biopsy specimens were reviewed. Lipogranuloma, steatosis and steato-fibrosis were evaluated with combined hematoxylin and eosin and Masson’s trichrome staining. RESULTS: Fifty-eight (15.4%) patients had lipogranuloma, including 46 patients with hepatitis C, 14 patients with fatty liver disease, and 5 pati...

  3. Vitamin E reduces liver stiffness in nonalcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    Aiko; Fukui; Naoto; Kawabe; Senju; Hashimoto; Michihito; Murao; Takuji; Nakano; Hiroaki; Shimazaki; Toshiki; Kan; Kazunori; Nakaoka; Masashi; Ohki; Yuka; Takagawa; Tomoki; Takamura; Hiroyuki; Kamei; Kentaro; Yoshioka

    2015-01-01

    AIM: To evaluate the efficacy of vitamin E treatment on liver stiffness in nonalcoholic fatty liver disease(NAFLD).METHODS: Thirty-eight NAFLD patients were administered vitamin E for > 1 year. The doses of vitamin E were 150, 300, or 600 mg; three times per day after each meal. Responses were assessed by liver enzyme levels [aspartate aminotransferase(AST), alanine aminotranferease(ALT), and γ-glutamyl transpeptidase(γ-GTP)], noninvasive scoring systems of hepatic fibrosis-4 [FIB-4 index and aspartate aminotransferaseto-platelet index(APRI)], and liver stiffness [velocity of shear wave(Vs)] measured by acoustic radiation force impulse elastography. Vs measurements were performed at baseline and 12 mo after baseline. The patients were genotyped for the patatin-like phospholipase domain containing 3(PNPLA3) polymorphisms and then divided into either the CC/CG or GG group to examine each group’s responses to vitamin E treatment. RESULTS: We found marked differences in the platelet count, serum albumin levels, alkaline phosphatase levels, FIB-4 index, APRI, and Vs at baseline depending on the PNPLA3 polymorphism. AST, ALT, and γ-GTP levels(all P < 0.001); FIB-4 index(P = 0.035); APRI(P < 0.001); and Vs(P < 0.001) significantly decreased from baseline to 12 mo in the analysis of all patients. In the subset analyses of PNPLA3 genotypes, AST levels(P = 0.011), ALT levels(P < 0.001), γ-GTP levels(P = 0.005), APRI(P = 0.036), and Vs(P = 0.029) in genotype GG patients significantly improved, and AST and ALT levels(both P < 0.001), γ-GTP levels(P = 0.003), FIB-4 index(P = 0.017), and APRI(P < 0.001) in genotype CC/CG patients. CONCLUSION: One year of vitamin E treatment improved noninvasive fibrosis scores and liver stiffness in NAFLD patients. The responses were similar between different PNPLA3 genotypes.

  4. Long term prognosis of fatty liver: risk of chronic liver disease and death

    DEFF Research Database (Denmark)

    Dam-Larsen, S; Franzmann, M; Andersen, I B

    2004-01-01

    and the risk of death in a cohort diagnosed with pure fatty liver without inflammation. METHODS: A total of 215 patients who had a liver biopsy performed during the period 1976-1987 were included in the study. The population consisted of 109 non-alcoholic and 106 alcoholic fatty liver patients. Median follow...... of Patients and the nationwide Registry of Causes of Death, and all admissions, discharge diagnoses, and causes of death were obtained. RESULTS: In the non-alcoholic fatty liver group, one patient developed cirrhosis during the follow up period compared with 22 patients in the alcoholic group. Survival...... estimates were significantly (palcoholic fatty liver group. Survival estimates in the non-alcoholic fatty liver group were not different from the Danish population. CONCLUSIONS: This study revealed...

  5. Therapeutic effect of osthole on hyperlipidemic fatty liver in rats

    Institute of Scientific and Technical Information of China (English)

    Yan ZHANG; Mei-lin XIE; Lu-jia ZHU; Zhen-lun GU

    2007-01-01

    Aim: To study the effects of osthole on hyperlipidemic fatty liver and investigate the possible mechanisms. Methods: A rat model with hyperlipidemic fatty liver was successfully established by feeding fatty milk for 6 weeks. The experimental rats were then treated with 5-20 mg/kg osthole for 6 weeks. The mouse hypedipi-demic model was induced by feeding fatty milk when they were treated with 10-20 mg/kg osthole for 3 weeks. Results: After treatment with osthole, the levels of rat serum total cholesterol (TC), triglyceride (TG) and low density lipoprotein-choles-terol significantly decreased as compared with the fatty liver model group (P<0.05 or P<0.01). Hepatic weight and its coefficient, the hepatic tissue contents of TC,TG, and malondialdehyde, also significantly decreased (P<0.05 or P<0.01). In fatty milk-induced hyperlipidemic mice, the post-heparin plasma activities of lipo-protein lipase (LPL), hepatic lipase (HL), and total lipase (TL) significantly increased after treatment with 10-20 mg/kg osthole for 3 weeks (P<0.05 or P<0.01).Importantly, the histological evaluation of rat liver demonstrated that osthole dramatically decreased lipid accumulation (P<0.01). Conclusion: Osthole was found to have therapeutic effects on fatty milk-induced rat fatty liver; the mecha-nisms might be associated with its anti-oxidation and the elevation of the activi-ties of LPL and HL.

  6. Free Fatty Acids Differentially Downregulate Chemokines in Liver Sinusoidal Endothelial Cells: Insights into Non-Alcoholic Fatty Liver Disease.

    Science.gov (United States)

    McMahan, Rachel H; Porsche, Cara E; Edwards, Michael G; Rosen, Hugo R

    2016-01-01

    Non-alcoholic fatty liver disease is a prevalent problem throughout the western world. Liver sinusoidal endothelial cells (LSEC) have been shown to play important roles in liver injury and repair, but their role in the underlying pathogenetic mechanisms of non-alcoholic fatty liver disease remains undefined. Here, we evaluated the effects of steatosis on LSEC gene expression in a murine model of non-alcoholic fatty liver disease and an immortalized LSEC line. Using microarray we identified distinct gene expression profiles following exposure to free fatty acids. Gene pathway analysis showed a number of differentially expressed genes including those involved in lipid metabolism and signaling and inflammation. Interestingly, in contrast to hepatocytes, fatty acids led to decreased expression of pro-inflammatory chemokines including CCL2 (MCP-1), CXCL10 and CXCL16 in both primary and LSEC cell lines. Chemokine downregulation translated into a significant inhibition of monocyte migration and LSECs isolated from steatotic livers demonstrated a similar shift towards an anti-inflammatory phenotype. Overall, these pathways may represent a compensatory mechanism to reverse the liver damage associated with non-alcoholic fatty liver disease.

  7. Free Fatty Acids Differentially Downregulate Chemokines in Liver Sinusoidal Endothelial Cells: Insights into Non-Alcoholic Fatty Liver Disease.

    Directory of Open Access Journals (Sweden)

    Rachel H McMahan

    Full Text Available Non-alcoholic fatty liver disease is a prevalent problem throughout the western world. Liver sinusoidal endothelial cells (LSEC have been shown to play important roles in liver injury and repair, but their role in the underlying pathogenetic mechanisms of non-alcoholic fatty liver disease remains undefined. Here, we evaluated the effects of steatosis on LSEC gene expression in a murine model of non-alcoholic fatty liver disease and an immortalized LSEC line. Using microarray we identified distinct gene expression profiles following exposure to free fatty acids. Gene pathway analysis showed a number of differentially expressed genes including those involved in lipid metabolism and signaling and inflammation. Interestingly, in contrast to hepatocytes, fatty acids led to decreased expression of pro-inflammatory chemokines including CCL2 (MCP-1, CXCL10 and CXCL16 in both primary and LSEC cell lines. Chemokine downregulation translated into a significant inhibition of monocyte migration and LSECs isolated from steatotic livers demonstrated a similar shift towards an anti-inflammatory phenotype. Overall, these pathways may represent a compensatory mechanism to reverse the liver damage associated with non-alcoholic fatty liver disease.

  8. Free Fatty Acids Differentially Downregulate Chemokines in Liver Sinusoidal Endothelial Cells: Insights into Non-Alcoholic Fatty Liver Disease

    Science.gov (United States)

    McMahan, Rachel H.; Porsche, Cara E.; Edwards, Michael G.; Rosen, Hugo R.

    2016-01-01

    Non-alcoholic fatty liver disease is a prevalent problem throughout the western world. Liver sinusoidal endothelial cells (LSEC) have been shown to play important roles in liver injury and repair, but their role in the underlying pathogenetic mechanisms of non-alcoholic fatty liver disease remains undefined. Here, we evaluated the effects of steatosis on LSEC gene expression in a murine model of non-alcoholic fatty liver disease and an immortalized LSEC line. Using microarray we identified distinct gene expression profiles following exposure to free fatty acids. Gene pathway analysis showed a number of differentially expressed genes including those involved in lipid metabolism and signaling and inflammation. Interestingly, in contrast to hepatocytes, fatty acids led to decreased expression of pro-inflammatory chemokines including CCL2 (MCP-1), CXCL10 and CXCL16 in both primary and LSEC cell lines. Chemokine downregulation translated into a significant inhibition of monocyte migration and LSECs isolated from steatotic livers demonstrated a similar shift towards an anti-inflammatory phenotype. Overall, these pathways may represent a compensatory mechanism to reverse the liver damage associated with non-alcoholic fatty liver disease. PMID:27454769

  9. Sonographic fatty liver, overweight and ischemic heart disease

    Institute of Scientific and Technical Information of China (English)

    Yu-Cheng Lin; Huey-Ming Lo; Jong-Dar Chen

    2005-01-01

    AIM: To demonstrate the prevalence of sonographic fatty liver, overweight and ischemic heart disease (IHD) among the male workers in Taiwan, and to investigate the possible association of these three factors.METHODS: From July to September 2003, a total of 2 088 male aircraft-maintenance workers aged from 22to 65 years (mean 40.5) underwent an annual health examination, including anthropometrical evaluation, blood pressure measurement, personal medical history assessment,biochemical blood analysis, abdominal ultrasonographic examination and digital electrocardiography (ECG). The Student's t-test, x2 test and multivariate logistic regression analysis were utilized to evaluate the relationship between IHD and salient risk factors.RESULTS: The all-over prevalence of overweight was 41.4%, and that of fatty liver was 29.5% (mild, moderate and severe fatty liver being 14.5%, 11.3%, and 3.7%,respectively); while the prevalence of ischemic changes on ECG was 17.1% in this study. The abnormal rates for conventional IHD risk factors including hypertension,dyslipidemia, hyperglycemia and overweight increased in accordance with the severity of fatty liver. Overweight and severity of fatty liver were independently associated with increased risks for developing IHD. Overweight subjects had a 1.32-fold (95%CI: 1.01-1.73) increased IHD risk. Participants with mild, moderate, and severe fatty liver had a 1.88-fold (95%CI: 1.37-2.6), 2.37-fold (95%CI: 1.66-3.37) and 2.76-fold (95%CI: 1.62-4.72)increased risk for developing IHD. The prevalence of ischemic ECG for the fatty liver-affected subjects with or without overweight was 30.1% and 19.1%, while that of overweight subjects free from fatty liver was 14.4%.Compared to the subjects without fatty liver nor overweight,IHD risk for the three subgroups above was as follows:OR: 2.95 (95%CI:2.31-4.09), OR: 1.60 (95%CI: 1.07-2.39)and OR: 1.11 (95%CI: 0.78-1.56), respectively.CONCLUSION: The presence of fatty liver and its severity should

  10. Ultrasonic elastography in clinical quantitative assessment of fatty liver

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM: To investigate the clinical application of ultrasonic elastography in quantitative assessment of fatty liver grading. METHODS: A total of 105 patients with fatty liver were divided into mild group (n = 46), moderate group (n = 39), and severe group (n = 20). Forty-five healthy individuals served as a normal control group. All patients who underwent routine ultrasound scan and further ultrasonic elastography were evaluated accordingly to the evaluation standards for ultrasonic elastography. The ratio of...

  11. Understanding mechanisms of the pathogenesis of nonalcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    Metin; Basaranoglu; Serra; Kayacetin; Nevin; Yilmaz; Ertugrul; Kayacetin; Orhan; Tarcin; Abdullah; Sonsuz

    2010-01-01

    A central issue in the understanding of the pathogenesis of nonalcoholic fatty liver disease is the problem of the underlying mechanisms which are not fully understood.In the setting of excessive central adiposity,insulin resistance is the major underlying cause of fat accumulation in hepatocytes.Because of the difficulties with human trials,several animal models have been developed for this purpose mainly characterized as follows:genetically disturbed or murine fatty liver,methionine-choline deficient diet...

  12. Uncoupling protein and nonalcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    JIN Xi; XIANG Zun; CHEN Yi-peng; MA Kui-fen; YE Yue-fang; LI You-ming

    2013-01-01

    Objective To review the current advances on the role of uncoupling protein (UCP) in the pathogenesis and progress of nonalcoholic fatty liver disease (NAFLD).Data sources A comprehensive search of the PubMed literature without restriction on the publication date was carried out using keywords such as UCP and NAFLD.Study selection Articles containing information related to NAFLD and UCP were selected and carefully analyzed.Results The typical concepts,up-to-date findings,and existing controversies of UCP2 in NAFLD were summarized.Besides,the effect of a novel subtype of UCP (hepatocellular down regulated mitochondrial carrier protein,HDMCP) in NAFLD was also analyzed.Finally,the concept that any mitochondrial inner membrane carrier protein may have,more or less,the uncoupling ability was reinforced.Conclusions Considering the importance of NAFLD in clinics and UCP in energy metabolism,we believe that this review may raise research enthusiasm on the effect of UCP in NAFLD and provide a novel mechanism and therapeutic target for NAFLD.

  13. Edaravone, a free radical scavenger, protects liver against valproic acid induced toxicity

    Directory of Open Access Journals (Sweden)

    Cakmak Neziha Hacihasanoglu

    2015-01-01

    Full Text Available Valproic acid (VPA, is a well established anticonvulsant drug that has been increasingly used in the treatment of many forms of generalized epilepsy. Edaravone (EDA; 3-methyl-1-phenyl-2-pyrazoline-5-one is a potent free radical scavenger. In this study, we aimed to investigate the effects of EDA on VPA-induced hepatic damage. Male Sprague Dawley rats were divided into four groups. Group I was control animals. Group II was control rats given valproic acid (500 mg kg-1 day for seven days. Group III was given only EDA (30 mg kg-1day for seven days. Group IV was given VPA+EDA (in same dose and time. EDA and VPA were given intraperitoneally. On the 8th day of experiment, blood samples and liver tissue were taken. Serum aspartate and alanine aminotransferase, alkaline phosphatase and bilirubin levels, liver myeloperoxidase, xanthine oxidase, adenosine deaminase, Na+/K+ATPase, sorbitol dehydrogenase, glutamate dehydrogenase, DT-diaphorase, arginase and thromboplastic activities, lipid peroxidation, protein carbonyl levels were increased whereas paraoxonase, biotinidase activities and glutathione levels were decreased in VPA group. Application of EDA with VPA protected against VPA-induced effects. These results demonstrated that administration of EDA is a potentially beneficial agent to reduce hepatic damage in VPA induced hepatotoxicity, probably by decreasing oxidative stress.

  14. Effect of liver fatty acid binding protein on fatty acid movement between liposomes and rat liver microsomes.

    Science.gov (United States)

    McCormack, M; Brecher, P

    1987-01-01

    Although movement of fatty acids between bilayers can occur spontaneously, it has been postulated that intracellular movement is facilitated by a class of proteins named fatty acid binding proteins (FABP). In this study we have incorporated long chain fatty acids into multilamellar liposomes made of phosphatidylcholine, incubated them with rat liver microsomes containing an active acyl-CoA synthetase, and measured formation of acyl-CoA in the absence or presence of FABP purified from rat liver. FABP increased about 2-fold the accumulation of acyl-CoA when liposomes were the fatty acid donor. Using fatty acid incorporated into liposomes made either of egg yolk lecithin or of dipalmitoylphosphatidylcholine, it was found that the temperature dependence of acyl-CoA accumulation in the presence of FABP correlated with both the physical state of phospholipid molecules in the liposomes and the binding of fatty acid to FABP, suggesting that fatty acid must first desorb from the liposomes before FABP can have an effect. An FABP-fatty acid complex incubated with microsomes, in the absence of liposomes, resulted in greater acyl-CoA formation than when liposomes were present, suggesting that desorption of fatty acid from the membrane is rate-limiting in the accumulation of acyl-CoA by this system. Finally, an equilibrium dialysis cell separating liposomes from microsomes on opposite sides of a Nuclepore filter was used to show that liver FABP was required for the movement and activation of fatty acid between the compartments. These studies show that liver FABP interacts with fatty acid that desorbs from phospholipid bilayers, and promotes movement to a membrane-bound enzyme, suggesting that FABP may act intracellularly by increasing net desorption of fatty acid from cell membranes. PMID:3446187

  15. Vascular Disease in Patients with Nonalcoholic Fatty Liver Disease

    NARCIS (Netherlands)

    Potze, Wilma; Siddiqui, M. Shadab; Sanyal, Arun J.

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) is increasingly being diagnosed and is considered to be the most frequent chronic liver disorder in Western countries. It represents a histopathological spectrum ranging from simple hepatic steatosis to steatohepatitis and finally cirrhosis. NAFLD is consider

  16. 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 nonalcoholic stea

  17. Animal models of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis

    OpenAIRE

    Takahashi, Yoshihisa; Soejima, Yurie; Fukusato, Toshio

    2012-01-01

    Nonalcoholic fatty liver disease (NAFLD) is a condition in which excess fat accumulates in the liver of a patient without a history of alcohol abuse. Nonalcoholic steatohepatitis (NASH), a severe form of NAFLD, can progress to liver cirrhosis and hepatocellular carcinoma. NAFLD is regarded as a hepatic manifestation of metabolic syndrome and incidence has been increasing worldwide in line with the increased prevalence of obesity, type 2 diabetes, and hyperlipemia. Animal models of NAFLD/NASH ...

  18. Olive oil consumption and non-alcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    Nimer Assy; Faris Nassar; Gattas Nasser; Maria Grosovski

    2009-01-01

    The clinical implications of non-alcoholic fatty liver diseases (NAFLD) derive from their potential to progress to fibrosis and cirrhosis. Inappropriate dietary fat intake, excessive intake of soft drinks, insulin resistance and increased oxidative stress results in increased free fatty acid delivery to the liver and increased hepatic triglyceride (TG) accumulation. An olive oil-rich diet decreases accumulation of TGs in the liver, improves postprandial TGs, glucose and glucagonlike peptide-1 responses in insulin-resistant subjects, and upregulates glucose transporter-2 expression in the liver. The principal mechanisms include: decreased nuclear factor-kappaB activation, decreased lowdensity lipoprotein oxidation, and improved insulin resistance by reduced production of inflammatory cytokines (tumor necrosis factor, interleukin-6) and improvement of jun N-terminal kinase-mediated phosphorylation of insulin receptor substrate-1. The beneficial effect of the Mediterranean diet is derived from monounsaturated fatty acids, mainly from olive oil. In this review, we describe the dietary sources of the monounsaturated fatty acids, the composition of olive oil, dietary fats and their relationship to insulin resistance and postprandial lipid and glucose responses in non-alcoholic steatohepatitis, clinical and experimental studies that assess the relationship between olive oil and NAFLD, and the mechanism by which olive oil ameliorates fatty liver, and we discuss future perspectives.

  19. Fatty liver: prospective comparative study with sonography and CT

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sung Jin; Kim, Y. M.; Kim, W. S.; Choi, B. I.; Lee, J. S.; Han, C. K.; Kim, C. W. [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1990-12-15

    To identify the reasonable criteria in detection of the degree of Fatty liver, we prospectively evaluated sonograms and CT scans in 33 Patients With bright liver on sonography. On sonograms, we analyzed the echogenicity of the liver, acoustic attenuation, and visualization of the portal vein and the diaphragm, Each criterion was scored from 0 to 2. CT criterion for fatty liver was assessed by the attenuation difference between the liver and the spleen on nonocontrast CT scans, The average sonographic grade for CT Grade I was 1.3, Grade II was 2.1,and Grade III was 2.8. The accurate detection rate of each sonographic grade was as follows, Grade

  20. Noninvasive investigations for non alcoholic fatty liver disease and liver fi brosis

    Institute of Scientific and Technical Information of China (English)

    Carmen; Fierbinteanu-Braticevici; Ion; Dina; Ana; Petrisor; Laura; Tribus; Lucian; Negreanu; Catalin; Carstoiu

    2010-01-01

    Non-alcoholic fatty liver disease (NAFLD) includes a spectrum of diseases that have insulin resistance in common and are associated with metabolic conditions such as obesity, type 2 diabetes mellitus, and dyslipidemia. NAFLD ranges from simple liver steatosis, which follows a benign course, to nonalcoholic steatohepatitis (NASH), a more severe entity, with necroinflmmation and f ibrosis, which can progress to cryptogenic cirrhosis and end-stage liver disease. Liver biopsy remains the gold standard for evalu...

  1. [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.

  2. Ultrasonographic diagnosis of fatty liver and relations with body index, serum lipid, and serum triglyceride

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Young Deog; Lee, S. H.; Lee, H. K.; Kim, D. H.; Kwon, K. H.; Kim, K. C. [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1989-12-15

    Hepatic fatty infiltration appears as an area of increased echogenicity. And many factors concerned to fatty infiltration. With 65 cases of fatty liver and 42 cases of normal group, we analyzed fatty liver with grading and attempt to find relations between grade of fatty liver and levels of body index, serum triglyceride, and serum lipid. And compared fatty liver with normal control group. Patients with fatty liver are higher percentage of supra-normal value in body index, serum lipid, and serum triglyceride than normal control group. As fatty infiltration progressed, serum lipid, serum trig-lyceride and body index are also increased. Conclusively ultrasonographic examination of liver with serum triglyceride, serum lipid, and body index are simple method, useful follow-up examination of fatty liver, and preventive routine check-up of chronic liver disease

  3. Nutrition and Nonalcoholic Fatty Liver Disease: The Significance of Cholesterol

    Directory of Open Access Journals (Sweden)

    Munechika Enjoji

    2012-01-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD is a common chronic liver disease that ranges in severity from simple steatosis to cirrhosis. NAFLD is considered to be associated with hepatic metabolic disorders, resulting in overaccumulation of fatty acids/triglycerides and cholesterol. The pathogenesis and progression of NAFLD are generally explained by the “two-hit theory.” Most studies of lipid metabolism in the NAFLD liver have focused on the metabolism of fatty acids/triglycerides; therefore, the impact of cholesterol metabolism is still ambiguous. In this paper, we review recent studies on NAFLD from the viewpoint of hepatic lipid metabolism-associated factors and discuss the impact of disordered cholesterol metabolism in the etiology of NAFLD. The clinical significance of managing cholesterol metabolism, an option for the treatment of NAFLD, is also discussed.

  4. NON-ALCOHOLIC FATTY LIVER DISEASE AT OUR INSTITUTE

    Directory of Open Access Journals (Sweden)

    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.

  5. Nonalcoholic Fatty Liver Disease and the Gut Microbiome.

    Science.gov (United States)

    Boursier, Jerome; Diehl, Anna Mae

    2016-05-01

    Recent progress has allowed a more comprehensive study of the gut microbiota. Gut microbiota helps in health maintenance and gut dysbiosis associates with chronic metabolic diseases. Modulation of short-chain fatty acids and choline bioavailability, lipoprotein lipase induction, alteration of bile acid profile, endogenous alcohol production, or liver inflammation secondary to endotoxemia result from gut dysbiosis. Modulation of the gut microbiota by pre/probiotics gives promising results in animal, but needs to be evaluated in human before use in clinical practice. Gut microbiota adds complexity to the pathophysiology of nonalcoholic fatty liver disease but represents an opportunity to discover new therapeutic targets.

  6. Caring for the woman with acute fatty liver of pregnancy.

    Science.gov (United States)

    Holub, Karen; Camune, Barbara

    2015-01-01

    Acute fatty liver of pregnancy, although rare, is usually a third trimester of pregnancy occurrence that may be life threatening for both the pregnant woman and the fetus. Often, the onset resembles gastroenteritis or cholecystitis and correct diagnosis is delayed. Because it can also present with preeclampsia and eclampsia, it may be mistakenly diagnosed as hemolysis, elevated liver enzymes, low platelet syndrome. This article presents diagnostic differences between liver conditions that can complicate pregnancy and management strategies for treating and maintaining the well-being of pregnant women, fetuses, and infants who are affected by acute fatty liver of pregnancy. Early recognition and rapid intervention from antepartum diagnosis through delivery and the postpartum period are required by the nursing team and medical providers to reduce maternal and neonatal morbidity and mortality.

  7. Mechanisms of amiodarone and valproic acid induced liver steatosis in mouse in vivo act as a template for other hepatotoxicity models

    NARCIS (Netherlands)

    Vitins, A.P.; Kienhuis, A.S.; Speksnijder, E.N.; Roodbergen, M.; Luijten, M.; Ven, van der L.T.M.

    2014-01-01

    Liver injury is the leading cause of drug-induced toxicity. For the evaluation of a chemical compound to induce toxicity, in this case steatosis or fatty liver, it is imperative to identify markers reflective of mechanisms and processes induced upon exposure, as these will be the earliest changes re

  8. Ketogenesis prevents diet-induced fatty liver injury and hyperglycemia

    OpenAIRE

    Cotter, David G.; Ercal, Baris; Huang, Xiaojing; Leid, Jamison M.; d’Avignon, D. André; Graham, Mark J.; Dietzen, Dennis J.; Brunt, Elizabeth M; Patti, Gary J.; Crawford, Peter A.

    2014-01-01

    Nonalcoholic fatty liver disease (NAFLD) spectrum disorders affect approximately 1 billion individuals worldwide. However, the drivers of progressive steatohepatitis remain incompletely defined. Ketogenesis can dispose of much of the fat that enters the liver, and dysfunction in this pathway could promote the development of NAFLD. Here, we evaluated mice lacking mitochondrial 3-hydroxymethylglutaryl CoA synthase (HMGCS2) to determine the role of ketogenesis in preventing diet-induced steatohe...

  9. Study on fatty liver diagnosed by abdominal ultrasonography and clinical laboratory findings

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Jeong Hwa [Cheju Halla College, Cheju (Korea, Republic of)

    2006-03-15

    The study obtained the following conclusions by making a comparative study on fatty liver diagnosed by abdominal ultrasonography and clinical laboratory findings. I surveyed the value of abdominal ultrasound in 400 patients without clinical symptoms at C Health Clinic Center, Seoul. Compare with blood pressure was high (systolic/diastolic) in 7.5%/4.5% on persons who were diagnosed fatty liver. At the time of the diagnosis, Total cholesterol level was increased in fatty liver patients, HDL-cholesterol level was high in fatty liver patients. And Trigryceride level was increased in fatty liver persons, LDL-cholesterol was high in fatty liver persons. SGOT level was increased in 5.5% on patients who were diagnosed fatty liver, 0% on persons who were normal and SGPT level was high in 29.5% on people who were diagnosed fatty liver, 0% on patients who were diagnosed normal.

  10. Nutritional recommendations for patients with non-alcoholic fatty liver diseases

    Institute of Scientific and Technical Information of China (English)

    Nimer Assy

    2011-01-01

    Fatty liver is the most common liver disease worldwide.Patients with fatty liver disease die primarily from cardiovascular disease and not from chronic liver diseases. Hyperglycemia and hyperinsulinemia induce lipogenesis, thereby increasing the hepatic pool of fatty acids. This pool is also increased by increased delivery of fatty acids through the diet or lipolysis in adipose tissue. Nutritional consultations and lifestyle modification are important in the treatment of non-alcoholic fatty liver disease (NAFLD). Among the dietary constituents, combination of vitamin D, vitamin E, and omega-3 fatty acids shows promise for the treatment of NAFLD.

  11. Free fatty acid-induced hepatic insulin resistance is attenuated following lifestyle intervention in obese individuals with impaired glucose tolerance

    DEFF Research Database (Denmark)

    Haus, Jacob M; Solomon, Thomas; Marchetti, Christine M;

    2010-01-01

    The objective of the study was to examine the effects of an exercise/diet lifestyle intervention on free fatty acid (FFA)-induced hepatic insulin resistance in obese humans.......The objective of the study was to examine the effects of an exercise/diet lifestyle intervention on free fatty acid (FFA)-induced hepatic insulin resistance in obese humans....

  12. Moro orange juice prevents fatty liver in mice

    Institute of Scientific and Technical Information of China (English)

    Federico Salamone; Marco Giorgio; Fabio Galvano; Giovanni Li Volti; Lucilla Titta; Lidia Puzzo; Ignazio Barbagallo; Francesco La Delia; Shira Zelber-Sagi; Michele Malaguarnera; Pier Giuseppe Pelicci

    2012-01-01

    AIM:To establish if the juice of Moro,an anthocyaninrich orange,may improve liver damage in mice with diet-induced obesity.METHODS:Eight-week-old mice were fed a high-fat diet (HFD) and were administrated water or Moro juice for 12 wk.Liver morphology,gene expression of lipid transcription factors,and metabolic enzymes were assessed.RESULTS:Mice fed HFD displayed increased body weight,insulin resistance and dyslipidemia.Moro juice administration limited body weight gain,enhanced insulin sensitivity,and decreased serum triglycerides and total cholesterol.Mice fed HFD showed liver steatosis associated with ballooning.Dietary Moro juice markedly improved liver steatosis by inducing the expression of peroxisome proliferator-activated receptor-a and its target gene acylCoA-oxidase,a key enzyme of lipid oxidation.Consistently,Moro juice consumption suppressed the expression of liver X receptor-o and its target gene fatty acid synthase,and restored liver glycerol-3-phosphate acyltransferase 1 activity.CONCLUSION:Moro juice counteracts liver steatogenesis in mice with diet-induced obesity and thus may represent a promising dietary option for the prevention of fatty liver.

  13. Non-alcoholic Fatty Liver Disease (NAFLD)--A Review.

    Science.gov (United States)

    Karim, M F; Al-Mahtab, M; Rahman, S; Debnath, C R

    2015-10-01

    Non-alcoholic fatty liver disease (NAFLD) is an emerging problem in Hepatology clinics. It is closely related to the increased frequency of overweight or obesity. It has recognised association with metabolic syndrome. Central obesity, diabetes mellitus, dyslipidemia are commonest risk factors. Association with hepatitis C genotype 3 is also recognised. NAFLD is an important cause of cyptogenic cirrhosis of liver. It affects all populations and all age groups. Most patients with NAFLD are asymptomatic or vague upper abdominal pain. Liver function tests are mostly normal or mild elevation of aminotranferases. Histological features almost identical to those of alcohol-induced liver damage and can range from mild steatosis to cirrhosis. Two hit hypothesis is prevailing theory for the development of NAFLD. Diagnosis is usually made by imaging tools like ultrasonogram which reveal a bright liver while liver biopsy is gold standard for diagnosis as well as differentiating simple fatty liver and non-alcoholic steatohepatitis (NASH). Prognosis is variable. Simple hepatic steatosis generally has a benign long-term prognosis. However, one to two third of NASH progress to fibrosis or cirrhosis and may have a similar prognosis as cirrhosis from other liver diseases. Treatment is mostly control of underlying disorders and dietary advice, exercise, insulin sensitizers, antioxidants, or cytoprotective agents. The prevalence of NAFLD is increasing. So it needs more research to address this problem.

  14. Stearoyl-CoA desaturase-1 (SCD1 augments saturated fatty acid-induced lipid accumulation and inhibits apoptosis in cardiac myocytes.

    Directory of Open Access Journals (Sweden)

    Hiroki Matsui

    Full Text Available Mismatch between the uptake and utilization of long-chain fatty acids in the myocardium leads to abnormally high intracellular fatty acid concentration, which ultimately induces myocardial dysfunction. Stearoyl-Coenzyme A desaturase-1 (SCD1 is a rate-limiting enzyme that converts saturated fatty acids (SFAs to monounsaturated fatty acids. Previous studies have shown that SCD1-deficinent mice are protected from insulin resistance and diet-induced obesity; however, the role of SCD1 in the heart remains to be determined. We examined the expression of SCD1 in obese rat hearts induced by a sucrose-rich diet for 3 months. We also examined the effect of SCD1 on myocardial energy metabolism and apoptotic cell death in neonatal rat cardiac myocytes in the presence of SFAs. Here we showed that the expression of SCD1 increases 3.6-fold without measurable change in the expression of lipogenic genes in the heart of rats fed a high-sucrose diet. Forced SCD1 expression augmented palmitic acid-induced lipid accumulation, but attenuated excess fatty acid oxidation and restored reduced glucose oxidation. Of importance, SCD1 substantially inhibited SFA-induced caspase 3 activation, ceramide synthesis, diacylglycerol synthesis, apoptotic cell death, and mitochondrial reactive oxygen species (ROS generation. Experiments using SCD1 siRNA confirmed these observations. Furthermore, we showed that exposure of cardiac myocytes to glucose and insulin induced SCD1 expression. Our results indicate that SCD1 is highly regulated by a metabolic syndrome component in the heart, and such induction of SCD1 serves to alleviate SFA-induced adverse fatty acid catabolism, and eventually to prevent SFAs-induced apoptosis.

  15. Audio-Visual Aid in Teaching "Fatty Liver"

    Science.gov (United States)

    Dash, Sambit; Kamath, Ullas; Rao, Guruprasad; Prakash, Jay; Mishra, Snigdha

    2016-01-01

    Use of audio visual tools to aid in medical education is ever on a rise. Our study intends to find the efficacy of a video prepared on "fatty liver," a topic that is often a challenge for pre-clinical teachers, in enhancing cognitive processing and ultimately learning. We prepared a video presentation of 11:36 min, incorporating various…

  16. Focally spared area of fatty liver caused by arterioportal shunt

    Energy Technology Data Exchange (ETDEWEB)

    Arita, Takeshi; Matsunaga, Naofumi [Yamaguchi Univ. School of Medicine (Japan); Honma, Yutaka [Shimonoseki City Hospital, Yamaguchi (Japan)] [and others

    1996-05-01

    We describe a case with a focally spared area in fatty liver caused by arterioportal shunt. Furthermore, we discuss the cause of the focally spared area related to a localized dilution or reduction in portal blood flow. 13 refs., 1 fig.

  17. Does vitamin C deficiency promote fatty liver disease development?

    DEFF Research Database (Denmark)

    Ipsen, David Højland; Tveden-Nyborg, Pernille; Lykkesfeldt, Jens

    2014-01-01

    Obesity and the subsequent reprogramming of the white adipose tissue are linked to human disease-complexes including metabolic syndrome and concurrent non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). The dietary imposed dyslipidemia promotes redox imbalance...

  18. Impact of variations in fatty liver on sonographic detection of focal hepatic lesions originally identified by CT

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Size; Tu, Rong; Nan, Ruixia; Liu, Guang Qing; Cui, Xiao Jing; Liang, Xian [Affiliated Hospital of Hainan Medical College, Haikou (China)

    2016-01-15

    The aim of this study was to investigate the influence of variations in fatty liver on the ultrasonographic detection of focal liver lesions. A total of 229 patients with varying degrees of fatty liver and focal liver lesions and 200 patients with focal liver lesions but no fatty liver were randomly selected for inclusion in groups I and II, respectively. Findings of focal liver lesions identified on computed tomography were taken as the reference, and findings on ultrasonography were compared with them. The number of focal liver lesions in groups I and II were 501 and 413, respectively. The ultrasonographic detection rates of focal liver lesions in groups I and II were 86.8% (435/501) and 94.2% (389/413), respectively. Comparison of the detection of the focal lesions between patients with and without fatty liver or different grades of fatty liver were as follows: mild fatty liver (162/177) vs. liver without fat infiltration (389/413) (P=0.277); mild fatty liver (162/177) vs. moderate fatty liver (190/212) (P=0.604); mild fatty liver (162/177) vs. severe fatty liver (83/112) (P<0.001); moderate fatty liver (190/212) vs. liver without fat infiltration (389/413) (P=0.051); moderate fatty liver (190/212) vs. severe fatty liver (83/112) (P<0.001); severe fatty liver (83/112) vs. liver without fat infiltration (389/413) (P<0.001); and fatty liver (435/501) vs. liver without fat infiltration (389/413) (P<0.001). Mild and moderate fatty liver are not significantly associated with the visualization of the lesion, while severe fatty liver usually impairs the detection of focal lesions in the liver. If a patient with severe fatty liver is suspected to have a liver tumor, ultrasonography should only be chosen cautiously in case of a missed diagnosis.

  19. Clinical Presentation and Patient Evaluation in Nonalcoholic Fatty Liver Disease.

    Science.gov (United States)

    Patel, Vaishali; Sanyal, Arun J; Sterling, Richard

    2016-05-01

    Nonalcoholic fatty liver disease (NAFLD) is a diagnosis of exclusion. Most patients are asymptomatic and diagnosed incidentally. Most patients remain undiagnosed. A high index of suspicion and serologic work-up to rule out alternative causes of liver disease is required. In NALFD, fibrosis correlates with outcomes, including mortality. To diagnose, assess severity, and monitor fibrosis, 2 noninvasive methods can be used. However, noninvasive tests are more helpful at extremes of fibrosis: excluding it or diagnosing advanced fibrosis. Liver biopsy is usually reserved for cases whereby noninvasive tests fail to accurately determine the degree of fibrosis or the diagnosis is unclear.

  20. Non-alcoholic fatty liver disease in children.

    Science.gov (United States)

    Janczyk, Wojciech; Socha, Piotr

    2012-06-01

    Non-alcoholic fatty liver disease is increasingly prevalent in children, together with obesity. Transaminases, tests for insulin resistance, ultrasonography and MRI are variably used as surrogates markers of steatosis. Other liver diseases, such as Wilson disease, should be excluded. A liver biopsy is performed in selected cases: young children, familial history of severe disease, inconclusive tests for other pathologies, suspected advanced fibrosis, hypertransaminasemia despite weight loss and in clinical trials. Weight reduction, and changes in lifestyle, are the front-line treatment. Drug therapy is under evaluation.

  1. Acute fatty liver of pregnancy: CT evaluation. Case report

    Energy Technology Data Exchange (ETDEWEB)

    Coche, G.; Moran, V.; Weill, F.S.; Boillot, A.; Miguet, J.P.; Hadni-Bresson, S.

    1988-05-01

    CT scans of two patients with acute fatty liver of pregnancy were reviewed in conjunction with the clinical evolution of this uncommon and potentially fatal disorder. In each of the CT scans, liver density measurements were less than those of the spleen. While the findings are non-specific, in the proper clinical context they are highly suggestive and may be the sole method of diagnosis, as these patients often have coagulation problems which rule out liver biopsy. It is an important diagnosis, as the high maternal and fetal mortality rates appear to be considerably reduced by early foetal delivery.

  2. Histopathology of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis.

    Science.gov (United States)

    Brown, Gregory Thomas; Kleiner, David E

    2016-08-01

    Nonalcoholic fatty liver disease (NAFLD) is the liver injury most often associated with disorders of insulin resistance, including obesity, diabetes and the metabolic syndrome. The term encompasses several patterns of liver injury, including a relatively benign condition of steatosis without hepatocellular injury, nonalcoholic steatohepatitis (NASH), and a pattern of zone 1 steatosis, inflammation and fibrosis mainly observed in prepubertal children. Staging and grading systems have been developed to characterize the histological changes in NAFLD, mainly as a tool for clinical research. The histological features of NAFLD across these different manifestations and the scoring systems used to evaluate disease severity are discussed.

  3. Probiotics in Nonalcoholic Fatty Liver Disease, Nonalcoholic Steatohepatitis, and Cirrhosis.

    Science.gov (United States)

    Qamar, Amir A

    2015-01-01

    With the growing epidemic of obesity, the incidence of both nonalcoholic fatty liver disease (NAFL) and nonalcoholic steatohepatitis (NASH) is increasing. The intestinal microbiota differs between individuals who are obese or have normal body mass indices. Animal studies have shown increased intestinal permeability in NAFL, NASH, and cirrhosis. This increases the risk of oxidative and inflammatory injury to the liver from intestinal microbacteria. It may also increase the risk of fatty acid injury and fatty deposition. Bacterial translocation is associated with increased portal hypertension and hepatic encephalopathy in cirrhosis. By preventing bacterial adhesion and translocation, probiotics may have a role in the management of patients with NAFL, NASH, and cirrhosis. Multiple small studies have suggested that probiotics improve some of the clinical markers of activity in patients with NAFL and NASH. Controlled studies have also shown improved outcomes in patients with cirrhosis who were treated with probiotics.

  4. Nonalcoholic fatty liver disease – an etiological approach

    Directory of Open Access Journals (Sweden)

    Florentina Ioniță Radu

    2014-06-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD is defined as the presence of fat in the liver (hepatic steatosis either on imaging or on liver histology only after the exclusion of secondary causes of fat accumulation in the liver (e.g. high alcohol drinking, drugs and other medical ailments. Considering the fact that there are many causes of hepatic steatosis, the term NAFLD is reserved for the liver disease that is predominantly associated with obesity and metabolic syndrome. The presence of inflammation and cell injury defines steatohepatitis (NASH which has the potential to evolve into cirrhosis and hepatocarcinoma, being, therefore, the stage of NAFLD most amenable to treatment. Among the treatments available, the most important are: weight loss, vitamin E and, last but not least, probiotics.

  5. 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.

  6. Effects of cold preservation and warm reperfusion on rat fatty liver

    Institute of Scientific and Technical Information of China (English)

    Bei Sun; Hong Chi Jiang; Da Xun Piao; Hai Quan Qiao; Ling Zhang

    2000-01-01

    INTRODUCTION Although liver transplantation for irreversible liver diseases is increasingly prevalent worldwide, patient die while waiting for donors because of organ shortages. One important problem commonly encountered is that fatty livers often affect the outcome of liver transplantation. It is reported that the incidence of abnormal fatty livers in autopsies after accidental death ranged from 15% to 24%.Since fatty livers may result in a primary nonfunction (PNF) liver graft, which contributes to an increased risk of mortality[1], they are usually out of consideration in liver transplantation.However, some fatty livers can be successfully transplanted. Therefore, how to choose fatty livers as donor organs correctly is the crux of success in liver transplantation.

  7. 4Ps medicine of the fatty liver: the research model of predictive, preventive, personalized and participatory medicine—recommendations for facing obesity, fatty liver and fibrosis epidemics

    OpenAIRE

    Trovato, Francesca Maria; Catalano, Daniela; Musumeci, Giuseppe; Trovato, Guglielmo M

    2014-01-01

    Relationship between adipose tissue and fatty liver, and its possible evolution in fibrosis, is supported by clinical and research experience. Given the multifactorial pathogenesis of non-alcoholic fatty liver disease (NAFLD), treatments for various contributory risk factors have been proposed; however, there is no single validated therapy or drug association recommended for all cases which can stand alone. Mechanisms, diagnostics, prevention and treatment of obesity, fatty liver and insulin ...

  8. Medium chain triglycerides dose-dependently prevent liver pathology in a rat model of nonalcoholic fatty liver disease

    Science.gov (United States)

    Obesity is often associated with a cluster of increased health risks collectively known as "Metabolic Syndrome" (MS). MS is often accompanied by development of fatty liver. Sometimes fatty liver results in damage leading to reduced liver function, and need for a transplant. This condition is known...

  9. Diffuse fatty infiltration of the liver: Pitfalls in computed tomography diagnosis

    Energy Technology Data Exchange (ETDEWEB)

    Loh, Y.H.; Dunn, G.D. [Concord Repatriation Hospital, Sydney, NSW, (Australia). Department of Radiology

    1997-11-01

    The presence of a fatty liver often complicates the interpretation of abdominal computed tomography (CT). Abnormalities in or adjacent to the liver, including dilated bile ducts, liver masses and subphrenic collections, may be masked by the fatty liver. Furthermore, normal structures may simulate pathological conditions. Five cases are presented to illustrate some of these diagnostic pitfalls. (authors). 9 refs., 1 tab., 5 figs.

  10. 13.2.Liver cirrhosis and fatty liver

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

    930313 Clinical research of portal hyperten-sion and relatives in liver cirrhosis.QIU Rihuo(仇日火),et al.175th Hosp,PLA,Chin J Digest1992;12 (4):220—222.Potral vein pressure (PVP) of portal vein hy-pertension (PVH) was studied in 40 patients ofcirrhosis guided by ultrasound with thin needlepereutaneous transhepatic measurement.The re-sults indicated that PVP were negatively corre-lated with liver volume,and correlated withspleen volume,degree of classification child’s

  11. Ultrasonographic Quantification of Fat Content in Fatty Liver Phantoms

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Il Young; Kim, Pyo Nyun; Joo, Gyung Soo; Kim, Ho Jung; Kim, Young Beom; Lee, Byoung Ho [Soonchunhyang University College of Medicine, Seoul (Korea, Republic of)

    1995-06-15

    Assuming that the fat content of certain tissue might be quantified by measurirrg the ultrasound echo level, we analyzed the ultrasound histograms obtained from the fatty liver phantoms that contained various amount of fat. Various amount of margarine(Mazola. Cliff wood. USA) was mixed with 2% of agarin solution state to produce fatty liver phantoms that contained 5, 10, 20, 30 and 40% of fat. We obtained ultrasound histogram from each fatty liver phantom in gel state. We used 2% agar gel as a control. The ultrasound histograms from the control phantom showed gradual increase in echo level as the depth from the surface increased. The echo level from the phantom that contained 5% of fat showed gradual increase and subsequent decrease with the peak echo level at the depth of 3cm. The echo levels from the phantoms that contained more in 5% of fat gradually decreased as the depth from the surface increased; the change becoming more pronounced as the fat content of the phantom increased. The echo levels measured at the depth of 1cm were 9.3(control), 29.6(5%phantom), 3l.3 (10% phantom), 26.3 (20% phantom), l8.8 (30% phantom), and l6dB (40% phantom). Fat content of fatty phantoms can not be quantified by measuring only echo level. Simultaneous measurement of attenuation of ultrasound, which is not easy to do and not done in this study, is prerequisite to quantify fat content

  12. Adiponectin and its receptors in rodent models of fatty liver disease and liver cirrhosis

    Institute of Scientific and Technical Information of China (English)

    Markus Neumeier; Jürgen Sch(o)lmerich; Christa Buechler; Claus Hellerbrand; Erwin G(a)bele; Roland Buettner; Cornelius Bollheimer; Johanna Weigert; Andreas Sch(a)ffler; Thomas S Weiss; Monika Lichtenauer

    2006-01-01

    AIM: To determine circulating and hepatic adiponectin in rodents with fatty liver disease or liver cirrhosis and investigate expression of the adiponectin receptors AdipoR1 on the mRNA and protein level and AdipoR2 on the mRNA level.METHODS: Fat fed rats were used as a model for fatty liver disease and bile duct ligation in mice to investigate cirrhotic liver. Expression of AdipoR1 and AdipoR2 mRNA was determined by real time RT-PCR. AdipoR1 protein was analysed by immunoblot. Adiponectin was measured by ELISA.RESULTS: Systemic adiponectin is reduced in fat fed rats but is elevated in mice after bile duct ligation (BDL). Hepatic adiponectin protein is lower in steatotic liver but not in the liver of BDL-mice when compared to controls. Adiponectin mRNA was not detected in human liver samples or primary human hepatocytes nor in rat liver but recombinant adiponectin is taken up by isolated hepatocytes in-vitro. AdipoR1 mRNA and AdipoR1 protein levels are similar in the liver tissue of control and fat fed animals whereas AdipoR2 mRNA is induced. AdipoR2 mRNA and AdipoR1 mRNA and protein is suppressed in the liver of BDL-mice.CONCLUSION: Our studies show reduced circulating adiponectin in a rat model of fatty liver disease whereas circulating adiponectin is elevated in a mouse model of cirrhosis and similar findings have been described in humans. Diminished hepatic expression of adiponectin receptors was only found in liver cirrhosis.

  13. Fatty liver in H63D homozygotes with hyperferritinemia

    Institute of Scientific and Technical Information of China (English)

    Giada Sebastiani; Daniel F Wallace; Susan E Davies; Vasu Kulhalli; Ann P Walker; James S Dooley

    2006-01-01

    To study the clinical correlates of the H63D mu-tation we have analysed the phenotype of H63D homozygotes identified through mutation analysis in a referral laboratory. A total of 366 blood samples referred for HFE analysis were screened for C282Y and H63D mutations. Four H63D homozygotes were identified.All had raised serum ferritin but normal transferrin saturation. They were negative for hepatitis B and C and only one patient consumed excess alcohol. In all 4 cases ultrasonography revealed fatty liver. In two patients a liver biopsy was done and showed mild siderosis with an unusual distribution and macrovesicular steatosis.These data confirm the association between fatty liver,hyperferritinaemia and increased hepatic iron, but do not clarify whether siderosis was related to steatosis rather than homozygosity for the H63D mutation. Patients with fatty liver may complicate the interpretation of data in population studies of the expression of H63D homozygosity.

  14. Soft drinks consumption and nonalcoholic fatty liver disease.

    Science.gov (United States)

    Nseir, William; Nassar, Fares; Assy, Nimer

    2010-06-07

    Nonalcoholic fatty liver disease (NAFLD) is a common clinical condition which is associated with metabolic syndrome in 70% of cases. Inappropriate dietary fat intake, excessive intake of soft drinks, insulin resistance and increased oxidative stress combine to increase free fatty acid delivery to the liver, and increased hepatic triglyceride accumulation contributes to fatty liver. Regular soft drinks have high fructose corn syrup which contains basic sugar building blocks, fructose 55% and glucose 45%. Soft drinks are the leading source of added sugar worldwide, and have been linked to obesity, diabetes, and metabolic syndrome. The consumption of soft drinks can increase the prevalence of NAFLD independently of metabolic syndrome. During regular soft drinks consumption, fat accumulates in the liver by the primary effect of fructose which increases lipogenesis, and in the case of diet soft drinks, by the additional contribution of aspartame sweetener and caramel colorant which are rich in advanced glycation end products that potentially increase insulin resistance and inflammation. This review emphasizes some hard facts about soft drinks, reviews fructose metabolism, and explains how fructose contributes to the development of obesity, diabetes, metabolic syndrome, and NAFLD.

  15. [Acute fatty liver in pregnancy: revealing fetal fatty acid oxidation disorders].

    Science.gov (United States)

    Lamireau, D; Feghali, H; Redonnet-Vernhet, I; Mesli, S; Carles, D; Brissaud, O

    2012-03-01

    Acute fatty liver of pregnancy (AFLP) and hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome are serious maternal illnesses occurring in the third trimester of pregnancy with significant perinatal and maternal mortality. AFLP may result from mitochondrial defects in the beta-oxidation of fatty acids, in particular a deficiency of the long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) in the fetus. Clinical findings in AFLP vary and its diagnosis is complicated by a significant overlap in clinical and biochemical features with HELLP syndrome. We report the case of 2 siblings who died, the first one in the neonatal period of asphyxia with multivisceral presentation and the second one from sudden death at 7 months. Autopsy of the latter infant revealed hepatic steatosis associated with cardiomyopathy, which led to suspicion of a fatty acid oxidation deficiency. Mutation analysis demonstrated that both children were homozygous for the common mutation c.1528G>C and the parents were heterozygous for this same mutation. This case demonstrates the importance of screening mothers with acute fatty liver disease of pregnancy and their children at birth for a metabolic disease. This article proposes several metabolic tests for mother and child suspected of having beta-oxidation of a fatty acid disorder.

  16. Focal fatty change in the liver that developed after cholecystectomy

    Institute of Scientific and Technical Information of China (English)

    Akinobu; Osame; Toshimichi; Mitsufuji; Shinichi; Kora; Kengo; Yoshimitsu; Daisuke; Morihara; Hideo; Kunimoto

    2014-01-01

    Focal fatty change of the segment IV of the liver has been attributed to local systemic venous inflow replacing the portal venous supply, which could develop or be accentuated after gastrectomy. However, focal fatty change due to aberrant pancreaticoduodenal vein that developed after cholecystectomy has never been reported. We report a 30-year-old man with such a rare lesion, which was initially misdiagnosed as a hepatocellular carcinoma, but was confirmed on computed tomography during selective gastroduodenal arteriography. The lesion disappeared 12 mo later without any intervention.

  17. [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

  18. Albumin-bound fatty acids induce mitochondrial oxidant stress and impair antioxidant responses in proximal tubular cells

    NARCIS (Netherlands)

    Ishola, D. A.; Post, J. A.; van Timmeren, M. M.; Bakker, S. J. L.; Goldschmeding, R.; Koomans, H. A.; Braam, B.; Joles, J. A.

    2006-01-01

    Albumin induces oxidative stress and cytokine production in proximal tubular cells (PTECs). Albumin-bound fatty acids (FAs) enhance tubulopathic effects of albumin in vivo. We proposed that FA aggravation of albumin-induced oxidative stress in PTECs might be involved. We hypothesized that mitochondr

  19. Rice endosperm protein slows progression of fatty liver and diabetic nephropathy in Zucker diabetic fatty rats.

    Science.gov (United States)

    Kubota, Masatoshi; Watanabe, Reiko; Yamaguchi, Miki; Hosojima, Michihiro; Saito, Akihiko; Fujii, Mikio; Fujimura, Shinobu; Kadowaki, Motoni

    2016-10-01

    We previously reported that rice endosperm protein (REP) has renoprotective effects in Goto-Kakizaki rats, a non-obese diabetic model. However, whether these effects occur in obese diabetes remains unclear. This study aimed to clarify the effects of REP on obese diabetes, especially on fatty liver and diabetic nephropathy, using the obese diabetic model Zucker diabetic fatty (ZDF) rats. In total, 7-week-old male ZDF rats were fed diets containing 20 % REP or casein (C) for 8 weeks. Changes in fasting blood glucose levels and urinary markers were monitored during the experimental period. Hepatic lipids and metabolites were measured and renal glomeruli were observed morphologically. HbA1c levels were significantly lower in rats fed REP, compared with C (Pdiabetes, fatty liver and diabetic nephropathy.

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

    Directory of Open Access Journals (Sweden)

    Luis Calzadilla Bertot

    2016-05-01

    Full Text Available 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.

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

    Science.gov (United States)

    Calzadilla Bertot, Luis; Adams, Leon Anton

    2016-01-01

    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. PMID:27213358

  2. Unusual fatty metamorphosis observed in diffuse liver metastases of stage 4S neuroblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Tazoe, Jun; Okuyama, Chio; Nishimura, Tsunehiko [Kyoto Prefectural University of Medicine, Department of Radiology, Graduate School of Medical Science, Kyoto City (Japan); Iehara, Tomoko; Hosoi, Hajime [Kyoto Prefectural University of Medicine, Department of Paediatrics, Graduate School of Medical Science, Kyoto City (Japan)

    2010-05-15

    We report a case of stage 4S neuroblastoma in which CT showed diffuse liver metastases containing a geographical fatty area in the periportal region. MRI showed this abnormality to correspond to an area with an unusual pattern of fatty change. {sup 123}I-metaiodobenzylguanidine (MIBG) scintigraphy demonstrated increased accumulation throughout the liver, except for the region showing fatty change. To the best of our knowledge, this is the first report of liver metastases from neuroblastoma with geographical fatty infiltration. (orig.)

  3. Nuclear medicine evaluation of focal fatty infiltration of the liver

    Energy Technology Data Exchange (ETDEWEB)

    Baker, M.K.; Schauwecker, D.S.; Wenker, J.C.; Kopecky, K.K.

    1986-07-01

    Focal fatty infiltration of the liver (FFIL) occasionally may be mistaken as metastatic disease, primary liver malignancy, or other space-occupying lesions on CT or ultrasound studies, especially if there is significant mass effect. In these confusing cases, Xe-133 liver imaging has been advocated for confirmation of FFIL, since such studies have been reported to be sensitive and specific. The authors present results of four Xe-133 and four Tc-99m sulfur colloid scans in six patients with FFIL. Xe-133 imaging was found useful for diagnostic confirmation in only one patient and was misleading in the other three. Routine liver-spleen imaging was a more reliable method of confirmation, since no focal defects were found in any of the patients.

  4. Studies on the hepatic hemodynamics of the patients with fatty liver by hepatic blood flow mapping

    Energy Technology Data Exchange (ETDEWEB)

    Kubo, Shuichi; Okajima, Tugio; Yamazaki, Yasurou (Toho Univ., Tokyo (Japan). School of Medicine)

    1991-12-01

    To investigate intrahepatic hemodynamics of the patients with fatty liver, the time to reach maximal enhancement (PT) of every 3 x 3 pixel was depicted by a gray scale throughout an area of maximal horizontal slice of CT of the liver to obtain blood flow mapping of the liver, and compared with those of normal, chronic hepatitis and cirrhosis. Mottles of deep gray, light gray or black pixels were distributed throughout the liver slice of fatty liver. Although the mean PT of a ROI of fatty liver was longer than normal and shorter than that of cirrhosis and the same as that of chronic hepatitis, the map of fatty liver was different from that of chronic hepatitis. When the distribution of PT was expressed by their histogram, it was known that PT of fatty liver had a wider range than that of chronic hepatitis. The range was the same as that of cirrhosis. In one case of fatty liver, the deep gray pixels was increased when fatty infiltration of the liver was improved. It was concluded that the intrahepatic blood flow of fatty liver was impaired in a way not similar to chronic hepatitis or liver cirrhosis, which could be clearly seen by hepatic blood flow mapping, and which seemed to be reversible with the improvement of fatty liver. (author).

  5. 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.

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

    Science.gov (United States)

    Lu, Wenxia; Li, Sainan; Li, Jingjing; Wang, Jianrong; Zhang, Rong; Zhou, Yuqing; Yin, Qin; Wang, Fan; Xia, Yujing; Liu, Tong; Lu, Jie; Zhou, Yingqun

    2016-01-01

    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. PMID:27651787

  7. Functional pitch of a liver: fatty liver disease diagnosis with photoacoustic spectrum analysis

    Science.gov (United States)

    Xu, Guan; Meng, Zhuoxian; Lin, Jiandie; Carson, Paul; Wang, Xueding

    2014-03-01

    To provide more information for classification and assessment of biological tissues, photoacoustic spectrum analysis (PASA) moves beyond the quantification of the intensities of the photoacoustic (PA) signals by the use of the frequency-domain power distribution, namely power spectrum, of broadband PA signals. The method of PASA quantifies the linear-fit to the power spectrum of the PA signals from a biological tissue with 3 parameters, including intercept, midband-fit and slope. Intercept and midband-fit reflect the total optical absorption of the tissues whereas slope reflects the heterogeneity of the tissue structure. Taking advantage of the optical absorption contrasts contributed by lipid and blood at 1200 and 532 nm, respectively and the heterogeneous tissue microstructure in fatty liver due to the lipid infiltration, we investigate the capability of PASA in identifying histological changes of fatty livers in mouse model. 6 and 9 pairs of normal and fatty liver tissues from rat models were examined by ex vivo experiment with a conventional rotational PA measurement system. One pair of rat models with normal and fatty livers was examined non-invasively and in situ with our recently developed ultrasound and PA parallel imaging system. The results support our hypotheses that the spectrum analysis of PA signals can provide quantitative measures of the differences between the normal and fatty liver tissues and that part of the PA power spectrum can suffice for characterization of microstructures in biological tissues. Experimental results also indicate that the vibrational absorption peak of lipid at 1200nm could facilitate fatty liver diagnosis.

  8. Peran Antioksidan pada Non Alcoholic Fatty Liver Disease (NAFLD

    Directory of Open Access Journals (Sweden)

    Yusri Diane Jurnalis

    2014-01-01

    Full Text Available AbstrakNonalcoholic Fatty Liver Disease (NAFLD merupakan penyebab tersering penyakit hati kronik pada anak dan remaja diseluruh dunia. NAFLD berhubungan dengan obesitas, diabetes melitus tipe 2 dan sindrom metabolik. Resistensi insulin memegang peranan penting dalam patogenesis molecular terjadinya NAFLD. Ketidakseimbangan prooksidan dan antioksidan pada sel hepatosis menentukan progresifitas penyakit ini. Sebagai antioksidan telah dilakukan penelitian mengenai efek antioksidan vitamin E, vitamin C, betaine, N-asetil sistein, probucol dan silymarin. Antioksidan tersebut memperlihatkan perbaikan fungsi hepar dan gambaran histopatologis.Kata kunci: Arial 9 NAFLD, resistensi insulin, antioksidanAbstractNonalcoholic fatty liver disease (NAFLD is the most common cause of liver disease in pediatric and adolescent population. NAFLD related with obesity, type 2 diabetes mellitus and metabolic syndrome. Insulin resistance and oxidative stress have important role in molecular pathogenesis of NAFLD. Prooxidant and antioxidant factor in hepatosit can determine progressivity of liver disease. As antioxidant agent for treatment NAFLD have been studied effect of vitamin E, vitamin C, betaine, N-acetyl cystein, probucol and sylimarin. They have been shown improvement of liver function test and histopathologycal feature.Keywords:NAFLD, insulin resistance, antioxidant

  9. Plasma phospholipids and fatty acid composition differ between liver biopsy-proven nonalcoholic fatty liver disease and healthy subjects

    Science.gov (United States)

    Ma, D W L; Arendt, B M; Hillyer, L M; Fung, S K; McGilvray, I; Guindi, M; Allard, J P

    2016-01-01

    Background: There is growing evidence that nonalcoholic fatty liver disease (NAFLD) is associated with perturbations in liver lipid metabolism. Liver phospholipid and fatty acid composition have been shown to be altered in NAFLD. However, detailed profiles of circulating lipids in the pathogenesis of NAFLD are lacking. Objective: Therefore, the objective of the present study was to examine circulating lipids and potential mechanisms related to hepatic gene expression between liver biopsy-proven simple steatosis (SS), nonalcoholic steatohepatitis (NASH) and healthy subjects. Subjects: Plasma phospholipid and fatty acid composition were determined in 31 healthy living liver donors as healthy controls (HC), 26 patients with simple hepatic steatosis (SS) and 20 with progressive NASH. Hepatic gene expression was analyzed by Illumina microarray in a subset of 22 HC, 16 SS and 14 NASH. Results: Concentrations of phosphatidylethanolamine (PE) increased relative to disease progression, HCFatty acid composition of phospholipids was also remodeled. In particular, docosahexaenoic and arachidonic acid were higher (P<0.05) in SS and NASH relative to HC in PS. Differentially expressed hepatic genes included ETNK1 and PLSCR1 that are involved in PE synthesis and PS transport, respectively. Conclusions: The present study demonstrates that there is a disruption in phospholipid metabolism that is present in SS, but more pronounced in NASH. Intervention studies targeted at lipid metabolism could benefit SS and NASH. PMID:27428872

  10. Gender-based differences in the relationship between fatty liver disease and atherosclerosis

    Science.gov (United States)

    Kim, Hyun-Jin; Lim, Chae-Wan; Lee, Jae hyuk; Park, Hyung-Bok; Suh, Yongsung; Cho, Yoon-Hyeong; Choi, Tae-Young; Hwang, Eui-Seok; Cho, Deok-Kyu; Kim, Hyun-Jin

    2016-01-01

    Summary Background Carotid intima–media thickness (CIMT) is a surrogate of subclinical atherosclerosis. Fatty liver disease is also linked to increased risk of cardiovascular events. The aim of this study was to evaluate the association between fatty liver disease and CIMT according to gender. Methods Patients who had undergone carotid and abdominal ultrasound between June 2011 and December 2013 were retrospectively evaluated. The differences between the CIMT values measured in the common carotid artery and the prevalence of carotid plaque in patients with fatty liver disease and those with normal livers were investigated. Results Out of a total of 1 121 patients, the men had more fatty liver disease than the women. The mean CIMT of the men was significantly higher than that of the women, and the men had more plaque than the women. The women with fatty liver disease had a significantly higher mean CIMT value and more plaque than the women with normal livers. The differences between the men with fatty liver and those with normal livers in mean CIMT values and in the prevalence of plaque were not significant. In the women, multivariate analysis showed that fatty liver disease was independently associated with subclinical atherosclerosis [adjusted hazards ratio (HR) 1.65, 95% confidence interval (CI) 1.007–2.697, p = 0.047]. Conclusions The men had more fatty liver disease, carotid plaque and higher CIMT values than the women. Fatty liver disease was a useful predictor of atherosclerosis, especially for the female study patients. PMID:26972662

  11. Dietary approach in the treatment of nonalcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    Silvia; Marinho; Ferolla; Luciana; Costa; Silva; Maria; de; Lourdes; Abreu; Ferrari; Aloísio; Sales; da; Cunha; Flaviano; dos; Santos; Martins; Cláudia; Alves; Couto; Teresa; Cristina; Abreu; Ferrari

    2015-01-01

    Nonalcoholic fatty liver disease(NAFLD) has been identified as one of the most prevalent chronic liver disease in adults and children populations. NAFLD is usually associated with the metabolic syndrome(MS), which is chiefly related to insulin resistance and its consequences. Insulin resistance has a crucial role in the pathogenesis of hepatic steatosis and potentially nonalcoholic steatohepatitis(NASH). Because of the contemporary epidemics of MS and obesity, the burden of NAFLD is also expected to rise. Unhealthy diets, such as the so-called western diet, are enriched in fructose, trans-fatty acids and saturated fat and seem to be associated with the development of NAFLD. In human studies, certain dietary sugars, particularly fructose, are used as a substrate for lipogenesis leading to hepatic fatty infiltration, inflammation, and possibly fibrosis. Other investigations have shown that fat consumption especially cholesterol and trans/saturated fatty acids are also steatogenic and seem to increase visceral adiposity. The identification of specific dietary components that favor the development of NASH could be important for the management of this disorder. This review focuses on the effects of different dietary approaches to prevent and treat NAFLD emphasizing the macronutrients and energy composition.

  12. Roles of liver innate immune cells in nonalcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Nonalcoholic fatty liver disease (NAFLD) has become the most common liver disease in the United States and other developed countries and is expected to increase in the next few years. Emerging data suggest that some patients with NAFLD may progress to nonalcoholic steatohepatitis (NASH), cirrhosis and even hepatocellular carcinoma. NAFLD can also promote the development and progression of disease in other organ systems, such as the cardiovascular and endocrine (i.e. diabetes) systems. Thus, understanding th...

  13. Management of non-alcoholic fatty liver disease in 2015

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    There is no single pharmacologic therapy that hasbeen approved to treat nonalcoholic fatty liver diseasein the general population. The backbone of therapycurrently includes intensive lifestyle modification withestablished targets for diet and weight loss. The useof unsweetened, unfiltered coffee along with limitinghigh fructose corn syrup have emerged as beneficialdietary recommendations. The use of empiric oralhypoglycemic agents and vitamin E, however, has notbeen widely accepted. Developing bariatric surgicaltechniques are promising, but additional studies withlong-term follow up are needed before it can be widelyrecommended. Finally, liver transplantation is an increasinglyfrequent consideration once complications of endstagedisease have developed. The future treatmentof those with nonalcoholic fatty liver disease will likelyinvolve a personalized approach. The importance of thegut microbiome in mediating hepatocyte inflammationand intestinal permeability is emerging and may offeravenues for novel treatment. The study of anti-fibroticagents such as pentoxifylline and FXR agonists holdpromise and new pathways, such as hepatocyte cannabinoidreceptor antagonists are being studied. Withthe incidence of obesity and the metabolic syndromeincreasing throughout the developed world, the futurewill continue to focus on finding novel agents and newapplications of existing therapies to help prevent andto mediate the progression of nonalcoholic fatty liverdisease.

  14. Ursolic acid inhibits the development of nonalcoholic fatty liver disease by attenuating endoplasmic reticulum stress.

    Science.gov (United States)

    Li, Jian-Shuang; Wang, Wen-Jun; Sun, Yu; Zhang, Yu-Hao; Zheng, Ling

    2015-05-01

    Ursolic acid (UA) is a natural pentacyclic triterpenoid compound, which is enriched with many herbs and plants, such as apple, cranberry and olive. UA performs multiple biological activities including anti-oxidation, anti-inflammation, anti-cancer and hepatoprotection. However, the exact mechanism underlying the hepatoprotective activity of UA remains unclear. In this study, the effects of UA on the development of nonalcoholic fatty liver disease (NAFLD) were investigated. In vivo, UA treatment (0.14%, w/w) significantly decreased the liver weight, serum levels of ALT/AST and hepatic steatosis in db/db mice (a type 2 diabetic mouse model). In vitro, UA treatment (10-30 μg ml(-1)) significantly decreased palmitic acid induced intracellular lipid accumulation in L02 cells. Our results suggested that the beneficial effects of UA on NAFLD may be due to its ability to increase lipid β-oxidation and to inhibit the hepatic endoplasmic reticulum (ER) stress. Together, UA may be further considered as a natural compound for NAFLD treatment.

  15. Liver histology according to the presence of metabolic syndrome in nonalcoholic fatty liver disease cases

    Institute of Scientific and Technical Information of China (English)

    Hüseyin Saadettin Uslusoy; Selim Giray Nak; Macit Gülten; Zeynep Blylkll

    2009-01-01

    AIM: To investigate the histologic features of the liver in nonalcoholic fatty liver disease (NAFLD) cases according to the presence of metabolic syndrome or its individual components.METHODS: We enrolled 81 patients (40 male, 41 female) who were diagnosed with fatty liver by ultrasonographic scan and fulfilled the inclusion criteria. First anamnesis, anthropometric, clinical, laboratory and imaging features of all participants were recorded and then liver biopsy was performed after gaining consent from patients. Diagnosis of metabolic syndrome was dependent on patients having 3 or more out of 5 risk criteria defined by the WHO. Biopsy specimens were assessed according to Brunt et al's classification.RESULTS: Sixty-nine of the 81 patients had nonalcoholic steatohepatitis (NASH), 11 had simple fatty liver and 1 had cirrhosis according to histologic evaluation.Comparisons were made between two groups of NASH patients, those with and without metabolic syndrome.We did not detect statistically significant differences in liver histology between NASH patients with and without metabolic syndrome.CONCLUSION: NASH can progress without metabolic risk factors or the presence of metabolic syndrome.

  16. Protective Effect of Unsaturated Fatty Acids on Palmitic Acid-Induced Toxicity in Skeletal Muscle Cells is not Mediated by PPARδ Activation.

    Science.gov (United States)

    Tumova, Jana; Malisova, Lucia; Andel, Michal; Trnka, Jan

    2015-10-01

    Unsaturated free fatty acids (FFA) are able to prevent deleterious effects of saturated FFA in skeletal muscle cells although the mechanisms involved are still not completely understood. FFA act as endogenous ligands of peroxisome proliferator-activated receptors (PPAR), transcription factors regulating the expression of genes involved in lipid metabolism. The aim of this study was to determine whether activation of PPARδ, the most common PPAR subtype in skeletal muscle, plays a role in mediating the protective effect of unsaturated FFA on saturated FFA-induced damage in skeletal muscle cells and to examine an impact on mitochondrial respiration. Mouse C2C12 myotubes were treated for 24 h with different concentrations of saturated FFA (palmitic acid), unsaturated FFA (oleic, linoleic and α-linolenic acid), and their combinations. PPARδ agonist GW501516 and antagonist GSK0660 were also used. Both mono- and polyunsaturated FFA, but not GW501516, prevented palmitic acid-induced cell death. Mono- and polyunsaturated FFA proved to be effective activators of PPARδ compared to saturated palmitic acid; however, in combination with palmitic acid their effect on PPARδ activation was blocked and stayed at the levels observed for palmitic acid alone. Unsaturated FFA at moderate physiological concentrations as well as GW501516, but not palmitic acid, mildly uncoupled mitochondrial respiration. Our results indicate that although unsaturated FFA are effective activators of PPARδ, their protective effect on palmitic acid-induced toxicity is not mediated by PPARδ activation and subsequent induction of lipid regulatory genes in skeletal muscle cells. Other mechanisms, such as mitochondrial uncoupling, may underlie their effect.

  17. Translational approaches: from fatty liver to non-alcoholic steatohepatitis.

    Science.gov (United States)

    Rosso, Natalia; Chavez-Tapia, Norberto C; Tiribelli, Claudio; Bellentani, Stefano

    2014-07-21

    Over the past few decades, non-alcoholic fatty liver disease (NAFLD) has become one, if not the most common, cause of chronic liver disease affecting both adults and children. The increasing number of cases at an early age is the most worrying aspect of this pathology, since it provides more time for its evolution. The spectrum of this disease ranges from liver steatosis to steatohepatitis, fibrosis and in some cases, hepatocellular carcinoma. NAFLD may not always be considered a benign disease and hepatologists must be cautious in the presence of fatty liver. This should prompt the use of the available experimental models to understand better the pathogenesis and to develop a rational treatment of a disease that is dangerously increasing. In spite of the growing efforts, the pathogenesis of NAFLD is still poorly understood. In the present article we review the most relevant hypotheses and evidence that account for the progression of NAFLD to non-alcoholic steatohepatitis (NASH) and fibrosis. The available in vitro and in vivo experimental models of NASH are discussed and revised in terms of their validity in translational studies. These studies must be aimed at the discovery of the still unknown triggers or mediators that induce the progression of hepatic inflammation, apoptosis and fibrosis.

  18. Nonalcoholic fatty liver disease: Noninvasive methods of diagnosing hepatic steatosis

    Directory of Open Access Journals (Sweden)

    Rasha AlShaalan

    2015-01-01

    Full Text Available Hepatic steatosis is the buildup of lipids within hepatocytes. It is the simplest stage in nonalcoholic fatty liver disease (NAFLD. It occurs in approximately 30% of the general population and as much as 90% of the obese population in the United States. It may progress to nonalcoholic steatohepatitis, which is a state of hepatocellular inflammation and damage in response to the accumulated fat. Liver biopsy remains the gold standard tool to diagnose and stage NAFLD. However, it comes with the risk of complications ranging from simple pain to life-threatening bleeding. It is also associated with sampling error. For these reasons, a variety of noninvasive radiological markers, including ultrasound, computed tomography, magnetic resonance spectroscopy, and the controlled attenuation parameter using transient elastography and Xenon-133 scan have been proposed to increase our ability to diagnose NAFLD, hence avoiding liver biopsy. The aim of this review is to discuss the utility and accuracy of using available noninvasive diagnostic modalities for fatty liver in NAFLD.

  19. Ketogenesis prevents diet-induced fatty liver injury and hyperglycemia.

    Science.gov (United States)

    Cotter, David G; Ercal, Baris; Huang, Xiaojing; Leid, Jamison M; d'Avignon, D André; Graham, Mark J; Dietzen, Dennis J; Brunt, Elizabeth M; Patti, Gary J; Crawford, Peter A

    2014-12-01

    Nonalcoholic fatty liver disease (NAFLD) spectrum disorders affect approximately 1 billion individuals worldwide. However, the drivers of progressive steatohepatitis remain incompletely defined. Ketogenesis can dispose of much of the fat that enters the liver, and dysfunction in this pathway could promote the development of NAFLD. Here, we evaluated mice lacking mitochondrial 3-hydroxymethylglutaryl CoA synthase (HMGCS2) to determine the role of ketogenesis in preventing diet-induced steatohepatitis. Antisense oligonucleotide-induced loss of HMGCS2 in chow-fed adult mice caused mild hyperglycemia, increased hepatic gluconeogenesis from pyruvate, and augmented production of hundreds of hepatic metabolites, a suite of which indicated activation of the de novo lipogenesis pathway. High-fat diet feeding of mice with insufficient ketogenesis resulted in extensive hepatocyte injury and inflammation, decreased glycemia, deranged hepatic TCA cycle intermediate concentrations, and impaired hepatic gluconeogenesis due to sequestration of free coenzyme A (CoASH). Supplementation of the CoASH precursors pantothenic acid and cysteine normalized TCA intermediates and gluconeogenesis in the livers of ketogenesis-insufficient animals. Together, these findings indicate that ketogenesis is a critical regulator of hepatic acyl-CoA metabolism, glucose metabolism, and TCA cycle function in the absorptive state and suggest that ketogenesis may modulate fatty liver disease.

  20. Multifocal fatty infiltration of the liver; Report of six cases

    Energy Technology Data Exchange (ETDEWEB)

    Hashimoto, Hiromi; Nakatsuka, Haruki; Tsubakimoto, Mitsuo; Ogawa, Ryuhei; Kashihara, Takeshi (Itami City Hospital, Osaka (Japan)); Murata, Katsuko; Nakamura, Kenji; Tamaoka, Koichi; Onoyama, Yasuto

    1990-09-01

    Images of computed tomography (CT), ultrasonography (US), angiography and radionuclide imaging were analyzed in six cases of multifocal fatty infiltration of the liver. Histologic confirmation of fatty infiltration was obtained in one patient by percutaneous biopsy. In the remaining patients, presumptive confirmation of the diagnosis was based on the CT number in one patient and partial or complete resolution of the lesions on repeat CT scans or US in 4 patients. CT and US were performed in all six patients. CT scans demonstrated multiple round areas of low attenuation within both lobes of the liver in all cases. US studies showed hyperechoic foci in three cases and diffuse inhomogeneous hyperechogenicity in three cases. Hepatic arteriograms in five cases and liver scintigrams in four cases showed evidence of space-occupying lesions. In all no cases, the lesions completely or partially resolved in follow-up CT and US, and in four cases the lesions disappeared within two months, so follow-up examinations within about 2 months are necessary to differentiate them from liver neoplasms. (author).

  1. Chalcones suppress fatty acid-induced lipid accumulation through a LKB1/AMPK signaling pathway in HepG2 cells.

    Science.gov (United States)

    Zhang, Tianshun; Yamamoto, Norio; Ashida, Hitoshi

    2014-06-01

    Excessive lipid accumulation in the liver has been proposed to cause hyperlipidemia, diabetes and fatty liver disease. 4-Hydroxyderricin (4HD), xanthoangelol (XAG), cardamonin (CAR) and flavokawain B (FKB) are chalcones that have exhibited various biological effects against obesity, inflammation, and diabetes; however, little is known about the inhibitory effects of these chalcones on fatty liver disease. In the present study, we investigated the ability of 4HD, XAG, CAR, and FKB to reduce lipid accumulation in hepatocytes. When HepG2 cells were treated with a mixture of fatty acids (FAs; palmitic acid : oleic acid = 1 : 2 ratio), significant lipid accumulation was observed. Under the same experimental conditions, addition of chalcones at 5 μM significantly suppressed the FA-induced lipid accumulation. We found that the expression of sterol regulatory element-binding protein-1 (SREBP-1), a key molecule involved in lipogenesis, was decreased in these chalcone-treated cells. We also found that these chalcones increased the expression of peroxisome proliferator-activated receptor α (PPARα), which is involved in FA oxidation. Moreover, these chalcones increased phosphorylation of AMP-activated protein kinase (AMPK) and liver kinase B1 (LKB1), upstream regulators of SREBP-1 and PPARα. We confirmed that an AMPK inhibitor, compound C, reversed chalcone-induced changes in SREBP-1 and PPARα expression in the HepG2 cells. Collectively, we found that 4HD, XAG, CAR, and XAG attenuated lipid accumulation through activation of the LKB1/AMPK signaling pathway in HepG2 cells.

  2. Comparative effects of curcumin and its analog on alcohol- and polyunsaturated fatty acid-induced alterations in circulatory lipid profiles.

    Science.gov (United States)

    Rukkumani, Rajagopalan; Aruna, Kode; Varma, Penumathsa Suresh; Rajasekaran, Kallikat Narayanan; Menon, Venugopal P

    2005-01-01

    Excessive alcohol intake induces hyperlipidemia. Studies suggest that natural principles and their analogs are known to possess anti-hyperlipidemic properties. In the present work we tested the effect of curcumin, an active principle of turmeric (Curcuma longa), and a curcumin analog on alcohol- and thermally oxidized polyunsaturated fatty acid (deltaPUFA)- induced hyperlipidemia. Male albino Wistar rats were used for the experimental study. Anti-hyperlipidemic activity of curcumin and curcumin analog was evaluated by analyzing the levels of cholesterol, triglycerides (TGs), phospholipids (PLs), and free fatty acids (FFAs). The results showed that the levels of cholesterol, TGs, PLs, and FFAs were increased significantly in alcohol-, deltaPUFA-, and alcohol + deltaPUFA-treated groups, which were brought down significantly on treatment with either of the curcuminoids. Curcumin analog treatment was found to be more effective than curcumin treatment. From the results obtained, we conclude that both curcumin and its analog effectively protect the system against alcohol- and deltaPUFA-induced hyperlipidemia and are possible candidates for the treatment of hyperlipidemia.

  3. Animal models of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis

    Institute of Scientific and Technical Information of China (English)

    Yoshihisa Takahashi; Yurie Soejima; Toshio Fukusato

    2012-01-01

    Nonalcoholic fatty liver disease (NAFLD) is a condition in which excess fat accumulates in the liver of a patient without a history of alcohol abuse.Nonalcoholic steatohepatitis (NASH),a severe form of NAFLD,can progress to liver cirrhosis and hepatocellular carcinoma.NAFLD is regarded as a hepatic manifestation of metabolic syndrome and incidence has been increasing worldwide in line with the increased prevalence of obesity,type 2 diabetes,and hyperlipemia.Animal models of NAFLD/NASH give crucial information,not only in elucidating pathogenesis of NAFLD/NASH but also in examining therapeutic effects of various agents.An ideal model of NAFLD/NASH should correctly reflect both hepatic histopathology and pathophysiology of human NAFLD/NASH.Animal models of NAFLD/NASH are divided into genetic,dietary,and combination models.In this paper,we review commonly used animal models of NAFLD/NASH referring to their advantages and disadvantages.

  4. Animal models of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis.

    Science.gov (United States)

    Takahashi, Yoshihisa; Soejima, Yurie; Fukusato, Toshio

    2012-05-21

    Nonalcoholic fatty liver disease (NAFLD) is a condition in which excess fat accumulates in the liver of a patient without a history of alcohol abuse. Nonalcoholic steatohepatitis (NASH), a severe form of NAFLD, can progress to liver cirrhosis and hepatocellular carcinoma. NAFLD is regarded as a hepatic manifestation of metabolic syndrome and incidence has been increasing worldwide in line with the increased prevalence of obesity, type 2 diabetes, and hyperlipemia. Animal models of NAFLD/NASH give crucial information, not only in elucidating pathogenesis of NAFLD/NASH but also in examining therapeutic effects of various agents. An ideal model of NAFLD/NASH should correctly reflect both hepatic histopathology and pathophysiology of human NAFLD/NASH. Animal models of NAFLD/NASH are divided into genetic, dietary, and combination models. In this paper, we review commonly used animal models of NAFLD/NASH referring to their advantages and disadvantages.

  5. Animal models of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis

    Science.gov (United States)

    Takahashi, Yoshihisa; Soejima, Yurie; Fukusato, Toshio

    2012-01-01

    Nonalcoholic fatty liver disease (NAFLD) is a condition in which excess fat accumulates in the liver of a patient without a history of alcohol abuse. Nonalcoholic steatohepatitis (NASH), a severe form of NAFLD, can progress to liver cirrhosis and hepatocellular carcinoma. NAFLD is regarded as a hepatic manifestation of metabolic syndrome and incidence has been increasing worldwide in line with the increased prevalence of obesity, type 2 diabetes, and hyperlipemia. Animal models of NAFLD/NASH give crucial information, not only in elucidating pathogenesis of NAFLD/NASH but also in examining therapeutic effects of various agents. An ideal model of NAFLD/NASH should correctly reflect both hepatic histopathology and pathophysiology of human NAFLD/NASH. Animal models of NAFLD/NASH are divided into genetic, dietary, and combination models. In this paper, we review commonly used animal models of NAFLD/NASH referring to their advantages and disadvantages. PMID:22654421

  6. Soluble FGFR4 extracellular domain inhibits FGF19-induced activation of FGFR4 signaling and prevents nonalcoholic fatty liver disease

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Qiang [State Key Laboratory of Stress Cell Biology, School of Life Sciences, Xiamen University, Xiamen (China); The First Affiliated Hospital of Xiamen University, Xiamen (China); Jiang, Yuan; An, Yuan; Zhao, Na; Zhao, Yang [State Key Laboratory of Stress Cell Biology, School of Life Sciences, Xiamen University, Xiamen (China); Yu, Chundong, E-mail: cdyu@xmu.edu.cn [State Key Laboratory of Stress Cell Biology, School of Life Sciences, Xiamen University, Xiamen (China)

    2011-06-17

    Highlights: {yields} Soluble FGFR4 extracellular domain (FGFR4-ECD) was effectively expressed. {yields} FGFR4-ECD inhibited FGF19-induced activation of FGFR4 signaling. {yields} FGFR4-ECD reduced palmitic acid-induced steatosis of HepG2 cells. {yields} FGFR4-ECD reduced tetracycline-induced fatty liver in mice. {yields} FGFR4-ECD partially restored tetracycline-repressed PPAR{alpha} expression. -- Abstract: Fibroblast growth factor receptor 4 (FGFR4) is a transmembrane tyrosine kinase receptor that plays a crucial role in the regulation of hepatic bile acid and lipid metabolism. FGFR4 underlies high-fat diet-induced hepatic steatosis, suggesting that inhibition of FGFR4 activation may be an effective way to prevent or treat nonalcoholic fatty liver disease (NAFLD). To determine whether neutralization of FGFR4 ligands by soluble FGFR4 extracellular domain (FGFR4-ECD) can inhibit the activation of FGFR4, we constructed FGFR4-ECD expression vector and showed that FGFR4-ECD was effectively expressed in cells and secreted into culture medium. FGFR4-ECD inhibited FGF19-induced activation of FGFR4 signaling and reduced steatosis of HepG2 induced by palmitic acid in vitro. Furthermore, in a tetracycline-induced fatty liver model, expression of FGFR4-ECD in mouse liver reduced the accumulation of hepatic lipids and partially restored the expression of peroxisome proliferator-activated receptor {alpha} (PPAR{alpha}), which promotes the mitochondrial fatty acid beta-oxidation but is repressed by tetracycline. Taken together, these results demonstrate that FGFR4-ECD can block FGFR4 signaling and prevent hepatic steatosis, highlighting the potential value of inhibition of FGFR4 signaling as a method for therapeutic intervention against NAFLD.

  7. Nonalcoholic fatty liver disease and polycystic ovary syndrome.

    Science.gov (United States)

    Vassilatou, Evangeline

    2014-07-14

    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.

  8. Orthotopic liver transplantation in non-alcoholic fatty liver disease patients.

    Science.gov (United States)

    Burra, Patrizia; Germani, Giacomo

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) is a frequent etiology of liver disease in Western Countries and non-alcoholic steato-hepatitis (NASH) is becoming a leading indication for liver transplantation in US, with constant increase overtime. Specific co-morbidities correlated to the presence of obesity and associated with metabolic syndrome should always be ruled out in patients affected by NASH-related end-stage liver disease, who are potential candidates for liver transplantation. Patients transplanted for NAFLD present similar outcomes compared with patients transplanted for other indications. With regards to post-transplant outcomes in obese patients, available data are contradictory, with reported increased mortality only in patients with BMI >40. A new multidisciplinary protocol of liver transplantation and sleeve gastrectomy seems to be effective and safe in obese patients who were not able to lose weight before liver transplantation. However prospective studies are needed. The NASH recurrence rate after liver transplantation ranges between 20-40%, but its variability largely depends on the methodology used for the diagnosis (i.e. liver tests, liver histology or imaging technique).

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

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    C.P.M.S. Oliveira

    2006-02-01

    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.

  10. 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.

  11. Exercise and the liver: implications for therapy in fatty liver disorders.

    Science.gov (United States)

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

    2012-02-01

    The increasing recognition that fatty liver plays a direct role in the pathogenesis of cardiovascular and metabolic disease has resulted in significant research enquiry into the efficacy of lifestyle therapy in modulating liver fat. Recently, this has extended to the specific investigation of a possible independent benefit of physical activity/exercise in nonalcoholic fatty liver disease (NAFLD). In this article we review the effect of acute and regular exercise (training) on metabolism, including liver glucose and lipid metabolism, and the available human trials that have compared the benefit of regular exercise versus a nonexercise control on liver fat. The limited human research suggests that exercise can reduce liver fat and that this benefit may be mediated, in part, by a reduction in hepatic lipogenesis. The relative importance of extrahepatic adaptations and acute versus regular exercise in explaining this benefit are discussed. From a clinical perspective, the revelation of a benefit of exercise per se offers a novel approach for liver fat reduction, and highlights the importance of incorporating fitness assessment and prescription in the management of patients with fatty liver disorders. Implementation of exercise therapy in a clinical setting is arguably the biggest challenge because evidence shows that mere provision of information about the benefits of exercise and/or exercise prescription to the patient does not translate to positive outcomes. Rather, the focus should be on implementing strategies to promote behavior change including regular contact and assessment with a health care professional, self-monitoring, and personalization of goals that focus on changing physical activity behavior.

  12. Preoperative detection of colorectal liver metastases in fatty liver: MDCT or MRI?

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    Kulemann, Vanessa, E-mail: vanessa.kulemann@meduniwien.ac.at [Department of Radiology, Medical University of Vienna (Austria); Schima, Wolfgang [KH Goettlicher Heiland, Vienna (Austria); Tamandl, Dietmar; Kaczirek, Klaus; Gruenberger, Thomas [Department of Surgery, Medical University of Vienna (Austria); Wrba, Friedrich [Department of Pathology, Medical University of Vienna (Austria); Weber, Michael; Ba-Ssalamah, Ahmed [Department of Radiology, Medical University of Vienna (Austria)

    2011-08-15

    Objective: To compare the diagnostic value of multidetector computed tomography (MDCT) and magnetic resonance imaging (MRI) in the preoperative detection of colorectal liver metastases in diffuse fatty infiltration of the liver, associated with neoadjuvant chemotherapy. Materials and methods: Twenty preoperative tri-phasic MDCT (4-64-row, Siemens) and dynamic contrast-enhanced MRI (1.5 T or 3.0 T, Siemens) examinations of patients with colorectal cancer and liver metastases in diffuse steatosis were retrospectively evaluated. All patients underwent surgical resection for liver metastases (time interval 1-60 days). The amount of fatty infiltration of the liver was determined histopathologically by semi-quantitative percent-wise estimation and ranged from 25 to 75%. Results: Overall, 51 metastases were found by histopathology of the resected liver segments/lobes. The size of the metastases ranged from 0.4 to 13 cm, with 18 (35%) being up to 1 cm in diameter. In the overall rating, MDCT detected 33/51 lesions (65%), and MRI 45/51 (88%). For lesions up to 1 cm, MDCT detected only 2/18 (11%) and MRI 12/18 (66%). One false positive lesion was detected by MDCT. Statistical analysis showed that MRI is markedly superior to MDCT, with a statistically significant difference (p < .001), particularly for the detection of small lesions ({<=}1 cm; p < .004). There was no significant difference between the two modalities in the detection of lesions > 1 cm. Conclusion: For the detection of colorectal liver metastases after neoadjuvant chemotherapy and consecutive diffuse fatty infiltration of the liver, MRI is superior to MDCT, especially for the detection of small lesions.

  13. Diagnosis of fatty liver. Comparison of ultrasonographic and computed tomographic findings to histological features

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    Saitoh, Shuichi; Nagamine, Takeaki; Takagi, Hitoshi and others

    1988-12-01

    Diagnostic values of various ultrasonographic findings were evaluated from fatty infiltration ratio calculated by liver specimens in 42 patients. The ratio of the CT number of liver to those of spleen were also compared with fatty infiltration ratio in 11 patients. Fatty bandless sign one plus (perirenal bright echo between the liver and the right kidney is masked partially) or more and the fatty score 3 (it is calculated by several ultrasonographic findings) and the less than 0.90 of the ratio of CT number of liver to those of spleen were useful for diagnosis of fatty liver, the sensitivity was 100%, 87.5%, 85.7% and the accuracy was 78.1%, 81.8%, 81.8% respectively. It was considered that these criteria were suitable in screening study of fatty liver.

  14. Correlation between Abdominal Fat Amount and Fatty Liver, using Liver to Kidney Echo Ratio on Ultrasound

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    Park, Yanhg Shin; Lee, Chang Hee; Choi, Kyung Mook; Lee, Jong Mee; Choi, Jae Woong; Kim, Kyeong Ah; Park, Cheol Min [Korea University Guro Hospital, Korea University College of Medicine, Seoul (Korea, Republic of)

    2012-08-15

    It has been generally recognized that fatty liver can often be seen in the obese population. This study was conducted in order to evaluate the association between fatty liver and abdominal fat volume. A total of 105 patients who visited our obesity clinic in the recent three years underwent fat CT scans and abdominal US. Attenuation difference between liver and spleen on CT was considered as a reference standard for the diagnosis of fatty liver. On US, the echogenicity of the liver parenchyma was measured in three different regions of interest (ROI) close to the adjacent right kidney in the same slice, avoiding vessels, bile duct, and calcification. Similar measurements were performed in the right renal cortex. The mean values were calculated automatically on the histogram of the ROI using the PACS program. The hepatorenal echogenicity ratio (HER; mean hepatic echogenicity/ mean renal echogenicity) was then calculated. Abdominal fat volume was measured using a 3 mm slice CT scan at the L4/5 level and was calculated automatically using a workstation. Abdominal fat was classified according to total fat (TF), visceral fat (VF), and subcutaneous fat (SF). We used Pearson's bivariate correlation method for assessment of the correlation between HER and TF, VF, and SF, respectively. Significant correlation was observed between HER and abdominal fat (TF, VF, and SF). HER showed significant correlation with VF and TF (r = 0.491 and 0.402, respectively; p = 0.000). The correlation between HER and SF (r = 0.255, p = 0.009) was less significant than for VF or TF. Fat measurement (HER) by hepatic ultrasound correlated well with the amount of abdominal fat. In particular, the VF was found to show a stronger association with fatty liver than SF.

  15. Essential phospholipids in fatty liver: a scientific update

    Directory of Open Access Journals (Sweden)

    Gundermann KJ

    2016-05-01

    Full Text Available Karl-Josef Gundermann,1 Simon Gundermann,2 Marek Drozdzik,1 VG Mohan Prasad3 1Department of Pharmacology, Pomeranian Medical University, Szczecin, Poland; 2Department of Radiology, Hospital Hohenlind, Cologne, Germany; 3VGM Hospital Institute of Gastroenterology, Coimbatore, India Aim: Although essential phospholipids (EPL from soybean are often used in membrane-associated disorders and diseases, their high quality of purification and effects on prevalent liver diseases, especially on fatty liver diseases (FLDs of different origin, are still widely unknown and a matter of continuous active research. The aim of this article is to review, discuss, and summarize the available results of EPL in the treatment of FLD. Methods: Database research was carried out on Medline, Embase, Cochrane Library, country-specific journals, and follow-up literature citations for relevant hepatogastroenterological articles published between 1988 and 2014. We searched for and reviewed only those papers that indicated minimum extraction amount of 72% (3-sn-phosphatidylcholine from soybean as being necessary to treat patients with a considerable amount of 1,2-dilinoleoylphosphatidylcholine as a key component in EPL. Results: EPL has a well-established mode of action, therapeutic effectiveness, and lack of toxicity, which ensures clinically relevant efficacy-to-safety ratio. It influences membrane-dependent cellular functions and shows anti-inflammatory, antioxidant, antifibrogenic, antiapoptotic, membrane-protective, and lipid-regulating effects. Due to its positive effects on membrane composition and functions, it accelerates the improvement or normalization of subjective symptoms; pathological, clinical, and biochemical findings; hepatic imaging; and liver histology. It is justified to administer EPL together with other therapeutic measurements in the liver. Conclusion: Pharmacological and clinical results confirm the efficacy of EPL in the treatment of FLD. Keywords

  16. Acid-induced structural modifications of unsaturated Fatty acids and phenolic olive oil constituents by nitrite ions: a chemical assessment.

    Science.gov (United States)

    Napolitano, Alessandra; Panzella, Lucia; Savarese, Maria; Sacchi, Raffaele; Giudicianni, Italo; Paolillo, Livio; d'Ischia, Marco

    2004-10-01

    The structural modifications of the unsaturated fatty acid components of triglycerides in extra virgin olive oil (EVOO) following exposure to nitrite ions in acidic media were determined by two-dimensional (2D) NMR spectroscopy, aided by (15)N labeling and GC analysis, allowing investigation of the matrix without fractionation steps. In the presence of excess nitrite ions in a 1% sulfuric acid/oil biphasic system, extensive double bond isomerization of the oleic/linoleic acid components of triglycerides was observed associated with nitration/oxidation processes. Structurally modified species were identified as E/Z-nitroalkene, 1,2-nitrohydroxy, and 3-nitro-1-alkene(1,5-diene) derivatives based on (1)H, (13)C, and (15)N 2D NMR analysis in comparison with model compounds. Minor constituents of EVOO, including phenolic compounds and tocopherols, were also substantially modified by nitrite-derived nitrating species, even under milder reaction conditions relevant to those occurring in the gastric compartments. Novel nitrated derivatives of tyrosol, hydroxytyrosol, and oleuropein (6-8) were identified by LC/MS analysis of the polar fraction of EVOO and by comparison with synthetic samples. Overall, these results provide the first systematic description at the chemical level of the consequences of exposing EVOO to nitrite ions at acidic pH and offer an improved basis for further investigations in the field of toxic nitrosation/nitration reactions and dietary antinitrosating agents.

  17. Nonalcoholic Fatty Liver Disease in Patients Investigated for Elevated Liver Enzymes

    Directory of Open Access Journals (Sweden)

    Krikor Kichian

    2003-01-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD is a common diagnosis among patients referred to gastroenterology and hepatology clinics for the evaluation of elevated liver enzymes. The diagnosis of NAFLD is supported by blood work to exclude other liver diseases, and by ultrasound evidence of fat in the liver in patients without a significant history of alcohol intake. The gold standard, however, is a liver biopsy to show the typical histological features of NAFLD, which are almost identical to those of alcohol-induced liver damage and can range from mild steatosis to cirrhosis. A variety of retrospective series have linked NAFLD to obesity, diabetes, hyperlipidemia, total parenteral nutrition, jejunoileal bypass surgery and certain medications. A subset of patients with NAFLD that had an initial presentation of elevated liver enzymes was studied. Two hundred and two patients were reviewed, of whom 49 met the inclusion criteria including a liver biopsy. Patients were excluded if insufficient data were available, if the patients had a significant history of ethanol intake or if they had other coexisting liver disease. These patients were seen between 1996 and 2000 in gastroenterology and hepatology clinics in two community hospitals and one regional liver transplant centre in Edmonton, Alberta. NAFLD was associated with a spectrum of changes in the liver ranging from mild steatosis to more significant steatosis with inflammation and fibrosis. Cases of NAFLD with steatosis and mixed inflammatory infiltration but lacking ballooning degeneration or fibrosis were prevalent in young (20 to 40 years of age patients with no other significant medical history except for obesity. NAFLD with biopsies showing significant fibrosis and ballooning cell degeneration was associated with obesity, diabetes and older age. It was concluded that, in this predominantly outpatient setting, age over 40 years and diabetes at any age are risk factors for both nonalcoholic

  18. Pharmacologic therapy for nonalcoholic fatty liver disease in adults.

    Science.gov (United States)

    Malinowski, Scott S; Byrd, Jennifer S; Bell, Allison M; Wofford, Marion R; Riche, Daniel M

    2013-02-01

    Nonalcoholic fatty liver disease (NAFLD) is characterized by the accumulation of triglycerides in hepatocytes in the absence of excessive alcohol intake, ranging in severity from simple steatosis to nonalcoholic steatohepatitis (NASH). Nonalcoholic steatohepatitis can ultimately progress to cirrhosis and hepatocellular carcinoma. NAFLD is associated with cardiometabolic risk factors and is the most common chronic liver disease among adults in the Western Hemisphere. Although simple steatosis is generally considered a self-limiting disease, evidence suggests an increased risk of cardiovascular disease, and, less conclusively, mortality, among individuals with NAFLD and/or NASH. The current standard of care for the treatment of patients with NAFLD focuses on lifestyle interventions, particularly diet and exercise. There is a lack of consensus regarding the most effective and appropriate pharmacologic therapy. A PubMed search was conducted using the medical subject heading terms "fatty liver" and "steatohepatitis." This review focuses on the current pharmacologic options available for treating adults with NAFLD and/or NASH. Continued investigation of drugs or combinations that improve NAFLD progression is crucial. Clinicians, particularly pharmacists, must take an active role in identification and appropriate selection of pharmacotherapy for NAFLD.

  19. Multidisciplinary Pharmacotherapeutic Options for Nonalcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    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.

  20. Predicting incident fatty liver using simple cardio-metabolic risk factors at baseline

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    Sung Ki-Chul

    2012-07-01

    Full Text Available Abstract Background Non alcoholic fatty liver disease (NAFLD is associated with increased risk of type 2 diabetes and chronic liver disease but identifying patients who have NAFLD without resorting to expensive imaging tests is challenging. In order to help identify people for imaging investigation of the liver who are at high risk of NAFLD, our aim was to: a identify easily measured risk factors at baseline that were independently associated with incident fatty liver at follow up, and then b to test the diagnostic performance of thresholds of these factors at baseline, to predict or to exclude incident fatty liver at follow up. Methods 2589 people with absence of fatty liver on ultrasound examination at baseline were re-examined after a mean of 4.4 years in a Korean occupational cohort study. Multi-variable logistic regression analyses were used to identify baseline factors that were independently associated with incident fatty liver at follow up. The diagnostic performance of thresholds of these baseline factors to identify people with incident fatty liver at follow-up was assessed using receiver operating characteristic (ROC curves. Results 430 incident cases of fatty liver were identified. Several factors were independently associated with incident fatty liver: increased triglyceride (per mmol/l increase OR 1.378 [95%CIs 1.179, 1.611], p 9/L increase OR 1.004 [1.001, 1.006], p = 0.001; were each independently associated with incident fatty liver. Binary thresholds of the five factors were applied and the area under the ROC curve for incident fatty liver was 0.75 (95%CI 0.72–0.78 for the combination of all five factors above these thresholds. Conclusion Simple risk factors that overlap considerably with risk factors for type 2 diabetes allow identification of people at high risk of incident fatty liver at who use of hepatic imaging could be targeted.

  1. Clinical Significance of the Degree of Fatty Liver Diagnosed by Ultrasonography

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    Kim, Yong Kyun [Dept. of Diagnostic Radiology, Koeralife Daejeon Healthcare Center, Daejeon (Korea, Republic of)

    2008-06-15

    Fatty liver is one of the most commonly found disease by abdominal ultrasonography. The status of fatty liver is classified into mild, moderate and severe degrees. The study was conducted to investigate the clinical significance of fatty liver using ultrasonography. Test set consisted of 2,185 patients who visited D healthcare center in Daejeon to receive an abdominal ultrasonic test from January to December 2007. Out of the 2185 patients, 524 patients was diagnosed as fatty liver (290 male and 234 female patients). They were divided into three groups, group I for mild degree. II for moderate degree, and III for severe degree, depending on the echo of liver parenchyma, the sound attenuation, and the visibility of intrahepatic blood vessels and diaphragm. Then the correlation of obesity indices, liver function tests and metabolic syndrome was analyzed for males and females separately. As for the degree of fatty liver, 350 cases (66.8%) were classified as group I, 153 cases (29.2%) as group II, and 21 cases (4.1%) as group III. In addition, severe degree of fatty liver was more frequently found in males than in females. The mean ages of three groups for males were 46.1, 44.5, and 39.1, and those for females were 48.8, 50.2, 52.4, respectively. Males with lower mean ages have severely of fatty liver for both males and females. The results in this study show that the classification into three degrees of fatty liver in ultrasonography practice is helpful to treat and observe the progress of fatty liver. In addition, careful examination is required to measure the severity of fatty liver as well as detection of it. A standardized method to classify the degree of fatty liver is also needed for more objective measurement.

  2. End-stage nonalcoholic fatty liver disease: evaluation of pathomorphologic features and relationship to cryptogenic cirrhosis from study of explant livers in a living donor liver transplant program.

    Science.gov (United States)

    Nayak, Nabeen C; Vasdev, Nandini; Saigal, Sanjiv; Soin, Arvinder S

    2010-03-01

    In a proportion of liver cirrhosis, the etiology continues to remain elusive. It is uncertain whether and to what extent cirrhosis evolving from nonalcoholic fatty liver disease contributes to this group of cryptogenic cirrhosis because the clinicopathologic features of nonalcoholic fatty liver disease cirrhosis are largely unknown. We explored these facets by examining the explant livers and clinical data in living donor liver transplant recipients. Among 103 adult liver transplant recipients with different types of chronic liver disease, 30 had a pre-liver transplant diagnosis of cryptogenic cirrhosis. A final categorization of the native liver disease was attempted in these cases on the basis of detail pathomorphological findings in adequately sampled explant liver correlated with careful review of pre-liver transplant clinical data. Of the 30 cryptogenic cirrhosis cases, 19 (63.3%) finally labeled as nonalcoholic fatty liver disease cirrhosis showed histologic features in several respects different from those reported for the early and established phases of nonalcoholic fatty liver disease. Steatosis was infrequent and focal or even absent, whereas variable grades of Mallory hyaline and inflammation were consistently present. Ductular proliferation and hydropic change of hepatocytes were also frequent. Only 9 (47%) of the 19 cases had nonalcoholic fatty liver disease associated risk factors like diabetes and obesity. It was concluded that appreciation of quantitative and qualitative differences in hepatic morphology between the cirrhotic and the early/established stage of nonalcoholic fatty liver disease will help in making a correct diagnosis of nonalcoholic fatty liver disease cirrhosis in the proper clinical setting. When appropriate criteria are used, nonalcoholic fatty liver disease appears to account for close to two thirds of cases currently labeled as cryptogenic cirrhosis.

  3. Should nonalcoholic fatty liver disease be regarded as a hepatic illness only?

    Institute of Scientific and Technical Information of China (English)

    Giovanni Tarantino

    2007-01-01

    The highly increasing prevalence of obesity and type 2 diabetes mellitus in the general population makes nonalcoholic fatty liver disease the most common diagnosis in every-day practices. Lifestyle changes (mainly exercise withdrawal and weight gain) have probably heightened the prevalence of nonalcoholic fatty liver disease. Mortality in patients with Nonalcoholic Fatty Liver Disease is significantly higher when compared with that of the same age-gender general population.Hepatologists claim to bear a new burden, being Nonalcoholic Fatty Liver Disease strongly linked to systemic diseases.

  4. Relationship between genetic polymorphism of cytochrome P450IIE1 and fatty liver

    Institute of Scientific and Technical Information of China (English)

    Yun-Feng Piao; Jing-Tao Li; Yang Shi

    2003-01-01

    AIM: To study the correlation between genetic polymorphism of cytochrome P450IIE1 (CYPIIE1) and fatty liver.METHODS: Peripheral blood mononuclear cells were collected in 56 patients with fatty liver, 26 patients without fatty liver and 20 normal controls. Then PCR-RFLP was used to analyze genetic polymorphism of CYPIIE1 in monocytes on the region of Pst I and Rsa I.RESULTS: The frequency of homozygotic C1 gene in patients with alcoholic fatty liver (28.6 %), obese fatty liver (38.5 %), or diabetic fatty liver (33.3 %) was significantly lower than that of the corresponding patients without fatty liver (100 %, 100 % and 80 % respectively), while the frequency of C2 genes, including C1/C2 and C2/C2, was significantly higher (71.4 %/0 %, 61.5 %/0 %, and 66.7 %/20 %) (P0.05).CONCLUSION: The genetic polymorphism of CYPIIE1 on the position of Pst I and Rsa I is related to the susceptibility of fatty liver. Besides, C2 gene may play a key role in the pathogenesis of fatty liver.

  5. Involvement of dynamin-related protein 1 in free fatty acid-induced INS-1-derived cell apoptosis.

    Science.gov (United States)

    Peng, Liang; Men, Xiuli; Zhang, Wenjian; Wang, Haiyan; Xu, Shiqing; Fang, Qing; Liu, Honglin; Yang, Wenying; Lou, Jinning

    2012-01-01

    Elevated extracellular free fatty acids (FFAs) can induce pancreatic beta cell apoptosis, thereby contributing to the pathogenesis of type 2 diabetes mellitus (T2D). Mitochondrial dysfunction has been implicated in FFA-induced beta cell apoptosis. However, molecular mechanisms linking mitochondrial dysfunction and FFA-induced beta cell apoptosis are not clear. Dynamin-related protein 1 (DRP-1) is a mitochondrial fission modulator. In this study, we investigated its role in FFA-induced INS-1 beta cell apoptosis. DRP-1 protein was promptly induced in INS-1 cells and rat islets after stimulation by FFAs, and this DRP-1 upregulation was accompanied by increased INS-1 cell apoptosis. Induction of DRP-1 expression significantly promoted FFA-induced apoptosis in DRP-1 WT (DRP-1 wild type) inducible INS-1-derived cell line, but not in DRP-1K38A (a dominant negative mutant of DRP-1) inducible INS-1-derived cell line. To validate these in vitro results, we transplanted DRP-1 WT or DRP-1 K38A cells into renal capsules of streptozotocin (STZ)-treated diabetic mice to study the apoptosis in xenografts. Consistent with the in vitro results, the over-expression of DRP-1 led to aggravated INS-1-derived cell apoptosis triggered by FFAs. In contrast, dominant-negative suppression of DRP-1 function as represented by DRP-1 K38A significantly prevented FFA-induced apoptosis in xenografts. It was further demonstrated that mitochondrial membrane potential decreased, while cytochrome c release, caspase-3 activation, and generation of reactive oxygen species (ROS) were enhanced by the induction of DRP-1WT, but prevented by DRP-1 K38A in INS-1-derived cells under FFA stimulation. These results indicated that DRP-1 mediates FFA-induced INS-1-derived cell apoptosis, suggesting that suppression of DRP-1 is a potentially useful therapeutic strategy for protecting against beta cell loss that leads to type 2 diabetes.

  6. Sonographic Findings of Cavernous Hemangioma in Fatty Liver

    Energy Technology Data Exchange (ETDEWEB)

    Hahm, Jin Kyeung; Kim, Ki Whang; Yoon, Sang Wook; Kim, Tae Hoon; Lee, Jong Tae; Yoo, Hyung Sik; Kim, Myung Jin [Yonsei University College of Medicine, Seoul (Korea, Republic of); Ji, Hoon [Aju Univeristy, College of Medicine, Suwon (Korea, Republic of)

    1995-06-15

    Typical cavernous hemangioma presents no diagnostic difficulty at sonography. However, in cases of atypical hemangioma, further evaluation is needed to differentiate it from malignancy. On the other hand, thcechogenicity of the lesion may be iso echo or hypoecho when it occurs in association with fatty liver. We analyzed the sonographic features of hemangioma in fatty liver. We reviewed the sonograms of 22 lesions from 19 patients. We divided the lesions into two groups; the lesion measuring less than 3cm in diameter (group I) and the lesions measuring same or greater than 3cm (group II). The lesions of each group were analyzed in terms of location, shape, distinction of margin, internal echogenicity, posterior enhancement, lateral shadowing, and peritumoral hypoechoic halo. The lesions were located in subcapsular or perivascular areain 86%. They strowed round or lobulated shape with well defined margin in 82%. Internal echo of the lesions was hypoechoic in 82% and homogeneous in 64%. Posterior enhancement was seen in 77%. The posterior wall of the lesion was distinct in 68%. There was no statistical difference in incidence of each finding described above between the two groups except the internal echogenicity(p<0.05). All of the four hyperechoic lesions measured greater than 3cmin diameter, and three of them showed uneven thickness of echogenic rind. Definitive diagnosis of hemangioma could be obtained in 82%. In remaining 18% of hemangioma, the lesions showed peripheral hypoechoic halo and lateral shadowing that made the diagnosis of hemangioma difficult. However, the possibility of hemangioma could be suggested because they showed haemangiomas internal eye-catching and posterior enhancement. Hepatic cavernous hemangioma presents with variable eye-catching as compared to the surrounding tissue when it is associated with fatty liver disease, Thus, in differentiating hemangiomas from other localized hepatic mass, other characteristics such as homogeneity of the

  7. CEUS and Fibroscan in non-alcoholic fatty liver disease and non-alcoholic steatohepatitis

    OpenAIRE

    Cocciolillo, Sila; Parruti, Giustino; Marzio, Leonardo

    2014-01-01

    AIM: To determine intra-hepatic blood flow and liver stiffness in patients with non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) using contrast-enhanced ultrasound and fibroscan.

  8. 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.

  9. Possibilities for preventing fatty liver in cows during peripartal period

    Directory of Open Access Journals (Sweden)

    Šamanc Horea

    2008-01-01

    Full Text Available The objective of these investigations was to examine possibilities for preventing fatty liver in cows during the peripartal period using the preparation HEPARENOL which includes methionine, lysine and choline in its composition. Investigations were performed on cattle of the Holstein breed whose average production during their last lactation was 8120 liters. The cows included in the experiment were divided into three groups of 10 cows each. Cows of the first group were administered the preparation HEPARENOL perorally 5-7 days before partus in daily doses of 50 ml per animal, and then daily during the first seven days after parturition in daily doses of 100 ml per animal. The second group of cows were administered the preparation in the same way as the first group, but they also received vitamin C injected deep i.m. in doses of 1000 mg per animal per day. The third group of cows were not exposed to any treatment and served as the control group. The body condition of the cows was marked according to the system Elanco Animal Health Bulletin Al 8478. Blood samples were taken by puncture of the jugular vein before the beginning of treatment, and on the third and 12th days after partus. The glucose concentration was determined in the blood samples. On the 12th day after partus, liver tissue samples were taken by biopsy for pathohistological examinations. Since the cows were fed in the same way and were in the same phase of the production-reproduction cycle, the average score of the body condition before treatment was approximately the same. However, on the 3rd day after partus, cows of the second experimental group showed average values that were significantly lower in comparison with the other two groups of cows. It is very interesting that a significantly lower value of glycemia (x=1.93±0.34 mmol/l was established in the same group of cows at this time. In cows of the first experimental and the control group, glycemia was approximately the same

  10. [Research advances in pediatric nonalcoholic fatty liver disease].

    Science.gov (United States)

    Dai, Dong-Ling

    2015-01-01

    In recent years, nonalcoholic fatty liver disease (NAFLD) has increased because of the growing prevalence of obesity and overweight in the pediatric population. It has become the most common form of chronic liver diseases in children and the related research on NAFLD is expanded. The "two-hit" and "multiple hit" hypothesis have been widely accepted, and some research has shown that genetic, diet structure and environmental factors appear to play a crucial role in the development of pediatric NAFLD. Though it is expected by researchers, there is not an available satisfactory noninvasive marker for the diagnosis of this disease. Fortunately, some new non-invasive prediction scores for pediatric NAFLD have been developed. There is currently no established special therapy, and lifestyle intervention should be adequate for most cases of NAFLD in children. This article reviews the advances in the current knowledge and ideas concerning pediatric NAFLD, and discusses the diagnosis, perspective therapies and scoring methods for this disease.

  11. 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.

  12. [Pediatric nonalcoholic fatty liver disease/nonalcoholic steatohepatitis].

    Science.gov (United States)

    Takahashi, Yoshihisa; Fukusato, Toshio; Inui, Ayano; Fujisawa, Tomoo

    2012-10-01

    Nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) is a hepatic disease associated with metabolic syndrome. In recent years, pediatric NAFLD has increased in line with the increased prevalence of pediatric obesity. The estimated prevalence of pediatric NAFLD is 2.6-9.6%. With regard to the pathogenesis of NAFLD/ NASH, the "two-hit" or "multiple-hit" hypothesis is widely accepted, and many genetic and environmental factors are associated with the development of NAFLD/NASH. Liver biopsy is regarded as the gold standard for the diagnosis of NAFLD/NASH. Pediatric NAFLD has different histopathological characteristics from those of adult NAFLD. Although pharmacotherapy has been studied in clinical trials, lifestyle modification by diet and exercise remains the mainstay of treatment for NAFLD/NASH.

  13. Statins in nonalcoholic fatty liver disease and steatohepatitis: updated review.

    Science.gov (United States)

    Nseir, William; Mahamid, Mahmud

    2013-03-01

    Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease that refers to the presence of hepatic steatosis without significant intake of alcohol. NAFLD is an asymptomatic disease that can progress to nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma. The most common cause of mortality in patients with NAFLD or NASH is cardiovascular disease (CVD). Currently, the treatment of NAFLD focuses on gradual weight loss and life style modifications. However, multifactorial treatment of NAFLD or NASH risk factors may be needed to reduce the likelihood of these patients developing CVD. This review discusses the mechanisms that link hyperlipidemia and NAFLD. In addition, the review focuses on the safety and efficacy of statins in patients with NAFLD or NASH, and their effect on the extent of hepatic steatosis and fibrosis based on human studies.

  14. Glycosyltransferases and non-alcoholic fatty liver disease.

    Science.gov (United States)

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

    2016-02-28

    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.

  15. Genetics of Nonalcoholic Fatty Liver Disease: An Overview

    Institute of Scientific and Technical Information of China (English)

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

    2013-01-01

    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.

  16. Noninvasive diagnosis of pediatric nonalcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    Hye Ran Yang

    2013-02-01

    Full Text Available Because nonalcoholic steatohepatitis can progress towards cirrhosis even in children, early detection of hepatic fibrosis and accurate diagnosis of nonalcoholic fatty liver disease (NAFLD are important. Although liver biopsy is regarded as the gold standard of diagnosis, its clinical application is somewhat limited in children due to its invasiveness. Noninvasive diagnostic methods, including imaging studies, biomarkers of inflammation, oxidative stress, hepatic apoptosis, hepatic fibrosis, and noninvasive hepatic fibrosis scores have recently been developed for diagnosing the spectrum of NAFLD, particularly the severity of hepatic fibrosis. Although data and validation are still lacking for these noninvasive modalities in the pediatric population, these methods may be applicable for pediatric NAFLD. Therefore, noninvasive imaging studies, biomarkers, and hepatic fibrosis scoring systems may be useful in the detection of hepatic steatosis and the prediction of hepatic fibrosis, even in children with NAFLD.

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

    Directory of Open Access Journals (Sweden)

    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.

  18. Maternal ethanol consumption during pregnancy enhances bile acid-induced oxidative stress and apoptosis in fetal rat liver.

    Science.gov (United States)

    Perez, Maria J; Velasco, Elena; Monte, Maria J; Gonzalez-Buitrago, Jose M; Marin, Jose J G

    2006-08-15

    Ethanol is able to cross the placenta, which may cause teratogenicity. Here we investigated whether ethanol consumption during pregnancy (ECDP), even at doses unable to cause malformation, might increase the susceptibility of fetal rat liver to oxidative insults. Since cholestasis is a common condition in alcoholic liver disease and pregnancy, exposure to glycochenodeoxycholic acid (GCDCA) has been used here as the oxidative insult. The mothers received drinking water without or with ethanol from 4 weeks before mating until term, when placenta, maternal liver, and fetal liver were used. Ethanol induced a decreased GSH/GSSG ratio in these organs, together with enhanced gamma-glutamylcysteine synthetase and glutathione reductase activities in both placenta and fetal liver. Lipid peroxidation in placenta and fetal liver was enhanced by ethanol, although it had no effect on caspase-3 activity. Although the basal production of reactive oxygen species (ROS) was higher by fetal (FHs) than by maternal (AHs) hepatocytes in short-term cultures, the production of ROS in response to the presence of varying GCDCA concentrations was higher in AHs and was further increased by ECDP, which was associated to a more marked impairment in mitochondrial function. Moreover, GCDCA-induced apoptosis was increased by ECDP, as revealed by enhanced Bax-alpha/Bcl-2 ratio (both in AHs and FHs) and the activity of caspase-8 (only in AHs) and caspase-3. In sum, our results indicate that although AHs are more prone than FHs to producing ROS, at doses unable to cause maternal liver damage ethanol consumption causes oxidative stress and apoptosis in fetal liver.

  19. Correlation of hepatic {sup 18}F-fluorodeoxyglucose uptake with fatty liver

    Energy Technology Data Exchange (ETDEWEB)

    An, Young Sil; Yoon, Joon Kee; Hong, Seon Pyo; Joh, Chul Woo; Yoon, Seok Nam [Ajou University School of Medicine, Suwon (Korea, Republic of)

    2006-10-15

    Liver demonstrates heterogeneous FDG uptake and sometimes it shows abnormally increased uptake even though there is no malignant tissue. However, there was no previous study to correlate these various pattern of hepatic FDG uptake with benign liver disease. Therefore, we evaluated the significance of hepatic FDG uptake associated with various clinical factors including fatty liver, liver function tests and lipid profiles. We reviewed a total of 188 patients (male/female: 120/68, mean age: 50 {+-} 9) who underwent PET/CT for screening of malignancy. Patients with DM, impaired glucose tolerance, previous severe hepatic disease or long-term medication history were excluded. The FDG uptake in liver was analyzed semi-quantitatively using ROI on transaxial images (segment 8) and we compared mean standardized uptake value (SUV) between fatty liver and non-fatty liver group. We also evaluated the correlation between hepatic FDG uptake and various clinical factors including serum liver function test (ALT, AST), {gamma} -GT, total cholesterol and triglyceride concentration. The effect of alcoholic history and body mass index on hepatic FDG uptake was analyzed within the fatty liver patients. The hepatic FDG uptake of fatty liver group was significantly higher than that of non-fatty liver group. Serum total cholesterol and triglyceride concentration showed significant correlation with hepatic FDG uptake. However, there was no significant correlation between other factors (ALT, AST, and {gamma} -GT) and FDG uptake. Also there was no difference of mean SUV between normal and abnormal groups on the basis of alcoholic history and body mass index within fatty liver patients. Fatty liver and high serum triglyceride concentration were the independent factors affecting hepatic FDG uptake according to multivariate analysis. In conclusion, hepatic FDG uptake was strongly correlated with fatty liver and serum triglyceride concentration.

  20. Tissue distribution comparison between healthy and fatty liver rats after oral administration of hawthorn leaf extract.

    Science.gov (United States)

    Yin, Jingjing; Qu, Jianguo; Zhang, Wenjie; Lu, Dongrui; Gao, Yucong; Ying, Xixiang; Kang, Tingguo

    2014-05-01

    Hawthorn leaves, a well-known traditional Chinese medicine, have been widely used for treating cardiovascular and fatty liver diseases. The present study aimed to investigate the therapeutic basis treating fatty liver disease by comparing the tissue distribution of six compounds of hawthorn leaf extract (HLE) in fatty liver rats and healthy rats after oral administration at first day, half month and one month, separately. Therefore, a sensitive and specific HPLC method with internal standard was developed and validated to determine chlorogenic acid, vitexin-4''-O-glucoside, vitexin-2''-O-rhamnoside, vitexin, rutin and hyperoside in the tissues including heart, liver, spleen, kidney, stomach and intestine. The results indicated that the six compounds in HLE presented some bioactivity in treating rat fatty liver as the concentrations of the six compounds varied significantly in inter- and intragroup comparisons (healthy and/or fatty liver group).

  1. Assessment of Liver Viscoelasticity for the Diagnosis of Early Stage Fatty Liver Disease Using Transient Elastography

    Science.gov (United States)

    Remenieras, Jean-Pierre; Dejobert, Maelle; Bastard, Cécile; Miette, Véronique; Perarnau, Jean-Marc; Patat, Frédéric

    Nonalcoholic fatty liver disease (NAFLD) is characterized by accumulation of fat within the Liver. The main objective of this work is (1) to evaluate the feasibility of measuring in vivo in the liver the shear wave phase velocity dispersion cs(ω) between 20 Hz and 90 Hz using vibration-controlled transient elastography (VCTE); (2) to estimate through the rheological Kelvin-Voigt model the shear elastic μ and shear viscosity η modulus; (3) to correlate the evolution of these viscoelastic parameters on two patients at Tours Hospital with the hepatic fat percentage measured with T1-weighted gradient-echo in-and out-phase MRI sequence. For the first volunteer who has 2% of fat in the liver, we obtained μ = 1233 ± 133 Pa and η = 0.5 ± 0.4 Pa.s. For the patient with 22% of fat, we measure μ = 964 ± 91 Pa and η = 1.77 ± 0.3 Pa.s. In conclusion, this novel method showed to be sensitive in characterizing the visco-elastic properties of fatty liver.

  2. Biological characterization of liver fatty acid binding gene from miniature pig liver cDNA library.

    Science.gov (United States)

    Gao, Y H; Wang, K F; Zhang, S; Fan, Y N; Guan, W J; Ma, Y H

    2015-01-01

    Liver fatty acid binding proteins (L-FABP) are a family of small, highly conserved, cytoplasmic proteins that bind to long-chain fatty acids and other hydrophobic ligands. In this study, a full-length enriched cDNA library was successfully constructed from Wuzhishan miniature pig, and then the L-FABP gene was cloned from this cDNA library and an expression vector (pEGFP-N3-L-FABP) was constructed in vitro. This vector was transfected into hepatocytes to test its function. The results of western blotting analysis demonstrated that the L-FABP gene from our full-length enriched cDNA library regulated downstream genes, including the peroxisome proliferator-activated receptor family in hepatocytes. This study provides a theoretical basis and experimental evidence for the application of L-FABP for the treatment of liver injury.

  3. Fatty acid biosynthesis VII. Substrate control of chain-length of products synthesised by rat liver fatty acid synthetase

    DEFF Research Database (Denmark)

    Hansen, Heinz Johs. Max; Carey, E.M.; Dils, R.

    1970-01-01

    - 1. Gas-liquid and paper chromatography have been used to determine the chain-lengths of fatty acids synthesised by purified rat liver fatty acid synthetase from [1-14C]acetyl-CoA, [1,3-14C2]malonyl-CoA and from [1-14C]acetyl-CoA plus partially purified rat liver acetyl-CoA carboxylase. - 2...

  4. Transcriptional networks implicated in human nonalcoholic fatty liver disease.

    Science.gov (United States)

    Ye, Hua; Liu, Wei

    2015-10-01

    The transcriptome of nonalcoholic fatty liver disease (NAFLD) was investigated in several studies. However, the implications of transcriptional networks in progressive NAFLD are not clear and mechanisms inducing transition from nonalcoholic simple fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH) are still elusive. The aims of this study were to (1) construct networks for progressive NAFLD, (2) identify hub genes and functional modules in these networks and (3) infer potential linkages among hub genes, transcription factors and microRNAs (miRNA) for NAFLD progression. A systems biology approach by combining differential expression analysis and weighted gene co-expression network analysis (WGCNA) was utilized to dissect transcriptional profiles in 19 normal, 10 NAFL and 16 NASH patients. Based on this framework, 3 modules related to chromosome organization, proteasomal ubiquitin-dependent protein degradation and immune response were identified in NASH network. Furthermore, 9 modules of co-expressed genes associated with NAFL/NASH transition were found. Further characterization of these modules defined 13 highly connected hub genes in NAFLD progression network. Interestingly, 11 significantly changed miRNAs were predicted to target 10 of the 13 hub genes. Characterization of modules and hub genes that may be regulated by miRNAs could facilitate the identification of candidate genes and pathways responsible for NAFL/NASH transition and lead to a better understanding of NAFLD pathogenesis. The identified modules and hub genes may point to potential targets for therapeutic interventions.

  5. Epidemiology and risk factors of nonalcoholic fatty liver disease (NAFLD).

    Science.gov (United States)

    Duseja, Ajay; Chalasani, Naga

    2013-12-01

    The nonalcoholic fatty liver disease (NAFLD) is defined as the presence of hepatic steatosis, determined by either imaging or histology, in the absence of secondary causes of hepatic fat accumulation. Nonalcoholic fatty liver is defined as the presence of hepatic steatosis with no evidence of hepatocellular injury in the form of ballooning of the hepatocytes or fibrosis. NASH is defined as the presence of hepatic steatosis and inflammation with hepatocyte injury (ballooning) with or without fibrosis. Although initial epidemiological studies have focused on its prevalence in the Western countries, it is becoming increasingly clear that NAFLD is highly prevalent in the Asia Pacific region, and there may be important distinctions in its phenotype between Asia Pacific and Western countries. Of particular interest are "lean NAFLD" and the "urban-rural divide," which will be discussed in this review article. Obesity, dyslipidemia, type 2 diabetes and metabolic syndrome are established risk factors for developing NAFLD. Many other risk factors (e.g., hypothyroidism, polycystic ovary syndrome, obstructive sleep apnea, hypopituitarism and hypogonadism) for NAFLD have been described in the Western countries, but these associations are yet to be investigated adequately in the Asia Pacific region.

  6. 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.

  7. Saturated fatty acids induce post-transcriptional regulation of HAMP mRNA via AU-rich element-binding protein, human antigen R (HuR).

    Science.gov (United States)

    Lu, Sizhao; Mott, Justin L; Harrison-Findik, Duygu Dee

    2015-10-02

    Iron is implicated in fatty liver disease pathogenesis. The human hepcidin gene, HAMP, is the master switch of iron metabolism. The aim of this study is to investigate the regulation of HAMP expression by fatty acids in HepG2 cells. For these studies, both saturated fatty acids (palmitic acid (PA) and stearic acid (SA)) and unsaturated fatty acid (oleic acid (OA)) were used. PA and, to a lesser extent, SA, but not OA, up-regulated HAMP mRNA levels, as determined by real-time PCR. To understand whether PA regulates HAMP mRNA at the transcriptional or post-transcriptional level, the transcription inhibitor actinomycin D was employed. PA-mediated induction of HAMP mRNA expression was not blocked by actinomycin D. Furthermore, PA activated HAMP 3'-UTR, but not promoter, activity, as shown by reporter assays. HAMP 3'-UTR harbors a single AU-rich element (ARE). Mutation of this ARE abolished the effect of PA, suggesting the involvement of ARE-binding proteins. The ARE-binding protein human antigen R (HuR) stabilizes mRNA through direct interaction with AREs on 3'-UTR. HuR is regulated by phosphorylation-mediated nucleo-cytoplasmic shuttling. PA activated this process. The binding of HuR to HAMP mRNA was also induced by PA in HepG2 cells. Silencing of HuR by siRNA abolished PA-mediated up-regulation of HAMP mRNA levels. PKC is known to phosphorylate HuR. Staurosporine, a broad-spectrum PKC inhibitor, inhibited both PA-mediated translocation of HuR and induction of HAMP expression. Similarly, rottlerin, a novel class PKC inhibitor, abrogated PA-mediated up-regulation of HAMP expression. In conclusion, lipids mediate post-transcriptional regulation of HAMP throughPKC- and HuR-dependent mechanisms.

  8. Impact of variations in fatty liver on sonographic detection of focal hepatic lesions originally identified by CT

    Directory of Open Access Journals (Sweden)

    Size Wu

    2016-01-01

    Full Text Available Purpose: The aim of this study was to investigate the influence of variations in fatty liver on the ultrasonographic detection of focal liver lesions. Methods: A total of 229 patients with varying degrees of fatty liver and focal liver lesions and 200 patients with focal liver lesions but no fatty liver were randomly selected for inclusion in groups I and II, respectively. Findings of focal liver lesions identified on computed tomography were taken as the reference, and findings on ultrasonography were compared with them. Results: The number of focal liver lesions in groups I and II were 501 and 413, respectively. The ultrasonographic detection rates of focal liver lesions in groups I and II were 86.8% (435/501 and 94.2% (389/413, respectively. Comparison of the detection of the focal lesions between patients with and without fatty liver or different grades of fatty liver were as follows: mild fatty liver (162/177 vs. liver without fat infiltration (389/413 (P=0.277; mild fatty liver (162/177 vs. moderate fatty liver (190/212 (P=0.604; mild fatty liver (162/177 vs. severe fatty liver (83/112 (P<0.001; moderate fatty liver (190/212 vs. liver without fat infiltration (389/413 (P=0.051; moderate fatty liver (190/212 vs. severe fatty liver (83/112 (P<0.001; severe fatty liver (83/112 vs. liver without fat infiltration (389/413 (P<0.001; and fatty liver (435/501 vs. liver without fat infiltration (389/413 (P<0.001. Conclusion: Mild and moderate fatty liver are not significantly associated with the visualization of the lesion, while severe fatty liver usually impairs the detection of focal lesions in the liver. If a patient with severe fatty liver is suspected to have a liver tumor, ultrasonography should only be chosen cautiously in case of a missed diagnosis.

  9. Comparison of liver enzymes level and sonographic findings value with liver biopsy findings in nonalcoholic fatty liver disease patients

    Science.gov (United States)

    Khodadoostan, Mahsa; Shariatifar, Behzad; Motamedi, Narges; Abdolahi, Hadi

    2016-01-01

    Background: This study aimed to examine the relationship between sonographic diagnosis of fatty liver and liver enzyme level with histopathologic abnormalities and liver biopsy findings in patient with the nonalcoholic fatty liver disease (NAFLD). Materials and Methods: This cross-sectional study conducted on 109 patients with diagnosed and under treatment NAFLD refer to Gastroenterology Clinics of AL Zahra Hospital in Isfahan, Iran. Age, sex, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) level recorded for all patients. Liver ultrasonography was performed for all patients. Steatosis grading and fibrosis stage were evaluated by liver biopsy. Results: We enrolled 109 subjects with NAFLD who had an indication for liver biopsy and met inclusion criteria of our study. Of these, 78 subjects (71.6%) were male and 31 subjects (28.4) were female. Mean age was 40.17 ± 11.01 years old. Our results showed there was a statistically significant relationship between ultrasonographic findings and histologic findings based on biopsy. There was statistically significant relationship between liver enzyme (ALT, AST and ALP) level and ultrasonographic findings, but there was no significant relationship between AST and ALT level and histologic findings, but the relationship between ALP level and histologic findings (steatosis and fibrosis) was statistically significant (P = 0.01). Conclusion: Ultrasonographic finding may be can use to identify nonalcoholic steatohepatitis and stage of fibrosis in patients with NAFLD, but AST and ALT level is not reliable screening test to identify stage of fibrosis and steatosis in these patients. Therefore, liver biopsy remains the gold standard for establishing steatohepatitis and advanced fibrosis in patients with NAFLD. PMID:27099853

  10. Assessment of US score and CT number for diagnosis of fatty liver

    Energy Technology Data Exchange (ETDEWEB)

    Ogasawara, Tetsuo; Tanda, Shigeru; Lim, Insu; Oota, Keisuke; Taima, Tadashi

    1987-07-01

    The author evaluates US and CT for diagnosis of fatty liver in 70 cases with fatty change of the liver. We tried to score the US findings of the fatty change, i.e., ''bright liver pattern'', ''liver-kidney contrast'', ''vascular blurring'', ''deep attenuation'', and the usefulness of the scoring was examined. Comparing with CT number, US score was more sensitive, but had no significant correlation with the amount of the fat in the liver and with the abnormality of the liver function tests. The results indicate that US should be used as a primary screening examination, and for the further evaluation of the fatty change of the liver, CT should be carried out.

  11. Pediatric nonalcoholic fatty liver disease, metabolic syndrome and cardiovascular risk

    Institute of Scientific and Technical Information of China (English)

    Lucia Pacifico; Valerio Nobili; Caterina Anania; Paola Verdecchia; Claudio Chiesa

    2011-01-01

    Nonalcoholic fatty liver disease (NAFLD) encompasses a range of liver histology severity and outcomes in the absence of chronic alcohol use. The mildest form is simple steatosis in which triglycerides accumulate within hepatocytes. A more advanced form of NAFLD, nonalcoholic steatohepatitis, includes inflammation and liver cell injury, progressive to cryptogenic cirrhosis. NAFLD has become the most common cause of chronic liver disease in children and adolescents. The recent rise in the prevalence rates of overweight and obesity likely explains the NAFLD epidemic worldwide. NAFLD is strongly associated with abdominal obesity, type 2 diabetes, and dyslipidemia, and most patients have evidence of insulin resistance. Thus, NAFLD shares many features of the metabolic syndrome (MetS), a highly atherogenic condition, and this has stimulated interest in the possible role of NAFLD in the development of atherosclerosis. Accumulating evidence suggests that NAFLD is associated with a significantly greater overall mortality than in the general population, as well as with increased prevalence of cardiovascular disease (CVD), independently of classical atherosclerotic risk factors. Yet, several studies including the pediatric population have reported independent associations between NAFLD and impaired flow-mediated vasodilatation and increased carotid artery intimal medial thickness-two reliable markers of subclinical atherosclerosis-after adjusting for cardiovascular risk factors and MetS. Therefore, the rising prevalence of obesity-related MetS and NAFLD in childhood may lead to a parallel increase in adverse cardiovascular outcomes. In children, the cardiovascular system remains plastic and damage-reversible if early and appropriate interventions are established effectively. Therapeutic goals for NAFLD should address nutrition, physical activity, and avoidance of smoking to prevent not only end-stage liver disease but also CVD.

  12. Indian patients with nonalcoholic fatty liver disease presenting with raised transaminases are different at presentation

    Institute of Scientific and Technical Information of China (English)

    Ajay Duseja; Naveen Kaita; Ashim Das; Radha Krishan Dhiman; Yogesh Kumar Chawla; Reena Das; Sanjay Bhadada; Ravinder Sialy; Kiran Kumar Thumburu; Anil Bhansali

    2007-01-01

    @@ TO THE EDITOR We read with great interest the article, "Non-alcoholic fatty liver disease may not be a severe disease at presentation among Asian Indians" by Madan et al in the recent issue of WJG. Twenty-eight (55%) out of 51 patients with nonalcoholic fatty liver disease (NAFLD) who presented with abnormal transaminases had histological evidence of nonalcoholic steatohepatitis (NASH).

  13. Gut-liver axis, nutrition, and non-alcoholic fatty liver disease.

    Science.gov (United States)

    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.

  14. Association between sonographic diagnosis of fatty liver with histopathologic abnormalities and liver biopsy findings in middle age patient with non-alcoholic fatty liver disease

    Science.gov (United States)

    Kalantari, Hamid; Moradi, Farhad; Hassanzade, Akbar

    2016-01-01

    Background: Liver biopsy is required to diagnose non-alcoholic steatohepatitis in patients with suspected non-alcoholic fatty liver disease (NAFLD). This study aimed to examine the relationship between sonographic diagnosis of fatty liver with histopathologic abnormalities and liver biopsy findings in patient with NAFLD. Materials and Methods: In this cross-sectional study, a total of 180 patients, with an age range of 18-60 year old, with NAFLD based on ultrasonograghic findings were evaluated. Age, sex, body mass index, diabetes mellitus, hypertension, family history of liver disease and laboratory parameters recorded for all patients. Hence, grade of steatosis and stage of fibrosis were evaluated by liver biopsy. Results: A total of 220 patients were enrolled. Liver biopsy was performed in 180 patients. Mean age was 43 ± 10.6 years old and 66% were male. Ultrasonograghic findings showed mild, moderate and severe NAFLD was define in 100 (55.5%), 72 (40%) and 8 (4.5%) of patients, respectively. Liver biopsies showed that steatosis scores of <5%, 5-33% and 33-66% was define in 56 (31%), 116 (64%) and 9 (5%) of patients, respectively. Furthermore, fibrosis was defined as follow; none 92 (51%), mild 68 (38%), moderate 11 (6%), bridging 5 (3%) and cirrhosis 3 (2%) patients. There was no statistically significant relationship between ultrasonograghic findings and steatosis scores (P = 0.44), but statistically significant relationship was found between ultrasonograghic findings and fibrosis stage (P = 0.017). Conclusion: Findings revealed that, in patients with NAFLD, ultrasonographic finding were not in associate to steatosis, but were in relation with fibrosis stage. PMID:27563632

  15. Iron and non-alcoholic fatty liver disease

    Science.gov (United States)

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

    2016-01-01

    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. PMID:27688653

  16. Probiotics as a complementary therapeutic approach innonalcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    Silvia Marinho Ferolla; Geyza Nogueira de Almeida Armiliato; Cláudia Alves Couto; Teresa Cristina Abreu Ferrari

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) is currentlyrecognized as one of the most common causes ofchronic liver disease. It involves a spectrum of conditionsthat include pure steatosis without inflammation,steatohepatitis, fibrosis and cirrhosis. The key factorin the pathophysiology of NAFLD is insulin resistancethat determines lipid accumulation in the hepatocytesand, thus, oxidative stress, which is followed byinflammatory response. However, NAFLD pathogenesisis still largely unknown and has been extensivelyinvestigated. Although life style modification with theaim of losing weight has been advocated to treat thisdisorder, its effectiveness is limited; additionally, thereis no specific pharmacologic treatment until nowadays.Recent evidence suggests that the gut microbiota mayplay a role in the development of insulin resistance,hepatic steatosis, necroinflammation and fibrosis.Differences in gut microbiota between NAFLD patientsand lean individuals as well as presence of smallintestinal bacterial overgrowth in NAFLD subjects havebeen demonstrated. Furthermore, some data indicatethat the immunoregulatory effects of probiotics maybe beneficial in NAFLD treatment as they modulatethe intestinal microbiota; improve epithelial barrierfunction and strengthen the intestinal wall decreasingits permeability; reduce bacterial translocation andendotoxemia; improve intestinal inflammation; andreduce oxidative and inflammatory liver damage. Inthis article, we review the clinical trials on the useof probiotics in the treatment of NAFLD and discussthe effects of these agents and their efficacy as anemerging therapeutic resource to treat NAFLD patients.

  17. Histopathology of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis.

    Science.gov (United States)

    Takahashi, Yoshihisa; Fukusato, Toshio

    2014-11-14

    Nonalcoholic fatty liver disease (NAFLD), a hepatic manifestation of metabolic syndrome, is the most common chronic liver disease, and the prevalence is rapidly increasing worldwide. Nonalcoholic steatohepatitis (NASH), the severe form of NAFLD, can progress to liver cirrhosis and hepatocellular carcinoma (HCC). Although noninvasive clinical scores and image-based diagnosis for NAFLD have improved, histopathological evaluation of biopsy specimens remains the gold standard for diagnosing NAFLD/NASH. Steatosis, lobular inflammation, and hepatocellular ballooning are all necessary components for the diagnosis of NASH; fibrosis is also typically observed. Other histopathological abnormalities commonly observed in NASH include hepatocellular glycogenated nuclei, lipogranulomas, and acidophil bodies. The characteristics of pediatric NAFLD/NASH differ from adult NAFLD/NASH. Specifically, steatosis and portal inflammation are more severe in pediatric NAFLD, while intralobular inflammation and perisinusoidal fibrosis are milder. Although interobserver agreement for evaluating the extent of steatosis and fibrosis is high, agreement is low for intralobular and portal inflammation. A recently reported histological variant of HCC, steatohepatitic HCC (SH-HCC), shows features that resemble non-neoplastic steatohepatitis, and is thought to be strongly associated with underlying NASH. In this report, we review the histopathological features of NAFLD/NASH.

  18. Rodent models of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis.

    Science.gov (United States)

    Imajo, Kento; Yoneda, Masato; Kessoku, Takaomi; Ogawa, Yuji; Maeda, Shin; Sumida, Yoshio; Hyogo, Hideyuki; Eguchi, Yuichiro; Wada, Koichiro; Nakajima, Atsushi

    2013-11-04

    Research in nonalcoholic fatty liver disease (NAFLD), including nonalcoholic steatohepatitis (NASH), has been limited by the availability of suitable models for this disease. A number of rodent models have been described in which the relevant liver pathology develops in an appropriate metabolic context. These models are promising tools for researchers investigating one of the key issues of NASH: not so much why steatosis occurs, but what causes the transition from simple steatosis to the inflammatory, progressive fibrosing condition of steatohepatitis. The different rodent models can be classified into two large groups. The first includes models in which the disease is acquired after dietary or pharmacological manipulation, and the second, genetically modified models in which liver disease develops spontaneously. To date, no single rodent model has encompassed the full spectrum of human disease progression, but individual models can imitate particular characteristics of human disease. Therefore, it is important that researchers choose the appropriate rodent models. The purpose of the present review is to discuss the metabolic abnormalities present in the currently available rodent models of NAFLD, summarizing the strengths and weaknesses of the established models and the key findings that have furthered our understanding of the disease's pathogenesis.

  19. Acute Fatty Liver of Pregnancy: A Clinical-Paraclinical Survey

    Directory of Open Access Journals (Sweden)

    Mohammad Jafari

    2015-02-01

    Full Text Available Background Acute Fatty Liver of Pregnancy (AFLP is one of the serious complications of the pregnancy period. Surveying the laboratory and clinical signs is effective in timely prognosis and fast treatment of this illness. Objectives The current study aimed to evaluate AFLP among the hospitalized subjects. Patients and Methods This retrospective study was conducted on clinical and preclinical records of 25 females with AFLP for maternal and perinatal prognosis from 2000 to 2009. The data was analyzed using SPSS ver. 19. Results The patients aged 16 - 45 years old with one to four pregnancies (pregnancy; they were 24 to 39 weeks pregnant with the mean of 33.56 weeks, and 56% were multifarious. The most prevalent clinical symptoms were nausea, vomiting, abdominal pain, headache, pruritus, and icterus. The laboratory signs included disorders of liver, coagulation, kidney, and hypoglycemia. Nausea and vomiting in the first and second age groups (Group 1, patients were 35 years. were the most prevalent symptoms. No patient had fever, ascites, and polydipsia. There was one case of mother and fetal death. Conclusions In the current study, the clinical and paraclinical signs of AFLP were mostly - liver, coagulation, kidney, and hypoglycemia disorders. Considering that patients mostly refer in three phases of clinical, laboratory, and complications, it is essential to evaluate the suspected ones who present clinical symptoms especially nausea, vomiting and abdominal pain.

  20. Hepatic enzyme concentrations as indicators of nonalcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    Alvina Alvina

    2016-02-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD has emerged as a world-wide problem because it runs an asymptomatic course, ultimately leading to cirrhosis of the liver and portal hypertension, resulting in death. The prevalence of the disease accounts for 3-24% of the population in several countries. Generally there are increased concentrations of hepatic enzymes as markers of liver damage, such as serum glutamic oxaloacetic transaminase (SGOT, serum glutamic pyruvic transaminase (SGPT and gamma glutamyl transferase (GGT. The aim of the present study was to determine the concentrations of hepatic enzymes as markers of NAFLD. The study design was cross-sectional, involving 90 subjects meeting the inclusion and exclusion criteria. The degree of severity NAFLD was determined by ultrasonography and the concentrations of SGOT, SGPT and GGT by automated clinical chemistry analyzer. The results indicated that there were 32 subjects with mild NAFLD (35.6%, 35 subjects with moderate NAFLD (38.9% and 23 subjects with severe NAFLD (25.6%. There was a significant difference in degree of NAFLD by gender (p<0.05, where severe NAFLD was more frequent in males than in females. Concentrations of SGOT, SGPT and GGT were significantly different between degrees of NAFLD (p<0.05. The conclusion is that SGOT, SGPT and GGT concentrations are indicators of degree of NAFLD.

  1. Non-alcoholic fatty liver disease in 2015

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    There is worldwide epidemic of non-alcoholic fatty liverdisease (NAFLD). NAFLD is a clinical entity related tometabolic syndrome. Majority of the patients are obesebut the disease can affect non-obese individuals aswell. Metabolic factors and genetics play important rolesin the pathogenesis of this disorder. The spectrum ofdisorders included in NAFLD are benign macrovesicularhepatic steatosis, non-alcoholic steatohepatitis, hepaticfibrosis, cirrhosis of liver and hepatocellular carcinoma.Although the disease remains asymptomatic mostof the time, it can slowly progress to end stage liverdisease. It will be the most common indication of livertransplantation in the future. It is diagnosed by abnormalliver chemistry, imaging studies and liver biopsy. Asthere are risks of potential complications during liverbiopsy, many patients do not opt for liver biopsy. Thereare some noninvasive scoring systems to find outwhether patients have advanced hepatic fibrosis. At thepresent time, there are limited treatment options whichinclude lifestyle modification to loose weight, vitaminE and thioglitazones. Different therapeutic agents arebeing investigated for optimal management of thisentity. There are some studies done on incretin basedtherapies in patients with NAFLD. Other potential agentswill be silent information regulator protein Sirtuin andantifibrotic monoclonal antibody Simtuzumab againstlysyl oxidase like molecule 2. But they are still in theinvestigational phase.

  2. Sulfur Amino Acids in Diet-induced Fatty Liver: A New Perspective Based on Recent Findings

    Directory of Open Access Journals (Sweden)

    John I. Toohey

    2014-06-01

    Full Text Available The relationship of sulfur amino acids to diet-induced fatty liver was established 80 years ago, with cystine promoting the condition and methionine preventing it. This relationship has renewed importance today because diet-induced fatty liver is relevant to the current epidemics of obesity, non-alcoholic fatty liver disease, metabolic syndrome, and type 2 diabetes. Two recent papers provide the first evidence linking sulfane sulfur to diet-induced fatty liver opening a new perspective on the problem. This review summarizes the early data on sulfur amino acids in fatty liver and correlates that data with current knowledge of sulfur metabolism. Evidence is reviewed showing that the lipotropic effect of methionine may be mediated by sulfane sulfur and that the hepatosteatogenic effect of cystine may be related to the removal of sulfane sulfur by cysteine catabolites. Possible preventive and therapeutic strategies are discussed.

  3. Final results of a long-term, clinical follow-up in fatty liver patients

    DEFF Research Database (Denmark)

    Dam-Larsen, Sanne; Becker, Ulrik; Franzmann, Maria-Benedicte

    2009-01-01

    OBJECTIVE: There is increasing focus on non-alcoholic fatty liver disease (NAFLD). The aim of the present study was to conduct a long-term clinical follow-up of patients with biopsy-confirmed fatty liver without inflammation or significant fibrosis (pure fatty liver), to analyse for potential risk....... All admissions, discharge diagnoses and causes of death during follow-up were collected. All surviving patients were invited to a clinical follow-up. RESULTS: The follow-up period was 20.4 and 21.0 years, respectively, for the NAFLD and alcoholic fatty liver disease (AFLD) groups. Two NAFLD patients...... of death. Patients with AFLD died primarily from cirrhosis and other alcohol-related disorders, whereas in patients with NAFLD the main causes of death were cardiovascular disease and cancer. CONCLUSIONS: For patients with pure non-alcoholic fatty liver, survival was good and independent...

  4. Liver transplantation for nonalcoholic fatty liver disease: new challenges and new opportunities.

    Science.gov (United States)

    Shaker, Mina; Tabbaa, Adam; Albeldawi, Mazen; Alkhouri, Naim

    2014-05-14

    Nonalcoholic fatty liver disease (NAFLD) is becoming rapidly one of the most common indications for orthotopic liver transplantation in the world. Development of graft steatosis is a significant problem during the post-transplant course, which may happen as a recurrence of pre-existing disease or de novo NAFLD. There are different risk factors that might play a role in development of graft steatosis including post-transplant metabolic syndrome, immune-suppressive medications, genetics and others. There are few studies that assessed the effects of NAFLD on graft and patient survival; most of them were limited by the duration of follow up or by the number of patients. With this review article we will try to shed light on post-liver transplantation NAFLD, significance of the disease, how it develops, risk factors, clinical course and treatment options.

  5. Acute fatty liver of pregnancy: analysis of five consecutive cases from a tertiary centre.

    Science.gov (United States)

    Barber, M A; Eguiluz, I; Martín, A; Plasencia, W; Valle, L; García, J A

    2010-04-01

    Acute fatty liver of pregnancy is a rare cause of jaundice and liver failure associated with high maternal and fetal mortality. We analysed five consecutive cases of acute fatty liver of pregnancy, along with the associated morbidity, mortality and complications. Between January 1999 and January 2008, a total of 68,524 deliveries were assisted at the Obstetrics and Gynaecology Department of the Hospital Universitario Materno-Infantil de Canarias (Canaries University Hospital Maternity Ward); among them, five cases of acute fatty liver of pregnancy were identified.

  6. Acute fatty liver of pregnancy. CT scan imaging in 4 cases

    Energy Technology Data Exchange (ETDEWEB)

    Coche, G.; Moran, V.; Schmitt, M.; Boillot, A.; Miguet, J.P.; Hadni-Bresson, S.; Weill, F.S.

    1987-03-01

    Acute fatty liver of pregnancy is a disease of the third trimester, generally considered to be rare and to have a grave prognosis. Histologically the characteristic fine droplet steatosis usually produces distinct vacuolization. Successful treatment depends on accurate diagnosis and early delivery. Computed tomography is of value in the diagnosis of fatty liver through liver and spleen attenuation value measurements. We reviewed 4 cases of acute fatty liver of pregnancy. Computed tomography was performed in two cases and was very helpful in the diagnosis of this condition.

  7. WJH 6th Anniversary Special Issues(7): Nonalcoholic fatty liver disease Pathogenesis and therapeutic approaches for non-alcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    Hye-jin; Yoon; Bong; Soo; Cha

    2014-01-01

    Non-alcoholic fatty liver disease affects approximately one-third of the population worldwide, and its incidence continues to increase with the increasing prevalence of other metabolic disorders such as type 2 diabetes. As non-alcoholic fatty liver disease can progress to liver cirrhosis, its treatment is attracting greater attention. The pathogenesis of non-alcoholic fatty liver disease is closely associated with insulin resistance and dyslipidemia, especially hypertriglyceridemia. Increased serum levels of free fatty acid and glucose can cause oxidative stress in the liver and peripheral tissue, leading to ectopic fat accumulation, especially in the liver. In this review, we summarize the mechanism underlying the progression of hepatic steatosis to steatohepatitis and cirrhosis. We also discuss established drugs that are already being used to treat non-alcoholic fatty liver disease, in addition to newly discovered agents, with respect to their mechanisms of drug action, focusing mainly on hepatic insulin resistance. As well, we review clinical data that demonstrate the efficacy of these drugs, together with improvements in biochemical or histological parameters.

  8. Protection effect of trigonelline on liver of rats with non-alcoholic fatty liver diseases

    Institute of Scientific and Technical Information of China (English)

    Dong-Fang Zhang; Fan Zhang; Jin Zhang; Rui-Ming Zhang; Ran Li

    2015-01-01

    Objective:To study the effect of trigonelline on the change of indicators of serum transaminase, lipoprotein and liver lipid of model rats with non-alcoholic fatty liver diseases and on the expression level of Bcl-2 and Bax proteins.Methods:A total of 45 SD rats were randomly divided into Fthe control group, model group and trigonelline intervention group. Rats in the control group were fed with the common diet, while rats in the model group and intervention group were fed with the high fat diet. 8 weeks later, the intervention group received the intragastric administration of trigonellin e (with the dosage of 40 mg/kg/d) for 8 weeks; while control group and model group received the intragastric administration of saline with the equal dosage. Blood was taken from the abdominal aorta of rats 8 weeks later, detecting the level of a series of indicators of ALT, AST, TG, TC, HDL-C and LDL-C in the serum. After the rats were sacrificed, detect the indicators of TG, TC, SOD and MDA in the liver tissue of rats, as well as the expression of Bcl-2 and Bax in the liver tissue.Results: Results of histopathologic examination showed that the damage degree of liver for rats in the trigonellineintervention group was smaller than the one in the model group, with significantly reduced hepatic steatosis and the partially visible hepatic lobule. The levels of ALT, AST, TC and LDL-C in the serum of rats in the trigonelline group were significantly reduced, while the change in the levels of TG and HDL-C was not significantly different. The levels of TG, TC and MDA in the liver tissues were significantly decreased, while the level of SOD significantly increased; the expression of Bcl-2 protein in the liver tissues of rats in the trigonelline intervention group was significantly increased, while the expression of Bax protein significantly decreased.Conclusions: The trigonelline contributes to the therapeutic effect of non-alcoholic fatty liver diseases. It can also increase the

  9. Experimental study of osthole on treatment of hyperlipidemic and alcoholic fatty liver in animals

    Institute of Scientific and Technical Information of China (English)

    Fang Song; Mei-Lin Xie; Lu-Jia Zhu; Ke-Ping Zhang; Jie Xue; Zhen-Lun Gu

    2006-01-01

    AIM: To evaluate the effects of osthole on fatty liver,and investigate the possible mechanism.METHODS: A quail model with hyperlipidemic fatty liver and rat model with alcoholic fatty liver were set up by feeding high fat diet and alcohol, respectively. These experimental animals were then treated with osthole 5-20 mg/kg for 6 wk, respectively. Whereafter, the lipid in serum and hepatic tissue, and coefficient of hepatic weight were measured.RESULTS: After treatment with osthole the levels of serum total cholesterol (TC), triglyceride (TG), lower density lipoprotein-cholesterol (LDL-C), coefficient of hepatic weight, and the hepatic tissue contents of TC and TG were significantly decreased. The activity of superoxide dismutase (SOD) in liver was improved.In alcohol-induced fatty liver rats, the level of malondialdehyde (MDA) in liver was decreased. In high fat-induced fatty liver quails, glutathione peroxidase (GSH-PX) in liver was significantly improved. The histological evaluation of liver specimens demonstrated that the osthole dramatically decreased lipid accumulation.CONCLUSION: These results suggested that osthole had therapeutic effects on both alcohol and high fatinduced fatty liver. The mechanism might be associated with its antioxidation.

  10. Troglitazone prevented the development of fatty liver under obese and diabetic condition in Otsuka Long-Evans Tokushima fatty rats

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    We aimed to clarify the effects of troglitazone to prevent the development of fatty liver in Otsuka Long-Evans Tokushima fatty (OLETF) rats, an obese type2 diabetes model. Treatment of 0.2% troglitazone for 16 weeks significantly decreased blood glucose, serum insulin and free fatty acid (FFA) concentration (P<0.05 for each) in the OLETF rats leaving their food intake, body weight and general fat pad weight unaffected compared with those of their lean littermates, Long-Evans Tokushima Otsuka (LETO) rats. Troglitazone restored increase in liver weight and hepatic triglyceride(TG) content of the OLETF rats (P<0.05 for each). These findings were accertained by histological examination which showed that fat deposition, necrosis and vacuolization of hepatocyte, markers for fatty liver, were diminished by troglitazone treatment. Messenger RNA expression of microsomal triglyceride transfer protein in the liver, a marker for hepatic TG output, was not significantly different between OLETF and LETO rats with or without troglitazone treatment. Fatty acid composition such as C18∶1(oleic acid) showed no remarkable change after troglitazone treatment in OLETF rats, indicating no dietary influence to hepatic lipogenesis. These indicate that reduction in circulating FFA level may be one of the main mechanisms for troglitazone to prevent the development of insulin resistance and fatty liver.

  11. Recommendations for Diagnosis, Referral for Liver Biopsy, and Treatment of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis.

    Science.gov (United States)

    Spengler, Erin K; Loomba, Rohit

    2015-09-01

    Nonalcoholic fatty liver disease (NAFLD) is the primary cause of chronic liver disease in the United States, afflicting an estimated 80 to 100 million Americans. Nonalcoholic fatty liver disease is a spectrum of liver diseases composed of nonalcoholic fatty liver and nonalcoholic steatohepatitis (NASH). Although nonalcoholic fatty liver has a negligible risk of progression, patients with NASH often develop cirrhosis or hepatocellular carcinoma. Although liver biopsy is required to diagnose NASH, only patients with a high risk of NASH or advanced fibrosis require this evaluation. Despite the high prevalence of NAFLD, well-defined screening recommendations are currently lacking. In this review, suggestions for screening, diagnosis, and initial work-up of NAFLD are given on the basis of established guidelines and recent publications. Proposed drug treatments of NASH are also discussed, highlighting the study outcomes, as well as proposed uses and limitations of these drugs. The literature was searched in PubMed using search terms nonalcoholic fatty liver disease and nonalcoholic steatohepatitis, with filters of "English language." A date range of January 1, 2000, to May 1, 2015, was used for the search. The bibliographies of key references were also searched manually, and seminal publications before the year 2000 were included.

  12. Clinical features and risk factors of patients with fatty liver in Guangzhou area

    Institute of Scientific and Technical Information of China (English)

    Qi-Kui Chen; Hai-Ying Chen; Kai-Hong Huang; Ying-Qiang Zhong; Ji-Ao Han; Zhao-Hua Zhu; Xiao-Dong Zhou

    2004-01-01

    AIM: There is still no accepted conclusion regarding the clinical features and related risk factors of patients with fatty liver. The large-scale clinical studies have not carried out yet in Guangzhou area. The aim of the present study was to investigate the clinical features and related risk factors of patients with fatty liver in Guangzhou area. METHODS: A total of 413 cases with fatty liver were enrolled in the study from January 1998 to May 2002. Retrospective case-control study was used to evaluate the clinical featuresand related risk factors of fatty liver with logistic regression.RESULTS: Obesity (OR: 21.204), alcohol abuse (OR: 18.601),type 2 diabetes mellitus (OR: 4.461), serum triglyceride (TG)(OR: 3.916), serum low-density lipoprotein cholesterol (LDL-C)(OR: 1.840) and fasting plasma glucose (FPG) (OR: 1.535)were positively correlated to the formation of the fatty liver. The levels of serum alanine aminotransferase (ALT) and gammaglutamyltransferase (GGT) increased mildly in the patients withfatty liver and were often less than 2-fold of the normal limit.The higher abnormalities of aspartate aminotransferase (AST)levels (42.9%) with Asr/ALT more than 2(17.9%) were found in patients with alcoholic fatty liver (AFL) than those with nonalcoholic fatty liver (NAFL) (16.9% and 5.0% respectively). The elevation of serum TG, cholesterol (CHOL), LDL-C was more common in patients with NAFL than with AFL.CONCLUSION: Obesity, alcohol abuse, type 2 diabetes mellitus and hyperlipidemia may be independent risk factors of fatty liver. The mildly abnormal hepatic functions can be found in patients with fatty liver. More obvious damages of liver function with AST/ALT usually more than 2 were noted in patients with AFL.

  13. Non-alcoholic fatty liver disease: is iron relevant?

    Science.gov (United States)

    O'Brien, Julia; Powell, Lawrie W

    2012-01-01

    Non-alcoholic fatty liver disease (NAFLD) is a common and ubiquitous disorder (Bedogni et al. in Hepatology 42:44-52, 2005; Bellentani et al. in Ann Intern Med 132:112-117, 2000) which in a proportion of subjects leads to non-alcoholic steatohepatitis (NASH), advanced liver disease and hepatocellular carcinoma. Although the factors responsible for progression of disease are still uncertain, there is evidence that insulin resistance (IR) is a key operative mechanism (Angulo et al. in Hepatology 30:1356-1362, 1999) and that two stages are involved. The first is the accumulation of triglycerides in hepatocytes followed by a "second hit" which promotes cellular oxidative stress. Several factors may be responsible for the induction of oxidative stress but hepatic iron has been implicated in various studies. The topic is controversial, however, with early studies showing an association between hepatic iron (with or without hemochromatosis gene mutations) and the progression to hepatic fibrosis. Subsequent studies, however, could not confirm an association between the presence of hepatic iron and any of the histological determinants of NAFLD or NASH. Recent studies have reactivated interest in this subject firstly, with the demonstration that hepatic iron loading increases liver cholesterol synthesis with increased lipid deposition in the liver increasing the cellular lipid burden and secondly, a large clinical study has concluded that hepatocellular iron deposition is associated with an increased risk of hepatic fibrosis, thus, strongly supporting the original observation made over a decade ago. An improvement in insulin sensitivity has been demonstrated following phlebotomy therapy but a suitably powered controlled clinical trial is required before this treatment can be implemented.

  14. Does vitamin C deficiency promote fatty liver disease development?

    DEFF Research Database (Denmark)

    Ipsen, David Højland; Tveden-Nyborg, Pernille; Lykkesfeldt, Jens

    2014-01-01

    Obesity and the subsequent reprogramming of the white adipose tissue are linked to human disease-complexes including metabolic syndrome and concurrent non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). The dietary imposed dyslipidemia promotes redox imbalance...... se has been shown to result in reduced plasma VitC, and the distribution of body fat in obesity has been shown to have an inverse relationship with VitC plasma levels. Recently, a number of epidemiological studies have indicated a VitC intake below the recommended daily allowance (RDA) in NAFLD...... in disease progression in specific subgroups. This review discusses the currently available data from human surveys and experimental models in search of a putative role of VitC deficiency in the development of NAFLD and NASH....

  15. Dietary Fat Content Effects on Concentrations of Liver and Intestinal Fatty Acid Binding Proteins

    OpenAIRE

    Murakami, Hiroshi; Sakai, Yasuo; Ohta, Kazutoshi; Hatakeyama, Katsuyoshi

    1998-01-01

    Two fatty acid binding proteins, liver and intestinal, have been identified in the rat intestine. Both are thought to be closely related to the absorption and metabolism of fatty acids in the intestinal epithelium. However, the underlying mechanism is not clearly understood. The purpose of this study was therefore to investigate the roles of these two fatty acid binding proteins in the intestinal absorption of fatty acids. Rats were fed diets varying in fat content for two or four weeks. Live...

  16. Resveratrol inhibits nonalcoholic fatty liver disease in rats

    Directory of Open Access Journals (Sweden)

    Irastorza Belen

    2008-09-01

    Full Text Available Abstract Background The prevalence of nonalcoholic fatty liver disease (NAFLD is high. NAFLD is linked to obesity, diabetes mellitus, and hypertriglyceridemia. Approximately 20% of patients with NAFLD will eventually develop cirrhosis. Our purpose was to investigate whether resveratrol decreased hepatic steatosis in an animal model of steatosis, and whether this therapeutic approach resulted in a decrease in tumor necrosis factor α (TNF-α production, lipid peroxidation and oxidative stress. Methods Male Wistar CRL: Wi (Han (225 g rats were randomized into three groups. A control group (n = 12 was given free access to regular dry rat chow for 4 weeks. The steatosis (n = 12 and resveratrol (n = 12 groups were given free access to feed (a high carbohydrate-fat free modified diet and water 4 days per week, and fasted for the remaining 3 days for 4 weeks. Rats in the resveratrol group were given resveratrol 10 mg daily by the oral route. All rats were killed at 4 weeks and assessed for fatty infiltration and bacterial translocation. Levels of TNF-α in serum, hepatic malondialdehyde (MDA, oxidative stress (superoxide dismutase, glutathione peroxidase, catalase and nitric oxide synthase and biochemical parameters were measured. Results Fat deposition was decreased in the resveratrol group as compared to the steatosis group (Grade 1 vs Grade 3, P P P P Conclusion Resveratrol decreased NAFLD severity in rats. This effect was mediated, at least in part, by TNF-α inhibition and antioxidant activities.

  17. Dietary habits and behaviors associated with nonalcoholic fatty liver disease.

    Science.gov (United States)

    Yasutake, Kenichiro; Kohjima, Motoyuki; Kotoh, Kazuhiro; Nakashima, Manabu; Nakamuta, Makoto; Enjoji, Munechika

    2014-02-21

    Nonalcoholic fatty liver disease (NAFLD) is one of the most frequent causes of health problems in Western (industrialized) countries. Moreover, the incidence of infantile NAFLD is increasing, with some of these patients progressing to nonalcoholic steatohepatitis. These trends depend on dietary habits and life-style. In particular, overeating and its associated obesity affect the development of NAFLD. Nutritional problems in patients with NAFLD include excess intake of energy, carbohydrates, and lipids, and shortages of polyunsaturated fatty acids, vitamins, and minerals. Although nutritional therapeutic approaches are required for prophylaxis and treatment of NAFLD, continuous nutrition therapy is difficult for many patients because of their dietary habits and lifestyle, and because the motivation for treatment differs among patients. Thus, it is necessary to assess the nutritional background and to identify nutritional problems in each patient with NAFLD. When assessing dietary habits, it is important to individually evaluate those that are consumed excessively or insufficiently, as well as inappropriate eating behaviors. Successful nutrition therapy requires patient education, based on assessments of individual nutrients, and continuing the treatment. In this article, we update knowledge about NAFLD, review the important aspects of nutritional assessment targeting treatment success, and present some concrete nutritional care plans which can be applied generally.

  18. Investigating Nonalcoholic Fatty Liver Disease in a Liver-on-a-Chip Microfluidic Device

    Science.gov (United States)

    Simonelli, Maria Chiara; Giannitelli, Sara Maria; Businaro, Luca; Trombetta, Marcella; Rainer, Alberto

    2016-01-01

    Background and Aim Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease worldwide, ranging from simple steatosis to nonalcoholic steatohepatitis, which may progress to cirrhosis, eventually leading to hepatocellular carcinoma (HCC). HCC ranks as the third highest cause of cancer-related death globally, requiring an early diagnosis of NAFLD as a potential risk factor. However, the molecular mechanisms underlying NAFLD are still under investigation. So far, many in vitro studies on NAFLD have been hampered by the limitations of 2D culture systems, in which cells rapidly lose tissue-specific functions. The present liver-on-a-chip approach aims at filling the gap between conventional in vitro models, often scarcely predictive of in vivo conditions, and animal models, potentially biased by their xenogeneic nature. Methods HepG2 cells were cultured into a microfluidically perfused device under free fatty acid (FFA) supplementation, namely palmitic and oleic acid, for 24h and 48h. The device mimicked the endothelial-parenchymal interface of a liver sinusoid, allowing the diffusion of nutrients and removal of waste products similar to the hepatic microvasculature. Assessment of intracellular lipid accumulation, cell viability/cytotoxicity and oxidative stress due to the FFA overload, was performed by high-content analysis methodologies using fluorescence-based functional probes. Results The chip enables gradual and lower intracellular lipid accumulation, higher hepatic cell viability and minimal oxidative stress in microfluidic dynamic vs. 2D static cultures, thus mimicking the chronic condition of steatosis observed in vivo more closely. Conclusions Overall, the liver-on-a-chip system provides a suitable culture microenvironment, representing a more reliable model compared to 2D cultures for investigating NAFLD pathogenesis. Hence, our system is amongst the first in vitro models of human NAFLD developed within a microfluidic device in a sinusoid

  19. Postpartum Acute Liver Dysfunction: A Case of Acute Fatty Liver of Pregnancy Developing Massive Intrahepatic Calcification

    Science.gov (United States)

    Bhat, Khalid Javid; Shovkat, Rabia; Samoon, Hamad Jeelani

    2015-01-01

    The function of the liver is particularly affected by the unique physiologic milieu of the pregnancy. Pregnancy-related liver diseases encompass a spectrum of different etiologies that are related to gestation or one of its complications. Hepatic calcification, a rare entity, is usually associated with infectious, vascular, or neoplastic lesions in the liver. To the best of our knowledge, only one case of rapidly occurring pregnancy-related intrahepatic calcification has been documented in a patient with severe eclampsia or hemolysis, elevated liver enzymes and low platelet count (HELLP) syndrome. Here we present a case of immediate “postpartum” acute fatty liver of pregnancy (AFLP) in a 23-year-old hypertensive primigravida, complicated by acute renal dysfunction who developed dense intrahepatic calcification in less than a month after the initial diagnosis. A multidisciplinary approach for the management was used, to which the patient responded aptly. This case illustrates the first description of intrahepatic calcification in AFLP syndrome and highlights some of the challenges met in making the final diagnosis. PMID:27785315

  20. 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

    2016-01-01

    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. PMID:27347998

  1. Gut-liver axis and probiotics: their role in non-alcoholic fatty liver disease.

    Science.gov (United States)

    Paolella, Giulia; Mandato, Claudia; Pierri, Luca; Poeta, Marco; Di Stasi, Martina; Vajro, Pietro

    2014-11-14

    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.

  2. The Correlation of Sonographic Finding of Fatty Liver with Hematologic Examination and Body Fat Percentage

    Energy Technology Data Exchange (ETDEWEB)

    Cheon, Hae Kyung [Dept. of Radiology, Sun General Hospital, Daejeon (Korea, Republic of); Lee, Tae Yong; Kim, Young Ran [Dept. of Preventive Medicine and Public Health College of Midicin, Chungnam National University, Daejeon (Korea, Republic of)

    2009-12-15

    Ultrasonography has been used as a basic examination of a medical check up for prevention and diagnostics of diseases. Even the person who has no particular subjective symptoms can have a variety of diseases. Especially fatty liver is found in many cases. In this study, we tested 3582 persons who are in between the ages of 15 to 81 and observed that 1390 persons had fatty liver while 2192 persons are normal. We classified the grade of fatty liver and compared their life styles with the results of liver function test and BMI. The results are as follows. Ratio of the subjects who had a fatty liver is 38.8%. Male and female ratio was 46.2% and 24.2%. On the correlation among the fatty liver, the body mass index and the body fat, the average value of body mass index and body fat were significantly higher in the group of the fatty liver than in those of the normal liver. The influence of the related factor and the correlation on the fatty liver was shown that it was more related with the order of age, body mass index, triglyceride, ALT, body fat, sex, HDL-Cholesterol, LDL-Cholesterol, and GGT. The result of the ultrasonography carried out for the purpose of regular health check up indicates that even the 38.8% of those who was diagnosed as normal condition could have the fatty liver and have possibility of other diseases. Therefore, if there are any troubles related to liver function and lipid through hematologic examination or when practicing follow-up study with ultrasonography concerning the correlation relation between the body fat and dietary preference, alcohol consumption and exercise, the ultrasonography is definitely useful for prevention and treatment of diseases.

  3. '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

  4. Sex Steroid Modulation of Fatty Acid Utilization and Fatty Acid Binding Protein Concentration in Rat Liver

    Science.gov (United States)

    Ockner, Robert K.; Lysenko, Nina; Manning, Joan A.; Monroe, Scott E.; Burnett, David A.

    1980-01-01

    The mechanism by which sex steroids influence very low density hepatic lipoprotein triglyceride production has not been fully elucidated. In previous studies we showed that [14C]oleate utilization and incorporation into triglycerides were greater in hepatocyte suspensions from adult female rats than from males. The sex differences were not related to activities of the enzymes of triglyceride biosynthesis, whereas fatty acid binding protein (FABP) concentration in liver cytosol was greater in females. These findings suggested that sex differences in lipoprotein could reflect a sex steroid influence on the availability of fatty acids for hepatocellular triglyceride biosynthesis. In the present studies, sex steroid effects on hepatocyte [14C]oleate utilization and FABP concentration were investigated directly. Hepatocytes from immature (30-d-old) rats exhibited no sex differences in [14C]oleate utilization. With maturation, total [14C]oleate utilization and triglyceride biosynthesis increased moderately in female cells and decreased markedly in male cells; the profound sex differences in adults were maximal by age 60 d. Fatty acid oxidation was little affected. Rats were castrated at age 30 d, and received estradiol, testosterone, or no hormone until age 60 d, when hepatocyte [14C]oleate utilization was studied. Castration virtually eliminated maturational changes and blunted the sex differences in adults. Estradiol or testosterone largely reproduced the appropriate adult pattern of [14C]oleate utilization regardless of the genotypic sex of the treated animal. In immature females and males, total cytosolic FABP concentrations were similar. In 60-d-old animals, there was a striking correlation among all groups (females, males, castrates, and hormone-treated) between mean cytosolic FABP concentration on the one hand, and mean total [14C]oleate utilization (r = 0.91) and incorporation into triglycerides (r = 0.94) on the other. In 30-d-old animals rates of [14C

  5. Valproic acid and nonalcoholic fatty liver disease: A possibleassociation?

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Valproic acid (VPA) is one of the most prescribed drugsin children with newly diagnosed epilepsy. Weightgain and obesity have been observed as side effectsof VPA. These are often linked with other metabolicdisturbances such as development of insulin resistance,dyslipidemia, metabolic syndrome (MetS) and nonalcoholicfatty liver disease or nonalcoholic fatty liverdisease (NAFLD). NAFLD refers to a group of liverdisorders with marked hepatic steatosis. It is associatedwith an increased incidence of cardiovascular diseasesand overall reduced life expectancy. NAFLD occurs in20%-25% of the general population and it is knownto be the most common cause of chronic liver disease.NAFLD therefore represents a major public healthissue worldwide. This study reviews and summarizesrelevant literature that supports the existence of anassociation between VPA therapy and the developmentof NAFLD in children. Long-term VPA-therapy appearsto be associated with an increased risk of developingNAFLD. Further studies are needed to clarify thepathogenic mechanisms that lie behind this associationand to standardize the options for the use of thisdrug in overweight patients and in those with risks fordeveloping MetS and NAFLD.

  6. Bile acid receptors and nonalcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    With the high prevalence of obesity, diabetes, and otherfeatures of the metabolic syndrome in United States,nonalcoholic fatty liver disease (NAFLD) has inevitablybecome a very prevalent chronic liver disease and isnow emerging as one of the leading indications for livertransplantation. Insulin resistance and derangementof lipid metabolism, accompanied by activation ofthe pro-inflammatory response and fibrogenesis, areessential pathways in the development of the moreclinically significant form of NAFLD, known as nonalcoholicsteatohepatitis (NASH). Recent advances inthe functional characterization of bile acid receptors,such as farnesoid X receptor (FXR) and transmembraneG protein-coupled receptor (TGR) 5, have providedfurther insight in the pathophysiology of NASH andhave led to the development of potential therapeutictargets for NAFLD and NASH. Beyond maintaining bileacid metabolism, FXR and TGR5 also regulate lipidmetabolism, maintain glucose homeostasis, increaseenergy expenditure, and ameliorate hepatic inflammation.These intriguing features have been exploitedto develop bile acid analogues to target pathways inNAFLD and NASH pathogenesis. This review providesa brief overview of the pathogenesis of NAFLD andNASH, and then delves into the biological functions ofbile acid receptors, particularly with respect to NASHpathogenesis, with a description of the associatedexperimental data, and, finally, we discuss the prospectsof bile acid analogues in the treatment of NAFLD andNASH.

  7. The prevalence of nonalcoholic fatty liver disease in the Americas.

    Science.gov (United States)

    López-Velázquez, Jorge A; Silva-Vidal, Karen V; Ponciano-Rodríguez, Guadalupe; Chávez-Tapia, Norberto C; Arrese, Marco; Uribe, Misael; Méndez-Sánchez, Nahum

    2014-01-01

    Nonalcoholic fatty liver disease (NAFLD) is an alarming public health problem. The disease is one of the main causes of chronic liver disease worldwide and is directly linked to the increased prevalence of obesity and type 2 diabetes mellitus (T2DM) in the general population. The worldwide prevalence of NAFLD has been estimated at 20-30%, but the prevalence is unknown in the Americas because of a lack of epidemiological studies. However, given the trends in the prevalence of diabetes and obesity, the prevalence of NAFLD and its consequences are expected to increase in the near future. The aim of the present study is to present the current data on the prevalence of NAFLD in the Americas. We performed an electronic search of the main databases from January 2000 to September 2013 and identified 356 reports that were reviewed. We focused on the epidemiology and prevalence of known NAFLD risk factors including obesity, T2DM, and the metabolic syndrome (MS). The prevalence of the MS was highest in the United States, Mexico, Costa Rica, Puerto Rico, Chile, and Venezuela. In addition, Puerto Rico, Guyana, and Mexico have the highest prevalence of T2DM in the Americas, while USA has the most people with T2DM. In conclusion, the prevalence rates of NAFLD and obesity were highest in the United States, Belize, Barbados, and Mexico.

  8. 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.

  9. Non-alcoholic fatty liver disease, diet and gut microbiota.

    Science.gov (United States)

    Finelli, Carmine; Tarantino, Giovanni

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) is a severe liver disease that is increasing in prevalence with the worldwide epidemic of obesity and its related insulin-resistance state. Evidence for the role of the gut microbiota in energy storage and the subsequent development of obesity and some of its related diseases is now well established. More recently, a new role of gut microbiota has emerged in NAFLD. The gut microbiota is involved in gut permeability, low-grade inflammation and immune balance, it modulates dietary choline metabolism, regulates bile acid metabolism and produces endogenous ethanol. All of these factors are molecular mechanisms by which the microbiota can induce NAFLD or its progression toward overt non-alcoholic steatohepatitis. Modification of the gut microbiota composition and/or its biochemical capacity by specific dietary or pharmacological interventions may advantageously affect host metabolism. Large-scale intervention trials, investigating the potential benefit of prebiotics and probiotics in improving cardiometabolic health in high-risk populations, are fervently awaited.

  10. Metabolic aspects of adult patients with nonalcoholic fatty liver disease

    Science.gov (United States)

    Abenavoli, Ludovico; Milic, Natasa; Di Renzo, Laura; Preveden, Tomislav; Medić-Stojanoska, Milica; De Lorenzo, Antonino

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver disease and it encompasses a spectrum from simple steatosis to steatohepatitis, fibrosis, or cirrhosis. The mechanisms involved in the occurrence of NAFLD and its progression are probably due to a metabolic profile expressed within the context of a genetic predisposition and is associated with a higher energy intake. The metabolic syndrome (MS) is a cluster of metabolic alterations associated with an increased risk for the development of cardiovascular diseases and diabetes. NAFLD patients have more than one feature of the MS, and now they are considered the hepatic components of the MS. Several scientific advances in understanding the association between NAFLD and MS have identified insulin resistance (IR) as the key aspect in the pathophysiology of both diseases. In the multi parallel hits theory of NAFLD pathogenesis, IR was described to be central in the predisposition of hepatocytes to be susceptible to other multiple pathogenetic factors. The recent knowledge gained from these advances can be applied clinically in the prevention and management of NAFLD and its associated metabolic changes. The present review analyses the current literature and highlights the new evidence on the metabolic aspects in the adult patients with NAFLD. PMID:27610012

  11. NHE1 deficiency in liver: Implications for non-alcoholic fatty liver disease

    Energy Technology Data Exchange (ETDEWEB)

    Prasad, Vikram, E-mail: prasadvm@ucmail.uc.edu [Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine (United States); Chirra, Shivani [Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine (United States); Kohli, Rohit [Department of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children’s Hospital, University of Cincinnati, Cincinnati, OH 45267 (United States); Shull, Gary E. [Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine (United States)

    2014-07-25

    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{sup +}/H{sup +} 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. Effect of Zingiber officinale on fatty liver induced by oxytetracycline in albino rats

    Directory of Open Access Journals (Sweden)

    Eman G.E. Helal* , Samia M. Abd El-Wahab* , Atef M. Moussa Sharaf**

    2012-01-01

    Full Text Available Fatty liver causes were markedly increased in Egyptian people throughout last years. People prefer to use the medicinal plants instead of using chemical compounds because they are cheap and have few side effects compared to chemical compounds. Ginger is a natural dietary rhizome with anti-oxidative, anti-inflammatory, and anti-carcinogenic activities. The aim of this study was to evaluate the possible potential therapeutic and protective effects of Zingiber officinale (ginger against oxytetracyclin-induced fatty liver in an attempt to understand its mechanism of action, which may pave the way for possible therapeutic applications. Material and Methods: Albino rats were divided into two major groups, 15 rats for each. The first group was divided into three sub-groups: a control, b fatty liver group; that was injected intraperitonealy with oxytetracycline (120mg/kg for three consecutive days and c ginger treated group; which was treated with ginger water extract (125 mg/kg for 30 days after fatty liver induction . All animals were scarified after 33 days of the beginning of the experiment. The second group was divided into three subgroups: a control, b fatty liver group; that was injected intraperitonealy with oxytetracycline (120 mg/kg for three consecutive days and c ginger protective group; which received ginger for 15 days before induction of fatty liver, then sacrificed after induction of fatty liver (3 days. Blood samples were collected for biochemical analysis. Liver specimens were obtained and fixed in 10% formalin for histological study. Results: Fatty liver groups showed high significant increase in serum glucose, cholesterol, triglycerides, LDL cholesterol, ALAT, ASAT, GGT, LDH, urea, creatinine and A/G ratio while total protein, albumin, globulin and HDL cholesterol were significantly decreased compared to control group. These biochemical changes were accompanied with histopathological alterations in fatty liver tissue. The treatment

  13. (1)H-Nuclear Magnetic Resonance-Based Plasma Metabolic Profiling of Dairy Cows with Fatty Liver.

    Science.gov (United States)

    Xu, Chuang; Sun, Ling-Wei; Xia, Cheng; Zhang, Hong-You; Zheng, Jia-San; Wang, Jun-Song

    2016-02-01

    Fatty liver is a common metabolic disorder of dairy cows during the transition period. Historically, the diagnosis of fatty liver has involved liver biopsy, biochemical or histological examination of liver specimens, and ultrasonographic imaging of the liver. However, more convenient and noninvasive methods would be beneficial for the diagnosis of fatty liver in dairy cows. The plasma metabolic profiles of dairy cows with fatty liver and normal (control) cows were investigated to identify new biomarkers using (1)H nuclear magnetic resonance. Compared with the control group, the primary differences in the fatty liver group included increases in β-hydroxybutyric acid, acetone, glycine, valine, trimethylamine-N-oxide, citrulline, and isobutyrate, and decreases in alanine, asparagine, glucose, γ-aminobutyric acid glycerol, and creatinine. This analysis revealed a global profile of endogenous metabolites, which may present potential biomarkers for the diagnosis of fatty liver in dairy cows.

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

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Kyoung Yeon [Dept. of Radiology, Anseong Hanju Clinic, Anseong (Korea, Republic of); Lim, Hyun Soo [Dept. of Biomedical Engineering, Chungnam University, Daejeon (Korea, Republic of)

    2012-03-15

    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.

  15. Elevated endotoxin levels in non-alcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    Kumar Sudhesh

    2010-03-01

    Full Text Available Abstract Background Emerging data indicate that gut-derived endotoxin may contribute to low-grade systemic inflammation in insulin resistant states. This study aimed to examine the importance of serum endotoxin and inflammatory markers in non-alcoholic fatty liver disease (NAFLD patients, with and without type 2 diabetes mellitus (T2DM, and to explore the effect of treatment with a lipase inhibitor, Orlistat, on their inflammatory status. Methods Fasted serum from 155 patients with biopsy proven NAFLD and 23 control subjects were analysed for endotoxin, soluble CD14 (sCD14, soluble tumour necrosis factor receptor II (sTNFRII and various metabolic parameters. A subgroup of NAFLD patients were re-assessed 6 and 12 months after treatment with diet alone (n = 6 or diet plus Orlistat (n = 8. Results Endotoxin levels were significantly higher in patients with NAFLD compared with controls (NAFLD: 10.6(7.8, 14.8 EU/mL; controls: 3.9(3.2, 5.2 EU/mL, p Sub-cohort treatment with Orlistat in patients with NAFLD showed significant decreases in ALT (p = 0.006, weight (p = 0.005 and endotoxin (p = 0.004 compared with the NAFLD, non-Orlistat treated control cohort at 6 and 12 months post therapy, respectively. Conclusions Endotoxin levels were considerably increased in NAFLD patients, with marked increases noted in early stage fibrosis compared with controls. These results suggest elevated endotoxin may serve as an early indicator of potential liver damage, perhaps negating the need for invasive liver biopsy. As endotoxin may promote insulin resistance and inflammation, interventions aimed at reducing endotoxin levels in NAFLD patients may prove beneficial in reducing inflammatory burden.

  16. 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...

  17. PPAR/RXR Regulation of Fatty Acid Metabolism and Fatty Acid -Hydroxylase (CYP4 Isozymes: Implications for Prevention of Lipotoxicity in Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    James P. Hardwick

    2009-01-01

    Full Text Available Fatty liver disease is a common lipid metabolism disorder influenced by the combination of individual genetic makeup, drug exposure, and life-style choices that are frequently associated with metabolic syndrome, which encompasses obesity, dyslipidemia, hypertension, hypertriglyceridemia, and insulin resistant diabetes. Common to obesity related dyslipidemia is the excessive storage of hepatic fatty acids (steatosis, due to a decrease in mitochondria -oxidation with an increase in both peroxisomal -oxidation, and microsomal -oxidation of fatty acids through peroxisome proliferator activated receptors (PPARs. How steatosis increases PPAR activated gene expression of fatty acid transport proteins, peroxisomal and mitochondrial fatty acid -oxidation and -oxidation of fatty acids genes regardless of whether dietary fatty acids are polyunsaturated (PUFA, monounsaturated (MUFA, or saturated (SFA may be determined by the interplay of PPARs and HNF4 with the fatty acid transport proteins L-FABP and ACBP. In hepatic steatosis and steatohepatitis, the -oxidation cytochrome P450 CYP4A gene expression is increased even with reduced hepatic levels of PPAR. Although numerous studies have suggested the role ethanol-inducible CYP2E1 in contributing to increased oxidative stress, Cyp2e1-null mice still develop steatohepatitis with a dramatic increase in CYP4A gene expression. This strongly implies that CYP4A fatty acid -hydroxylase P450s may play an important role in the development of steatohepatitis. In this review and tutorial, we briefly describe how fatty acids are partitioned by fatty acid transport proteins to either anabolic or catabolic pathways regulated by PPARs, and we explore how medium-chain fatty acid (MCFA CYP4A and long-chain fatty acid (LCFA CYP4F -hydroxylase genes are regulated in fatty liver. We finally propose a hypothesis that increased CYP4A expression with a decrease in CYP4F genes may promote the progression of steatosis to

  18. Ultrasonographic diagnosis of fatty liver in preoperative evaluation of living liver donor candidates: Histologic correlation

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Seong Hyun; Lee, Won Jae; Lim, Hyo Keun; Kim, Soo Ah; Kim, Seung Hoon; Lee, Soon Jin; Lim, Jae Hoon [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2003-03-15

    To analyze the correlation between the ultrasonographic (US) grading system of fatty liver (FL) and histologic grading system in living liver donor candidates and to investigate the clinical significance of this qualitative US grading system in the selection of living donor candidates. For a recent 21-month period, ninety three living donor candidates who underwent both preoperative US and parenchymal biopsy of the liver were consecutively selected. FL was ultrasonographically graded using the well-known three-Point grading system (ie, mild, moderate and severe degrees) whereas histologic grade of FL was divided into minimal (<10%), mild (11-30%), moderate (31-60%) and severe (>60%) degrees depending upon the percentages of each of macrovesicular, microvesicular and total fat-containing hepatocytes. US grade and histologic grade of FL in each patient were retrospectively correlated according to the US and pathologic records in their databases. Statistical analysis was conducted with the chi-square test and linear by linear association. US findings included the normal liver, mild FL, and moderate FL in 63, 23 and 7 patients, respectively. Analyzed with the total fat content, 38 of 63 patients (60%) whose US finding was normal proved to have FL of various histologic grades. Meanwhile, US grade of FL correlated well with the histologic grade in 16 (53%) of 30 patients who showed mild or moderate FL on US, and in the remaining patients, US grade was more commonly underestimated compared to the histologic grade. All patients with moderate FL on US Proved to have either moderate or severe FL at histology. US grade statistically correlated well with the histologic grade classified by either the total or macrovesicular fat contents (p<.001) while a poor correlation was seen when histologic grade using the microvesicular fat content was used. The well-known qualitative US grading system of fatty liver seems to show a relatively good correlation with the histologic grade

  19. Prevalence of nonalcoholic fatty liver among administrative officers in Shanghai: an epidemiological survey

    Institute of Scientific and Technical Information of China (English)

    Lei Shen; Jian-Gao Fan; Yan Shao; Min-De Zeng; Jun-Rong Wang; Guo-Hao Luo; Ji-Qiang Li; Si-Yao Chen

    2003-01-01

    AIM: To determine the prevalence of nonalcoholic fatty liver in a specific population in Shanghai by an epidemiological survey, and to analyze risk factors of fatty liver.METHODS: Total 4009 administrative officers who denied regular alcohol drinking participated in the survey, and underwent physical examination and laboratory tests. The important parameters were body mass index (BMI), waist hip circumferences ratio (WHR) and levels of serum lipids.Diagnosis of fatty liver was based on established real-time ultrasonographic criteria, the presence of an ultrasonographic pattern consistent with "bright liver", with evident ultrasonographic contrast between hepatic and renal parenchyma, vessel blurring, and narrowing of the lumen of the hepatic veins. Analysis of data was performed through SPSS for Windows statistical package.RESULTS: The overall prevalence of fatty liver was 12.9 %,15.8 % in males and 7.5 % in females, and the prevalence of fatty liver in males younger than 50 years old, was significantly higher (13.3 %) than that of in females (2.7 %).But the difference between the sexes became less significant in people older than 50 years (19.1% vs 18.1%). The prevalence of fatty liver was increased with age; this was markedly presented in females younger than 50 years.Multiple variant regression analysis demonstrated that the prevalence of fatty liver was positively correlated to several risk factors, including male, aging (>50yr), hyperlipidemia,impaired glucose tolerance/diabetes mellitus, hypertension and overweight/obesity.CONCLUSION: There is a high prevalence of nonalcoholic fatty liver among certain population in Shanghai, to which overweight and hyperlipidemia are closely relevant.

  20. OXPHOS-Mediated Induction of NAD+ Promotes Complete Oxidation of Fatty Acids and Interdicts Non-Alcoholic Fatty Liver Disease.

    Science.gov (United States)

    Akie, Thomas E; Liu, Lijun; Nam, Minwoo; Lei, Shi; Cooper, Marcus P

    2015-01-01

    OXPHOS is believed to play an important role in non-alcoholic fatty liver disease (NAFLD), however, precise mechanisms whereby OXPHOS influences lipid homeostasis are incompletely understood. We previously reported that ectopic expression of LRPPRC, a protein that increases cristae density and OXPHOS, promoted fatty acid oxidation in cultured primary hepatocytes. To determine the biological significance of that observation and define underlying mechanisms, we have ectopically expressed LRPPRC in mouse liver in the setting of NAFLD. Interestingly, ectopic expression of LRPPRC in mouse liver completely interdicted NAFLD, including inflammation. Consistent with mitigation of NAFLD, two markers of hepatic insulin resistance--ROS and PKCε activity--were both modestly reduced. As reported by others, improvement of NAFLD was associated with improved whole-body insulin sensitivity. Regarding hepatic lipid homeostasis, the ratio of NAD+ to NADH was dramatically increased in mouse liver replete with LRPPRC. Pharmacological activators and inhibitors of the cellular respiration respectively increased and decreased the [NAD+]/[NADH] ratio, indicating respiration-mediated control of the [NAD+]/[NADH] ratio. Supporting a prominent role for NAD+, increasing the concentration of NAD+ stimulated complete oxidation of fatty acids. Importantly, NAD+ rescued impaired fatty acid oxidation in hepatocytes deficient for either OXPHOS or SIRT3. These data are consistent with a model whereby augmented hepatic OXPHOS increases NAD+, which in turn promotes complete oxidation of fatty acids and protects against NAFLD.

  1. Bile salt recognition by human liver fatty acid binding protein.

    Science.gov (United States)

    Favretto, Filippo; Santambrogio, Carlo; D'Onofrio, Mariapina; Molinari, Henriette; Grandori, Rita; Assfalg, Michael

    2015-04-01

    Fatty acid binding proteins (FABPs) act as intracellular carriers of lipid molecules, and play a role in global metabolism regulation. Liver FABP (L-FABP) is prominent among FABPs for its wide ligand repertoire, which includes long-chain fatty acids as well as bile acids (BAs). In this work, we performed a detailed molecular- and atomic-level analysis of the interactions established by human L-FABP with nine BAs to understand the binding specificity for this important class of cholesterol-derived metabolites. Protein-ligand complex formation was monitored using heteronuclear NMR, steady-state fluorescence spectroscopy, and mass spectrometry. BAs were found to interact with L-FABP with dissociation constants in the narrow range of 0.6-7 μm; however, the diverse substitution patterns of the sterol nucleus and the presence of side-chain conjugation resulted in complexes endowed with various degrees of conformational heterogeneity. Trihydroxylated BAs formed monomeric complexes in which single ligand molecules occupied similar internal binding sites, based on chemical-shift perturbation data. Analysis of NMR line shapes upon progressive addition of taurocholate indicated that the binding mechanism departed from a simple binary association equilibrium, and instead involved intermediates along the binding path. The co-linear chemical shift behavior observed for L-FABP complexes with cholate derivatives added insight into conformational dynamics in the presence of ligands. The observed spectroscopic features of L-FABP/BA complexes, discussed in relation to ligand chemistry, suggest possible molecular determinants of recognition, with implications regarding intracellular BA transport. Our findings suggest that human L-FABP is a poorly selective, universal BA binder.

  2. SIRT7 represses Myc activity to suppress ER stress and prevent fatty liver disease.

    Science.gov (United States)

    Shin, Jiyung; He, Ming; Liu, Yufei; Paredes, Silvana; Villanova, Lidia; Brown, Katharine; Qiu, Xiaolei; Nabavi, Noushin; Mohrin, Mary; Wojnoonski, Kathleen; Li, Patrick; Cheng, Hwei-Ling; Murphy, Andrew J; Valenzuela, David M; Luo, Hanzhi; Kapahi, Pankaj; Krauss, Ronald; Mostoslavsky, Raul; Yancopoulos, George D; Alt, Frederick W; Chua, Katrin F; Chen, Danica

    2013-11-14

    Nonalcoholic fatty liver disease is the most common chronic liver disorder in developed countries. Its pathogenesis is poorly understood, and therapeutic options are limited. Here, we show that SIRT7, an NAD(+)-dependent H3K18Ac deacetylase, functions at chromatin to suppress ER stress and prevent the development of fatty liver disease. SIRT7 is induced upon ER stress and is stabilized at the promoters of ribosomal proteins through its interaction with the transcription factor Myc to silence gene expression and to relieve ER stress. SIRT7-deficient mice develop chronic hepatosteatosis resembling human fatty liver disease. Myc inactivation or pharmacological suppression of ER stress alleviates fatty liver caused by SIRT7 deficiency. Importantly, SIRT7 suppresses ER stress and reverts the fatty liver disease in diet-induced obese mice. Our study identifies SIRT7 as a cofactor of Myc for transcriptional repression and delineates a druggable regulatory branch of the ER stress response that prevents and reverts fatty liver disease.

  3. Quantitative characterization of fatty liver disease using x-ray scattering

    Science.gov (United States)

    Elsharkawy, Wafaa B.; Elshemey, Wael M.

    2013-11-01

    Nonalcoholic fatty liver disease (NAFLD) is a dynamic condition in which fat abnormally accumulates within the hepatocytes. It is believed to be a marker of risk of later chronic liver diseases, such as liver cirrhosis and carcinoma. The fat content in liver biopsies determines its validity for liver transplantation. Transplantation of livers with severe NAFLD is associated with a high risk of primary non-function. Moreover, NAFLD is recognized as a clinically important feature that influences patient morbidity and mortality after hepatic resection. Unfortunately, there is a lack in a precise, reliable and reproducible method for quantification of NAFLD. This work suggests a method for the quantification of NAFLD. The method is based on the fact that fatty liver tissue would have a characteristic x-ray scattering profile with a relatively intense fat peak at a momentum transfer value of 1.1 nm-1 compared to a soft tissue peak at 1.6 nm-1. The fat content in normal and fatty liver is plotted against three profile characterization parameters (ratio of peak intensities, ratio of area under peaks and ratio of area under fat peak to total profile area) for measured and Monte Carlo simulated x-ray scattering profiles. Results show a high linear dependence (R2>0.9) of the characterization parameters on the liver fat content with a reported high correlation coefficient (>0.9) between measured and simulated data. These results indicate that the current method probably offers reliable quantification of fatty liver disease.

  4. Nutritional Modulation of Non-Alcoholic Fatty Liver Disease and Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Hannele Yki-Järvinen

    2015-11-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD covers a spectrum of disorders ranging from simple steatosis (non-alcoholic fatty liver, NAFL to non-alcoholic steatohepatitis (NASH and cirrhosis. NAFL increases the risk of liver fibrosis. If the liver is fatty due to causes of insulin resistance such as obesity and physical inactivity, it overproduces glucose and triglycerides leading to hyperinsulinemia and a low high-density lipoprotein (HDL cholesterol concentration. The latter features predispose to type 2 diabetes and cardiovascular disease (CVD. Understanding the impact of nutritional modulation of liver fat content and insulin resistance is therefore of interest for prevention and treatment of NAFLD. Hypocaloric, especially low carbohydrate ketogenic diets rapidly decrease liver fat content and associated metabolic abnormalities. However, any type of caloric restriction seems effective long-term. Isocaloric diets containing 16%–23% fat and 57%–65% carbohydrate lower liver fat compared to diets with 43%–55% fat and 27%–38% carbohydrate. Diets rich in saturated (SFA as compared to monounsaturated (MUFA or polyunsaturated (PUFA fatty acids appear particularly harmful as they increase both liver fat and insulin resistance. Overfeeding either saturated fat or carbohydrate increases liver fat content. Vitamin E supplementation decreases liver fat content as well as fibrosis but has no effect on features of insulin resistance.

  5. Amelioration effects of traditional Chinese medicine on alcohol-induced fatty liver

    Institute of Scientific and Technical Information of China (English)

    Hyun-Jeong Kwon; Yun-Young Kim; Se-Young Choung

    2005-01-01

    AIM: To examine the effects of traditional Chinese medicine (TCM) on alcohol-induced fatty liver in rats. TCM consists of Astragalus membranaceus, Morus alba, Crataegus pinnatifida,Alisma orientale, Salvia miltiorrhiza, and Pueraria lobata.METHODS: The rats were separated randomly into five groups. One (the CD group) was fed a control diet for 10 wk, another (the ED group) fed an ethanol-containing isocaloric liquid diet for 10 wk, and the last three (the TCM group) were fed an ethanol-containing isocaloric liquid TCM2000, respectively) weekly during the last 4 wk.RESULTS: ED group developed fatty liver according to lipid profile and liver histological findings. Compared with the control group, liver/body weight, serum triglyceride (TG) and total cholesterol (TC), liver TG and TC, serum alanine aminotransferase (ALT) and aspartic aminotransferase (AST) significantly increased in the ED group.Whereas, in the rats administered with TCM, liver/body weight, serum TG and TC, liver TG and TC, serum ALT and AST were significantly decreased, and the degree of hepatic lipid droplets was markedly improved compared with those in the ED group.CONCLUSION: TCM treatment causes significant reduction in alcohol-induced lipid hepatic accumulation,reversing fatty liver and liver damage, and can be usedas a remedy for alcoholic fatty liver.

  6. Current treatment options for nonalcoholic fatty liver disease and nonalcoholic steatohepatitis.

    Science.gov (United States)

    Beaton, Melanie D

    2012-06-01

    Nonalcoholic fatty liver disease is the leading cause of liver disease in western society. It is a cause of end-stage liver disease, with increased mortality secondary to cirrhosis and its complications. It is also recognized that cardiovascular disease is a significant cause of death in these patients. Significant work evaluating various treatments has been performed in recent years; however, to date, no ideal therapy exists. Lifestyle modification remains the cornerstone of management. The present article reviews the current status of various treatment modalities evaluated in nonalcoholic fatty liver disease.

  7. Cholesterol Interactions with Fatty Acids and DMPC Phospholipids of Liver Membranes

    Directory of Open Access Journals (Sweden)

    Prateek Shukla

    2016-12-01

    Full Text Available Cholesterol and fatty acidsis important subject in liver to different model of regulation for realizing the evolution of vertebrates. The major solubility of cholesterol in bilayers of glycerol-phospholipids is between 65 and 50 mole%,relevant on the bilayerof lipid membrane but they cannot alone form multi layered structures. Livers from the transgenic rat showed increases in mRNAs encoding various enzymes of cholesterol synthesis, the LDL’s receptor and fatty acid synthesis. Based on our previous works we have modeled and simulated various molecules of that Cholesterol in binding to membrane. A number of computational chemistry studies carried out to understand of the cholesterol parallel to fatty acid synthesis (FAS for preventing the fatty liver disease.In this work ELF, LOL, ECP, electrical properties such as electron densities, energy densities, and potential energy densities, eta index forsome of the fatty acidshave been calculated.

  8. Does Vitamin C Deficiency Promote Fatty Liver Disease Development?

    Directory of Open Access Journals (Sweden)

    David Højland Ipsen

    2014-12-01

    Full Text Available Obesity and the subsequent reprogramming of the white adipose tissue are linked to human disease-complexes including metabolic syndrome and concurrent non-alcoholic fatty liver disease (NAFLD and non-alcoholic steatohepatitis (NASH. The dietary imposed dyslipidemia promotes redox imbalance by the generation of excess levels of reactive oxygen species and induces adipocyte dysfunction and reprogramming, leading to a low grade systemic inflammation and ectopic lipid deposition, e.g., in the liver, hereby promoting a vicious circle in which dietary factors initiate a metabolic change that further exacerbates the negative consequences of an adverse life-style. Large epidemiological studies and findings from controlled in vivo animal studies have provided evidence supporting an association between poor vitamin C (VitC status and propagation of life-style associated diseases. In addition, overweight per se has been shown to result in reduced plasma VitC, and the distribution of body fat in obesity has been shown to have an inverse relationship with VitC plasma levels. Recently, a number of epidemiological studies have indicated a VitC intake below the recommended daily allowance (RDA in NAFLD-patients, suggesting an association between dietary habits, disease and VitC deficiency. In the general population, VitC deficiency (defined as a plasma concentration below 23 μM affects around 10% of adults, however, this prevalence is increased by an adverse life-style, deficiency potentially playing a broader role in disease progression in specific subgroups. This review discusses the currently available data from human surveys and experimental models in search of a putative role of VitC deficiency in the development of NAFLD and NASH.

  9. Nonalcoholic fatty liver disease in asymptomatic Brazilian adolescents

    Institute of Scientific and Technical Information of China (English)

    Raquel Rocha; Helma Pinchemel Cotrim; Almir Galv(a)o Vieira Bitencourt; Daniel Batista Valente Barbosa; Adméia Souza Santos; Alessandro de Moura Almeida; Bruno Cunha; Isabel Guimar(a)es

    2009-01-01

    AIM: To evaluate the prevalence and clinical characteristics of Nonalcoholic fatty liver disease (NAFLD) among asymptomatic Brazilian adolescents.METHODS: Transversal observational study included asymptomatic adolescents with central obesity from private and public schools in Salvador-Bahia, northeastern Brazil. The children answered a questionnaire that included age, gender, race, and medical history, and were submitted to a complete physical exam and abdominal ultrasound. Biochemical exams included: ALT, AST, GGT,C reactive protein (CRP), fasting glucose, insulin, cholesterol and triglycerides. Criteria for NAFLD included: the presence of steatosis in ultrasound and/or high level of ALT, negative or occasional historic of intake of alcohol (≤ 140 g/wk), negative investigation for hepatitis A, B, C,auto-immune hepatitis, Wilson disease and hemochromatosis.RESULTS: From October, 2005 to October, 2006, the study included 1801 subjects between 11 and 18 years of age and a mean age of 13.7±2.0 years.One hundred ninety-nine had central obesity. The prevalence of NAFLD was 2.3%, most of whom were male and white. Insulin resistance (IR) was observed in 22.9% of them and had positive correlations with ALT and GGT ( P < 0.05). Elevated CRP was observed in 6.9% of the cases; however, it was not associated with WC,IR or liver enzymes.CONCLUSION: The prevalence of NAFLD in Brazilian adolescents was low. The ethnicity may have influence this frequency in the population studied, which had a large proportion of African descendents.

  10. Comparative efficacy of interventions on nonalcoholic fatty liver disease (NAFLD)

    Science.gov (United States)

    Sawangjit, Ratree; Chongmelaxme, Bunchai; Phisalprapa, Pochamana; Saokaew, Surasak; Thakkinstian, Ammarin; Kowdley, Kris V.; Chaiyakunapruk, Nathorn

    2016-01-01

    Abstract Background: The prevalence of nonalcoholic fatty liver disease (NAFLD) has significantly increased over the last decades. Despite existence of several interventions, there remains unclear which interventions work the best. Methods: A systematic review and network meta-analysis of randomized trials comparing efficacy of all treatment options in NAFLD were performed to determine comparative efficacy and safety of interventions in the management of NAFLD. Several electronic databases were searched up to Nov 15, 2015. Outcomes include liver histological outcomes (i.e., fibrosis), all-cause mortality, cirrhosis, and safety. A network meta-analysis was applied to estimate pooled risk ratios (RR). Quality of evidence was assessed using GRADE criteria. Results: A total of 44 studies (n = 3802) were eligible. When compared with placebo, obeticholic acid (OCA) was the only intervention that significantly improved fibrosis with RR (95% CI) of 1.91 (1.15, 3.16), while pentoxyfylline (PTX) demonstrated improved fibrosis without statistical significance with RR (95% CI) of 2.27 (0.81, 6.36). Only thiazolidinedione (TZD) and vitamin E use resulted in significant increase in resolution of NASH, while OCA, TZD, and vitamin E significantly improved other outcomes including NAS, steatosis, ballooning, and inflammation outcomes. Quality of evidence varied from very low (i.e., metformin, PTX on mean change of ballooning grade) to high (OCA, TZD, vitamin E on improving histological outcomes). Limitations of this study were lack of relevant long-term outcomes (e.g., cirrhosis, death, safety), possible small study effect, and few head-to-head studies. Conclusions: Our study suggests potential efficacy of OCA, TZD, and vitamin E in improving histologic endpoints in NAFLD. These findings are however based on a small number of studies. Additional studies are awaited to strengthen this network meta-analysis. PMID:27512874

  11. Altered Hepatic Transport by Fetal Arsenite Exposure in Diet-Induced Fatty Liver Disease.

    Science.gov (United States)

    Ditzel, Eric J; Li, Hui; Foy, Caroline E; Perrera, Alec B; Parker, Patricia; Renquist, Benjamin J; Cherrington, Nathan J; Camenisch, Todd D

    2016-07-01

    Non-alcoholic fatty liver disease can result in changes to drug metabolism and disposition potentiating adverse drug reactions. Furthermore, arsenite exposure during development compounds the severity of diet-induced fatty liver disease. This study examines the effects of arsenite potentiated diet-induced fatty liver disease on hepatic transport in male mice. Changes were detected for Mrp2/3/4 hepatic transporter gene expression as well as for Oatp1a4/2b1/1b2. Plasma concentrations of Mrp and Oatp substrates were increased in arsenic exposure groups compared with diet-only controls. In addition, murine embryonic hepatocytes and adult primary hepatocytes show significantly altered transporter expression after exposure to arsenite alone: a previously unreported phenomenon. These data indicate that developmental exposure to arsenite leads to changes in hepatic transport which could increase the risk for ADRs during fatty liver disease.

  12. [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.

  13. Positional specificity of saturated and unsaturated fatty acids in phosphatidic acid from rat liver

    NARCIS (Netherlands)

    Possmayer, F.; Scherphof, G.L.; Dubbelman, T.M.A.R.; Golde, L.M.G. van; Deenen, L.L.M. van

    1969-01-01

    1. 1. The relative incorporation of a number of radioactive fatty acids into the different glycerolipids of rat liver microsomes has been investigated. 2. 2. Studies on the distribution of the radioactivity incorporated into phosphatidylcholine, phosphatidylethanolamine and phosphatidic acid showed

  14. Focal spared area in fatty liver simulating a mass. Scintigraphic evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Newman, J.S.; Oates, E.; Arora, S.; Kaplan, M. (Department of Radiology, New England Medical Center Hospitals, Tufts University School of Medicine, Boston, MA (USA))

    1991-07-01

    The characterization of focally spared areas in a fatty liver may at times be problematic. This report illustrates the unique diagnostic role that combined xenon-133/technetium-99m sulfur colloid scintigraphy can play in such cases.

  15. Aspects of the regulation of long-chain fatty acid oxidation in bovine liver

    Energy Technology Data Exchange (ETDEWEB)

    Jesse, B.W.; Emery, R.S.; Thomas, J.W.

    1986-09-01

    Factors involved in regulation of bovine hepatic fatty acid oxidation were examined using liver slices. Fatty acid oxidation was measured as the conversion of l-(/sup 14/C) palmitate to /sup 14/CO/sub 2/ and total (/sup 14/C) acid-soluble metabolites. Extended (5 to 7 d) fasting of Holstein cows had relatively little effect on palmitate oxidation to acid-soluble metabolites by liver slices, although oxidation to CO/sup 2/ was decreased. Feeding a restricted roughage, high concentrate ration to lactating cows resulted in inhibition of palmitate oxidation. Insulin, glucose, and acetate inhibited palmitate oxidation by bovine liver slices. The authors suggest the regulation of bovine hepatic fatty acid oxidation may be less dependent on hormonally induced alterations in enzyme activity as observed in rat liver and more dependent upon action of rumen fermentation products or their metabolites on enzyme systems involved in fatty acid oxidation.

  16. Semiquantitative analysis of fatty liver using spectroscopic imaging by dephasing amplitude changing (SIDAC)

    Energy Technology Data Exchange (ETDEWEB)

    Ohtomo, Kuni; Yamada, Shinwa; Aoyama, Hiromu

    1987-08-01

    The potential utility of spectroscopic imaging by dephasing amplitude changing (SIDAC) was evaluated in fatty infiltration in rats induced by cholesterol and ethanol. There was an excellent correlation between the in vivo fat-to-water ratio obtained from SIDAC and that in liver specimens from in vitro measurement (r = 0.97). SIDAC is a promising method for semiquantitative analysis of fatty infiltration of the liver.

  17. Sex Difference in the Association between Serum Homocysteine Level and Non-Alcoholic Fatty Liver Disease

    Science.gov (United States)

    Won, Bo-Youn; Lee, Soo-Hyun; Yun, Sung-Hwan; Kim, Moon-Jong; Park, Kye-Seon; Kim, Young-Sang; Haam, Ji-Hee; Kim, Hyung-Yuk; Kim, Hye-Jung; Park, Ki-Hyun

    2016-01-01

    Background The relationship between serum homocysteine levels and non-alcoholic fatty liver disease is poorly understood. This study aims to investigate the sex-specific relationship between serum homocysteine level and non-alcoholic fatty liver disease in the Korean population. Methods This cross-sectional study included 150 men and 132 women who participated in medical examination programs in Korea from January 2014 to December 2014. Patients were screened for fatty liver by abdominal ultrasound and patient blood samples were collected to measure homocysteine levels. Patients that consumed more than 20 grams of alcohol per day were excluded from this study. Results The homocysteine level (11.56 vs. 8.05 nmol/L) and the proportion of non-alcoholic fatty liver disease (60.7% vs. 19.7%) were significantly higher in men than in women. In men, elevated serum homocysteine levels were associated with a greater prevalence of non-alcoholic fatty liver disease (quartile 1, 43.6%; quartile 4, 80.6%; P=0.01); however, in females, there was no significant association between serum homocysteine levels and the prevalence of non-alcoholic fatty liver disease. In the logistic regression model adjusted for age and potential confounding parameters, the odds ratio for men was significantly higher in the uppermost quartile (model 3, quartile 4: odds ratio, 6.78; 95% confidential interval, 1.67 to 27.56); however, serum homocysteine levels in women were not associated with non-alcoholic fatty liver disease in the crude model or in models adjusted for confounders. Conclusion Serum homocysteine levels were associated with the prevalence of non-alcoholic fatty liver disease in men. PMID:27468343

  18. Carotid lesions in outpatients with nonalcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    Stefano Ramilli; Stefano Pretolani; Antonio Muscari; Barbara Pacelli; Vincenzo Arienti

    2009-01-01

    AIM: To ascertain whether carotid lesions are more prevalent in outpatients with incidental findings of nonalcoholic fatty liver disease (NAFLD) at abdominal ultrasound (US). METHODS: One hundred and fifty-four consecutive outpatients (age range 24-90 years, both sexes) referred by general practitioners for abdominal US, and drinking less than 20 g alcohol/day, underwent carotid US for an assessment of carotid intima-media thickness (c-IMT) and carotid plaque prevalence. Hepatic steatosis, visceral fat thickness and subcutaneous fat thickness were also assessed at ultrasonography. RESULTS: Higher c-IMT values were found in the presence of NAFLD (90 patients), even after adjustment for indices of general and abdominal obesity and for the principal cardiovascular risk factors (0.84 ± 0.10 mm vs 0.71 ± 0.10 mm, P < 0.001). The prevalence of carotid plaques was 57.8% in the patients with NAFLD vs 37.5% in the patients without this condition ( P = 0.02). The adjusted relative risk of having carotid plaques for paients with NAFLD was 1.85 (95% CI: 1.33-2.57, P < 0.001). CONCLUSION: An incidental finding of hepatic steatosis may suggest the presence of silent carotid atherosclerotic lesions.

  19. Association between nonalcoholic fatty liver disease and coronary artery disease

    Directory of Open Access Journals (Sweden)

    Consuelo P. Vilar

    2013-06-01

    Full Text Available OBJECTIVE: Although some investigations have shown a relationship between nonalcoholic fatty liver disease (NAFLD and cardiovascular diseases, there are few studies analyzing the relationship between NAFLD and coronary artery disease (CAD. The aim of this article was to review the relationship between NAFLD and CAD and the methods of diagnosis used to assess such relationship. METHODS: A review was performed using search engines of indexed scientific material, including MEDLINE (by PubMed, Web of Science, IBECS, and LILACS, to identify articles published in Portuguese, English, and Spanish until August, 2012. The studies were eligible if they included the following data: place and year of publication, prevalence and methods used to diagnose NAFLD (ultrasound, computed tomography, nuclear magnetic resonance, or biopsy and CAD (coronary angiography, or computed tomography, and the exclusion of patients due to alcohol consumption greater than 20 g/day. RESULTS: Ten articles were selected, most of which were cross-sectional studies. The studies mostly observed the association between NAFLD and the presence and severity of CAD. CONCLUSION: The analysis of the review showed that evaluating the existence of NAFLD in patients with CAD from its subclinical form up to the symptomatic clinical form is important due to the higher risk of acute myocardial infarction and consequent increase of mortality.

  20. Telomere Dysfunction in Nonalcoholic Fatty Liver Disease and Cryptogenic Cirrhosis.

    Science.gov (United States)

    Laish, Ido; Mannasse-Green, Batya; Hadary, Ruth; Biron-Shental, Tal; Konikoff, Fred M; Amiel, Aliza; Kitay-Cohen, Yona

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) and cryptogenic cirrhosis (CC) are considered preneoplastic conditions that might progress to hepatocellular carcinoma. We evaluated parameters of telomere dysfunction in these patient groups to study the correlation between telomere length and the progression of NAFLD. We analyzed peripheral lymphocytes from 22 patients with NAFLD, 20 patients with CC, and 20 healthy, age-matched controls. Telomere length was analyzed using quantitative fluorescence in situ hybridization, and cellular senescence was evaluated by the percentage of cells with senescence-associated heterochromatin foci. The expression of telomerase reverse transcriptase (hTERT) mRNA was measured using polymerase chain reaction, and telomere capture (TC) was assessed with 2 Cytocell probes, 15qter and 13qter. Shorter telomere length and increased cellular senescence was demonstrated in patients with NAFLD, compared to the CC patients and healthy controls. While hTERT mRNA was significantly decreased, TC was increased in CC patients, compared to the NAFLD group and healthy individuals. Thus, there is a correlation between hTERT mRNA expression and telomere length in patients with NAFLD, which might be related to associated metabolic disorders and the risk of malignant transformation. Patients with CC, on the contrary, elongate their telomeres through the TC mechanism.

  1. Naturally Occurring Stilbenoid TSG Reverses Non-Alcoholic Fatty Liver Diseases via Gut-Liver Axis.

    Directory of Open Access Journals (Sweden)

    Pei Lin

    Full Text Available The gut-liver axis is largely involved in the development of non-alcoholic fatty liver disease (NAFLD. We investigated whether 2, 3, 5, 4'-tetrahydroxy-stilbene-2-O-β-D-glucoside (TSG could reverse NAFLD induced by a high-fat diet (HFD and whether it did so via the gut-liver axis. Results showed that TSG could reduce the accumulation of FFA and it did so by reducing the expression of L-FABP and FATP4. TSG regulated gut microbiota balanced and increased the protein expression of ZO-1 and occludin, which could improve the function of the intestinal mucosal barrier and reduce serum LPS content by about 25%. TSG reduced TL4 levels by 56% and NF-κB expression by 23% relative to the NAFLD model group. This suggests that prevention of NAFLD by TSG in HFD-fed rats is mediated by modulation of the gut microbiota and TLR4/NF-κB pathway, which may alleviate chronic low-grade inflammation by reducing the exogenous antigen load on the host.

  2. Topical Formulation Comprising Fatty Acid Extract from Cod Liver Oil: Development, Evaluation and Stability Studies

    OpenAIRE

    2016-01-01

    The purpose of this study was to develop a pharmaceutical formulation containing fatty acid extract rich in free omega-3 fatty acids such as eicosapentaenoic acid and docosahexaenoic acid for topical use. Although the health benefits of cod liver oil and other fish oils taken orally as a dietary supplement have been acknowledged and exploited, it is clear that their use can be extended further to cover their antibacterial properties. In vitro evaluation showed that 20% (v/v) fatty acid extrac...

  3. Alcoholic fatty liver in rats: Role of fat and ethanol intake

    Energy Technology Data Exchange (ETDEWEB)

    Sankaran, H.; Deveney, C.W. (VA Medical Centers, Portland, OR (United States)); Larkin, E.C.; Rao, G.A. (VA Medical Centers, Martinez, CA (United States))

    1991-03-11

    The claim that high intake of both ethanol and fat is essential to induce fatty liver and high blood alcohol levels (BAL) was tested. Two groups of rats were fed liquid diets containing 26% and 36% of calories as ethanol respectively. After 4 weeks, all rats were bled for BAL and some were sacrificed to obtain liver morphology. Remaining rats in Group 1 (26% ethanol) were switched to 36% ethanol diet and Group 2 (36% ethanol) to 26% ethanol diet. All rats were sacrificed after 4 weeks to obtain blood for BAL and liver morphology. The results indicate that high ethanol intake and high fat ingestion is not the criterion for induction of fatty liver. Inadequate ingestion of macronutrients plays a major role in alcoholic fatty liver and BAL.

  4. Sex impact on the quality of fatty liver and its genetic determinism in mule ducks.

    Science.gov (United States)

    Marie-Etancelin, C; Retailleau, B; Alinier, A; Vitezica, Z G

    2015-09-01

    Recent changes to French regulations now allow farmers to produce "foie gras" from both male and female mule ducks. The aim of this study was to assess the quality of female fatty liver and to compare, from a phenotypic and genetic point of view, liver quality in males and females. A total of 914 mule ducks (591 males and 323 females), hatched in a single pedigree batch, were reared until 86 d of age and then force-fed for 12 d, before being slaughtered. Carcasses and livers were weighed and liver quality was assessed by grading the extent of liver veining and measuring the liver melting rate, either after sterilization of 60 g of liver or pasteurization of 180 g of liver. Sexual dimorphism was observed in favor of males, with a difference of approximately 10% in carcass and liver weights and up to 54% for the liver melting rate. Moreover, one-third of female livers showed moderate to high veining, whereas this was not the case for male livers. The fatty livers of female mule ducks are, therefore, of poorer quality and could not be transformed into a product with the appellation "100% fatty liver." According to sex and parental line, heritability values ranged from 0.12 ± 0.05 to 0.18 ± 0.07 for fatty liver weight and from 0.09 ± 0.05 to 0.18 ± 0.05 for the 2 melting rate traits. The genetic correlations between the fatty liver weight and both melting rates were high (greater than +0.80) in the Muscovy population, whereas in the Pekin population, the liver weight and melting rates were less strongly correlated (estimates ranging from +0.36 ± 0.30 to +0.45 ± 0.28). Selection for lower liver melting rates without reducing the liver weight would, therefore, be easier to achieve in the Pekin population. Finally, as the 2 melting rate measurements are highly correlated (0.91 and over 0.95 for phenotypic and genetic correlations, respectively), we suggest using the easiest method, that is, sterilization of 60 g of liver.

  5. Differential DNA methylation of genes involved in fibrosis progression in non-alcoholic fatty liver disease and alcoholic liver disease.

    OpenAIRE

    Zeybel, Müjdat; Hardy, Timothy; Robinson, Stuart M.; Fox, Christopher; Anstee, Quentin M.; Ness, Thomas; Masson, Steven; Masson, Steven; French, Jeremy; White, Steve; Mann, Jelena

    2015-01-01

    RESEARCH Open Access Differential DNA methylation of genes involved in fibrosis progression in non-alcoholic fatty liver disease and alcoholic liver disease Müjdat Zeybel1, Timothy Hardy1, Stuart M Robinson1, Christopher Fox1, Quentin M Anstee1, Thomas Ness2, Steven Masson1, John C Mathers1, Jeremy French1, Steve White1 and Jelena Mann1* Abstract Background: Chronic liver injury can lead to the development of liver fibrosis and cirrhosis but only in a minority of patie...

  6. EX VIVO STUDY OF QUANTITATIVE ULTRASOUND PARAMETERS IN FATTY RABBIT LIVERS

    Science.gov (United States)

    Ghoshal, Goutam; Lavarello, Roberto J.; Kemmerer, Jeremy P.; Miller, Rita J.; Oelze, Michael L.

    2012-01-01

    Nonalcoholic fatty liver disease (NAFLD) affects more than 30% of Americans, and with increasing problems of obesity in the United States, NAFLD is poised to become an even more serious medical concern. At present, accurate classification of steatosis (fatty liver) represents a significant challenge. In this study, the use of high-frequency (8 to 25 MHz) quantitative ultrasound (QUS) imaging to quantify fatty liver was explored. QUS is an imaging technique that can be used to quantify properties of tissue giving rise to scattered ultrasound. The changes in the ultrasound properties of livers in rabbits undergoing atherogenic diets of varying durations were investigated using QUS. Rabbits were placed on a special fatty diet for 0, 3, or 6 weeks. The fattiness of the livers was quantified by estimating the total lipid content of the livers. Ultrasonic properties, such as speed of sound, attenuation, and backscatter coefficients, were estimated in ex vivo rabbit liver samples from animals that had been on the diet for varying periods. Two QUS parameters were estimated based on the backscatter coefficient: effective scatterer diameter (ESD) and effective acoustic concentration (EAC), using a spherical Gaussian scattering model. Two parameters were estimated based on the backscattered envelope statistics (the k parameter and the μ parameter) according to the homodyned K distribution. The speed of sound decreased from 1574 to 1565 m/s and the attenuation coefficient increased from 0.71 to 1.27 dB/cm/MHz, respectively, with increasing fat content in the liver. The ESD decreased from 31 to 17 μm and the EAC increased from 38 to 63 dB/cm3 with increasing fat content in the liver. A significant increase in the μ parameter from 0.18 to 0.93 scatterers/mm3 was observed with increasing fat content in the liver samples. The results of this study indicate that QUS parameters are sensitive to fat content in the liver. PMID:23062376

  7. The Effects of Metabolic Surgery on Fatty Liver Disease and Nonalcoholic Steatohepatitis.

    Science.gov (United States)

    Clanton, Jesse; Subichin, Michael

    2016-08-01

    Nonalcoholic fatty liver disease (NAFLD) is an under-recognized but increasingly important manifestation of the metabolic syndrome. Bariatric surgery, both through direct weight loss and more indirect effects on insulin resistance and improvements in inflammatory proteins, can have a profound effect on NAFLD, resulting in improvement or resolution of even high-grade liver disease.

  8. Metabolic adaptations in models of fatty liver disease : Of mice and math

    NARCIS (Netherlands)

    Hijmans, Brenda

    2017-01-01

    The increasing incidence of overweight is accompanied by a plethora of medical symptoms together called the metabolic syndrome. Non-alcoholic fatty liver disease, characterized by persistent storage of lipids in the liver, is regarded as the hepatic component of the metabolic syndrome. An imbalance

  9. The Potential of Flavonoids in the Treatment of Non-alcoholic Fatty Liver Disease

    NARCIS (Netherlands)

    van de Wier, B.; Koek, Ger H.; Bast, Aalt; Haenen, Guido R.M.

    2015-01-01

    The contemporary pathophysiological model of non-alcoholic fatty liver disease (NAFLD) consists of multiple parallel pathways with a dynamic cross talk that cumulate in steatosis and inflammation and ultimately fibrosis, cirrhosis, liver failure and hepatocellular carcinoma. So far, no pharmacologic

  10. Omega-3 fatty acids for the treatment of non-alcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    Matteo Nicola Dario Di Minno; Anna Russolillo; Roberta Lupoli; Pasquale Ambrosino; Alessandro Di Minno; Giovanni Tarantino

    2012-01-01

    Non-alcoholic fatty liver disease (NAFLD) has been recognized as a major health burden.It is the most important cause of chronic liver disease and a major independent cardiovascular risk factor.Lacking a definite treatment for NAFLD,a specific diet and an increase in physical activity represent the most commonly used therapeutic approaches.In this review,major literature data about the use of omega-3 polyunsaturated fatty acids (n-3 PUFAs) as a potential treatment of NAFLD have been described.n-3 PUFAs,besides having a beneficial impact on most of the cardio-metabolic risk factors (hypertension,hyperlipidemia,endothelial dysfunction and atherosclerosis) by regulating gene transcription factors [i.e.,peroxisome proliferator-activated receptor (PPAR)α,PPARγ,sterol regulatory element-binding protein-1,carbohydrate responsive element-binding protein],impacts both lipid metabolism and on insulin sensitivity.In addition to an enhancement of hepatic beta oxidation and a decrease of the endogenous lipid production,n-3 PUFAs are able to determine a significant reduction of the expression of pro-inflammatory molecules (tumor necrosis factor-α and interleukin-6) and of oxygen reactive species.Further strengthening the results of the in vitro studies,both animal models and human intervention trials,showed a beneficial effect of n-3 PUFAs on the severity of NAFLD as expressed by laboratory parameters and imaging measurements.Despite available results provided encouraging data about the efficacy of n-3 PUFAs as a treatment of NAFLD in humans,well-designed randomized controlled trials of adequate size and duration,with histological endpoints,are needed to assess the long-term safety and efficacy of PUFA,as well as other therapies,for the treatment of NAFLD and non-alcoholic steatohepatitis patients.It is worthwhile to consider that n-3 PUFAs cannot be synthesized by the human body and must be derived from exogenous sources (fish oil,flaxseeds,olive oil) which are typical foods

  11. Non-alcoholic fatty liver disease: a new epidemic in children.

    Science.gov (United States)

    Ciocca, Mirta; Ramonet, Margarita; Álvarez, Fernando

    2016-12-01

    Non-alcoholic fatty liver disease is considered one of the most common causes of liver disease in adults and children, consistent with the increased prevalence of obesity in both populations worldwide. It is a multifactorial condition involving a broad spectrum of liver diseases than range from simple steatosis to steatohepatitis, and characterized by histological findings of inflammation and fibrosis. Its pathogenesis and progression are not fully understood yet, and a more complete understanding of liver disease may aid in developing new therapies and noninvasive diagnostic tools. Liver biopsy remains the gold standard for disease staging. Although lifestyle and diet modifications are the keys in non-alcoholic fatty liver disease treatment, the development of new drugs may be promising for patients failing first-line therapy.

  12. Smoking is not associated with nonalcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    Norberto C Chavez-Tapia; Javier Lizardi-Cervera; Oliver Perez-Bautista; Martha H Ramos-Ostos; Misael Uribe

    2006-01-01

    AIM: To analyze the relationship between smoking and nonalcoholic fatty liver disease (NAFLD).METHODS: This is a cross-sectional study of a healthy population, carried out in a check-up unit of a university hospital in Mexico City. We enrolled 933 subjects, 368 current smokers (cases) and 565 persons who had never smoked (controls). Demographic, metabolic and biochemical variables were measured in the two groups. NAFLD was determined by ultrasound and metabolic syndrome according to ATPⅢ.RESULTS: A total of 548 men (205 cases and 343 controls) and 337 women (114 cases and 223 controls) were included in the analysis. Statistical differences between cases and controls were observed only in high blood pressure prevalence (6.6% vs 11.3%, P <0.05; cases and controls respectively), high-density lipoproteins (1.00 + 0.26 vs 1.06 + 0.28 mmol/L, P <0.005), triglycerides (2.18 + 1.49 vs 1.84 + 1.1 mmol/L,P < 0.001), and erythrocyte sedimentation rate (11.3± 9.3 vs 13.5 ± 11.9 mm/h, P < 0.001). No differences were observed in the prevalence of NAFLD (22.27%vs 29.68%, P = NS) and metabolic syndrome (41.69%vs 36.74%, P = NS). Univariate analysis showed that smoking was not a risk factor for NAFLD (OR = 0.89, 95% CI 0.65-1.21).CONCLUSION: No differences in NAFLD prevalence were observed between current smokers and nonsmokers, and furthermore, no differences were observed in heavy smokers (more than 20 packs/year), indicating that there is no relationship between smoking and NAFLD.

  13. A case of acute viral hepatitis interfering with acute fatty liver disease of pregnancy

    Directory of Open Access Journals (Sweden)

    Abdulkadir Turgut

    2013-03-01

    Full Text Available Acute hepatitis A is a rarely seen infection during pregnancy.In terms of clinical and laboratory findings, it can beinterfere with acute fatty liver disease which can be quitemortal during pregnancy. Since liver function tests are elevatedin both conditions, hepatitis A infection should alsobe kept in mind in differential diagnosis. We present a 30year-old pregnant woman with 35 weeks of gestation whopresented to our clinic with a suspection of acute fattyliver disease but finally diagnosed as acute hepatitis A infection.J Clin Exp Invest 2013; 4 (1: 123-125Key words: Hepatitis A, pregnancy, acute fatty liver disease

  14. The blind men 'see' the elephant-the many faces of fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Nonalcoholic fatty liver disease (NAFLD) is a group of diseases with excess fat in liver in the absence of a poorly defined limit of alcohol consumption.Most common variety,a universal public health problem,is associated with insulin resistance caused by a host of genetic and epigenetic defects modulated by life style and environmental factors.In fact the term NAFLD is loose to incorporate so many etiologies except alcoholism and few other etiologies,presenting as fat in liver.However as a sign fatty liver is very important in predicting the risk of diabetes,cardiovascular disease,stroke,cirrhosis and cancer,Abnormal fat accumulation can result from several defects in nuclear receptors associated with lipid sensing,synthesis and oxidation like LXR,FXR,SREBP,ChREBP and PPAR;defects in the lipid influx-efflux channels,insulin signaling,proteins involved in fatty add catabolism,defects in adipose tissue development and function,inappropriate nutrition and finally defects in neural regulatory mechanisms.The progress of the disease is determined by the basic defects which results in fat accumulation, an individual's immunological response to the accumulated fat and its derivatives and the oxidant stress response.Congregation of unrelated genetic defects under same diagnosis 'NAFLD'can result in inefficient patient management.Further studies are required to understand the molecular basis of fatty liver to enable a personalized management of diseases presenting as fatty liver in the absence of alcohol abuse.

  15. A "systems medicine" approach to the study of non-alcoholic fatty liver disease.

    Science.gov (United States)

    Petta, Salvatore; Valenti, Luca; Bugianesi, Elisabetta; Targher, Giovanni; Bellentani, Stefano; Bonino, Ferruccio

    2016-03-01

    The prevalence of fatty liver (steatosis) in the general population is rapidly increasing worldwide. The progress of knowledge in the physiopathology of fatty liver is based on the systems biology approach to studying the complex interactions among different physiological systems. Similarly, translational and clinical research should address the complex interplay between these systems impacting on fatty liver. The clinical needs drive the applications of systems medicine to re-define clinical phenotypes, assessing the multiple nature of disease susceptibility and progression (e.g. the definition of risk, prognosis, diagnosis criteria, and new endpoints of clinical trials). Based on this premise and in light of recent findings, the complex mechanisms involved in the pathology of fatty liver and their impact on the short- and long-term clinical outcomes of cardiovascular, metabolic liver diseases associated with steatosis are presented in this review using a new "systems medicine" approach. A new data set is proposed for studying the impairments of different physiological systems that have an impact on fatty liver in different subsets of subjects and patients.

  16. Fatty metamorphosis of the liver in patients with breast cancer:Possible associated factors

    Institute of Scientific and Technical Information of China (English)

    Cheng-Hsin Chu; Shee-Chan Lin; Shou-Chuan Shih; Chin-Roa Kao; Sun-Yen Chou

    2003-01-01

    AIM: To investigate the relationship between breast cancer and fatty liver in Chinese patients.METHODS: The study group consisted of 217 patients with newly diagnosed breast cancers and the control group of 182 subjects undergoing routine health examination in the same hospital. All subjects were female and the groups were matched for date of study. Ultrasound scanning was performed by the same operator using a 3.5 mHz transducer.Steatosis of the liver was diagnosed based on the criteria of Saverymuttu et al. Clinical variables were statistically analyzed.RESULTS: Fatty liver was diagnosed in 98 patients of the study group and 37 patients of the control group, a significant difference was found in incidence (98/217, 45.2 % and 37/182, 20.3 %; P<0.0001). On univariate analysis, fatty liver in breast cancer patients was associated with overweight,hyperlipidemia, and hepatitis. On multivariate analysis in the same patients, obesity and hyperlipidemia were significantly associated with fatty liver.CONCLUSION: The cause of fatty liver in women with breast cancer may be multifactorial. The present study confirms its link with overweight and hyperlipidemia.

  17. Nonalcoholic Fatty Liver Disease in Chronic Hepatitis B and C Patients from Western Amazon

    OpenAIRE

    Nascimento, A. C. M.; D. R. Maia; Neto, S. M.; Lima, E. M.; Twycross, M.; Baquette, R. F.; Lobato, C. M. O.

    2012-01-01

    Nonalcoholic fatty liver disease (NAFLD) includes a wide spectrum of histological conditions, extending from simple steatosis to end-stage liver failure. The aim of this study was to examine the prevalence of NAFLD and its associations in chronic hepatitis B and C patients. Methods. We included all patients diagnosed with chronic hepatitis B and C who underwent a liver biopsy between January 2010 and October 2011 (n = 104). Parameters studied included hepatitis type, anthropometric data, hist...

  18. Comparing Effects of Medication Therapy and Exercise Training with Diet on Liver enzyme Levels and Liver Sonography in Patients with Non-Alcoholic Fatty Liver Disease (NAFLD

    Directory of Open Access Journals (Sweden)

    Azadeh Nabizadeh Haghighi

    2016-03-01

    Full Text Available Background & Objectives: Non-alcoholic fatty liver disease, characterized by the deposition of fat in liver cells, can cause fibrosis, cirrhosis, and liver cell damage if not controlled. The aim of this study is to compare the effects of medication therapy and exercise training with diet on liver enzyme levels and liver sonography in patients with non-alcoholic fatty liver disease (NAFLD. Materials & Methods :In this quasi-experimental study, female patients with non-alcoholic fatty liver were randomly divided into two groups: medication therapy (n = 10 and exercise therapy (n = 10 for 8 weeks. During this period, the exercise group performed exercise training three days a week for 90 minutes per session. The drug was given to the medication group. In both groups, the diet was 500 calories less than their daily energy. Before and after intervention, blood tests and liver sonography were executed. All statistical analyses were done using SPSS for Windows version 20. Comparisons between and within groups were performed by Student's t-test and Wilcoxon test on paired and unpaired data. P < 0.05 was considered statistically significant. Results :In both groups, liver enzyme levels and disease severity in sonography reduced significantly (p<0.05. Conclusion: The findings of the present research showed that both methods of therapy have the same effect on reducing the severity of NAFLD.

  19. ACOUSTIC RADIATION FORCE IMPULSE IS EQUIVALENT TO LIVER BIOPSY TO EVALUATE LIVER FIBROSIS IN PATIENTS WITH CHRONIC HEPATITIS C AND NONALCOHOLIC FATTY LIVER DISEASE

    Directory of Open Access Journals (Sweden)

    Juliana Ayres de Alencar Arrais GUERRA

    2015-09-01

    Full Text Available BackgroundLiver biopsy is recommended as the gold standard method for assessing the stage of liver fibrosis in patients with chronic liver disease. However, it is invasive, with potential risks and complications. Elastography is an ultrasound technique that provides information of changes in the liver tissue, evaluating tissue elasticity and acoustic radiation force impulse is one of the available techniques.ObjectiveThe main objective of this study was to evaluate the sensitivity and specificity of acoustic radiation force impulse comparing to liver biopsy to evaluate fibrosis in patients with chronic hepatitis C virus and nonalcoholic fatty liver disease.MethodsTwenty four patients were included, everyone underwent liver biopsy and acoustic radiation force impulse, and the results were compared with values described in the literature by several authors.ResultsIn the population of patients with chronic hepatitis C, our data were better correlated with data published by Carmen Fierbinteanu-Braticevici et al., with an accuracy of 82.4%, sensitivity of 71.4% and specificity of 90%. For nonalcoholic fatty liver disease, our data were better correlated with data published by Masato Yoneda et al., with an accuracy of 85.7%, sensitivity 80% and specificity of 100%.ConclusionAcoustic radiation force impulse is a method with good accuracy to distinguish initial fibrosis from advanced fibrosis in hepatitis C virus and nonalcoholic fatty liver disease and can replace biopsy in most cases.

  20. Cardiovascular disease risk factors in patients with non-alcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    Novaković Tatjana

    2013-01-01

    Full Text Available Introduction. Clinical, epidemiological and biochemical studies strongly support the concept that the non-alcoholic fatty liver disease is a hepatic manifestation of the metabolic syndrome. Insulin resistance is a common factor connecting obesity, diabetes, hypertension and dyslipidemia with fatty liver and the progression of hepatic disease to steatohepatitis, fibrosis, cirrhosis and hepatocellular carcinoma. Since identification of cardiovascular risk factors is the first step in their prevention, the aim of this study was to analyze the prevalence of some risk factors in patients with fatty liver. Material and Methods. The study included 130 patients who met metabolic syndrome criteria; their demographic and anthropometric characteristics were analyzed and some clinical characteristics were determined, such as smoking habit, arterial pressure and alcohol intake. Routine biochemical analyses were carried out by a standard laboratory procedure. Hepatic steatosis was detected by the abdominal ultrasound. Modified criteria of the National Cholesterol Education Program Adult Treatment Panel III were used to describe the metabolic syndrome. Results. The study group consisted of 72 subjects (55.38%, who had been found by ultrasound to have fatty liver, whereas the control group included 58 respondents (44.62% without pathological ultrasound findings. Differences in the number of fatty liver were highly statistically significant between the groups. The values of body mass index (33.56±6.05 vs 30.56±4.23 kg/m2; p = 0.001, glucose (6.23±0.95 vs 5.76±0.88 mmol/l; p<0.01 and cholesterol (6.66±1.30 vs 6.23±0.95; p <0.05 were significantly higher in the patients with fatty liver than in those without fatty liver. Conclusion. Our results indicate that the patients from the study group had a high percentage of cardiovascular risk factors.

  1. Protective effect of alcohol consumption for fatty liver but not metabolic syndrome

    Institute of Scientific and Technical Information of China (English)

    Masahide Hamaguchi; Takao Kojima; Akihiro Ohbora; Noriyuki Takeda; Michiaki Fukui; Takahiro Kato

    2012-01-01

    AIM: To investigate the effect of alcohol on the metabolic syndrome (MS) and fatty liver in Japanese men and women. METHODS: A cross-sectional study was conducted in a medical health checkup program at a general hospital. This study involved 18 571 Japanese men and women, 18-88 years of age, with a mean body mass index of 22.6 kg/m2. A standardized questionnaire was administered. The total amount of alcohol consumed per week was calculated, and categorized into four grades. Fatty liver was examined by ultrasound modified criteria of the revised National Cholesterol Education Program Adult Treatment Panel Ⅲ and the new International Diabetes Federation. RESULTS: The prevalence of fatty liver decreased in men and women with light to moderate alcohol consumption, whereas the prevalence of MS was not so changed. The prevalence of fatty liver of any grade in men was lower than that in those with no or minimal alcohol consumption. In women with light to moderate alcohol consumption, prevalence of fatty liver was lower than that in women with no or minimal alcohol consumption. By logistic regression analysis, the odds ratio (OR) for MS in women with light alcohol consumption was decreased to < 1.0, but this change was not clear in men. The OR for fatty liver was clearly < 1.0 in men with any level of alcohol consumption and in women with light to moderate consumption. CONCLUSION: Light to moderate alcohol consumption has a favorable effect for fatty liver, but not for MS in Japanese men and women.

  2. Identification of Plants That Inhibit Lipid Droplet Formation in Liver Cells: Rubus suavissimus Leaf Extract Protects Mice from High-Fat Diet-Induced Fatty Liver by Directly Affecting Liver Cells

    Science.gov (United States)

    Takahashi, Tomohiro; Sugawara, Wataru; Takiguchi, Yuya; Takizawa, Kento; Nakabayashi, Ami; Nakamura, Mitsuo; Nagano-Ito, Michiyo; Ichikawa, Shinichi

    2016-01-01

    Fatty liver disease is a condition in which abnormally large numbers of lipid droplets accumulate in liver cells. Fatty liver disease induces inflammation under conditions of oxidative stress and may result in cancer. To identify plants that protect against fatty liver disease, we examined the inhibitory effects of plant extracts on lipid droplet formation in mouse hepatoma cells. A screen of 98 water extracts of plants revealed 4 extracts with inhibitory effects. One of these extracts, Rubus suavissimus S. Lee (Tien-cha or Chinese sweet tea) leaf extract, which showed strong inhibitory effects, was tested in a mouse fatty liver model. In these mouse experiments, intake of the plant extract significantly protected mice against fatty liver disease without affecting body weight gain. Our results suggest that RSE directly affects liver cells and protects them from fatty liver disease. PMID:27429636

  3. High-fat diets rich in medium- versus long-chain fatty acids induce distinct patterns of tissue specific insulin resistance

    NARCIS (Netherlands)

    Vogel-van den Bosch, J. de; Berg, S.A.A. van den; Bijland, S.; Voshol, P.J.; Havekes, L.M.; Romijn, H.A.; Hoeks, J.; Beurden, D. van; Hesselink, M.K.C.; Schrauwen, P.; Dijk, K.W. van

    2011-01-01

    Excess dietary long-chain fatty acid (LCFA) intake results in ectopic lipid accumulation and insulin resistance. Since medium-chain fatty acids (MCFA) are preferentially oxidized over LCFA, we hypothesized that diets rich in MCFA result in a lower ectopic lipid accumulation and insulin resistance co

  4. Study on 64-layer Spiral Computed Tomography Perfusion Imaging in Patients with Fatty Liver

    Institute of Scientific and Technical Information of China (English)

    RAO Xiao-hui; SU Qi; CAI Lei; QIN Jia-sheng; CAI Li-quan; HONG He; WANG Kang-hua; AI Zhi-guo; ZHANG Sheng

    2014-01-01

    Objective:To analyze the changes of hemodynamics of patients with fatty liver by detecting their blood perfusion parameter changes with Philips Brilliance 64-layer spiral computed tomography (CT) perfusion technique. Methods: A total of 74 patients undergoing 64-layer spiral CT perfusion imaging were selected as study objects, in which 39 were with fatty liver and the other 35 were healthy people. The parameters of liver blood perfusion were observed. Results: Hepatic arterial perfusion (Art.Perf), portal perfusion (Port.Perf) and total perfusion (Total.Perf) values as well as hepatic perfusion index (HPI) were (18.4±4.1), (71.5±14.2) and (93.2±6.7) mL/100 g·min as well as (25.15±5.22)% in control group, in which the Art.Perf, Port.Perf and Total.Perf were in close association with the severity of fatty liver and of great significance. Art.Perf of patients with mild, moderate and severe fatty liver was (15.4±4.0), (7.3±9.6) and (4.1±1.3) mL/100 g·min, Port.Perf was (56.5±10.7), (48.6±6.8) and (37.0±4.1) mL/100 g·min and Total.Perf was (71.3±5.7), (55.7±5.8) and (40.2±5.0) mL/100 g·min, respectively. However, HPI could not be considered as the evaluation index for the severity of fatty liver. Conclusion:CT perfusion imaging of liver can relfect blood changes of patients with fatty liver, which can be used to evaluate their blood-supply condition, thus providing more diagnostic evidences for the clinic.

  5. Study on 64-layer Spiral Computed Tomography Perfusion Imaging in Patients with Fatty Liver

    Directory of Open Access Journals (Sweden)

    RAO Xiao-hui

    2014-12-01

    Full Text Available Objective: To analyze the changes of hemodynamics of patients with fatty liver by detecting their blood perfusion parameter changes with Philips Brilliance 64-layer spiral computed tomography (CT perfusion technique. Methods: A total of 74 patients undergoing 64-layer spiral CT perfusion imaging were selected as study objects, in which 39 were with fatty liver and the other 35 were healthy people. The parameters of liver blood perfusion were observed. Results: Hepatic arterial perfusion (Art.Perf, portal perfusion (Port.Perf and total perfusion (Total.Perf values as well as hepatic perfusion index (HPI were (18.4±4.1, (71.5±14.2 and (93.2±6.7 mL/100 g·min as well as (25.15±5.22% in control group, in which the Art.Perf, Port.Perf and Total.Perf were in close association with the severity of fatty liver and of great significance. Art.Perf of patients with mild, moderate and severe fatty liver was (15.4±4.0, (7.3±9.6 and (4.1±1.3 mL/100 g·min, Port.Perf was (56.5±10.7, (48.6±6.8 and (37.0±4.1 mL/100 g·min and Total.Perf was (71.3±5.7, (55.7±5.8 and (40.2±5.0 mL/100 g·min, respectively. However, HPI could not be considered as the evaluation index for the severity of fatty liver. Conclusion: CT perfusion imaging of liver can reflect blood changes of patients with fatty liver, which can be used to evaluate their blood-supply condition, thus providing more diagnostic evidences for the clinic.

  6. Total lipids and fatty acid profile in the liver of wild and farmed catla catla fish

    Energy Technology Data Exchange (ETDEWEB)

    Hassan, M.; Shaihid chatha, S. A.; Tahira, I.; Hussain, B.

    2010-07-01

    This experimental work was aimed to study the moisture content, total lipids and fatty acid profile in the liver of wild and farmed freshwater major carp Catla catla of three different weight categories designated as W{sub 1} (601-900g), W{sub 2} (901- 1200)g and W{sub 3} (1201-1500g). Seven fish specimens of each of the three weight categories of wild and farmed Catla catla were obtained from Trimu Head, Jhang and Fish Hatchery, Satiana Road and Faisalabad, respectively. The fish were dissected to remove the liver and after weighing, liver samples were prepared and subjected to chemical analysis. Wild Catla catla liver had a significantly (p <0.05) higher moisture content as compared to the farmed species. Farmed Catla catla deposited significantly (p < 0.05) higher lipid contents in liver. Proportions of saturated fatty acids varied irregularly in the lipids of the liver from both wild and farmed Catla catla. Saturated fatty acids C12:0, C14:0, C16:0, C18:0, C20:0 and C22:0 were identified with considerable percentages in the liver of Catla catla from both habitats and monounsaturated fatty acid C18:1 was found in considerable amounts in the liver of both major carp. Polyunsaturated fatty acids such as C18:3 (n-6) and C20: 2 (n-6) were detected in the liver of the wild fish of W{sub 2} and W{sub 3} and was similar in the W{sub 3} weight category of the farmed species. (Author) 22 refs.

  7. Effects of n-3 polyunsaturated fatty acids from seal oils on nonalcoholic fatty liver disease associated with hyperlipidemia

    Institute of Scientific and Technical Information of China (English)

    Feng-Shang Zhu; Su Liu; Xi-Mei Chen; Zhi-Gang Huang; Dong-Wei Zhang

    2008-01-01

    AIM: To investigate the efficacy and safety of n-3 polyunsaturated fatty acids (PUFA) from seal oils for patients with nonalcoholic fatty liver disease (NAFLD) associated with hyperlipidemia. METHODS: One hundred and forty-four patients with NAFLD associated with hyperlipidemia were included in the 24-wk, randomized, controlled trial. The patients were randomized into two groups. Group A (n = 72) received recommended diet and 2 g n-3 PUFA from seal oils, three times a day. Group B (n = 72) received recommended diet and 2 g placebo, three times a day. Primary endpoints were fatty liver assessed by symptom scores, liver alanine aminotransferase (ALT) and serum lipid levels after 8, 12, 16, and 24 wk. Hepatic fat infiltration was detected by ultrasonography at weeks 12 and 24 after treatment. RESULTS: A total of 134 patients (66 in group A, 68 in group B) were included in the study except for 10 patients who were excluded from the study. After 24 wk of treatment, no change was observed in body weight, fasting blood glucose (FBG), renal function and blood cells of these patients. Total symptom scores, ALT and triglyceride (TG) levels decreased more significantly in group A than in group B (P < 0.05). As expected, there was a tendency toward improvement in aspartate aminotransferase (AST), 7-glutamyltranspeptidase (GGT), and total cholesterol (TCHO) and high-density lipoprotein (HDL) cholesterol levels (P < 0.05) after administration in the two groups. However, no significant differences were found between the two groups. The values of low-density lipoprotein (LDL) were significantly improved in group A (P < 0.05), but no significant change was found in group B at different time points and after a 24-wk treatment. After treatment, complete fatty liver regression was observed in 19.70% (13/66) of the patients, and an overall reduction was found in 53.03% (35/66) of the patients in group A. In contrast, in group B, only five patients (7.35%, 5/68) achieved complete fatty

  8. Medium chain triglycerides dose-dependently prevent liver pathology in a rat model of non-alcoholic fatty liver disease

    Science.gov (United States)

    Metabolic syndrome is often accompanied by development of hepatic steatosis and less frequently by nonalcoholic fatty liver disease (NAFLD) leading to nonalcoholic steatohepatitis (NASH). Replacement of corn oil with medium chain triacylglycerols (MCT) in the diets of alcohol-fed rats has been show...

  9. Metabolic liver disease of obesity and role of adipose tissue in the pathogenesis of nonalcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    Kamran Qureshi; Gary A Abrams

    2007-01-01

    Nonalcoholic fatty liver disease (NAFLD) is an increasingly recognized cause of liver-related morbidity and mortality.It can develop secondary to numerous causes but a great majority of NAFLD cases occur in patients who are obese or present with other components of metabolic syndrome (hypertension, dyslipidemia, diabetes). This is called primary NAFLD and insulin resistance plays a key role in its pathogenesis. Obesity is characterized by expanded adipose tissue, which is under a state of chronic inflammation. This disturbs the normal storage and endocrine functions of adipose tissue. In obesity, the secretome (adipokines, cytokines, free fatty acids and other lipid moieties) of fatty tissue is amplified, which through its autocrine, paracrine actions in fat tissue and systemic effects especially in the liver leads to an altered metabolic state with insulin resistance (IR). IR leads to hyperglycemia and reactive hyperinsulinemia, which stimulates lipid-accumulating processes and impairs hepatic lipid metabolism. IR enhances free fatty acid delivery to liver from the adipose tissue storage due to uninhibited lipolysis. These changes result in hepatic abnormal fat accumulation, which may initiate the hepatic IR and further aggravate the altered metabolic state of whole body. Hepatic steatosis can also be explained by the fact that there is enhanced dietary fat delivery and physical inactivity. IR and NAFLD are also seen in various lipodystrophic states in contrary to popular belief that these problems only occur due to excessive adiposity in obesity. Hence, altered physiology of adipose tissue is central to development of IR,metabolic syndrome and NAFLD.

  10. The cytochrome P450 epoxygenase pathway regulates the hepatic inflammatory response in fatty liver disease.

    Directory of Open Access Journals (Sweden)

    Robert N Schuck

    Full Text Available Fatty liver disease is an emerging public health problem without effective therapies, and chronic hepatic inflammation is a key pathologic mediator in its progression. Cytochrome P450 (CYP epoxygenases metabolize arachidonic acid to biologically active epoxyeicosatrienoic acids (EETs, which have potent anti-inflammatory effects. Although promoting the effects of EETs elicits anti-inflammatory and protective effects in the cardiovascular system, the contribution of CYP-derived EETs to the regulation of fatty liver disease-associated inflammation and injury is unknown. Using the atherogenic diet model of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis (NAFLD/NASH, our studies demonstrated that induction of fatty liver disease significantly and preferentially suppresses hepatic CYP epoxygenase expression and activity, and both hepatic and circulating levels of EETs in mice. Furthermore, mice with targeted disruption of Ephx2 (the gene encoding soluble epoxide hydrolase exhibited restored hepatic and circulating EET levels and a significantly attenuated induction of hepatic inflammation and injury. Collectively, these data suggest that suppression of hepatic CYP-mediated EET biosynthesis is an important pathological consequence of fatty liver disease-associated inflammation, and that the CYP epoxygenase pathway is a central regulator of the hepatic inflammatory response in NAFLD/NASH. Future studies investigating the utility of therapeutic strategies that promote the effects of CYP-derived EETs in NAFLD/NASH are warranted.

  11. Therapeutic effect of Pleurotus eryngii cellulose on experimental fatty liver in rats.

    Science.gov (United States)

    Huang, J F; Zhan, T; Yu, X L; He, Q A; Huang, W J; Lin, L Z; Du, Y T; Pan, Y T

    2016-02-26

    The aim of this study was to explore the therapeutic effect of Pleurotus eryngii cellulose on experimental fatty liver in rats. Rats were fed high-fat fodder to establish a rat fatty liver model, and were then fed different concentrations of Pleurotus eryngii cellulose for six weeks. Lipitor was used as a positive control. Measured levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), and total triglyceride (TG); the activity of malondialdehyde (MDA), superoxide dismutase (SOD), hepatic lipase (HL), and lipoprotein lipase; and liver histopathological changes. Successfully established rat fatty liver model after feeding high-fat fodder for one week. A diet of P. eryngii cellulose for six weeks significantly reduced ALT, AST, TC, and TG levels in rat serum (P 0.05). SOD activity increased significantly, while MDA and HL activity decreased (P < 0.05); fatty degeneration and fat accumulation both decreased in hepatic tissue. Hepatic protection of P. eryngii cellulose showed dose-related effect. P. eryngii cellulose can affect lipid metabolism, having therapeutic effects on fatty liver in rats.

  12. Effect of Telmisartan or Losartan for Treatment of Nonalcoholic Fatty Liver Disease: Fatty Liver Protection Trial by Telmisartan or Losartan Study (FANTASY

    Directory of Open Access Journals (Sweden)

    Takumi Hirata

    2013-01-01

    Full Text Available Aim. This study compared the effects of telmisartan and losartan on nonalcoholic fatty liver disease (NAFLD and biochemical markers of insulin resistance in hypertensive NAFLD patients with type 2 diabetes mellitus. Methods. This was a randomized, open-label, parallel-group comparison of therapy with telmisartan or losartan. Nineteen hypertensive NAFLD patients with type 2 diabetes were randomly assigned to receive telmisartan at a dose of 20 mg once a day (n=12 or losartan at a dose of 50 mg once a day (n=7 for 12 months. Body fat area as determined by CT scanning and hepatic fat content based on the liver-to-spleen (L/S ratio, as well as several parameters of glycemic and lipid metabolism, were compared before and after 12 months. Results. The telmisartan group showed a significant decline in serum free fatty acid (FFA level (from 0.87±0.26 to 0.59±0.22 mEq/L (mean ± SD, P=0.005 and a significant increase in L/S ratio (P=0.049 evaluated by CT scan, while these parameters were not changed in the losartan group. Conclusion. Although there was no significant difference in improvement in liver enzymes with telmisartan and losartan treatment in hypertensive NAFLD patients with type 2 diabetes after 12 months, it is suggested that telmisartan may exert beneficial effects by improving fatty liver.

  13. Differentiation between true focal liver lesions and pseudolesions in patients with fatty liver: evaluation of helical CT criteria

    Energy Technology Data Exchange (ETDEWEB)

    Soyer, Philippe; Sirol, Marc; Fargeaudou, Yann; Duchat, Florent; Hamzi, Lounis; Boudiaf, Mourad; Guerrache, Youcef; Rymer, Roland [Lariboisiere Hospital-AP-HP-GHU Nord et University Paris 7, Departments of Abdominal Imaging, Paris (France); Aout, Mounir; Vicaut, Eric [Lariboisiere Hospital-AP-HP-GHU Nord et University Paris 7, Clinical Research Unit, Paris (France)

    2010-07-15

    To determine the potential of helical CT for differentiating true lesions from pseudolesions in patients with fatty liver. Helical CT of 44 patients with diffuse fatty liver (22 with true lesions; 22 with pseudolesions) were reviewed by two observers with regard to morphological features of visible lesions. Univariate analysis was used to detect discriminating criteria for the diagnosis of true lesions. Interobserver agreement was excellent for 9/10 morphological criteria (kappa = 0.831-1). True lesions were more frequently distant from the liver capsule (50.00% vs. 4.55%), located in the right lobe (72.73% vs. 31.82%), round (86.36% vs. 54.55%), heterogeneous (27.27% vs. 0.00%) and had ill-defined margins (40.91% vs. 13.64%) compared with pseudolesions (P < 0.05). Using univariate analysis, a location distant from the liver capsule was the most discriminating variable to differentiate between true and pseudolesions (P = 0.0060). Hyperattenuating content and round shape were the most sensitive criteria (sensitivity = 90.91% and 86.36%, respectively) for the diagnosis of true lesions, and heterogeneity, vascular displacement and encapsulation were the three most specific ones (specificity = 100.00%). Best accuracy was obtained with an association of the three variables (accuracy = 86.36%). Helical CT provides objective and discriminating morphological criteria to differentiate between true lesions and pseudolesions in patients with fatty liver. (orig.)

  14. Alanine Aminotransferase Elevation in Obese Infants and Children: A Marker of Early Onset Non Alcoholic Fatty Liver Disease

    OpenAIRE

    Engelmann, Guido; Hoffmann, Georg Friedrich; Grulich-Henn, Juergen; Teufel, Ulrike

    2014-01-01

    Background: Elevated aminotransferases serve as surrogate markers of non-alcoholic fatty liver disease, a feature commonly associated with the metabolic syndrome. Studies on the prevalence of fatty liver disease in obese children comprise small patient samples or focus on those patients with liver enzyme elevation. Objectives: We have prospectively analyzed liver enzymes in all overweight and obese children coming to our tertiary care centre. Patients and Methods: In a prospective study 224 h...

  15. [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.

  16. The effectiveness of metformin in patients with metabolic syndrome and nonalcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    S A Butrova

    2008-06-01

    Full Text Available The mechanism of action of metformin is realized through activation of cAMP-dependent protein kinase, leading to a decrease hepatic glucose production as well as to decrease the synthesis of triglycerides and an increase in fat oxidation. Several studies have demonstrated the positive effect of the drug in non-alcoholic fatty liver disease, manifested in reducing the activity of enzymes, reducing the size of the liver and insulin resistance. The aim of our study was to evaluate the effectiveness of metformin in patients with metabolic syndrome and nonalcoholic fatty liver disease. The study found that the use Siofor 850 mg 2 times a day in conjunction with a reduced-calorie nutrition in patients with metabolic syndrome and nonalcoholic fatty liver disease leads to a significant reduction in insulin resistance associated with decreased activity of transaminases, improvement of metabolic parameters. The therapy Siofor majority of patients (60% with metabolic syndrome and nonalcoholic fatty liver disease achieved a clinically significant weight loss and improved body composition. Application Siofor improves lifestyle changes in obese patients with non-alcoholic liver disease dirovoy and metabolic disorders.

  17. Xenon-133 hepatic retention ratio: A useful index for fatty liver quantification

    Energy Technology Data Exchange (ETDEWEB)

    Yeh, S.H.; Wu, L.C.; Wang, S.J.; Lin, H.C.; Liu, R.S.; Lee, S.D.; Wu, J.C. (Veterans General Hospital, Taipei (Taiwan))

    1989-10-01

    Xenon-133 hepatic retention ratio was developed for quantifying fatty liver. Data were acquired in frame mode in the hepatic region and both lung bases for 5 min after rebreathing 20 mCi of gaseous {sup 133}Xe and for another 5 min during washout. Static ({sup 99m}Tc)sulfur colloid liver imaging was performed with the patient in the identical position immediately after the ventilation study and data were stored for liver localization. A hepatic time-activity curve corrected for background activity was generated. The 133Xe retention ratio was derived by dividing the activity at 3.5 min after washout by the peak activity. The data of 16 controls and 20 patients with fatty liver were analyzed. The retention ratio (mean +/- s.d.) was greatly increased in patients with fatty infiltration (0.43 +/- 0.20 vs. 0.04 +/- 0.08 in controls, p less than 0.001). There was a strong positive correlation between the {sup 133}Xe retention ratios and percentage of fat on biopsy as assessed by the amount of the liver tissue occupied by fat globules on H E stained sections. The {sup 133}Xe hepatic retention ratio is a simple, accurate and clinically useful index of detecting, quantifying and managing fatty infiltration of the liver.

  18. IMPACTS OF HIGH DIETARY FAT ON SERUM CHOLESTEROL AND DEVELOPMENT OF FATTY LIVER IN RATS

    Directory of Open Access Journals (Sweden)

    Rajesh Pandey et al

    2012-09-01

    Full Text Available The present study was designed to evaluate the impacts of high dietary fat on serum Total cholesterol and fatty liver syndrome in rats. Rats are fed on diets containing cholesterol; they develop fatty livers which are characterized by the presence in the liver of excessive amounts of cholesteryl esters, and glyceride. Increasement of glyceride content depend on a number of factors, such as the dietary contents of choline, While the nature of the "cholesterol" fatty liver and the effects on its composition of a number of dietary and other factors. In the present paper, we investigated the quantitative changes which occur in the "cholesterol" fatty liver, as a result of variations in the fat content of the diet, with particular reference to the deposition of cholesterol and of glyceride on diets of constant cholesterol content. Investigation was conducted on 90 day old Wister rats. It was observed that the serum TC values in rats of groups B and C were higher than control group. Furthermore, the serum TC and TG value was higher in rats of group C than group B. Grossly, the livers of rats of groups B and C were enlarged, pale in colour, soft in consistency and were having petechial haemorrhages with fat and fibrin deposits. Histopathologically, livers of groups B and C showed fatty infiltration, haemorrhages and mass of eosinophilic materials. The vacuoles coalesced to create clear space that displaced the nucleus to the periphery of the cell. The results suggested that addition of dietary fat from animal and vegetable sources in the diet of rats not only resulted in increase in serum TC and TG but also in marked macroscopic and microscopic changes in vital organ liver.

  19. Focal sparing around the gallbladder in fatty liver. A usual sign for the diagnosis of borderline cases by CT

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Kemin; Hiramatsu, Yoshihiro; Yunoki, Masanori; Hirano, Yoko

    1989-02-01

    In evaluating fatty liver with CT, the residual normal liver tissues without fat deposits are occasionally detected on CT as high attenuation regions, especially surrounding the gallbladder. This study examined the incidence of this phenomenon in terms of the diagnostic value of CT in fatty liver. Fifty-seven patients with fatty liver were examined with CT. The incidence of focal sparing area was the highest in the gallbladder bed (42/57, 74%), followed by the interlobar fissure or subcapsular area (13, 23%), quadrate lobe (8, 14%), caudate lobe (2, 4%), and right lobe (one, 1.8%). These CT appearances were of spot, band, ring, and the mixed type. In 38 patients, fatty liver was too moderate to be detected without CT attenuation numbers. Among them, 27 patients (71%) had focal sparing area surrounding the gallbladder. This CT appearance seemed to be of significance in preventing the missing of moderate fatty liver. (Namekawa, K).

  20. Nine-year incident diabetes is predicted by fatty liver indices: the French D.E.S.I.R. study

    Directory of Open Access Journals (Sweden)

    Vol Sylviane

    2010-06-01

    Full Text Available Abstract Background Fatty liver is known to be linked with insulin resistance, alcohol intake, diabetes and obesity. Biopsy and even scan-assessed fatty liver are not always feasible in clinical practice. This report evaluates the predictive ability of two recently published markers of fatty liver: the Fatty Liver Index (FLI and the NAFLD fatty liver score (NAFLD-FLS, for 9-year incident diabetes, in the French general-population cohort: Data from an Epidemiological Study on the Insulin Resistance syndrome (D.E.S.I.R. Methods At baseline, there were 1861 men and 1950 women, non-diabetic, aged 30 to 65 years. Over the follow-up, 203 incident diabetes cases (140 men, 63 women were identified by diabetes-treatment or fasting plasma glucose ≥ 7.0 mmol/l. The FLI includes: BMI, waist circumference, triglycerides and gamma glutamyl transferase, and the NAFLD-FLS: the metabolic syndrome, diabetes, insulin, alanine aminotransferase, and asparate aminotransferase. Logistic regression was used to determine the odds ratios for incident diabetes associated with categories of the fatty liver indices. Results In comparison to those with a FLI Conclusions These fatty liver indexes are simple clinical tools for evaluating the extent of liver fat and they are predictive of incident diabetes. Physicians should screen for diabetes in patients with fatty liver.

  1. 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; Vinciguerra, Manlio; García-Monzón, Carmelo; Hofker, Marten H; Dyck, Jason Rb; Koonen, Debby P Y

    2014-01-01

    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 si

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

    NARCIS (Netherlands)

    Sheedfar, F.; Sung, M.M.; Aparicio-Vergara, M.; Kloosterhuis, N.J.; Miquilena-Colina, M.E.; Vargas-Castrillon, J.; Febbraio, M.; Jacobs, R.L.; Bruin, A. de; Vinciguerra, M.; Garcia-Monzon, C.; Hofker, M.H.; Dyck, J.R.; Koonen, D.P.

    2014-01-01

    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 si

  3. Exome-wide association study identifies a TM6SF2 variant that confers susceptibility to nonalcoholic fatty liver disease

    DEFF Research Database (Denmark)

    Kozlitina, Julia; Smagris, Eriks; Stender, Stefan

    2014-01-01

    Nonalcoholic fatty liver disease (NAFLD) is the most common form of liver disease. To elucidate the molecular basis of NAFLD, we performed an exome-wide association study of liver fat content. Three variants were associated with higher liver fat levels at the exome-wide significance level of 3...

  4. The Role of TCA Cycle Anaplerosis in Ketosis and Fatty Liver in Periparturient Dairy Cows

    Directory of Open Access Journals (Sweden)

    Heather M. White

    2015-08-01

    Full Text Available The transition to lactation period in dairy cattle is characterized by metabolic challenges, negative energy balance, and adipose tissue mobilization. Metabolism of mobilized adipose tissue is part of the adaptive response to negative energy balance in dairy cattle; however, the capacity of the liver to completely oxidize nonesterified fatty acids may be limited and is reflective of oxaloacetate pool, the carbon carrier of the tricarboxylic acid cycle. Alternative metabolic fates of acetyl-CoA from nonesterified fatty acids include esterification to triacylglycerides and ketogenesis, and when excessive, these pathways lead to fatty liver and ketosis. Examination of the anaplerotic and cataplerotic pull of oxaloacetate by the tricarboxylic acid cycle and gluconeogenesis may provide insight into the balance of oxidation and esterification of acetyl-CoA within the liver of periparturient dairy cows.

  5. 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.

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

    Science.gov (United States)

    ... PubMed Central Kahali B, Halligan B, Speliotes EK. Insights from Genome-Wide Association Analyses of Nonalcoholic Fatty ... healthcare professional . About Genetics Home Reference Site Map Customer Support Selection Criteria for Links USA.gov Copyright ...

  7. Interleukin-34 as a fibroblast-derived marker of liver fibrosis in patients with non-alcoholic fatty liver disease

    Science.gov (United States)

    Shoji, Hirotaka; Yoshio, Sachiyo; Mano, Yohei; Kumagai, Erina; Sugiyama, Masaya; Korenaga, Masaaki; Arai, Taeang; Itokawa, Norio; Atsukawa, Masanori; Aikata, Hiroshi; Hyogo, Hideyuki; Chayama, Kazuaki; Ohashi, Tomohiko; Ito, Kiyoaki; Yoneda, Masashi; Nozaki, Yuichi; Kawaguchi, Takumi; Torimura, Takuji; Abe, Masanori; Hiasa, Yoichi; Fukai, Moto; Kamiyama, Toshiya; Taketomi, Akinobu; Mizokami, Masashi; Kanto, Tatsuya

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD) is a common cause of chronic non-viral liver disease. Activation of macrophages and hepatic stellate cells is a critical step that promotes liver fibrosis. We aimed to explore the feasibility of interleukin-34 (IL-34), a key regulator of macrophages, as a fibrosis marker in patients with NAFLD. We enrolled 197 liver biopsy-proven NAFLD patients. We evaluated the serum levels of IL-34, macrophage-colony stimulating factor (M-CSF), soluble CD163 (sCD163), 40 cytokines/chemokines, hyaluronic acid, type IV collagen 7s, and clinically-approved fibrosis scores. IL-34 increased with the progression of fibrosis and was an independent marker for liver fibrosis. Immunostaining experiments, using resected liver specimens from NAFLD patients, revealed that IL-34 was mainly expressed on liver fibroblasts. IL-34 based fibrosis score (0.0387*IL-34 (pg/ml) + 0.3623*type IV collagen 7s (ng/ml) + 0.0184*age (year)–1.1850) was a practical predictive model of liver fibrosis. Using receiver-operating characteristic analyses, the area under the curve, sensitivity, and specificity of IL-34 based fibrosis score were superior or comparable to the other fibrosis biomarkers and scores. In conclusion, the IL-34 based fibrosis score, including serum IL-34, type IV collagen 7s and age, is a feasible diagnostic marker of liver fibrosis in NAFLD patients. PMID:27363523

  8. Hepatic phenotype of liver fatty acid binding protein gene-ablated mice

    OpenAIRE

    Martin, Gregory G.; Atshaves, Barbara P.; Huang, Huan; McIntosh, Avery L.; Williams, Brad J.; Pai, Pei-Jing; Russell, David H.; Kier, Ann B.; Schroeder, Friedhelm

    2009-01-01

    Although the function of liver fatty acid binding protein in hepatic fatty acid metabolism has been extensively studied, its potential role in hepatic cholesterol homeostasis is less clear. Although hepatic cholesterol accumulation was initially reported in L-FABP-null female mice, that study was performed with early N2 backcross generation mice. To resolve whether the hepatic cholesterol phenotype in these L-FABP−/− mice was attributable to genetic inhomogeneity, these L-FABP−/− mice were fu...

  9. Focal Sparing of the Fatty Liver Caused by a Nontumorous Arterioportal Shunt

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Min Woo; Kim, Young Jun; Jeon, Hae Jeong; Lee, Nam Ju; Moon, Sung Gyu; Yi, Jeong Geun [Konkuk University Hospital, Seoul (Korea, Republic of)

    2007-06-15

    We present two cases of focal fatty sparing caused by a nontumorous arterioportal shunt. Two patients underwent ultrasonography (US) as a part of routine medical screening, which revealed a hypoechoic lesion in the diffuse fatty liver. Each lesion appeared to be an arterioportal shunt on triphasic mutidetector computed tomography (CT) and was seen as being slightly hyperdense on noncontrast CT. No tumors were delineated around or within the arterioportal shunt. Both lesions remained unchanged on six-month follow-up US

  10. Non-invasive diagnosis of nonalcoholic fatty liver and nonalcoholic steatohepatitis.

    Science.gov (United States)

    Adams, Leon A; Feldstein, Ariel E

    2011-02-01

    Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the USA and many other parts of the world. Its prevalence continues to rise; currently affecting about one in four adults and 10% of children in the USA. NAFLD represents a wide spectrum of conditions ranging from fatty liver, which in general follows a benign, no-progressive clinical course, to nonalcoholic steatohepatitis (NASH), a more serious form of NAFLD that may progress to cirrhosis and end-stage liver disease. Currently, the diagnosis of NASH requires an invasive liver biopsy with drawbacks of sampling and interpretation error. Clinical risk factors for NASH include diabetes and the metabolic syndrome; however, these are not sufficiently predictive of the condition by themselves. Routine liver enzyme levels are not reliable; however, novel plasma hepatocyte cell death markers either alone or in combination with clinical risk factors are potential non-invasive diagnostic tools for the future. This review provides a concise overview of the role non-invasive diagnostic tools for the differentiation of fatty liver from NASH as well as for the determination of presence and extent of fibrosis.

  11. The fatty liver dystrophy (fld) mutation: Developmentally related alterations in hepatic triglyceride metabolism and protein expression

    Energy Technology Data Exchange (ETDEWEB)

    Reue, K.; Rehnmark, S.; Cohen, R.D.; Leete, T.H.; Doolittle, M.H. [West Los Angeles VA Medical Center, CA (United States). Lipid Research Lab.]|[Univ. of California, Los Angeles, CA (United States). Dept. of Medicine; Giometti, C.S.; Mishler, K. [Argonne National Lab., IL (United States); Slavin, B.G. [Univ. of Southern California, Los Angeles, CA (United States)

    1997-07-01

    Fatty liver dystrophy (fld) is an autosomal recessive mutation in mice characterized by hypertriglyceridemia and development of a fatty liver in the early neonatal period. Also associated with the fld phenotype is a tissue-specific deficiency in the expression of lipoprotein lipase and hepatic lipase, as well as elevations in hepatic apolipoprotein A-IV and apolipoprotein C-II mRNA levels. Although these lipid abnormalities resolve at the age of weaning, adult mutant mice exhibit a peripheral neuropathy associated with abnormal myelin formation. The fatty liver in fld/fld neonates is characterized by the accumulation of large triglyceride droplets within the parenchymal cells, and these droplets persist within isolated hepatocytes maintained in culture for several days. To identify the metabolic defect that leads to lipid accumulation, the authors investigated several aspects of cellular triglyceride metabolism. The mutant mice exhibited normal activity of acid triacylglycerol lipase, an enzyme thought to be responsible for hydrolysis of dietary triglycerides in the liver. Metabolic labeling studies performed with oleic acid revealed that free fatty acids accumulate in the liver of 3 day old fld/fld mice, but not in adults. This accumulation in liver was mirrored by elevated free fatty acid levels in plasma of fld/fld neonates, with levels highest in very young mice and returning to normal by the age of one month. Quantitation of fatty acid oxidation in cells isolated from fld/fld neonates revealed that oxidation rate is reduced 60% in hepatocytes and 40% in fibroblasts; hepatocytes from adult fld/fld mice exhibited an oxidation rate similar to those from wild-type mice.

  12. 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.

  13. 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.

  14. Evaluation of usefulness of [sup 99m]Tc-GSA liver scintigraphy on fatty liver in the rat

    Energy Technology Data Exchange (ETDEWEB)

    Kimoto, Mitsunori; Akaki, Shiro; Kohno, Yoshihiro; Gohbara, Hideo; Sakae, Katsuyoshi; Nagaya, Isao; Takeda, Yoshihiro; Hiraki, Yoshio (Okayama Univ. (Japan). School of Medicine)

    1994-10-01

    [sup 99m]Tc-GSA is a new liver-imaging radiopharmaceutical which binds to the asialoglycoprotein receptors on the hepatocytes. We evaluated liver injury induced by fatty infiltration in the rats. Studies were performed in the Wistar rats under control conditions (6 cases), and with choline deficiency diet for 2, 4, 6, 10 and 12 weeks (6 cases respectively). [sup 99m]Tc-GSA was administered via the inferior vena cava. Immediately after injection, a dynamic imaging study was performed for 30 min. t[sub 90] (the time at which the liver time-activity curve reached 90% of its peak), K[sub u] and K[sub d] (calculated by 2 compartment model) were used as parameters which reflect on asialoglycoprotein receptors on the hepatocytes. t[sub 90] prolonged, and K[sub u] and K[sub d] decreased according to the severity of fatty infiltration. These results suggest that [sup 99m]Tc-GSA is useful for evaluating liver injury induced by fatty infiltration. (author).

  15. Focal sparing in fatty liver : Mimicking hypervascular tumor on gadolinium-enhanced opposed-phase gradient-echo images

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Dal Mo; Kim, Hak Soo; Kim, Hyung Sik; Jin, Wook; Cho, Seung Whi [Gachon Medical College, Incheon (Korea, Republic of)

    2001-12-01

    We describe the magnetic resonance imaging findings in a case of focal sparing in fatty liver that showed homogeneous hyperintensity on gadolinium-enhanced opposed-phase gradient-echo images and mimicked a hypervascular mass due to paradoxical suppression of signal intensity of surrounding liver parenchyma with fatty infiltration.

  16. Effects of emodin on treating murine nonalcoholic fatty liver induced by high caloric laboratory chaw

    Institute of Scientific and Technical Information of China (English)

    Hui Dong; Fu-Er Lu; Zhi-Qiang Gao; Li-Jun Xu; Kai-Fu Wang; Xin Zou

    2005-01-01

    AIM: To investigate the effects of emodin on the treatment of non-alcoholic fatty liver in rats induced by high caloric laboratory chaw.METHODS: Non-alcoholic fatty liver model was successfully established by feeding with high caloric laboratory chaw for 12 wk. Then the model rats were randomly divided into 3 groups, namely model control group, emodin group and dietary treatment group. The rats in emodin group in othergroups were given distilled water of the same volume. The rats in model control group were fed with high caloric laboratory chaw while animals in other groups were fed with normal diet. Four weeks later, liver index (liver/body weight ratio), serum activities of liver-associated enzymes, blood lipid, fasting blood glucose, fasting plasma insulin, HOMA insulin resistance index (HOMA-IR), hepatic triglyceride content and histology features of all groups were assayed. The expression of hepatic peroxisomal proliferator activated receptor (PPAR) gamma was determined by RT-PCR.RESULTS: The body weight, liver index, serum activities of alanine aminotransferase (ALT), blood lipid, hepatic triglyceride content of model control group were significantly elevated, with moderate to severe hepatocyte steatosis.The expression of hepatic PPAR gamma mRNA was obviously reduced in model control group. Compared with model control group, the body weight, liver index, serum activities of ALT, blood lipids and hepatic triglyceride of emodin group significantly decreased and hepatic histology display was also greatly improved. Meanwhile, the expression of hepatic PPAR gamma mRNA was elevated.However, high serum activities of ALT and hyperlipidemia were persisted in dietary treatment group although liver index was decreased and liver histology was somewhat improved.CONCLUSION: It is suggested that emodin might be effective in the treatment of non-alcoholic fatty liver in rats. Its therapeutic mechanism could be associated with increasing the expression of hepatic PPAR gamma mRNA.

  17. Controversy in the diagnosis of pediatric non-alcoholic fatty liver disease

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    Marzuillo, Pierluigi; Grandone, Anna; Perrone, Laura; Miraglia del Giudice, Emanuele

    2015-01-01

    In the last years childhood obesity has reached epidemic diffusion with about 200 million school-age children worldwide being overweight or obese. Simultaneously, also the prevalence of obesity comorbidities has been increased and the non-alcoholic fatty liver disease (NAFLD) has become the most common form of liver disease in childhood. Also if there are some not-invasive diagnostic possibilities, the diagnostic gold standard is represented by hepatic biopsy giving to the clinicians the poss...

  18. The varied sonographic appearances of focal fatty liver disease: Review and diagnostic algorithm

    Energy Technology Data Exchange (ETDEWEB)

    Bhatnagar, G., E-mail: g.bhatnagar@nhs.net [Department of Radiology, Derriford Hospital, Plymouth (United Kingdom); Sidhu, H.S.; Vardhanabhuti, V.; Venkatanarasimha, N.; Cantin, P.; Dubbins, P. [Department of Radiology, Derriford Hospital, Plymouth (United Kingdom)

    2012-04-15

    Focal fat infiltration and focal fat sparing of the liver are less common than diffuse fat infiltration but present a greater diagnostic conundrum. Although typical features of these conditions are well described, there is a wide variety of different appearances. These atypical patterns present significant difficulty in differentiation from other pathological processes and often require additional investigation. We present an innovative diagnostic algorithm and illustrate its effectiveness in diagnosing focal fatty liver disease with typical and atypical examples.

  19. PNPLA3 Expression Is Related to Liver Steatosis in Morbidly Obese Women with Non-Alcoholic Fatty Liver Disease

    Science.gov (United States)

    Aragonès, Gemma; Auguet, Teresa; Armengol, Sandra; Berlanga, Alba; Guiu-Jurado, Esther; Aguilar, Carmen; Martínez, Salomé; Sabench, Fátima; Porras, José Antonio; Ruiz, Maikel Daniel; Hernández, Mercé; Sirvent, Joan Josep; Del Castillo, Daniel; Richart, Cristóbal

    2016-01-01

    Recent reports suggest a role for the Patatin-like phospholipase domain-containing protein 3 (PNPLA3) in the pathology of non-alcoholic fatty liver disease (NAFLD). Lipid deposition in the liver seems to be a critical process in the pathogenesis of NAFLD. The aim of the present work was to evaluate the association between the liver PNPLA3 expression, key genes of lipid metabolism, and the presence of NAFLD in morbidly obese women. We used real-time polymerase chain reaction (PCR) analysis to analyze the hepatic expression of PNPLA3 and lipid metabolism-related genes in 55 morbidly obese subjects with normal liver histology (NL, n = 18), simple steatosis (SS, n = 20), and non-alcoholic steatohepatitis (NASH, n = 17). Liver biopsies were collected during bariatric surgery. We observed that liver PNPLA3 expression was increased in NAFLD than in NL. It was also upregulated in SS than in NL. Interestingly, we found that the expression of PNPLA3 was significantly higher in severe than mild SS group. In addition, the expression of the transcription factors LXRα, PPARα, and SREBP2 was positively correlated with PNPLA3 liver expression. Regarding rs738409 polymorphism, GG genotype was positive correlated with the presence of NASH. In conclusion, our results show that PNPLA3 could be related to lipid accumulation in liver, mainly in the development and progression of simple steatosis. PMID:27128907

  20. PNPLA3 Expression Is Related to Liver Steatosis in Morbidly Obese Women with Non-Alcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Gemma Aragonès

    2016-04-01

    Full Text Available Recent reports suggest a role for the Patatin-like phospholipase domain-containing protein 3 (PNPLA3 in the pathology of non-alcoholic fatty liver disease (NAFLD. Lipid deposition in the liver seems to be a critical process in the pathogenesis of NAFLD. The aim of the present work was to evaluate the association between the liver PNPLA3 expression, key genes of lipid metabolism, and the presence of NAFLD in morbidly obese women. We used real-time polymerase chain reaction (PCR analysis to analyze the hepatic expression of PNPLA3 and lipid metabolism-related genes in 55 morbidly obese subjects with normal liver histology (NL, n = 18, simple steatosis (SS, n = 20, and non-alcoholic steatohepatitis (NASH, n = 17. Liver biopsies were collected during bariatric surgery. We observed that liver PNPLA3 expression was increased in NAFLD than in NL. It was also upregulated in SS than in NL. Interestingly, we found that the expression of PNPLA3 was significantly higher in severe than mild SS group. In addition, the expression of the transcription factors LXRα, PPARα, and SREBP2 was positively correlated with PNPLA3 liver expression. Regarding rs738409 polymorphism, GG genotype was positive correlated with the presence of NASH. In conclusion, our results show that PNPLA3 could be related to lipid accumulation in liver, mainly in the development and progression of simple steatosis.

  1. Treatment of non-alcoholic fatty liver disease with metformin versus lifestyle intervention in insulin-resistant adolescents.

    Science.gov (United States)

    Nadeau, Kristen J; Ehlers, Lindsay B; Zeitler, Philip S; Love-Osborne, Kathy

    2009-02-01

    The presence of fatty liver per ultrasound and liver-associated enzymes were measured in a select cohort of youth with both obesity and insulin resistance, and the effect of metformin on these parameters evaluated. Fifty obese, multiethnic, insulin-resistant adolescents (mean age 15.1 yr, mean body mass index 39.8 kg/m2) were randomized to receive lifestyle recommendations plus either twice per day doses of 850 mg of metformin or placebo. Fasting and post-glucose challenge biochemistries and liver ultrasounds were compared at baseline and 6 months. The prevalence of fatty liver was 74%, elevated alanine aminotransferase (ALT) 14%, aspartate aminotransferase (AST) 14%, and gamma-glutamyl transferase (GGT) 17%. Fatty liver was mild in 23%, moderate in 31%, and severe in 46%. Fatty liver was more common in male and Hispanic subjects and elevated ALT more common in Hispanic subjects. Subjects with fatty liver appeared more insulin resistant (higher fasting insulin and triglycerides, lower high-density lipoprotein cholesterol) and had higher ALT and AST. At 6 months, mean ALT, GGT, and fasting insulin improved significantly in all subjects. Fatty liver prevalence (p metformin compared to placebo. Non-alcoholic fatty liver disease (NAFLD) occurs with a high prevalence and severity in obese, insulin-resistant adolescents. While metformin plus lifestyle intervention appears promising, defining NAFLD therapies capable of preventing fibrosis and cirrhosis requires further study.

  2. Long- and Medium-Chain Fatty Acids Induce Insulin Resistance to a Similar Extent in Humans Despite Marked Differences in Muscle Fat Accumulation

    NARCIS (Netherlands)

    Hoeks, J.; Mensink, M.R.; Hesselink, M.K.C.; Ekroos, K.; Schrauwen, P.

    2012-01-01

    Context: Animal studies revealed that medium-chain fatty acids (MCFA), due to their metabolic characteristics, are not stored in skeletal muscle and may therefore not give rise to potentially hazardous lipid species impeding insulin signaling. Objective: We here hypothesized that infusion of medium-

  3. Nonalcoholic Fatty Liver Disease: Correlation of the Liver Parenchyma Fatty Acid with Intravoxel Incoherent Motion MR Imaging-An Experimental Study in a Rat Model.

    Directory of Open Access Journals (Sweden)

    Seung-Man Yu

    Full Text Available To prospectively evaluate the changes in fatty acid concentration after administrating a 60% high-fat diet to a non-alcoholic fatty liver disease rat model and to perform a correlation analysis between fatty acid with molecular diffusion (Dtrue, perfusion-related diffusion (Dfast, and perfusion fraction (Pfraction.This prospective study was approved by the appropriate ethics committee. Ten male Sprague-Dawley rats were fed a 60% high-fat diet until the study was finished. Point-resolved spectroscopy sequence 1H-MRS with TR = 1,500 msec, TE = 35 msec, NEX = 64, and 8×8×8 mm3 voxel was used to acquire magnetic resonance spectroscopy (MRS data. Diffusion-weighted imaging was performed on a two-dimensional multi-b value spin echo planar image with the following parameters: repetition time msec/echo time msec, 4500 /63; field of view, 120×120 msec2; matrix, 128×128; section thickness, 3 mm; number of repetition, 8; and multiple b value, 0, 25, 50, 75, 100, 200, 500, 1000 sec/mm2. Baseline magnetic resonance imaging and magnetic resonance spectroscopy data (control were acquired. 1H proton MRS and diffusion-weighted imaging were obtained every 2 weeks for 8 weeks. The individual contributions of the true molecular diffusion and the incoherent motions of water molecules in the capillary network to the apparent diffusion changes were estimated using a least-square nonlinear fitting in MatLab. A Wilcoxon signed-rank test with the Kruskal-Wallis test was used to compare each week's fatty acid mean quantification. Spearman's correlation coefficient was used to evaluate the correlation between each fatty acid (e.g., total lipid (TL, total saturated fatty acid (TSFA, total unsaturated fatty acid (TUSFA, total unsaturated bond (TUSB, and polyunsaturated bond (PUSB and intravoxel incoherent motion (IVIM mapping images (e.g., Dtrue, Dfast, and Pfraction.The highest mean TL value was at week 8 (0.278 ± 0.10 after the administration of the 60% high-fat diet

  4. PNPLA3-associated steatohepatitis: toward a gene-based classification of fatty liver disease.

    Science.gov (United States)

    Krawczyk, Marcin; Portincasa, Piero; Lammert, Frank

    2013-11-01

    Nonalcoholic fatty liver disease is one of the most common hepatic disorders worldwide. Given the high-calorie nutrition of children and adults, nonalcoholic fatty liver disease (NAFLD) is expected to become a major cause of cirrhosis and eventually liver transplantation. Familial clustering and ethnic differences indicate that genetic factors contribute to NAFLD. Recently, the common variant p.I148M of the enzyme adiponutrin (PNPLA3) has emerged as a major genetic determinant of hepatic steatosis and nonalcoholic steatohepatitis as well as its pathobiological sequelae fibrosis, cirrhosis, and hepatocellular cancer. PNPLA3 encodes a lipid droplet-associated, carbohydrate-regulated lipogenic and/or lipolytic enzyme. Homozygous carriers of the PNPLA3 variant are prone to develop cirrhosis in the absence of other risk factors such as alcohol or viral hepatitis. Here we review the plethora of studies that unraveled the association between PNPLA3 and NAFLD in children and adults, discuss its distinct effects on liver and metabolic traits, and introduce the term PNPLA3-associated steatohepatitis (PASH) as a novel gene-based liver disease. Given the prevalence of the risk allele in 40 to 50% of Europeans, the authors conclude that PNPLA3 should be considered in the diagnostic workup of fatty liver disease and that homozygous risk allele carriers might benefit from careful cancer surveillance.

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

    Institute of Scientific and Technical Information of China (English)

    Zhi-Jun He; Meng-Xian Wang; Min-Man Ning

    2016-01-01

    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.

  6. 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.

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

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    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.

  8. The pediatric NAFLD fibrosis index: a predictor of liver fibrosis in children with non-alcoholic fatty liver disease

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    Pietrobattista Andrea

    2009-05-01

    Full Text Available Abstract Background Liver fibrosis is a stage of non-alcoholic fatty liver disease (NAFLD which is responsible for liver-related morbidity and mortality in adults. Accordingly, the search for non-invasive markers of liver fibrosis has been the subject of intensive efforts in adults with NAFLD. Here, we developed a simple algorithm for the prediction of liver fibrosis in children with NAFLD followed at a tertiary care center. Methods The study included 136 male and 67 female children with NAFLD aged 3.3 to 18.0 years; 141 (69% of them had fibrosis at liver biopsy. On the basis of biological plausibility, readily availability and evidence from adult studies, we evaluated the following potential predictors of liver fibrosis at bootstrapped stepwise logistic regression: gender, age, body mass index, waist circumference, alanine transaminase, aspartate transaminase, gamma-glutamyl-transferase, albumin, prothrombin time, glucose, insulin, triglycerides and cholesterol. A final model was developed using bootstrapped logistic regression with bias-correction. We used this model to develop the 'pediatric NAFLD fibrosis index' (PNFI, which varies between 0 and 10. Results The final model was based on age, waist circumference and triglycerides and had a area under the receiver operating characteristic curve of 0.85 (95% bootstrapped confidence interval (CI with bias correction 0.80 to 0.90 for the prediction of liver fibrosis. A PNFI ≥ 9 (positive likelihood ratio = 28.6, 95% CI 4.0 to 201.0; positive predictive value = 98.5, 95% CI 91.8 to 100.0 could be used to rule in liver fibrosis without performing liver biopsy. Conclusion PNFI may help clinicians to predict liver fibrosis in children with NAFLD, but external validation is needed before it can be employed for this purpose.

  9. Molecular characterization, tissue expression, and polymorphism analysis of liver-type fatty acid binding protein in Landes geese.

    Science.gov (United States)

    Song, Z; Shao, D; Sun, X X; Niu, J W; Gong, D Q

    2015-01-01

    Liver weight is an important economic trait in the fatty goose liver industry. Liver-type fatty acid binding protein (L-FABP) is involved in the formation and metabolism of fatty acids. Thus, we hypothesized that sequence polymorphisms in L-FABP were associated with fatty liver weight in goose. We first isolated, sequenced, and characterized the goose L-FABP gene, which had not been previously reported. The goose L-FABP gene was 2490 bp and included 4 exons coding for a 126-amino acid protein. Analysis of expression levels of the goose L-FABP gene in different tissues showed that the expression level in the liver tissue was higher than in other tissues, and was significantly higher in the liver tissue of overfed geese than in control geese. Moreover, a single nucleotide polymorphism located at 774 bp in the gene was identified in a Landes goose population. To test whether this single nucleotide polymorphism was associated with fatty liver production, liver weight and the ratio of liver to carcass weights were determined for the 3 genotypes with this single nucleotide polymorphism (TT, TG, GG) in overfed Landes geese. Our data indicate that individuals with the GG genotype had higher values for the variables measured than those with the other 2 genotypes, suggesting that L-FABP can be a selection marker for the trait of fatty liver production in goose.

  10. Epicardial Adipose Tissue (EAT) Thickness Is Associated with Cardiovascular and Liver Damage in Nonalcoholic Fatty Liver Disease

    Science.gov (United States)

    Pisano, Giuseppina; Consonni, Dario; Tiraboschi, Silvia; Baragetti, Andrea; Bertelli, Cristina; Norata, Giuseppe Danilo; Dongiovanni, Paola; Valenti, Luca; Grigore, Liliana; Tonella, Tatiana; Catapano, Alberico; Fargion, Silvia

    2016-01-01

    Background and Aims Epicardial adipose tissue (EAT) has been proposed as a cardiometabolic and hepatic fibrosis risk factor in patients with non alcoholic fatty liver disease (NAFLD). Aim of this study was to evaluate the role of EAT in NAFLD by analyzing 1) the association between EAT, the other metabolic parameters and the severity of steatosis 2) the relationship between cardiovascular (cIMT, cplaques, E/A), liver (presence of NASH and significant fibrosis) damage and metabolic risk factors including EAT 3) the relationship between EAT and genetic factors strongly influencing liver steatosis. Methods In a cross-sectional study, we considered 512 consecutive patients with NAFLD (confirmed by biopsy in 100). EAT, severity of steatosis, carotid intima-media thickness (cIMT) and plaques were evaluated by ultrasonography and results analysed by multiple linear and logistic regression models. Variables independently associated with EAT (mm) were female gender (p = 0.003), age (p = 0.001), BMI (p = 0.01), diastolic blood pressure (p = 0.009), steatosis grade 2 (p = 0.01) and 3 (p = 0.04), fatty liver index (p = 0.001) and statin use (p = 0.03). Variables independently associated with carotid IMT were age (p = 0.0001), hypertension (p = 0.009), diabetes (p = 0.04), smoking habits (p = 0.04) and fatty liver index (p = 0.02), with carotid plaques age (p = 0.0001), BMI (p = 0.03), EAT (p = 0.02),) and hypertension (p = 0.02), and with E/A age (p = 0.0001), diabetes (p = 0.005), hypertension (p = 0.04) and fatty liver index (p = 0.004). In the 100 patients with available liver histology non alcoholic steatohepatitis (NASH) was independently associated with EAT (p = 0.04) and diabetes (p = 0.054) while significant fibrosis with EAT (p = 0.02), diabetes (p = 0.01) and waist circumference (p = 0.05). No association between EAT and PNPLA3 and TM6SF2 polymorphisms was found. Conclusion In patients with NAFLD, EAT is associated with the severity of liver and vascular damage

  11. Non-alcoholic fatty liver disease: An early mediator predicting metabolic syndrome in obese children?

    Institute of Scientific and Technical Information of China (English)

    Jun-Fen Fu; Hong-Bo Shi; Li-Rui Liu; Ping Jiang; Li Liang; Chun-Lin Wang; Xi-Yong Liu

    2011-01-01

    AIM: To investigate if non-alcoholic fatty liver disease (NAFLD) is an early mediator for prediction of metabolic syndrome, and if liver B-ultrasound can be used for its diagnosis.METHODS: We classified 861 obese children (6-16 years old) into three subgroups: group 0 (normal liver in ultrasound and normal transaminases); group 1 (fatty liver in ultrasound and normal transaminases); and group 2 (fatty liver in ultrasound and elevated transaminases).We measured the body mass index, waist and hip circumference,blood pressure, fasting blood glucose, insulin,homeostasis model assessment of insulin resistance (HOMA-IR), whole-body insulin sensitivity index (WBISI),lipid profile and transaminases in all the participants.The risk of developing metabolic syndrome (MS) was assessed according to the degree of liver fatty infiltration based on the B-ultrasound examination.RESULTS: Among the 861 obese children, 587 (68.18%)were classified as having NAFLD, and 221 (25.67%)as having MS. The prevalence of MS in NAFLD children (groups 1 and 2) was 37.64% (221/587), which was much higher than that in non-NAFLD group (group 0,12.04%) (P < 0.01). There were significantly higher incidences concerning every component of MS in group 2 compared with group 0 (P < 0.05). The incidence of NAFLD in MS patients was 84.61% (187/221), which was significantly higher than that of hypertension (57.46%,127/221) and glucose metabolic anomalies (22.62%,50/221), and almost equal to the prevalence of dyslipidemia (89.14%, 197/221). Based on the B-ultrasound scales, the presence of moderate and severe liver fatty infiltration carried a high risk of hypertension [odds ratio (OR): 2.18, 95% confidence interval (95% CI):1.27-3.75], dyslipidemia (OR: 7.99, 95% CI: 4.34-14.73),impaired fasting glucose (OR: 3.65, 95% CI: 1.04-12.85),and whole MS (OR: 3.77; 95% CI: 1.90-7.47, P < 0.01).The state of insulin resistance (calculated by HOMA-IR and WBISI) deteriorated as the degree of fatty infiltration increased

  12. Brain and Liver Headspace Aldehyde Concentration Following Dietary Supplementation with n-3 Polyunsaturated Fatty Acids.

    Science.gov (United States)

    Ross, Brian M; Babay, Slim; Malik, Imran

    2015-11-01

    Reactive oxygen species react with unsaturated fatty acids to form a variety of metabolites including aldehydes. Many aldehydes are volatile enough to be detected in headspace gases of blood or cultured cells and in exhaled breath, in particular propanal and hexanal which are derived from omega-3 and omega-6 polyunsaturated fatty acids, respectively. Aldehydes are therefore potential non-invasive biomarkers of oxidative stress and of various diseases in which oxidative stress is thought to play a role including cancer, cardiovascular disease and diabetes. It is unclear, however, how changes in the abundance of the fatty acid precursors, for example by altered dietary intake, affect aldehyde concentrations. We therefore fed male Wistar rats diets supplemented with either palm oil or a combination of palm oil plus an n-3 fatty acid (alpha-linolenic, eicosapentaenoic, or docosahexaenoic acids) for 4 weeks. Fatty acid analysis revealed large changes in the abundance of both n-3 and n-6 fatty acids in the liver with smaller changes observed in the brain. Despite the altered fatty acid abundance, headspace concentrations of C1-C8 aldehydes, and tissue concentrations of thiobarbituric acid reactive substances, did not differ between the 4 dietary groups. Our data suggest that tissue aldehyde concentrations are independent of fatty acid abundance, and further support their use as volatile biomarkers of oxidative stress.

  13. Mild Clinical Presentation of Acute Fatty Liver in the Second Trimester of Pregnancy

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    Alaeddine Yassin

    2011-01-01

    Full Text Available We report a case of 29 years old woman who was diagnosed with acute fatty liver of pregnancy at 23 weeks of gestation with unusual evolution (pregnancy prolonged until 36 weeks of gestation to draw attention on the possibility of occurrence of this pathology in the second trimester of pregnancy even with a milder clinical presentation and course.

  14. Activation of proteinase 3 contributes to nonalcoholic fatty liver disease and insulin resistance

    NARCIS (Netherlands)

    Toonen, Erik J.M.; Mirea, Andreea Manuela; Tack, Cees J.; Stienstra, Rinke; Ballak, Dov B.; Diepen, van Janna A.; Hijmans, Anneke; Chavakis, Triantafyllos; Dokter, Wim H.; Pham, Christine Tn; Netea, Mihai G.; Dinarello, Charles A.; Joosten, Leo A.B.

    2016-01-01

    Activation of inflammatory pathways is known to accompany development of obesity-induced nonalcoholic 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 proces

  15. Non-alcoholic fatty liver disease is associated with cardiovascular disease risk markers

    NARCIS (Netherlands)

    Edens, M. A.; Kuipers, F.; Stolk, R. P.

    2009-01-01

    Recognition of the link between non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD) has boosted research in this area. The main objective of this paper is to review the literature on NAFLD in the context of CVD, focussing on underlying mechanisms and treatment. Besides excessi

  16. 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 progressi

  17. Fatty infiltration of the liver in severely burned pediatric patients : Autopsy findings and clinical implications

    NARCIS (Netherlands)

    Barret, JP; Jeschke, MG; Herndon, DN

    2001-01-01

    Background. Trauma induces hypermetabolic responses that are characterized by the mobilization of all available substrates. The marked increase of peripheral lipolysis after a burn can lead to the development of fatty liver, which has been associated with immunodepression and increased mortality. Me

  18. 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 assoc

  19. Maternal mortality and severe maternal morbidity from acute fatty liver of pregnancy in the Netherlands

    NARCIS (Netherlands)

    Dekker, Ruth R.; Schutte, Joke M.; Stekelenburg, Jelle; Zwart, Joost J.; van Roosmalen, Jos

    2011-01-01

    Objective: To assess maternal death and severe maternal morbidity from acute fatty liver of pregnancy (AFLP) in the Netherlands. Study design: A retrospective study of all cases of maternal mortality in the Netherlands between 1983 and 2006 and all cases of severe maternal morbidity in the Netherlan

  20. 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...

  1. Solute carrier family 2 member 1 is involved in the development of nonalcoholic fatty liver disease

    DEFF Research Database (Denmark)

    Vazquez-Chantada, Mercedes; Gonzalez-Lahera, Aintzane; Martinez-Arranz, Ibon

    2013-01-01

    Susceptibility to develop nonalcoholic fatty liver disease (NAFLD) has genetic bases, but the associated variants are uncertain. The aim of the present study was to identify genetic variants that could help to prognose and further understand the genetics and development of NAFLD. Allele frequencies...

  2. Analysis of the ligand binding properties of recombinant bovine liver-type fatty acid binding protein

    DEFF Research Database (Denmark)

    Rolf, B; Oudenampsen-Krüger, E; Börchers, T

    1995-01-01

    The coding part of the cDNA for bovine liver-type fatty acid binding protein (L-FABP) has been amplified by RT-PCR, cloned and used for the construction of an Escherichia coli (E. coli) expression system. The recombinant protein made up to 25% of the soluble E. coli proteins and could be isolated...

  3. Changes of caveolin-1 in the livers of mice with nonalcoholic fatty liver disease caused by highfat diet

    Institute of Scientific and Technical Information of China (English)

    邱艳

    2013-01-01

    Objective To explore the role of caveolin-1 in nonalcoholic fatty liver disease (NAFLD) caused by high-fat diet.Methods A total of 12 ten-week-old male C57BL/6mice were fed with high-fat and high-cholesterol diet for14 weeks to establish the NAFLD animal model.And six syngeneic mice fed with normal diet at the same time were taken as control.All the mice were sacrificed by

  4. Omega 3 fatty acids induce a marked reduction of apolipoprotein B48 when added to fluvastatin in patients with type 2 diabetes and mixed hyperlipidemia: a preliminary report

    Directory of Open Access Journals (Sweden)

    González-Santos Pedro

    2009-01-01

    Full Text Available Abstract Backgorund Mixed hyperlipidemia is common in patients with diabetes. Statins, the choice drugs, are effective at reducing lipoproteins that contain apolipoprotein B100, but they fail to exert good control over intestinal lipoproteins, which have an atherogenic potential. We describe the effect of prescription omega 3 fatty acids on the intestinal lipoproteins in patients with type 2 diabetes who were already receiving fluvastatin 80 mg per day. Methods Patients with type 2 diabetes and mixed hyperlipidemia were recruited. Fasting lipid profile was taken when patients were treated with diet, diet plus 80 mg of fluvastatin and diet plus fluvastatin 80 mg and 4 g of prescription omega 3 fatty acids. The intestinal lipoproteins were quantified by the fasting concentration of apolipoprotein B48 using a commercial ELISA. Results The addition of 4 g of prescription omega 3 was followed by significant reductions in the levels of triglycerides, VLDL triglycerides and the triglyceride/HDL cholesterol ratio, and an increase in HDL cholesterol (P Conclusion Our preliminary findings therefore suggest an additional benefit on postprandial atherogenic particles when omega 3 fatty acids are added to standard treatment with fluvastatin.

  5. Editorial: Magnetic Resonance Elastography and Non-Alcoholic Fatty Liver Disease: Time for an Upgrade?

    Science.gov (United States)

    Flores, Avegail; Asrani, Sumeet K

    2016-07-01

    Elastography techniques, such as two-dimensional magnetic resonance elastography (2D-MRE) are increasingly used for the non-invasive assessment of liver fibrosis in patients with nonalchoholic fatty liver disease (NAFLD). Loomba et al. demonstrate that 3D-MRE (shear wave frequency 40 Hz) had even greater diagnostic accuracy than the commercially available 2D-MRE (shear wave frequency 60 Hz) in diagnosing advanced fibrosis (area under the receiver operator curve, AUROC 0.981 vs. 0.921, P<0. 05) using liver biopsy as reference standard. Despite limitations, MRE serves as an important tool in risk stratification for patients with NAFLD.

  6. Histology of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis in Adults and Children.

    Science.gov (United States)

    Kleiner, David E; Makhlouf, Hala R

    2016-05-01

    Nonalcoholic fatty liver disease (NAFLD) is the liver disease associated with obesity, diabetes, and the metabolic syndrome. Although steatosis is a key histologic feature, liver biopsies of patients with NAFLD can show a wide range of findings. Nonalcoholic steatohepatitis (NASH) is a progressive subtype of NAFLD first defined by analogy to alcoholic hepatitis. Young children may have an alternate pattern of progressive NAFLD characterized by a zone 1 distribution of steatosis, inflammation, and fibrosis. Several grading and staging systems exist, but all require adequate biopsies. Although NASH generally shows fibrosis progression over time, some patients show regression of disease.

  7. Longitudinal study of circulating oxidized LDL and HDL and fatty liver: the Cardiovascular Risk in Young Finns Study.

    Science.gov (United States)

    Kaikkonen, Jari E; Kresanov, Petri; Ahotupa, Markku; Jula, Antti; Mikkilä, Vera; Viikari, Jorma S A; Juonala, Markus; Hutri-Kähönen, Nina; Kähönen, Mika; Lehtimäki, Terho; Kangas, Antti J; Soininen, Pasi; Ala-Korpela, Mika; Raitakari, Olli T

    2016-01-01

    Oxidative reactions are thought to play a role in the inflammatory condition called fatty liver. It is unclear whether oxidized lipoprotein lipids or proteins are associated with future fatty liver. In the Cardiovascular Risk in Young Finns Study, we determined the circulating levels of LDL and HDL oxidized lipids and studied their associations with fatty liver assessed by ultrasonography. There were 1286 middle-aged subjects with normal liver and 288 subjects with fatty liver. Analysis of oxidized lipids consisted of conjugated dienes in isolated HDL (oxHDLlipids) and LDL (oxLDLlipids). Oxidized LDL was also measured with a method based on antibodies against oxidized apolipoprotein B (oxLDLprot). After adjustment for age, sex, leisure-time physical activity, body mass index, alcohol intake, smoking, serum LDL and HDL cholesterol as well as particle concentrations, participants with elevated oxLDLlipids (odds ratio for 1-SD change in oxLDLlipids = 1.27, p =0.011) had an increased risk for fatty liver. Similarly, a high oxidation score (oxLDLlipids + oxLDLprot) was directly associated with fatty liver (odds ratio=1.34, p = 0.012). The strongest direct association was seen with a high oxLDLlipids/oxHDLlipids ratio (odds ratio=1.49, p = 0.001). These data suggest that oxidized lipoprotein lipids are linked with the risk of fatty liver in middle-aged adults.

  8. A Maternal “Junk Food” Diet in Pregnancy and Lactation Promotes Nonalcoholic Fatty Liver Disease in Rat Offspring

    OpenAIRE

    Bayol, Stéphanie A; Simbi, Bigboy H.; Fowkes, Robert C.; Stickland, Neil C.

    2010-01-01

    With rising obesity rates, nonalcoholic fatty liver disease is predicted to become the main cause of chronic liver disease in the next decades. Rising obesity prevalence is attributed to changes in dietary habits with increased consumption of palatable junk foods, but maternal malnutrition also contributes to obesity in progeny. This study examines whether a maternal junk food diet predisposes offspring to nonalcoholic fatty liver disease. The 144 rat offspring were fed either a balanced chow...

  9. The Polyunsaturated Fatty Acids Arachidonic Acid and Docosahexaenoic Acid Induce Mouse Dendritic Cells Maturation but Reduce T-Cell Responses In Vitro.

    Science.gov (United States)

    Carlsson, Johan A; Wold, Agnes E; Sandberg, Ann-Sofie; Östman, Sofia M

    2015-01-01

    Long-chain polyunsaturated fatty acids (PUFAs) might regulate T-cell activation and lineage commitment. Here, we measured the effects of omega-3 (n-3), n-6 and n-9 fatty acids on the interaction between dendritic cells (DCs) and naïve T cells. Spleen DCs from BALB/c mice were cultured in vitro with ovalbumin (OVA) with 50 μM fatty acids; α-linolenic acid, arachidonic acid (AA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), linoleic acid or oleic acid and thereafter OVA-specific DO11.10 T cells were added to the cultures. Fatty acids were taken up by the DCs, as shown by gas chromatography analysis. After culture with arachidonic acid or DHA CD11c+ CD11b+ and CD11c+ CD11bneg DCs expressed more CD40, CD80, CD83, CD86 and PDL-1, while IAd remained unchanged. However, fewer T cells co-cultured with these DCs proliferated (CellTrace Violet low) and expressed CD69 or CD25, while more were necrotic (7AAD+). We noted an increased proportion of T cells with a regulatory T cell (Treg) phenotype, i.e., when gating on CD4+ FoxP3+ CTLA-4+, CD4+ FoxP3+ Helios+ or CD4+ FoxP3+ PD-1+, in co-cultures with arachidonic acid- or DHA-primed DCs relative to control cultures. The proportion of putative Tregs was inversely correlated to T-cell proliferation, indicating a suppressive function of these cells. With arachidonic acid DCs produced higher levels of prostaglandin E2 while T cells produced lower amounts of IL-10 and IFNγ. In conclusion arachidonic acid and DHA induced up-regulation of activation markers on DCs. However arachidonic acid- and DHA-primed DCs reduced T-cell proliferation and increased the proportion of T cells expressing FoxP3, indicating that these fatty acids can promote induction of regulatory T cells.

  10. Pentoxifylline ameliorates non-alcoholic fatty liver disease in hyperglycaemic and dyslipidaemic mice by upregulating fatty acid β-oxidation.

    Science.gov (United States)

    Ye, Jia-Hung; Chao, Jung; Chang, Ming-Ling; Peng, Wen-Huang; Cheng, Hao-Yuan; Liao, Jiunn-Wang; Pao, Li-Heng

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD), which includes simple steatosis, steatohepatitis, fibrosis, and cirrhosis, is characterised by abnormal fat accumulation in the liver in the absence of excessive alcohol intake. In patients with type 2 diabetes (T2D), concurrent NAFLD might increase the risk of chronic kidney disease and the mortality rate. Although several studies have examined the effectiveness of pentoxifylline (PTX) in NAFLD treatment, no results are available to verify the effectiveness of PTX in treating T2D associated with NAFLD. In this study, we developed a combined high-fat diet-induced obesity and low-dose streptozocin-induced hyperglycaemia mouse model to mimic the concurrent NAFLD and T2D pathological condition. By combining physiological assessments, pathological examinations, metabolomics studies on blood, urine, and liver, and measurements of gene and protein expression, we elucidated the effectiveness and the underlying mechanism of action of PTX in the hyperglycaemic and dyslipidaemic mice. Our results revealed that PTX ameliorated NAFLD in the hyperglycaemic and dyslipidaemic mice by upregulating fatty acid β-oxidation. Furthermore, the glycolysis pathway and branched-chain amino acid-related pathways in these mice were restored by PTX.

  11. Pentoxifylline ameliorates non-alcoholic fatty liver disease in hyperglycaemic and dyslipidaemic mice by upregulating fatty acid β-oxidation

    Science.gov (United States)

    Ye, Jia-Hung; Chao, Jung; Chang, Ming-Ling; Peng, Wen-Huang; Cheng, Hao-Yuan; Liao, Jiunn-Wang; Pao, Li-Heng

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD), which includes simple steatosis, steatohepatitis, fibrosis, and cirrhosis, is characterised by abnormal fat accumulation in the liver in the absence of excessive alcohol intake. In patients with type 2 diabetes (T2D), concurrent NAFLD might increase the risk of chronic kidney disease and the mortality rate. Although several studies have examined the effectiveness of pentoxifylline (PTX) in NAFLD treatment, no results are available to verify the effectiveness of PTX in treating T2D associated with NAFLD. In this study, we developed a combined high-fat diet-induced obesity and low-dose streptozocin-induced hyperglycaemia mouse model to mimic the concurrent NAFLD and T2D pathological condition. By combining physiological assessments, pathological examinations, metabolomics studies on blood, urine, and liver, and measurements of gene and protein expression, we elucidated the effectiveness and the underlying mechanism of action of PTX in the hyperglycaemic and dyslipidaemic mice. Our results revealed that PTX ameliorated NAFLD in the hyperglycaemic and dyslipidaemic mice by upregulating fatty acid β-oxidation. Furthermore, the glycolysis pathway and branched-chain amino acid-related pathways in these mice were restored by PTX. PMID:27612024

  12. 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.

  13. Counteracting roles of AMP deaminase and AMP kinase in the development of fatty liver.

    Directory of Open Access Journals (Sweden)

    Miguel A Lanaspa

    Full Text Available Fatty liver (hepatic steatosis is associated with nucleotide turnover, loss of ATP and generation of adenosine monophosphate (AMP. It is well known that in fatty liver, activity of the AMP-activated kinase (AMPK is reduced and that its stimulation can prevent hepatic steatosis by both enhancing fat oxidation and reducing lipogenesis. Here we show that another AMP dependent enzyme, AMPD2, has opposing effects on fatty acid oxidation when compared to AMPK. In human hepatocytres, AMPD2 activation -either by overexpression or by lowering intracellular phosphate levels with fructose- is associated with a significant reduction in AMPK activity. Likewise, silencing of AMPK spontaneously increases AMPD activity, demonstrating that these enzymes counter-regulate each other. Furthermore, we show that a downstream product of AMP metabolism through AMPD2, uric acid, can inhibit AMPK activity in human hepatocytes. Finally, we show that fructose-induced fat accumulation in hepatocytes is due to a dominant stimulation of AMPD2 despite stimulating AMPK. In this regard, AMPD2-deficient hepatocytes demonstrate a further activation of AMPK after fructose exposure in association with increased fatty acid oxidation, and conversely silencing AMPK enhances AMPD-dependent fat accumulation. In vivo, we show that sucrose fed rats also develop fatty liver that is blocked by metformin in association with both a reduction in AMPD activity and an increase in AMPK activity. In summary, AMPD and AMPK are both important in hepatic fat accumulation and counter-regulate each other. We present the novel finding that uric acid inhibits AMPK kinase activity in fructose-fed hepatocytes thus providing new insights into the pathogenesis of fatty liver.

  14. Serum asymmetric dimethylarginine levels are independently associated with procollagen III N-terminal peptide in nonalcoholic fatty liver disease patients.

    Science.gov (United States)

    Hyogo, Hideyuki; Yamagishi, Sho-Ichi; Maeda, Sayaka; Fukami, Kei; Ueda, Seiji; Okuda, Seiya; Nakahara, Takashi; Kimura, Yuki; Ishitobi, Tomokazu; Chayama, Kazuaki

    2014-02-01

    Although impaired synthesis and/or bioavailability of nitric oxide are considered to contribute to insulin resistance and the progression of liver disease in nonalcoholic fatty liver disease, role of asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide synthase, has not been examined. We examined retrospectively which anthropometric and metabolic parameters were independently associated with serum levels of asymmetric dimethylarginine in nonalcoholic fatty liver disease. A total of 194 consecutive biopsy-proven nonalcoholic fatty liver disease patients with or without type 2 diabetes were enrolled. Serum asymmetric dimethylarginine levels in nonalcoholic fatty liver disease patients were significantly higher, irrespective of the presence or absence of diabetes, than those in healthy control. Multiple stepwise regression analysis showed that decreased total protein and procollagen N-terminal peptide levels, markers of advanced liver disease and hepatic fibrosis, respectively, were independently associated with asymmetric dimethylarginine levels in nonalcoholic fatty liver disease subjects without diabetes, whereas soluble form of receptor for advanced glycation end products and density ratio of liver to spleen in computed tomography were independent correlates of asymmetric dimethylarginine in diabetic patients. The present study suggests that asymmetric dimethylarginine may be associated with nonalcoholic fatty liver disease, especially subjects without diabetes.

  15. A Public Health Issue that Increased Prevelance: Non-Acholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Muammer Kara

    2014-02-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD, is a liver disease, that occur in non alcohol users, with same histological features of alcoholic liver disease. The increased importance of NAFLD is depends on its close relation of current problems such as Type 2 Diabetes Mellitus and hyperlipidemia, and its high prevalence as %20-30, in Europe and Middle East. NAFLD has a wide spectrum from simple steatozis (SS, liver cell damage, non alcoholic steatohepatitis (NASH with inflammation to high stage fibrosis, and cirrhosis. Hepathocellular cancer and liver failure might develop in cirrhosis patients. Biopsy is gold standard for NAFLD diagnosis; differentiate from SS and NASH and defining NASH stages. Nutrition regulations and slow and continuous weight loss with regular exercises is still best treatment method [TAF Prev Med Bull 2014; 13(1.000: 65-76

  16. [Peculiarities of metabolic syndrome and nonalcogolic fatty liver disease in menopausal women].

    Science.gov (United States)

    Antelava, N A; Antelava, A V; Gongadze, M V; Okudzhava, M V; Pachkoriia, K Z; Gogolauri, M I

    2012-07-01

    Correlation between menopause metabolic syndrome and nonalcogolic fatty liver disease (NAFLD) is reviewed. NAFLD refers to a wide spectrum of liver disease ranging from simple fatty liver (steatosis), to nonalcoholic steatohepatitis, to cirrhosis. The causes and pathogenetic factors of the disease are still under investigation. The risk of development of NAFLD during menopause is twice higher in comparison with fertile age and abdominal obesity and insulin resistances is more apparent. This feature is associated with deficit of estrogens during menopause, as risk of development of NAFLD is diminished with substitutive hormonotherapy. The obesity, particularly in the period of menopause, is discussed as additive, independent risk factor of metabolic syndrome and of diseases of hepatobiliare and cardiovascular systems.

  17. Leptin and fatty liver disease%瘦素与脂肪性肝病

    Institute of Scientific and Technical Information of China (English)

    赵彩彦; 李丽

    2004-01-01

    脂肪性肝病(fatty liver disease,FLD)是遗传一环境一代谢应激相关因素所致的以肝细胞脂肪变性为主的临床病理综合征。FLD包括由酒精所致的酒精性肝病(alcoholic liver disease,ALD)和肥胖、高脂等代谢紊乱所致的非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)。在病理上分为单纯性脂肪肝、脂肪性肝炎、脂肪性肝纤维化和脂肪性肝硬化。在FLD的发生发展过程中,瘦素的作用日益受到重视。

  18. Observation on Effect of Treatment of Alcoholic Fatty Liver by Traditional Medical Therapy of Liver-Clearing, Dampness-Removing and Collaterals-Dredging

    Institute of Scientific and Technical Information of China (English)

    张诗军; 陈泽雄; 劳绍贤; 黄必军

    2002-01-01

    @@ Spirits of wine is one of the pathogenetic factors of liver damage which is merely secondary to hepatitis virus. The incidence of fatty liver in Chinese adults is 5%-9% now. It is reported that interleukin-8 (IL-8) and lipid peroxidation play an important role in development of alcoholic fatty liver and liver damage(1-3). The authors have observed the therapeutic effect in 30 patients of alcoholic fatty liver treated with Chinese herbal drugs for Liver-clearing, Dampness-removing and Collaterals-dredging (abbre. as CHD) from Aug. 1999 to June 2001 and explored the relationship between the effects of treatment and some indices, including IL-8, malonyldialdehyde (MDA) and superoxide dismutase (SOD).

  19. In vivo incorporation of labeled fatty acids in rat liver lipids after oral administration

    Energy Technology Data Exchange (ETDEWEB)

    Leyton, J.; Drury, P.J.; Crawford, M.A.

    1987-08-01

    Striking differences were found in the compartmentalization of fatty acids into liver lipid fractions. The saturated fatty acids--lauric, myristic, palmitic and stearic--were incorporated into phosphoglycerides at faster rates with increasing chain lengths, while triglyceride incorporation was almost uniform. The degree of incorporation of the unsaturated fatty acids into phosphoglycerides (structural) compared to triglyceride (storage and energy) was the converse of their oxidation rates. The incorporation of oleic, linoleic and alpha-linolenic acids was mainly into triglyceride, whereas dihomo-gamma-linolenic acid and arachidonic acid were preferentially incorporated into phosphoglycerides. The data suggest that distribution of each fatty acid is different depending on its destination for structural or energy function.

  20. 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.

  1. Markers of activated inflammatory cells correlate with severity of liver damage in children with nonalcoholic fatty liver disease.

    Science.gov (United States)

    De Vito, Rita; Alisi, Anna; Masotti, Andrea; Ceccarelli, Sara; Panera, Nadia; Citti, Arianna; Salata, Michele; Valenti, Luca; Feldstein, Ariel E; Nobili, Valerio

    2012-07-01

    Concomitantly to the obesity epidemic, nonalcoholic fatty liver disease (NAFLD) has become the leading cause of liver disease in children. NAFLD encompasses a spectrum of histological damage ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), with possible progression to cirrhosis. There is growing evidence that the immune system plays a pivotal role in the initiation and progression to NASH but the cellular nature of the hepatic inflammation is still unknown. The present study includes 34 children with biopsy-proven NAFLD. Liver damage was evaluated by the NAFLD activity score (NAS), and the inflammatory infiltrate was characterized by immunohistochemistry for CD45, CD3 and CD163 which are markers of leukocytes, T cells and activated Kupffer cells/macrophages, respectively. Our results have shown that CD45+ (Pchildren with severe histological activity (NAS≥5) compared to children with lower activity (NASchildren with severe histological activity. There was a significant association between the numbers of CD45+, CD3+ and CD163+ cells, regarding both the portal tract and liver lobule, and the severity of steatosis, ballooning and fibrosis (Pchildren with NAFLD. Moreover, a decrease in CD3+ cells may be involved in the pathogenesis of liver damage. Future studies should evaluate whether it can predict the progression of liver disease independently of established histological scores.

  2. Quantitative evaluation of {sup 99m}Tc-GSA for fatty liver and ischemia-reperfusion injury in rats

    Energy Technology Data Exchange (ETDEWEB)

    Kimoto, Mitsunori [Okayama Univ. (Japan). Medical School

    1996-04-01

    {sup 99m}Tc-GSA (GSA) liver scintigraphy was performed in rats with fatty liver and ischemia-reperfusion injury to study the usefulness of GSA in evaluating these pathological processes. Fatty liver was produced by feeding rats a choline-deficient diet. The rats with fatty liver were divided into five groups according to the length of the diet (controls, two weeks, six weeks, 10 weeks, and 12 weeks). In the rats dieted for two weeks and six weeks, regional hepatic ischemia was also induced by clamping the left hepatic artery and the left portal vein for 10 minutes, then reperfusion was performed for 15 minutes. GSA was administered via the IVC. t{sub 90}, or the time at which the liver time activity curve reached ninety percent of its peak value, was used as an index of GSA hepatic uptake, Ku and Kd, determined by two compartment analysis, were also used as indices. In rats of the fatty liver group, we confirmed microscopically that various degrees of fatty infiltration existed according to the diet period, and t{sub 90} became significantly longer according to the severity of fatty infiltration. Ku and Kd also decreased according to the severity of fatty infiltration. In the rats with fatty infiltration and ischemia-reperfusion injury, t{sub 90} also increased according to the severity of fatty infiltration, becoming longer than in the rats without ischemia-reperfusion injury. Quantitative analysis of GSA liver scintigraphy was useful for evaluating fatty liver and ischemia-reperfusion injury. (author).

  3. Induction of fatty liver by Coleus forskohlii extract through enhancement of de novo triglyceride synthesis in mice

    Directory of Open Access Journals (Sweden)

    Keizo Umegaki

    2014-01-01

    Full Text Available Coleus forskohlii extract (CFE, an herbal ingredient, is used for weight-loss products. CFE's alleged efficacy is attributed to forskolin. However, CFE has been shown to induce fatty liver in mice, with components other than forskolin playing a part in this effect. The present study addressed the underlying mechanism of CFE-induced fatty liver by analyzing changes in CFE-treated mice of lipid concentrations and of the levels of mRNAs encoding enzymes and transcription factors known to be related to fatty liver. Mice were fed a diet containing 0, 0.3 and 1% CFE for 2 weeks. CFE at 1% clearly induced fatty liver, as demonstrated by histological examination and confirmed by increases in triglyceride concentrations in liver. However, treated mice did not exhibit elevation in plasma levels of non-esterified fatty acids. Comprehensive analysis of liver mRNA levels revealed accumulation of multiple transcripts, including mRNAs encoding enzymes acetyl-CoA carboxylase and long-chain elongase; transcription factor peroxisome proliferator-activated receptor gamma (PPARγ; and lipid-droplet-associated fat-specific protein 27 (Fsp27. These findings suggest that the de novo synthesis and accumulation of triglyceride in the liver, through the enhanced expression of specific lipogenic mRNAs, is a major underlying mechanism of fatty liver induction by CFE.

  4. Bile Acid Nuclear Receptor Farnesoid X Receptor: Therapeutic Target for Nonalcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Sun-Gi Kim

    2016-12-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD is one of the causes of fatty liver, occurring when fat is accumulated in the liver without alcohol consumption. NAFLD is the most common liver disorder in advanced countries. NAFLD is a spectrum of pathology involving hepatic steatosis with/without inflammation and nonalcoholic steatohepatitis with accumulation of hepatocyte damage and hepatic fibrosis. Recent studies have revealed that NAFLD results in the progression of cryptogenic cirrhosis that leads to hepatocarcinoma and cardiovascular diseases such as heart failure. The main causes of NAFLD have not been revealed yet, metabolic syndromes including obesity and insulin resistance are widely accepted for the critical risk factors for the pathogenesis of NAFLD. Nuclear receptors (NRs are transcriptional factors that sense environmental or hormonal signals and regulate expression of genes, involved in cellular growth, development, and metabolism. Several NRs have been reported to regulate genes involved in energy and xenobiotic metabolism and inflammation. Among various NRs, farnesoid X receptor (FXR is abundantly expressed in the liver and a key regulator to control various metabolic processes in the liver. Recent studies have shown that NAFLD is associated with inappropriate function of FXR. The impact of FXR transcriptional activity in NAFLD is likely to be potential therapeutic strategy, but still requires to elucidate underlying potent therapeutic mechanisms of FXR for the treatment of NAFLD. This article will focus the physiological roles of FXR and establish the correlation between FXR transcriptional activity and the pathogenesis of NAFLD.

  5. Bile Acid Nuclear Receptor Farnesoid X Receptor: Therapeutic Target for Nonalcoholic Fatty Liver Disease

    Science.gov (United States)

    Kim, Sun-Gi; Kim, Byung-Kwon; Kim, Kyumin

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) is one of the causes of fatty liver, occurring when fat is accumulated in the liver without alcohol consumption. NAFLD is the most common liver disorder in advanced countries. NAFLD is a spectrum of pathology involving hepatic steatosis with/without inflammation and nonalcoholic steatohepatitis with accumulation of hepatocyte damage and hepatic fibrosis. Recent studies have revealed that NAFLD results in the progression of cryptogenic cirrhosis that leads to hepatocarcinoma and cardiovascular diseases such as heart failure. The main causes of NAFLD have not been revealed yet, metabolic syndromes including obesity and insulin resistance are widely accepted for the critical risk factors for the pathogenesis of NAFLD. Nuclear receptors (NRs) are transcriptional factors that sense environmental or hormonal signals and regulate expression of genes, involved in cellular growth, development, and metabolism. Several NRs have been reported to regulate genes involved in energy and xenobiotic metabolism and inflammation. Among various NRs, farnesoid X receptor (FXR) is abundantly expressed in the liver and a key regulator to control various metabolic processes in the liver. Recent studies have shown that NAFLD is associated with inappropriate function of FXR. The impact of FXR transcriptional activity in NAFLD is likely to be potential therapeutic strategy, but still requires to elucidate underlying potent therapeutic mechanisms of FXR for the treatment of NAFLD. This article will focus the physiological roles of FXR and establish the correlation between FXR transcriptional activity and the pathogenesis of NAFLD. PMID:28029021

  6. Role of hepatic lipogenesis in the susceptibility to fatty liver in the goose (Anser anser).

    Science.gov (United States)

    Mourot, J; Guy, G; Lagarrigue, S; Peiniau, P; Hermier, D

    2000-05-01

    In response to overfeeding, the Landes goose develops a fatty liver that is twice as large as that of the Poland goose, despite similar food intake. The role of hepatic lipogenesis in the genetic susceptibility to fatty liver was assessed in male overfed geese of the two breeds. For a similar hepatic protein content, total activities of malic enzyme, glucose-6-phosphate dehydrogenase, acetyl-Coa-carboxylase and fatty acid synthase, and specific activity and mRNA level of malic enzyme were about two-fold higher in the Landes goose. In the Poland goose, the weight of the fatty liver was correlated positively with the specific activity of ME and the VLDL concentration, which was not the case in the Landes breed. These results show that: (1) hepatic lipogenesis remains very active until the end of the overfeeding period; (2) the pentose-phosphate pathway may function in birds, contrary to what is assumed usually; (3) the level of hepatic lipogenesis is a major factor in the susceptibility to hepatic steatosis in different breeds of geese; and (4) ME activity may be a limiting factor of lipid synthesis in the less susceptible Poland breed.

  7. Genetics of non-alcoholic fatty liver disease: From susceptibility and nutrient interactions to management

    Science.gov (United States)

    Ravi Kanth, Vishnubhotla Venkata; Sasikala, Mitnala; Sharma, Mithun; Rao, Padaki Nagaraja; Reddy, Duvvuru Nageshwar

    2016-01-01

    Genetics plays an important role in determining the susceptibility of an individual to develop a disease. Complex, multi factorial diseases of modern day (diabetes, cardiovascular disease, hypertension and obesity) are a result of disparity between the type of food consumed and genes, suggesting that food which does not match the host genes is probably one of the major reasons for developing life style diseases. Non-alcoholic fatty liver is becoming a global epidemic leading to substantial morbidity. While various genotyping approaches such as whole exome sequencing using next generation sequencers and genome wide association studies have identified susceptibility loci for non-alcoholic fatty liver disease (NAFLD) including variants in patatin-like phospholipase domain containing 3 and transmembrane 6 superfamily member 2 genes apart from others; nutrient based studies emphasized on a combination of vitamin D, E and omega-3 fatty acids to manage fatty liver disease. However majority of the studies were conducted independent of each other and very few studies explored the interactions between the genetic susceptibility and nutrient interactions. Identifying such interactions will aid in optimizing the nutrition tailor made to an individual’s genetic makeup, thereby aiding in delaying the onset of the disease and its progression. The present topic focuses on studies that identified the genetic susceptibility for NAFLD, nutritional recommendations, and their interactions for better management of NAFLD. PMID:27458502

  8. Genetics of non-alcoholic fatty liver disease: From susceptibility and nutrient interactions to management

    Institute of Scientific and Technical Information of China (English)

    Vishnubhotla; Venkata; Ravi; Kanth; Mitnala; Sasikala; Mithun; Sharma; Padaki; Nagaraja; Rao; Duvvuru; Nageshwar; Reddy

    2016-01-01

    Genetics plays an important role in determining the susceptibility of an individual to develop a disease. Complex, multi factorial diseases of modern day(diabetes, cardiovascular disease, hypertension and obesity) are a result of disparity between the type of food consumed and genes, suggesting that food which does not match the host genes is probably one of the major reasons for developing life style diseases. Non-alcoholic fatty liver is becoming a global epidemic leading to substantial morbidity. While various genotyping approaches such as whole exome sequencing using next generation sequencers and genome wide association studies have identified susceptibility loci for non-alcoholic fatty liver disease(NAFLD) including variants in patatin-like phospholipase domain containing 3 and transmembrane 6 superfamily member 2 genes apart from others; nutrient based studies emphasized on a combination of vitamin D, E and omega-3 fatty acids to manage fatty liver disease. However majority of the studies were conducted independent of each other and very few studies explored the interactions between the genetic susceptibility and nutrient interactions. Identifying such interactions will aid in optimizing the nutrition tailor made to an individual’s genetic makeup, thereby aiding in delaying the onset of the disease and its progression. The present topic focuses on studies that identified the genetic susceptibility for NAFLD, nutritional recommendations, and their interactions for better management of NAFLD.

  9. Diet-induced metabolic hamster model of nonalcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    Bhathena J

    2011-06-01

    Full Text Available Jasmine Bhathena, Arun Kulamarva, Christopher Martoni, Aleksandra Malgorzata Urbanska, Meenakshi Malhotra, Arghya Paul, Satya PrakashBiomedical Technology and Cell Therapy Research Laboratory, Department of Biomedical Engineering, Artificial Cells and Organs Research Centre, Faculty of Medicine, McGill University, Montreal, Québec, CanadaBackground: Obesity, hypercholesterolemia, elevated triglycerides, and type 2 diabetes are major risk factors for metabolic syndrome. Hamsters, unlike rats or mice, respond well to diet-induced obesity, increase body mass and adiposity on group housing, and increase food intake due to social confrontation-induced stress. They have a cardiovascular and hepatic system similar to that of humans, and can thus be a useful model for human pathophysiology.Methods: Experiments were planned to develop a diet-induced Bio F1B Golden Syrian hamster model of dyslipidemia and associated nonalcoholic fatty liver disease in the metabolic syndrome. Hamsters were fed a normal control diet, a high-fat/high-cholesterol diet, a high-fat/high-cholesterol/methionine-deficient/choline-devoid diet, and a high-fat/high-cholesterol/choline-deficient diet. Serum total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, glucose, atherogenic index, and body weight were quantified biweekly. Fat deposition in the liver was observed and assessed following lipid staining with hematoxylin and eosin and with oil red O.Results: In this study, we established a diet-induced Bio F1B Golden Syrian hamster model for studying dyslipidemia and associated nonalcoholic fatty liver disease in the metabolic syndrome. Hyperlipidemia and elevated serum glucose concentrations were induced using this diet. Atherogenic index was elevated, increasing the risk for a cardiovascular event. Histological analysis of liver specimens at the end of four weeks showed increased fat deposition in the liver of animals fed

  10. Topical Formulation Comprising Fatty Acid Extract from Cod Liver Oil: Development, Evaluation and Stability Studies.

    Science.gov (United States)

    Ilievska, Biljana; Loftsson, Thorsteinn; Hjalmarsdottir, Martha Asdis; Asgrimsdottir, Gudrun Marta

    2016-06-01

    The purpose of this study was to develop a pharmaceutical formulation containing fatty acid extract rich in free omega-3 fatty acids such as eicosapentaenoic acid and docosahexaenoic acid for topical use. Although the health benefits of cod liver oil and other fish oils taken orally as a dietary supplement have been acknowledged and exploited, it is clear that their use can be extended further to cover their antibacterial properties. In vitro evaluation showed that 20% (v/v) fatty acid extract exhibits good activity against strains of the Gram-positive bacteria Staphylococcus aureus, Enterococcus faecalis, Streptoccoccus pyogenes and Streptoccoccus pneumonia. Therefore, free polyunsaturated fatty acids from cod liver oil or other fish oils can be used as safe and natural antibacterial agents. In this study, ointment compositions containing free fatty acids as active antibacterial agents were prepared by using various natural waxes and characterized. The effects of different waxes, such as carnauba wax, ozokerite wax, laurel wax, beeswax, rice bran wax, candelilla wax and microcrystalline wax, in the concentration range of 1% to 5% (w/w) on the ointment texture, consistency and stability were evaluated. The results showed significant variations in texture, sensory and rheological profiles. This was attributed to the wax's nature and chain composition. Microcrystalline wax gave the best results but laurel wax, beeswax and rice bran wax exhibited excellent texturing, similar sensory profiles and well-balanced rheological properties.

  11. Topical Formulation Comprising Fatty Acid Extract from Cod Liver Oil: Development, Evaluation and Stability Studies

    Science.gov (United States)

    Ilievska, Biljana; Loftsson, Thorsteinn; Hjalmarsdottir, Martha Asdis; Asgrimsdottir, Gudrun Marta

    2016-01-01

    The purpose of this study was to develop a pharmaceutical formulation containing fatty acid extract rich in free omega-3 fatty acids such as eicosapentaenoic acid and docosahexaenoic acid for topical use. Although the health benefits of cod liver oil and other fish oils taken orally as a dietary supplement have been acknowledged and exploited, it is clear that their use can be extended further to cover their antibacterial properties. In vitro evaluation showed that 20% (v/v) fatty acid extract exhibits good activity against strains of the Gram-positive bacteria Staphylococcus aureus, Enterococcus faecalis, Streptoccoccus pyogenes and Streptoccoccus pneumonia. Therefore, free polyunsaturated fatty acids from cod liver oil or other fish oils can be used as safe and natural antibacterial agents. In this study, ointment compositions containing free fatty acids as active antibacterial agents were prepared by using various natural waxes and characterized. The effects of different waxes, such as carnauba wax, ozokerite wax, laurel wax, beeswax, rice bran wax, candelilla wax and microcrystalline wax, in the concentration range of 1% to 5% (w/w) on the ointment texture, consistency and stability were evaluated. The results showed significant variations in texture, sensory and rheological profiles. This was attributed to the wax’s nature and chain composition. Microcrystalline wax gave the best results but laurel wax, beeswax and rice bran wax exhibited excellent texturing, similar sensory profiles and well-balanced rheological properties. PMID:27258290

  12. Topical Formulation Comprising Fatty Acid Extract from Cod Liver Oil: Development, Evaluation and Stability Studies

    Directory of Open Access Journals (Sweden)

    Biljana Ilievska

    2016-06-01

    Full Text Available The purpose of this study was to develop a pharmaceutical formulation containing fatty acid extract rich in free omega-3 fatty acids such as eicosapentaenoic acid and docosahexaenoic acid for topical use. Although the health benefits of cod liver oil and other fish oils taken orally as a dietary supplement have been acknowledged and exploited, it is clear that their use can be extended further to cover their antibacterial properties. In vitro evaluation showed that 20% (v/v fatty acid extract exhibits good activity against strains of the Gram-positive bacteria Staphylococcus aureus, Enterococcus faecalis, Streptoccoccus pyogenes and Streptoccoccus pneumonia. Therefore, free polyunsaturated fatty acids from cod liver oil or other fish oils can be used as safe and natural antibacterial agents. In this study, ointment compositions containing free fatty acids as active antibacterial agents were prepared by using various natural waxes and characterized. The effects of different waxes, such as carnauba wax, ozokerite wax, laurel wax, beeswax, rice bran wax, candelilla wax and microcrystalline wax, in the concentration range of 1% to 5% (w/w on the ointment texture, consistency and stability were evaluated. The results showed significant variations in texture, sensory and rheological profiles. This was attributed to the wax’s nature and chain composition. Microcrystalline wax gave the best results but laurel wax, beeswax and rice bran wax exhibited excellent texturing, similar sensory profiles and well-balanced rheological properties.

  13. Original Research: Effect of various dietary fats on fatty acid profile in duck liver: Efficient conversion of short-chain to long-chain omega-3 fatty acids.

    Science.gov (United States)

    Chen, Xi; Du, Xue; Shen, Jianliang; Lu, Lizhi; Wang, Weiqun

    2017-01-01

    Omega-3 fatty acids, especially long-chain omega-3 fatty acids, have been associated with potential health benefits for chronic disease prevention. Our previous studies found that dietary omega-3 fatty acids could accumulate in the meat and eggs in a duck model. This study was to reveal the effects of various dietary fats on fatty acid profile and conversion of omega-3 fatty acids in duck liver. Female Shan Partridge Ducks were randomly assigned to five dietary treatments, each consisting of 6 replicates of 30 birds. The experimental diets substituted the basal diet by 2% of flaxseed oil, rapeseed oil, beef tallow, or fish oil, respectively. In addition, a dose response study was further conducted for flaxseed and fish oil diets at 0.5%, 1%, and 2%, respectively. At the end of the five-week treatment, fatty acids were extracted from the liver samples and analyzed by GC-FID. As expected, the total omega-3 fatty acids and the ratio of total omega-3/omega-6 significantly increased in both flaxseed and fish oil groups when compared with the control diet. No significant change of total saturated fatty acids or omega-3 fatty acids was found in both rapeseed and beef tallow groups. The dose response study further indicated that 59-81% of the short-chain omega-3 ALA in flaxseed oil-fed group was efficiently converted to long-chain DHA in the duck liver, whereas 1% of dietary flaxseed oil could produce an equivalent level of DHA as 0.5% of dietary fish oil. The more omega-3 fatty acids, the less omega-6 fatty acids in the duck liver. Taken together, this study showed the fatty acid profiling in the duck liver after various dietary fat consumption, provided insight into a dose response change of omega-3 fatty acids, indicated an efficient conversion of short- to long-chain omega-3 fatty acid, and suggested alternative long-chain omega-3 fatty acid-enriched duck products for human health benefits.

  14. Does Lysosomial Acid Lipase Reduction Play a Role in Adult Non-Alcoholic Fatty Liver Disease?

    Directory of Open Access Journals (Sweden)

    Francesco Baratta

    2015-11-01

    Full Text Available Lysosomal Acid Lipase (LAL is a key enzyme involved in lipid metabolism, responsible for hydrolysing the cholesteryl esters and triglycerides. Wolman Disease represents the early onset phenotype of LAL deficiency rapidly leading to death. Cholesterol Ester Storage Disease is a late onset phenotype that occurs with fatty liver, elevated aminotransferase levels, hepatomegaly and dyslipidaemia, the latter characterized by elevated LDL-C and low HDL-C. The natural history and the clinical manifestations of the LAL deficiency in adults are not well defined, and the diagnosis is often incidental. LAL deficiency has been suggested as an under-recognized cause of dyslipidaemia and fatty liver. Therefore, LAL activity may be reduced also in non-obese patients presenting non-alcoholic fatty liver disease (NAFLD, unexplained persistently elevated liver transaminases or with elevation in LDL cholesterol. In these patients, it could be indicated to test LAL activity. So far, very few studies have been performed to assess LAL activity in representative samples of normal subjects or patients with NAFLD. Moreover, no large study has been carried out in adult subjects with NAFLD or cryptogenic cirrhosis.

  15. 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

    2017-01-01

    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, PGene-metabolite network analysis identified ccl2 and jun as hubs with the largest connections to other genes, which were mainly involved in tumor necrosis factor, P53, nuclear factor-kappa B, chemokine, peroxisome proliferator activated receptor and Toll-like receptor signaling pathways. The specifically regulated genes and metabolites in different NAFLD phenotypes constructed their own networks, which were mainly involved in the lipid and fatty acid metabolism 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. PMID:28082742

  16. Macrophage Activation in Pediatric Nonalcoholic Fatty Liver Disease (NAFLD Correlates with Hepatic Progenitor Cell Response via Wnt3a Pathway.

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    Guido Carpino

    Full Text Available Non-alcoholic fatty liver disease is one of the most important causes of liver-related morbidity in children. In non-alcoholic fatty liver disease, the activation of liver resident macrophage pool is a central event in the progression of liver injury. The aims of the present study were to evaluate the polarization of liver macrophages and the possible role of Wnt3a production by macrophages in hepatic progenitor cell response in the progression of pediatric non-alcoholic fatty liver disease. 32 children with biopsy-proven non-alcoholic fatty liver disease were included. 20 out of 32 patients were treated with docosahexaenoic acid for 18 months and biopsies at the baseline and after 18 months were included. Hepatic progenitor cell activation, macrophage subsets and Wnt/β-catenin pathway were evaluated by immunohistochemistry and immunofluorescence. Our results indicated that in pediatric non-alcoholic fatty liver disease, pro-inflammatory macrophages were the predominant subset. Macrophage polarization was correlated with Non-alcoholic fatty liver disease Activity Score, ductular reaction, and portal fibrosis; docosahexaenoic acid treatment determined a macrophage polarization towards an anti-inflammatory phenotype in correlation with the reduction of serum inflammatory cytokines, with increased macrophage apoptosis, and with the up-regulation of macrophage Wnt3a expression; macrophage Wnt3a expression was correlated with β-catenin phosphorylation in hepatic progenitor cells and signs of commitment towards hepatocyte fate. In conclusion, macrophage polarization seems to have a key role in the progression of pediatric non-alcoholic fatty liver disease; the modulation of macrophage polarization could drive hepatic progenitor cell response by Wnt3a production.

  17. Macrophage Activation in Pediatric Nonalcoholic Fatty Liver Disease (NAFLD) Correlates with Hepatic Progenitor Cell Response via Wnt3a Pathway

    Science.gov (United States)

    Renzi, Anastasia; De Stefanis, Cristiano; Stronati, Laura; Franchitto, Antonio; Alisi, Anna; Onori, Paolo; De Vito, Rita; Alpini, Gianfranco; Gaudio, Eugenio

    2016-01-01

    Non-alcoholic fatty liver disease is one of the most important causes of liver-related morbidity in children. In non-alcoholic fatty liver disease, the activation of liver resident macrophage pool is a central event in the progression of liver injury. The aims of the present study were to evaluate the polarization of liver macrophages and the possible role of Wnt3a production by macrophages in hepatic progenitor cell response in the progression of pediatric non-alcoholic fatty liver disease. 32 children with biopsy-proven non-alcoholic fatty liver disease were included. 20 out of 32 patients were treated with docosahexaenoic acid for 18 months and biopsies at the baseline and after 18 months were included. Hepatic progenitor cell activation, macrophage subsets and Wnt/β-catenin pathway were evaluated by immunohistochemistry and immunofluorescence. Our results indicated that in pediatric non-alcoholic fatty liver disease, pro-inflammatory macrophages were the predominant subset. Macrophage polarization was correlated with Non-alcoholic fatty liver disease Activity Score, ductular reaction, and portal fibrosis; docosahexaenoic acid treatment determined a macrophage polarization towards an anti-inflammatory phenotype in correlation with the reduction of serum inflammatory cytokines, with increased macrophage apoptosis, and with the up-regulation of macrophage Wnt3a expression; macrophage Wnt3a expression was correlated with β-catenin phosphorylation in hepatic progenitor cells and signs of commitment towards hepatocyte fate. In conclusion, macrophage polarization seems to have a key role in the progression of pediatric non-alcoholic fatty liver disease; the modulation of macrophage polarization could drive hepatic progenitor cell response by Wnt3a production. PMID:27310371

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

    Institute of Scientific and Technical Information of China (English)

    Marko Duvnjak; Ivan Leroti(c); Neven Bar(s)i(c); Vedran Toma(s)i(c); Lucija Virovi(c) Juki(c); Vedran Velagi(c)

    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 15percent 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.

  19. Modeling the relationships between quality and biochemical composition of fatty liver in mule ducks.

    Science.gov (United States)

    Theron, L; Cullere, M; Bouillier-Oudot, M; Manse, H; Dalle Zotte, A; Molette, C; Fernandez, X; Vitezica, Z G

    2012-09-01

    The fatty liver of mule ducks (i.e., French "foie gras") is the most valuable product in duck production systems. Its quality is measured by the technological yield, which is the opposite of the fat loss during cooking. The purpose of this study was to determine whether biochemical measures of fatty liver could be used to accurately predict the technological yield (TY). Ninety-one male mule ducks were bred, overfed, and slaughtered under commercial conditions. Fatty liver weight (FLW) and biochemical variables, such as DM, lipid (LIP), and protein content (PROT), were collected. To evaluate evidence for nonlinear fat loss during cooking, we compared regression models describing linear and nonlinear relations between biochemical measures and TY. We detected significantly greater (P = 0.02) linear relation between DM and TY. Our results indicate that LIP and PROT follow a different pattern (linear) than DM and showed that LIP and PROT are nonexclusive contributing factors to TY. Other components, such as carbohydrates, other than those measured in this study, could contribute to DM. Stepwise regression for TY was performed. The traditional model with FLW was tested. The results showed that the weight of the liver is of limited value in the determination of fat loss during cooking (R(2) = 0.14). The most accurate TY prediction equation included DM (in linear and quadratic terms), FLW, and PROT (R(2) = 0.43). Biochemical measures in the fatty liver were more accurate predictors of TY than FLW. The model is useful in commercial conditions because DM, PROT, and FLW are noninvasive measures.

  20. 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

  1. The Role of Dendritic Cells in Fibrosis Progression in Nonalcoholic Fatty Liver Disease

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    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.

  2. Correlation of HIFs/PPAR signaling pathway activation degree and lipid metabolism in liver tissue of alcoholic fatty liver rat model

    Institute of Scientific and Technical Information of China (English)

    Li-Ying Guo; Ya-Min Li; Qing-Chun Li

    2015-01-01

    Objective:To study the correlation of HIFs/PPAR signaling pathway activation degree and lipid metabolism in liver tissue of alcoholic fatty liver rat model.Methods:Adult SD rats were selected and alcoholic fatty liver rat models were established by alcohol administration and high-fat diet feeding. Liver tissue was collected and contents of HIF-1α, PPARγ and lipid metabolism-related enzymes were detected; serum was collected and contents of lipid metabolism indexes and liver cell damage indexes were detected.Results:(1) one week, two weeks, three weeks and four weeks after models were established, HIF-1αα in livers of the model group showed an increasing trend and PPARγ showed a decreasing trend; HIF-1α content was higher than that of the control group and PPARγ content was lower than that of the control group; (2) contents of apoCII, apoCIII,α-GST and GLDH in serum as well as levels of FAT, FABP1, FAS, ACC and ACAT-2 in liver tissue of the model group all significantly increased, and were positively correlated with HIF-1α and negatively correlated with PPARγ.Conclusion:Transcription factor HIF-1α content abnormally increases and PPARγ content abnormally decreases in liver tissue of alcoholic fatty liver rat models; it results in abnormal lipid metabolism and liver cell damage through increasing the expression of lipid metabolism-related enzymes in the liver.

  3. Immunological and molecular basis of nonalcoholic steatohepatitis and nonalcoholic fatty liver disease.

    Science.gov (United States)

    Radwan, Mohamed M; Radwan, Basil M; Nandipati, Kalyana C; Hunter, William J; Agrawal, Devendra K

    2013-08-01

    The prevalence of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) is rising worldwide with the increasing incidence of obesity, Type 2 diabetes mellitus and metabolic syndrome. NASH is currently one of the most common indications of liver transplantation in the United States. The immune system plays a major role in the pathogenesis of NAFLD/NASH. The metabolic changes, associated with obesity and metabolic syndrome, induce immunological responses resulting in NAFLD and further aggravation of the metabolic derangement in a feed-forward loop. Genetic and endocrine factors modulate the immunological and metabolic responses and determine the pathophysiological features of NAFLD. Histologically, NAFLD is a spectrum that ranges from simple hepatic steatosis to severe steatohepatitis, liver cirrhosis and/or hepatocellular carcinoma. Liver cirrhosis and hepatocellular carcinoma are responsible for the morbidity and mortality of the disease. This article is a critical evaluation of our current knowledge of the immunological and molecular basis of the disease.

  4. Genetic Factors in the Pathogenesis of Nonalcoholic Fatty Liver and Steatohepatitis.

    Science.gov (United States)

    Dongiovanni, Paola; Romeo, Stefano; Valenti, Luca

    2015-01-01

    Liver fat accumulation generally related to systemic insulin resistance characterizes nonalcoholic fatty liver disease (NAFLD), which in the presence of nonalcoholic steatohepatitis (NASH) can progress towards cirrhosis and hepatocellular carcinoma. Due to the epidemic of obesity, NAFLD is now the most frequent liver disease in Western countries. Epidemiological, familial, and twin studies provide evidence for a strong genetic component of NAFLD susceptibility. Recently, genome-wide association studies led to the identification of the major inherited determinants of hepatic fat accumulation: patatin-like phospholipase domain-containing 3 (PNPLA3) I148M gene and transmembrane 6 superfamily member 2 (TM6SF2) E167K gene variants, involved in lipid droplets remodelling and very low-density lipoproteins secretion, are the major determinants of interindividual differences in liver steatosis, and susceptibility to progressive NASH. In this review, we aimed to provide an overview of recent insights into the genetics of hepatic fat accumulation and steatohepatitis.

  5. Non-alcohol fatty liver disease in Asia: Prevention andplanning

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    AIM To review all of epidemiological aspects of nonalcoholicfatty liver disease (NAFLD) and also preventthis disease is examined.METHODS: We conducted a systematic reviewaccording to the PRISMA guidelines. All searches forwriting this review is based on the papers was foundin PubMed (MEDLINE), Cochrane database and Scopusin August and September 2014 for topic of NAFLD inAsia and the way of prevention of this disease, with nolanguage limitations. All relevant articles were accessedin full text and all relevant materials was evaluated andreviewed.RESULTS: NAFLD is the most common liver disorder inworldwide, with an estimated with 20%-30% prevalencein Western countries and 2%-4% worldwide. Theprevalence of NAFLD in Asia, depending on location(urban vs rural), gender, ethnicity, and age is variablebetween 15%-20%. According to the many studies inthe world, the relationship between NAFLD, obesity,diabetes mellitus, and metabolic syndrome (MS) isquiet obvious. Prevalence of NAFLD in Asian countriesseems to be lower than the Western countries but, ithas increased recently due to the rise of obesity, type 2diabetes and MS in this region. One of the main reasonsfor the increase in obesity, diabetes and MS in Asia isa lifestyle change and industrialization. Today, NAFLDis recognized as a major chronic liver disease in Asia.Therefore, prevention of this disease in Asian countriesis very important and the best strategy for preventionand control of NAFLD is lifestyle modifications. Lifestylemodification programs are typically designed to changebad eating habits and increase physical activity that isassociated with clinically significant improvements inobesity, type 2 diabetes and MS.CONCLUSION: Prevention of NAFLD is very important in Asian countries particularly in Arab countries becauseof high prevalence of obesity, diabetes and MS.

  6. Omega-3 polyunsaturated fatty acids promote liver regeneration after 90% hepatectomy in rats

    Institute of Scientific and Technical Information of China (English)

    Yu-Dong Qiu; Sheng Wang; Yue Yang; Xiao-Peng Yan

    2012-01-01

    AIM:To evaluate the effectiveness of omega-3 polyunsaturated fatty acid (ω-3 PUFA) administration on liver regeneration after 90% partial hepatectomy (PH) in METHODS:ω-3 PUFAs were intravenously injected in the ω-3 PUFA group before PH surgery.PH,sparing only the caudate lobe,was performed in both the control and the ω-3 PUFA group.Survival rates,liver weight/body weight ratios,liver weights,HE staining,transmission electron microscope imaging,nuclearassociated antigen Ki-67,enzyme-linked immunosorbent assay and signal transduction were evaluated to analyze liver regeneration.RESULTS:All rats in the control group died within 30 h after hepatectomy.Survival rates in the ω-3 PUFA group were 20/20 at 30 h and 4/20 1 wk after PH.Liver weight/body weight ratios and liver weights increased significantly in the ω-3 PUFA group.The structure of sinusoidal endothelial cells and space of Disse was greatly restored in the ω-3 PUFA group compared to the control group after PH.In the ω-3 PUFA group,interleukin (IL)-4 and IL-10 levels were significantly increased whereas IL-6 and tumor necrosis factor-α levels were dramatically decreased.In addition,activation of protein kinase B (Akt) and of signal transducer and activator of transcription 3 signaling pathway were identified at an earlier time after PH in the ω-3 PUFA group.CONCLUSION:Omega-3 polyunsaturated fatty acids may prevent acute liver failure and promote liver regeneration after 90% hepatectomy in rats.

  7. Effects of exercise training and diet on lipid kinetics during free fatty acid-induced insulin resistance in older obese humans with impaired glucose tolerance

    DEFF Research Database (Denmark)

    Solomon, Thomas; Haus, Jacob M; Marchetti, Christine M

    2009-01-01

    Elevated free fatty acids (FFA) are implicated with insulin resistance at the cellular level. However, the contribution of whole body lipid kinetics to FFA-induced insulin resistance is not well understood, and the effect of exercise and diet on this metabolic defect is not known. We investigated.......8 +/- 1.8 kg/m(2)) or a eucaloric (n = 8; 67 +/- 2 yr, 35.3 +/- 2.1 kg/m(2)) diet and aerobic exercise (1 h/day at 65% of maximal oxygen uptake) regimen. Lipid kinetics ([1-(14)C]palmitate) were assessed throughout a 7-h, 40 mU x m(-2) x min(-1) hyperinsulinemic euglycemic clamp, during which insulin...... the effect of 12 wk of exercise training with and without caloric restriction on FFA turnover and oxidation (FFA(ox)) during acute FFA-induced insulin resistance. Sixteen obese subjects with impaired glucose tolerance were randomized to either a hypocaloric (n = 8; -598 +/- 125 kcal/day, 66 +/- 1 yr, 32...

  8. TRB3 is involved in free fatty acid-induced INS-1-derived cell apoptosis via the protein kinase C δ pathway.

    Science.gov (United States)

    Qin, Jun; Fang, Ni; Lou, Jinning; Zhang, Wenjian; Xu, Shiqing; Liu, Honglin; Fang, Qing; Wang, Zai; Liu, Jiang; Men, Xiuli; Peng, Liang; Chen, Li

    2014-01-01

    Chronic exposure to free fatty acids (FFAs) may induce β cell apoptosis in type 2 diabetes. However, the precise mechanism by which FFAs trigger β cell apoptosis is still unclear. Tribbles homolog 3 (TRB3) is a pseudokinase inhibiting Akt, a key mediator of insulin signaling, and contributes to insulin resistance in insulin target tissues. This paper outlined the role of TRB3 in FFAs-induced INS-1 β cell apoptosis. TRB3 was promptly induced in INS-1 cells after stimulation by FFAs, and this was accompanied by enhanced INS-1 cell apoptosis. The overexpression of TRB3 led to exacerbated apoptosis triggered by FFAs in INS-1-derived cell line and the subrenal capsular transplantation animal model. In contrast, cell apoptosis induced by FFAs was attenuated when TRB3 was knocked down. Moreover, we observed that activation and nuclear accumulation of protein kinase C (PKC) δ was enhanced by upregulation of TRB3. Preventing PKCδ nuclear translocation and PKCδ selective antagonist both significantly lessened the pro-apoptotic effect. These findings suggest that TRB3 was involved in lipoapoptosis of INS-1 β cell, and thus could be an attractive pharmacological target in the prevention and treatment of T2DM.

  9. TRB3 is involved in free fatty acid-induced INS-1-derived cell apoptosis via the protein kinase C δ pathway.

    Directory of Open Access Journals (Sweden)

    Jun Qin

    Full Text Available Chronic exposure to free fatty acids (FFAs may induce β cell apoptosis in type 2 diabetes. However, the precise mechanism by which FFAs trigger β cell apoptosis is still unclear. Tribbles homolog 3 (TRB3 is a pseudokinase inhibiting Akt, a key mediator of insulin signaling, and contributes to insulin resistance in insulin target tissues. This paper outlined the role of TRB3 in FFAs-induced INS-1 β cell apoptosis. TRB3 was promptly induced in INS-1 cells after stimulation by FFAs, and this was accompanied by enhanced INS-1 cell apoptosis. The overexpression of TRB3 led to exacerbated apoptosis triggered by FFAs in INS-1-derived cell line and the subrenal capsular transplantation animal model. In contrast, cell apoptosis induced by FFAs was attenuated when TRB3 was knocked down. Moreover, we observed that activation and nuclear accumulation of protein kinase C (PKC δ was enhanced by upregulation of TRB3. Preventing PKCδ nuclear translocation and PKCδ selective antagonist both significantly lessened the pro-apoptotic effect. These findings suggest that TRB3 was involved in lipoapoptosis of INS-1 β cell, and thus could be an attractive pharmacological target in the prevention and treatment of T2DM.

  10. Dysregulation of iron and copper homeostasis innonalcoholic fatty liver

    Institute of Scientific and Technical Information of China (English)

    Elmar Aigner; Günter Weiss; Christian Datz

    2015-01-01

    Elevated iron stores as indicated by hyperferritinemiawith normal or mildly elevated transferrin saturationand mostly mild hepatic iron deposition are acharacteristic finding in subjects with non-alcoholicfatty liver disease (NAFLD). Excess iron is observedin approximately one third of NAFLD patients andis commonly referred to as the "dysmetabolic ironoverload syndrome". Clinical evidence suggests thatelevated body iron stores aggravate the clinical courseof NAFLD with regard to liver-related and extrahepaticdisease complications which relates to the fact thatexcess iron catalyses the formation of toxic hydroxylradicalssubsequently resulting in cellular damage. Ironremoval improves insulin sensitivity, delays the onsetof type 2 diabetes mellitus, improves pathologic liverfunction tests and likewise ameliorates NAFLD histology.Several mechanisms contribute to pathologic ironaccumulation in NAFLD. These include impaired ironexport from hepatocytes and mesenchymal Kupffer cellsas a consequence of imbalances in the concentrationsof iron regulatory factors, such as hepcidin, cytokines,copper or other dietary factors. This review summarizesthe knowledge about iron homeostasis in NAFLD andthe rationale for its therapeutic implications.

  11. Identification of protective components that prevent the exacerbation of goose fatty liver: Characterization, expression and regulation of adiponectin receptors.

    Science.gov (United States)

    Geng, Tuoyu; Yang, Biao; Li, Fuyuan; Xia, Lili; Wang, Qianqian; Zhao, Xing; Gong, Daoqing

    2016-01-01

    Fat accumulation in the liver is a natural process in goose, which prepares goose for long-distance migration. In contrast to mammalian fatty liver that usually progresses into an irreversible status, steatohepatitis, goose fatty liver can return to normal without obvious pathological damage, suggesting a protective system exists in goose liver. This study was to identify the components of this system. We first focused on goose adiponectin receptor 1 and 2 (Adipor1/2) as they have ceramidase activity, and can cleave ceramide, a group of proinflammatory signaling lipid species. Quantitative analysis indicated that tumor necrosis factor alpha (Tnfα), a key proinflammatory cytokine, was down-regulated in goose fatty liver by overfeeding. This inhibition of Tnfα was accompanied with reduced adiponectin and increased Adipor1/2 in the adipose tissues and in the livers of the overfed geese, respectively. To investigate the regulation of goose Adipor2 in the context of fatty liver, we treated goose primary hepatocytes with fatty liver associated factors. Data indicated that Adipor2 was upregulated by glucose and oleate but not palmitate. Its expression was even suppressed by high level of insulin. The regulation of Adipor1 by these factors was quite similar to that of Adipor2 except that glucose did not induce Adipor1. Together, these findings suggest the upregulation of Adipor1/2 may, at least partially, contribute to the inhibition of inflammation in goose fatty liver, and the expression of Adipor1/2 can be regulated by fatty liver-associated factors.

  12. Nonalcoholic fatty liver disease/steatohepatitis: epidemiology, pathogenesis, clinical presentation and treatment.

    Science.gov (United States)

    Milić, Sandra; Stimac, Davor

    2012-01-01

    Nonalcoholic fatty liver disease (NAFLD) is the most common chronic hepatic disorder in Western countries, with a prevalence of 20-30%. NAFLD comprises 'silent liver disease', in which simple steatosis is the only histological finding and which is benign in course, and nonalcoholic steatohepatitis, which is characterized by hepatocellular injury and inflammation with or without fibrosis. NAFLD is clinically important, because even benign fatty liver can progress to steatohepatitis in many patients, which can lead to liver cirrhosis and its complications and hepatocellular carcinoma. NAFLD is a hepatic manifestation of metabolic syndrome; it is closely related to other clinical features of metabolic syndrome, and thus to cardiovascular morbidity. There are several different noninvasive techniques for formal diagnosis and follow-up, but liver biopsy remains the gold standard. The most important therapeutic strategies include lifestyle changes, including changes in dietary habits aimed at weight loss and blood pressure regulation, with a consequent decrease in insulin resistance. For some patients with NAFLD/nonalcoholic steatohepatitis, pharmacological treatment is the best option, although further studies are needed to confirm its efficacy and tolerability.

  13. Diffuse Fatty Infiltration of the Liver: US Scoring System Correlated with CT and LFT

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jin Seong [Seoul district Armed Forces General Hospital, Seoul (Korea, Republic of)

    1994-12-15

    The present study was performed to estimate the accuracy of US examination in predicting the hepatic function in patients with diffuse fatty infiltration of the Liver. We compared the findings at US with the findings at CT and biochemical hepatic function test. US was performed by using 3.5MHz sector prove. We evaluated the US findings in terms or the degree of acoustic attenuation from the liver, the parenchymal echogenicity, the distinction of the portal vein wall, and the distinction of the diaphragm. Each parameter was graded into the numeric scores ranging from 0 to 2. The total US score was calculated from the scores of the four parameters. The total US score was compared with the difference in Hounsfield Units between the liver and spleen on nonenhanced CT images. The total US score was also compared with the aspartate(AST) and alanine transaminase(ALT) levels in peripheral blood. There was statistically significant correlation between the total US score and the difference in Hounsfield Unit between the liver and spleen on CT (r=0.7074, p<0.0001). When the total US score above 4 was considered as acriteria, the AST or ALT level were abnormal within the sensitivity of 90% and specificity of 60%. When the total US score above 5 was considered as a criteria, the sensitivity and specificity were 78% and 79%, respectively. In conclusion, US scoring system is useful in predicting the abnormal hepatic function in patients with diffuse fatty infiltration of the liver

  14. Changes in the fatty acid profile of lung, liver and serum of rats intratracheally given silica

    Energy Technology Data Exchange (ETDEWEB)

    Eskelson, C.D.; Stiffel, V.; Owen, J.A.; Chvapil, M.; Vickers, A.; Brendel, K.

    1988-01-01

    The esterified (E) and nonesterified (NE) fatty acid level and profile in the lung, serum, and liver of rats are significantly altered after intratracheal administration of silica. The changes include a silica-specific increase of the total long chain (C/sub 16/-C/sub 20:4/) fatty acid content in the lung, and a decrease in the serum and liver of both groups of rats intratracheally given silica and/or saline. In the silicotic lung, arachidonate and palmitate accumulated at the highest rate. A heat-labile, high-molecular weight component from lung homogenates increases lipogenesis in isolated hepatocytes in vitro. These findings, taken together with evidence indicating increased lipogenesis in the liver of rats treated with silica under identical conditions, suggest a lung-liver communication mechanism which coordinates lipid uptake by the lung and lipid synthesis and release by the liver. The stimulatory factor identified in lung homogenates might play an important regulatory role for hepatic lipogenesis in rats developing silicotic lungs.

  15. Protective Effects of Korean Red Ginseng against Alcohol-Induced Fatty Liver in Rats

    Directory of Open Access Journals (Sweden)

    Hyo Jin Lee

    2015-06-01

    Full Text Available The present study tested the hypothesis that Korean red ginseng (KRG provides a protective effect against alcoholic fatty liver. Male Sprague-Dawley rats were divided into four groups and fed a modified Lieber-DeCarli diet containing 5% (w/v alcohol or an isocaloric amount of dextrin-maltose for the controls for 6 weeks: normal control (CON, alcohol control (ET, and ET treated with 125 or 250 mg/kg body weight/day of KRG (RGL or RGH, respectively. Compared with the CON group, the ET group exhibited a significant increase in triglycerides, total cholesterol and the presence of lipid droplets in the liver, and a decrease in fat mass, which were all attenuated by KRG supplementation in adose-dependent manner. The mitigation was accompanied by AMP-activated protein kinase (AMPK signaling pathways in the liver and adipose tissue. In addition, suppression in the alcohol-induced changes of adipose adipokine mRNA expression was also observed in KRG supplementation group. These findings suggest that KRG may have the potential to ameliorate alcoholic fatty liver by suppressing inappropriate lysis of adipose tissue and preventing unnecessary de novo lipogenesis in the liver, which are mediated by AMPK signaling pathways. A mechanism for an interplay between the two organs is still needed to be examined with further assays.

  16. Type 2 diabetic patients with non-alcoholic fatty liver disease exhibit significant haemorheological abnormalities

    Institute of Scientific and Technical Information of China (English)

    Hui Dong; Fu'er Lu; Nan Wang; Xin Zou; Jingjing Rao

    2011-01-01

    Haemorheological abnormalities have been described in diabetes mellitus,as well as in non-alcoholic fatty liver disease (NAFLD).However,the relationship between the changes in liver fat content and haemorheology is unknown.The current study aims to show the correlation between haemorheological parameters and intrahepatic lipid content (IHLC) in patients with type 2 diabetes.The serum biochemical markers,such as fasting plasma glucose (FPG),haemoglobin A1c (HbA1c),liver enzymes,lipid profiles,and haemorheological properties,were examined.IHLC was quantified using proton magnetic resonance spectroscopy (1H-MRS) scanning of the liver.A significant correlation was observed between IHLC and whole blood viscosity at high,middle,and low shear rates.IHLC also positively correlated with haematocrit,the reduced whole blood viscosity at low and middle shear rates,and the erythrocyte aggregation index.Diabetic patients with NAFLD exhibited significant haemorheological abnormalities compared with patients without NAFLD.In summary,haemorheological disorders are linked to non-alcoholic fatty liver in type 2 diabetes.

  17. Influence of dietary fatty acids on endocannabinoid and N-acylethanolamine levels in rat brain, liver and small intestine

    DEFF Research Database (Denmark)

    Artmann, Andreas; Petersen, Gitte; Hellgren, Lars

    2008-01-01

    acid in brain, jejunum and liver. The OA-diet increased brain levels of anandamide and oleoylethanolamide (not 2-arachidonoylglycerol) without changing tissue fatty acid composition. The same diet increased oleoylethanolamide in liver. All five dietary fats decreased oleoylethanolamide in jejunum...... (AA)) on tissue levels of 2-arachidonoylglycerol, anandamide, oleoylethanolamide, palmitoylethanolamide, stearoylethanolamide, linoleoylethanolamide, eicosapentaenoylethanolamide, docosahexaenoylethanolamide and tissue fatty acid composition. The LA-diet increased linoleoylethanolamide and linoleic...... without changing levels of anandamide, suggesting that dietary fat may have an orexigenic effect. The AA-diet increased anandamide and 2-arachidonoylglycerol in jejunum without effect on liver. The FO-diet decreased liver levels of all N-acylethanolamines (except eicosapentaenoylethanolamide...

  18. 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.

  19. Overexpression of hepatic plasminogen activator inhibitor type 1 mRNA in rabbits with fatty liver

    Institute of Scientific and Technical Information of China (English)

    Jian-Gao Fan; Liang-Hua Chen; Zheng-Jie Xu; Min-De Zeng

    2001-01-01

    @@ INTRODUCTION Plasminogen activator inhibitor type 1 ( PAI-I ), an approximately Mr 50000 glycoprotein, is the major physiological inhibitor of plasminogen activators. It is not only the priming factor for atherosclerosis and coronary thrombosis[1-3] , but also participates in the genesis of chronic hepatitis and liver fibrosis[4-11] . However, there has been no available report yet about the research of hepatic PAl-1 gene expression in hyperlipidemia and fatty liver. The present study aimed to explore the change of hepatic PAl-1 mRNA and its plasma activity by means of animal model.

  20. [Non-alcoholic fatty liver disease (NAFLD) /non-alcoholic steatohepatitis (NASH) and nutrition].

    Science.gov (United States)

    Ishii, Kiyo-aki; Takamura, Toshinari

    2016-03-01

    Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive fat accumulation in the form of triglycerides in the hepatocytes. A more severe form of NAFLD with necrosis, inflammation, and fibrosis is called non-alcoholic steatohepatitis (NASH). The liver is located in the center of the body's organ network and acts as a coordinator of glucose and lipid metabolism. Therefore, it is important to perform nutritional therapy of patients with NAFLD/NASH while maintaining the energy balance in the entire body.

  1. Non-alcoholic fatty liver disease: is bariatric surgery the answer?

    Science.gov (United States)

    Pillai, Anjana A; Rinella, Mary E

    2009-11-01

    As the worldwide obesity epidemic continues to increase, the prevalence of non-alcoholic fatty liver disease (NAFLD) and specifically non-alcoholic steatohepatitis (NASH) will become increasingly prominent. NASH will surpass chronic hepatitis C infection as the primary indication for orthotopic liver transplantation in the near future. With the evolution of surgical techniques, bariatric surgery is currently recognized as the most effective method for achieving sustained weight loss and reversing numerous comorbidities in severely obese individuals. This review focuses on the potential risks and benefits of bariatric surgery in subjects with NAFLD and explores its role in the management of NASH in the obese patient.

  2. Pediatric nonalcoholic fatty liver disease:Overview with emphasis on histology

    Institute of Scientific and Technical Information of China (English)

    Yoshihisa; Takahashi; Toshio; Fukusato

    2010-01-01

    Nonalcoholic fatty liver disease(NAFLD) is a disease in which excessive fat accumulates in the liver of a patient without a history of alcohol abuse.This disease includes simple steatosis and nonalcoholic steatohepatitis(NASH).NAFLD/NASH is recognized as a hepatic manifestation of metabolic syndrome.In recent years,pediatric NAFLD has increased in line with the increased prevalence of pediatric obesity.The estimated prevalence of pediatric NAFLD is 2.6%-9.6%,and it is associated with sex,age,and ethnicity.W...

  3. Liver glycerol permeability and aquaporin-9 are dysregulated in a murine model of Non-Alcoholic Fatty Liver Disease.

    Directory of Open Access Journals (Sweden)

    Patrizia Gena

    Full Text Available One form of liver steatosis, namely Non-Alcoholic Fatty Liver Disease (NAFLD, is a worrisome health problem worldwide characterized by intrahepatic triacylglycerol (TG overaccumulation. NAFLD is a common feature of metabolic syndrome being often associated with obesity, dyslipidemia and diabetes and mostly closely linked to insulin resistance. The mechanism of NAFLD pathogenesis is object of intense investigation especially regarding complex systems ultimately resulting in excessive TG deposition in hepatocytes. However, scarce is the attention about the relevance of hepatic import of glycerol, the other primary source (as glycerol-3-phosphate of increased TG in hepatocytes. Obese leptin-deficient (ob/ob mice, an animal model of NAFLD, were used to evaluate the functional involvement of Aquaporin-9 (AQP9, the major pathway of liver glycerol entry, in hepatosteatosis. By RT-PCR and qPCR, the level of Aqp9 mRNA in the liver of starved obese mice was comparable with the corresponding control lean littermates. By immunoblotting, the AQP9 protein at the hepatocyte sinusoidal plasma membrane of obese mice was markedly lower (33% than lean mice, a finding fully confirmed by immunohistochemistry. By stopped-flow light scattering, the liver glycerol permeability of ob/ob mice was significantly lower (53% than lean mice, a finding consistent with both the observed down-regulation of AQP9 protein and increased level of plasma glycerol characterizing obese mice. In summary, our results suggest implication of AQP9 in liver steatosis. The reduction of hepatocyte AQP9 and, consequently, glycerol permeability might be a defensive mechanism to counteract further fat infiltration in liver parenchyma.

  4. Fatty liver, carotid disease and gallstones: A study of age-related associations

    Institute of Scientific and Technical Information of China (English)

    Amedeo Lonardo; Paola Loria; Silvia Lombardini; Federica Scaglioni; Stefano Ballestri; Anna Maria Verrone; Marco Bertolotti; Lucia Carulli; Dorval Ganazzi; Nicola Carulli

    2006-01-01

    AIM: To evaluate carotid intima-media thickening (IMT)and plaques, gallstone disease (GD) and fatty liver (FL)as a function of age.METHODS: In 449 subjects, FL and carotid disease were assessed ultrasonographically. In a subgroup of 65/449 patients with non-alcoholic fatty liver disease (NAFLD), carotid disease, GD and associated factors were determined.RESULTS: FL of unspecified etiology was more common in younger and GD in older individuals. FL subjects had an increased prevalence of IMT and a decreased prevalence of plaques and manifested carotid disease earlier. Plaques were more common in subjects with GD.Age was an independent predictor of carotid disease outcome and FL was a protective factor for plaques. In NAFLD, there was an inverse correlation between body weight and age and the latter independently predicted carotid findings.CONCLUSION: Cardiovascular risk in patients with FL and NAFLD needs to be assessed as a function of age and body weight.

  5. Impaired Insulin Suppression of VLDL-Triglyceride Kinetics in Non-alcoholic Fatty Liver Disease

    DEFF Research Database (Denmark)

    Poulsen, Marianne K; Nellemann, Birgitte; Stødkilde-Jørgensen, Hans;

    2016-01-01

    CONTEXT: Non-alcoholic fatty liver disease (NAFLD) is associated with glucose and lipid metabolic abnormalities. However, insulin suppression of VLDL-triglyceride (VLDL-TG) kinetics is not fully understood. OBJECTIVE: To determine VLDL-TG, glucose and palmitate kinetics during fasting and hyperin......CONTEXT: Non-alcoholic fatty liver disease (NAFLD) is associated with glucose and lipid metabolic abnormalities. However, insulin suppression of VLDL-triglyceride (VLDL-TG) kinetics is not fully understood. OBJECTIVE: To determine VLDL-TG, glucose and palmitate kinetics during fasting...... and hyperinsulinemia in men with (NAFLD+) and without NAFLD (NAFLD-). DESIGN: 27 non-diabetic, upper-body obese (WHR >0.9, BMI >28 kg/m(2)) men, 18 NAFLD+ and 9 NAFLD- determined by magnetic resonance spectroscopy, were enrolled.(14)C-labeled VLDL-TG and (3)H-labeled glucose and palmitate tracers were applied...... metabolic abnormalities associated with NAFLD and presumably diabetes....

  6. Acute fatty liver of pregnancy associated with severe acute pancreatitis: A case report

    Institute of Scientific and Technical Information of China (English)

    Cássio; Vieira; de; Oliveira; Alecsro; Moreira; Julio; P; Baima; Leticia; de; C; Franzoni; Talles; B; Lima; Fabio; da; S; Yamashiro; Kunie; Yabuki; Rabelo; Coelho; Ligia; Y; Sassaki; Carlos; Antonio; Caramori; Ferno; G; Romeiro; Giovanni; F; Silva

    2014-01-01

    Acute fatty liver of pregnancy is a rare disease that affects women in the third trimester of pregnancy. Although infrequent, the disease can cause maternal mortality. The diagnosis is not always clear until the pregnancy is terminated, and significant complications, such as acute pancreatitis, can occur. Pancreatic involvement typically only occurs in severe cases after the development of hepatic and renal impairment. To date, little knowledge is available regarding how the disease causes pancreatitis. Treatment involves supportive measures and pregnancy interruption. In this report, we describe a case of a previously healthy 26-year-old woman at a gestational age of 27 wk and 6 d who was admitted with severe abdominal pain and vomiting. This case illustrates the clinical and laboratory overlap between acute fatty liver of pregnancy and pancreatitis, highlighting the difficulties in differentiating each disease. Furthermore, the hypothesis for this overlapping is presented, and the therapeutic options are discussed.

  7. Acute fatty liver of pregnancy: An update on pathogenesis and clinical implications

    Institute of Scientific and Technical Information of China (English)

    Jamal A Ibdah

    2006-01-01

    Acute fatty liver of pregnancy (AFLP) is a serious maternal illness occurring in the third trimester of pregnancy with significant perinatal and maternal mortality. Till recently, it has been considered a mysterious illness. In this editorial, we review the recent advances in understanding the pathogenesis of AFLP and discuss the studies documenting a fetal-maternal interaction with a causative association between carrying a fetus with a defect in mitochondrial fatty acid oxidation and development of AFLP.Further, we discuss the impact of these recent advances on the offspring born to women who develop AFLP, such that screening for a genetic defect can be life saving to the newborn and would allow genetic counseling in subsequent pregnancies.The molecular basis and underlying mechanism for this unique fetal-maternal interaction causing maternal liver disease is discussed.

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

    Directory of Open Access Journals (Sweden)

    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.

  9. Ameliorative potential of Tamarindus indica on high fat diet induced nonalcoholic fatty liver disease in rats.

    Science.gov (United States)

    Sasidharan, Suja Rani; Joseph, Joshua Allan; Anandakumar, Senthilkumar; Venkatesan, Vijayabalaji; Madhavan, Chandrasekharan Nair Ariyattu; Agarwal, Amit

    2014-01-01

    Nonalcoholic fatty liver disease (NAFLD), the prevalence of which is rising globally with current upsurge in obesity, is one of the most frequent causes of chronic liver diseases. The present study evaluated the ameliorative effect of extract of Tamarindus indica seed coat (ETS) on high fat diet (HFD) induced NAFLD, after daily administration at 45, 90, and 180 mg/kg body weight dose levels for a period of 6 weeks, in albino Wistar rats. Treatment with ETS at all tested dose levels significantly attenuated the pathological alterations associated with HFD induced NAFLD viz. hepatomegaly, elevated hepatic lipid and lipid peroxides, serum alanine aminotransferase, and free fatty acid levels as well as micro-/macrohepatic steatosis. Moreover, extract treatment markedly reduced body weight and adiposity along with an improvement in insulin resistance index. The study findings, therefore suggested the therapeutic potential of ETS against NAFLD, acting in part through antiobesity, insulin sensitizing, and antioxidant mechanisms.

  10. Ameliorative Potential of Tamarindus indica on High Fat Diet Induced Nonalcoholic Fatty Liver Disease in Rats

    Directory of Open Access Journals (Sweden)

    Suja Rani Sasidharan

    2014-01-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD, the prevalence of which is rising globally with current upsurge in obesity, is one of the most frequent causes of chronic liver diseases. The present study evaluated the ameliorative effect of extract of Tamarindus indica seed coat (ETS on high fat diet (HFD induced NAFLD, after daily administration at 45, 90, and 180 mg/kg body weight dose levels for a period of 6 weeks, in albino Wistar rats. Treatment with ETS at all tested dose levels significantly attenuated the pathological alterations associated with HFD induced NAFLD viz. hepatomegaly, elevated hepatic lipid and lipid peroxides, serum alanine aminotransferase, and free fatty acid levels as well as micro-/macrohepatic steatosis. Moreover, extract treatment markedly reduced body weight and adiposity along with an improvement in insulin resistance index. The study findings, therefore suggested the therapeutic potential of ETS against NAFLD, acting in part through antiobesity, insulin sensitizing, and antioxidant mechanisms.

  11. An approach to diagnosis and management of acute fatty liver of pregnancy

    Directory of Open Access Journals (Sweden)

    Neha Gami

    2013-02-01

    Full Text Available Acute fatty liver of pregnancy is a rare life threatening cause of jaundice in the third trimester of pregnancy and early postpartum period and is associated with a poor outcome. The maternal and fetal outcome can be improved by a high index of suspicion, early diagnosis and prompt delivery. We report a case of a 30 year old parous lady with 36 weeks twin pregnancy with Acute Fatty Liver of Pregnancy [AFLP] and coagulation failure, she responded to prompt induction of labour and appropriate management of the coagulopathy and related complications. We provide a review of literature on jaundice in pregnancy and the clinical approach to management. [Int J Reprod Contracept Obstet Gynecol 2013; 2(1.000: 104-108

  12. Role of lipid peroxidation and antioxidant enzymes in omega 3 fatty acids induced suppression of breast cancer xenograft growth in mice

    Directory of Open Access Journals (Sweden)

    Cameron Ivan L

    2002-07-01

    Full Text Available Abstract Background Supplementing mice with high levels of dietary n-3 polyunsaturated fatty acids (PUFAs increases the n-3 PUFAs in cell membranes, increases the susceptibility of the cells for lipid peroxidation (LPO and decreases the growth rate of mammary and other tumors. However, the results of an earlier study indicated that a factor in addition to LPO was involved in the reduction in tumor growth in n-3 PUFAs fed mice. Athymic mice bearing MDA-MB-231 human breast carcinoma xenografts, were fed fish oil concentrate (FOC or control diets, with and without supplemental Vitamin E (2000 IU /kg diet and were sacrificed both before and after doxorubicin (DOX treatment to evaluate factors involved in tumor growth suppression. Results Prior to DOX, basal LPO in the tumor of 3% FOC fed mice was slightly higher than in the control fed mice and was decreased in mice consuming FOC with vitamin E. Vitamin E suppressed the DOX induced increase in LPO in the tumors of control mice, however, vitamin E was not sufficient to suppress a DOX induced increase in LPO in the tumors of FOC fed mice. The mean growth rate of tumors of FOC fed mice was significantly less than the mean growth rate of the tumors of control mice. Multiple regression analyses indicated that suppression of glutathione peroxidase (GPX activity by FOC prior to DOX therapy was more important than increased LPO as an explanation of tumor growth suppression. Tumor induced cachexia was decreased in mice consuming FOC. Conclusions It appears that the increased sensitivity to DOX was related to an FOC induced reduction in GPX activity. FOC reduced tumor induced cachexia.

  13. Marine omega-3 polyunsaturated fatty acids induce sex-specific changes in reinforcer-controlled behaviour and neurotransmitter metabolism in a spontaneously hypertensive rat model of ADHD

    Directory of Open Access Journals (Sweden)

    Dervola Kine S

    2012-12-01

    Full Text Available Abstract Background Previous reports suggest that omega-3 (n-3 polyunsaturated fatty acids (PUFA supplements may reduce ADHD-like behaviour. Our aim was to investigate potential effects of n-3 PUFA supplementation in an animal model of ADHD. Methods We used spontaneously hypertensive rats (SHR. SHR dams were given n-3 PUFA (EPA and DHA-enriched feed (n-6/n-3 of 1:2.7 during pregnancy, with their offspring continuing on this diet until sacrificed. The SHR controls and Wistar Kyoto (WKY control rats were given control-feed (n-6/n-3 of 7:1. During postnatal days (PND 25–50, offspring were tested for reinforcement-dependent attention, impulsivity and hyperactivity as well as spontaneous locomotion. The animals were then sacrificed at PND 55–60 and their neostriata were analysed for monoamine and amino acid neurotransmitters with high performance liquid chromatography. Results n-3 PUFA supplementation significantly enhanced reinforcement-controlled attention and reduced lever-directed hyperactivity and impulsiveness in SHR males whereas the opposite or no effects were observed in females. Analysis of neostriata from the same animals showed significantly enhanced dopamine and serotonin turnover ratios in the male SHRs, whereas female SHRs showed no change, except for an intermediate increase in serotonin catabolism. In contrast, both male and female SHRs showed n-3 PUFA-induced reduction in non-reinforced spontaneous locomotion, and sex-independent changes in glycine levels and glutamate turnover. Conclusions Feeding n-3 PUFAs to the ADHD model rats induced sex-specific changes in reinforcement-motivated behaviour and a sex-independent change in non-reinforcement-associated behaviour, which correlated with changes in presynaptic striatal monoamine and amino acid signalling, respectively. Thus, dietary n-3 PUFAs may partly ameliorate ADHD-like behaviour by reinforcement-induced mechanisms in males and partly via reinforcement-insensitive mechanisms

  14. S-Allyl cysteine improves nonalcoholic fatty liver disease in type 2 diabetes Otsuka Long-Evans Tokushima Fatty rats via regulation of hepatic lipogenesis and glucose metabolism.

    Science.gov (United States)

    Takemura, Shigekazu; Minamiyama, Yukiko; Kodai, Shintaro; Shinkawa, Hiroji; Tsukioka, Takuma; Okada, Shigeru; Azuma, Hideki; Kubo, Shoji

    2013-09-01

    It is important to prevent and improve diabetes mellitus and its complications in a safe and low-cost manner. S-Allyl cysteine, an aged garlic extract with antioxidant activity, was investigated to determine whether S-allyl cysteine can improve type 2 diabetes in Otsuka Long-Evans Tokushima Fatty rats with nonalcoholic fatty liver disease. Male Otsuka Long-Evans Tokushima Fatty rats and age-matched Long-Evans Tokushima Otsuka rats were used and were divided into two groups at 29 weeks of age. S-Allyl cysteine (0.45% diet) was administered to rats for 13 weeks. Rats were killed at 43 weeks of age, and detailed analyses were performed. S-Allyl cysteine improved hemoglobinA1c, blood glucose, triglyceride, and low-density lipoprotein cholesterol levels. Furthermore, S-allyl cysteine normalized plasma insulin levels. S-Allyl cysteine activated the mRNA and protein expression of both peroxisome proliferator-activated receptor α and γ, as well as inhibiting pyruvate dehydrogenase kinase 4 in Otsuka Long-Evans Tokushima Fatty rat liver. Sterol regulatory element-binding protein 1c and forkhead box O1 proteins were normalized by S-allyl cysteine in Otsuka Long-Evans Tokushima Fatty rat liver. In conclusions, these findings support the hypothesis that S-allyl cysteine has diabetic and nonalcoholic fatty liver disease therapeutic potential as a potent regulating agent against lipogenesis and glucose metabolism.

  15. Evaluation of Hepatic Vasculature in Fatty Liver Patients with Duplex Doppler Sonography

    Directory of Open Access Journals (Sweden)

    Nahid Sedighi

    2010-05-01

    Full Text Available Background/Objective: Duplex Doppler ultrasonography (US has been newly suggested as an important diagnostic technique in the non-invasive evaluation of hepatic vasculature and some hepatic parenchymal diseases. New findings suggest that diffuse fatty infiltration of the liver can alter normal hepatic vein and artery Doppler indices. The following study has been performed to evaluate the effect of fatty infiltration on portal vein indices."nPatients and Methods: Forty-eight patients with various degrees of fatty infiltration of the liver and 48 normal subjects without any signs of hepatic fatty infiltration in ultrasonography were examined using standard color Doppler sonography. Maximum and minimum peak velocity and resistance index were compared in the two groups."nResults: The mean of maximum peak velocity in the portal vein was 25.9±9.9 and 34.3±18.3 in the case and control group, respectively (P=0.006. The mean of minimum peak velocity in the portal vein was 19.2±9.9 and 18.7±8.7 in the case and control group, respectively (P=0.795. The mean of resistance index was 0.25±0.09 and 0.41±0.15 in the case and control group, respectively (P<0.001."nConclusion: The mean of maximum peak velocity and the mean of resistance index in the portal vein was significantly lower in patients with fatty infiltration compared to those who had no abnormality in the liver ultrasonography .

  16. Clinical assessment of hepatic de novo lipogenesis in non-alcoholic fatty liver disease.

    Science.gov (United States)

    Paglialunga, Sabina; Dehn, Clayton A

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD) is heralded as the next big global epidemic. Hepatic de novo lipogenesis (DNL), the synthesis of new fatty acids from non-lipid sources, is thought to play a pivotal role in the development of NAFLD. While there is currently no NAFLD-specific therapeutic agent available, pharmaceutical drugs aimed at reducing hepatic fat accretion may prove to be a powerful ally in the treatment and management of this disease. With a focus on NAFLD, the present review summarizes current techniques examining DNL from a clinical perspective, and describes the merits and limitations of three commonly used assays; stable-label isotope tracer studies, fatty acid indexes and indirect calorimetry as non-invasive measures of hepatic DNL. Finally, the application of DNL assessments in the pharmacological and nutraceutical treatment of NAFLD/NASH is summarized. In a clinical research setting, measures of DNL are an important marker in the development of anti-NAFLD treatments.

  17. Is the control of dietary cholesterol intake sufficiently effective to ameliorate nonalcoholic fatty liver disease?

    Institute of Scientific and Technical Information of China (English)

    Munechika; Enjoji; Makoto; Nakamuta

    2010-01-01

    In our examination of the distribution of abdominal fat,dietary intake and biochemical data in patients with nonalcoholic fatty liver disease(NAFLD),non-obese NAFLD patients without insulin resistance presented a characteristic pattern of dietary intake.Dietary cholesterol intake was superabundant in non-obese patients compared with obese patients,although total energy and carbohydrate intake was not excessive.Namely,excess cholesterol intake appears to be one of the main factors associated with NAFLD devel...

  18. Gut Microbiota and Nonalcoholic Fatty Liver Disease: Insights on Mechanism and Application of Metabolomics

    OpenAIRE

    Xuyun He; Guang Ji; Wei Jia; Houkai Li

    2016-01-01

    Gut microbiota are intricately involved in the development of obesity-related metabolic diseases such as nonalcoholic fatty liver disease (NAFLD), type 2 diabetes, and insulin resistance. In the current review, we discuss the role of gut microbiota in the development of NAFLD by focusing on the mechanisms of gut microbiota-mediated host energy metabolism, insulin resistance, regulation of bile acids and choline metabolism, as well as gut microbiota-targeted therapy. We also discuss the applic...

  19. Retrospective Study of Seven Cases with Acute Fatty Liver of Pregnancy

    OpenAIRE

    Ma Runmei; Suchi Dwivedi

    2013-01-01

    Objectives. Our aim is to explore the clinical outcome of patients with acute fatty liver of pregnancy (AFLP), and evaluate the effect of early diagnosis and treatment. Methods. Seven patients who were diagnosed with AFLP were retrospectively analyzed from February 2005 to January 2013. The clinical records of the patients with AFLP were reviewed for clinical features, laboratory examinations, and maternal and perinatal prognosis. Routine laboratory evaluation revealed hyperbilirubinemia, mod...

  20. Molecular mechanism of recombinant liver fatty acid binding protein's antioxidant activity

    OpenAIRE

    YAN, JING; Gong, Yuewen; She, Yi-Min; Wang, Guqi; Roberts, Michael S; Burczynski, Frank J.

    2009-01-01

    Hepatocytes expressing liver fatty acid binding protein (L-FABP) are known to be more resistant to oxidative stress than those devoid of this protein. The mechanism for the observed antioxidant activity is not known. We examined the antioxidant mechanism of a recombinant rat L-FABP in the presence of a hydrophilic (AAPH) or lipophilic (AMVN) free radical generator. Recombinant L-FABP amino acid sequence and its amino acid oxidative products following oxidation were identified by MALDI quadrup...

  1. Urinary liver-type fatty acid-binding protein change in gestational diabetes mellitus.

    Science.gov (United States)

    Fu, Wen-Jin; Wang, Du-Juan; Deng, Ren-Tang; Huang, Zhi-Hong; Chen, Mei-Lian; Jang, You-Ming; Wen, Shu; Yang, Hong-Ling; Huang, Xian-zhang

    2015-09-01

    We compared urinary liver-type fatty acid-binding protein (L-FABP) among non-pregnant and pregnant women with and without gestational diabetes mellitus (GDM). Higher urinary L-FABP was found in pregnant with and without GDM, and considerably higher urinary L-FABP was found in the GDM group compared with the non-GDM group. Hyperglycemia and anemia were related with high urinary L-FABP expression.

  2. Intestinal microbiota determines development of non-alcoholic fatty liver disease in mice

    OpenAIRE

    Le Roy, Tiphaine; Llopis, Marta; Lepage, Patricia; Bruneau, Aurelia; Rabot, Sylvie; Bevilacqua, Claudia; Martin, Patrice; Philippe, Catherine; Walker, Francine; Bado, Andre; Perlemuter, Gabriel; Cassard-Doulcier, Anne-Marie

    2013-01-01

    Objective: Non-alcoholic fatty liver disease (NAFLD) is prevalent among obese people and is considered the hepatic manifestation of metabolic syndrome. However, not all obese individuals develop NAFLD. Our objective was to demonstrate the role of the gut microbiota in NAFLD development using transplantation experiments in mice. [br/] Design: Two donor C57BL/6J mice were selected on the basis of their responses to a high-fat diet (HFD). Although both mice displayed similar body weight gain, on...

  3. Nonalcoholic Fatty Liver Disease: Dyslipidemia, Risk for Cardiovascular Complications, and Treatment Strategy

    OpenAIRE

    Zhang, Qing-Qing; Lu, Lun-Gen

    2015-01-01

    Studies have shown that nonalcoholic fatty liver disease (NAFLD) is strongly associated with several metabolic disorders and diseases, such as obesity, type 2 diabetes mellitus, and dyslipidemia. In NAFLD, dyslipidemia is manifested as increased serum triglyceride and low-density lipoprotein cholesterol levels and decreased high-density lipoprotein cholesterol levels, all of which are key risk factors for cardiovascular disease (CVD). CVD is a leading cause of mortality in NAFLD patients. Thu...

  4. Meat Characteristics, Fatty Liver Weight and Blood Biochemical Parameters in Force-Feeding Geese

    OpenAIRE

    2014-01-01

    A study on growth performance, meat characteristics, fatty liver weight and serum biochemical parameters (ASAT, ALAT, alkaline phosphatase, γ-glutamyltransferase, total cholesterol, triglycerides and creatinine) in Landes geese before and after force-feeding was carried out. The overfeeding of geese with corn was taken after 90-days of age. Frequency of daily force feeding was gradually increased from 2 to 5 until the 15th day of force feeding. During force-feeding period, the body weight inc...

  5. Obstructive sleep apnea syndrome and fatty liver: Association or causal link?

    Institute of Scientific and Technical Information of China (English)

    Mohamed; H; Ahmed; Christopher; D; Byrne

    2010-01-01

    Obstructive sleep apnea (OSA) is a complex disorder that consists of upper airway obstruction, chronic intermittent hypoxia and sleep fragmentation. OSA is well known to be associated with hypoxia, insulin resistance and glucose intolerance, and these factors can occur in the presence or absence of obesity and metabolic syndrome. Although it is well established that insulin resistance, glucose intolerance and obesity occur frequently with non-alcoholic fatty liver disease (NAFLD), it is now becoming apparen...

  6. Circulating extracellular vesicles with specific proteome and liver microRNAs are potential biomarkers for liver injury in experimental fatty liver disease.

    Directory of Open Access Journals (Sweden)

    Davide Povero

    Full Text Available BACKGROUND & AIM: Nonalcoholic fatty liver disease (NAFLD is the most common chronic liver disease in both adult and children. Currently there are no reliable methods to determine disease severity, monitor disease progression, or efficacy of therapy, other than an invasive liver biopsy. DESIGN: Choline Deficient L-Amino Acid (CDAA and high fat diets were used as physiologically relevant mouse models of NAFLD. Circulating extracellular vesicles were isolated, fully characterized by proteomics and molecular analyses and compared to control groups. Liver-related microRNAs were isolated from purified extracellular vesicles and liver specimens. RESULTS: We observed statistically significant differences in the level of extracellular vesicles (EVs in liver and blood between two control groups and NAFLD animals. Time-course studies showed that EV levels increase early during disease development and reflect changes in liver histolopathology. EV levels correlated with hepatocyte cell death (r2 = 0.64, p<0.05, fibrosis (r2 = 0.66, p<0.05 and pathological angiogenesis (r2 = 0.71, p<0.05. Extensive characterization of blood EVs identified both microparticles (MPs and exosomes (EXO present in blood of NAFLD animals. Proteomic analysis of blood EVs detected various differentially expressed proteins in NAFLD versus control animals. Moreover, unsupervised hierarchical clustering identified a signature that allowed for discrimination between NAFLD and controls. Finally, the liver appears to be an important source of circulating EVs in NAFLD animals as evidenced by the enrichment in blood with miR-122 and 192--two microRNAs previously described in chronic liver diseases, coupled with a corresponding decrease in expression of these microRNAs in the liver. CONCLUSIONS: These findings suggest a potential for using specific circulating EVs as sensitive and specific biomarkers for the noninvasive diagnosis and monitoring of NAFLD.

  7. 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 it

  8. Liver Fibrosis, but No Other Histologic Features, Is Associated With Long-term Outcomes of Patients With Nonalcoholic Fatty Liver Disease

    DEFF Research Database (Denmark)

    Angulo, Paul; Kleiner, David E; Dam-Larsen, Sanne

    2015-01-01

    BACKGROUND & AIMS: Histologic analysis of liver biopsy specimens allows for grading and staging of nonalcoholic fatty liver disease (NAFLD). We performed a longitudinal study to investigate the long-term prognostic relevance of histologic features for patients with NAFLD. METHODS: We performed...

  9. Impact of dietary fatty acids on muscle composition, liver lipids, milt composition and sperm performance in European eel

    DEFF Research Database (Denmark)

    Butts, Ian; Baeza, R.; Støttrup, Josianne;

    2015-01-01

    of dietary regime on muscle composition, and liver lipids prior to induced maturation, and the resulting sperm composition and performance. To accomplish this fish were reared on three "enhanced" diets and one commercial diet, each with different levels of fatty acids, arachidonic acid (ARA......), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). Neutral lipids from the muscle and liver incorporated the majority of the fatty acid profile, while phospholipids incorporated only certain fatty acids. Diet had an effect on the majority of sperm fatty acids, on the total volume of extractable milt...... induced medium milt volumes but had the highest sperm motility. EPA also seems important for sperm quality parameters since diets with higher EPA percentages had a higher volume of milt and higher sperm motility. In conclusion, dietary fatty acids had an influence on fatty acids in the tissues of male eel...

  10. Chronic Kidney Disease and Nonalcoholic Fatty Liver Disease Proven by Transient Elastography

    Directory of Open Access Journals (Sweden)

    Ivana Mikolasevic

    2013-09-01

    Full Text Available Background/Aim: Preliminary data suggest an association between chronic kidney disease (CKD and non-alcoholic fatty liver disease (NAFLD. The aim of this study was to further investigate the association between NAFLD and decreased kidney function. Methods: A total of 62 patients with CKD were enrolled in the study. Liver stiffness was used to detect liver fibrosis and CAP (controlled attenuation parameter was used to detect and quantify liver steatosis (Fibroscan®. NAFLD was defined by CAP values ≥238 dB.m-1. Results: CKD stage III was present in 29 patients (46.8% and CKD stage IV in 33 patients (53.2%. Out of 62 CKD patients 53 (85.5% had NAFLD and of these 14/53 patients (26.4% had also liver stiffness >7 kPa. The severity of liver steatosis was positively correlated with serum creatinine (r=0.399;pConclusion: The results suggest a high prevalence of NAFLD in CKD patients. The severity of liver steatosis is negatively correlated with kidney function. The study documents the value of ultrasonographic elastography as an effective non-invasive screening method for the diagnosis of NAFLD.

  11. Lipid-lowering agents in the management of nonalcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    Konstantinos; Tziomalos

    2014-01-01

    Nonalcoholic fatty liver disease(NAFLD) is the most common chronic liver disease in developed countries and is associated not only with increased risk for liver disease-related complications but also with higher cardiovascular morbidity. Accordingly, lipid-lowering agents are frequently considered in these patients to reduce cardiovascular risk. However, there have been concerns regarding the safety of these agents in patients with chronic liver diseases. In the present review, we discuss the safety of lipid-lowering agents in patients with NAFLD as well as their effects on both cardiovascular and liver disease in this population. Accumulating data suggest that statins are safe in patients with NAFLD and that they reduce the increased cardiovascular morbidity of this population. However, it is still unclear whether statins are also useful as a treatment for NAFLD per se, since there are very limited and conflicting data on their effects on liver histology. There is also very scarce evidence regarding the safety and efficacy of other lipid-lowering agents in patients with NAFLD. Randomized controlled studies are needed to evaluate the role of lipid-lowering agents and particularly statins for the prevention of both cardiovascular and liver disease-related complications in this high-risk population.

  12. Pentoxifylline and melatonin in combination with pioglitazone ameliorate experimental non-alcoholic fatty liver disease.

    Science.gov (United States)

    Zaitone, Sawsan; Hassan, Neven; El-Orabi, Naglaa; El-Awady, El-Sayed

    2011-07-15

    Insulin resistance, oxidative stress and cytokine imbalance are key pathophysiological mechanisms in non-alcoholic fatty liver disease (NAFLD). This study aimed at evaluating the effect of treatment with the insulin sensitizer, pioglitazone, the tumor necrosis factor-α inhibitor, pentoxifylline, and the antioxidant, melatonin and their combinations in rats with NAFLD. Rats were fed a high-fat diet (HFD) for eight weeks to induce NAFLD. For an additional eight weeks, rats were fed the HFD along with pioglitazone, pentoxifylline, melatonin alone or in combination. Liver index and insulin resistance index were calculated. Serum liver enzyme activities, total cholesterol, triglycerides and tumor necrosis factor-α (TNF-α) were determined. Tissue triglycerides, malondialdehyde and reduced glutathione were measured and liver injury was evaluated by histopathological examination. HFD induced severe hepatic steatosis, inflammation and fibrosis. In addition, liver index, insulin resistance index, activities of liver enzymes and serum level of total cholesterol, triglycerides and TNF-α were elevated. This was coupled with an increase in tissue triglycerides, malondialdehyde and depletion of reduced glutathione. Pioglitazone, pentoxifylline and melatonin, alone or in combination; reduced the insulin resistance index, activities of liver enzymes, hepatic malondialdehyde and increased hepatic reduced glutathione level. Pentoxifylline led to a decrease in serum TNF-α level, however, pioglitazone and melatonin reduced serum total cholesterol and triglycerides. In conclusion, data in this study indicate that pentoxifylline and melatonin can be used as promising adjuvant therapies to pioglitazone in the clinical management of NAFLD.

  13. Controversy in the diagnosis of pediatric non-alcoholic fatty liver disease.

    Science.gov (United States)

    Marzuillo, Pierluigi; Grandone, Anna; Perrone, Laura; Miraglia Del Giudice, Emanuele

    2015-06-07

    In the last years childhood obesity has reached epidemic diffusion with about 200 million school-age children worldwide being overweight or obese. Simultaneously, also the prevalence of obesity comorbidities has been increased and the non-alcoholic fatty liver disease (NAFLD) has become the most common form of liver disease in childhood. Also if there are some not-invasive diagnostic possibilities, the diagnostic gold standard is represented by hepatic biopsy giving to the clinicians the possibility to both diagnose the NAFLD and evaluate its progression to fibrosis or cirrhosis with greater certainty than other techniques. The use of liver biopsy in clinical practice causes debate among health care providers. Most patients with NAFLD have a good prognosis and, therefore, the risks of a liver biopsy seem to outweigh the clinical benefits. It represents an impractical screening procedure because it is both expensive and invasive and, moreover, sampling error of liver biopsy can result in substantial misdiagnosis and staging inaccuracies because histological lesions of non-alcoholic steatohepatitis are unevenly distributed throughout the liver parenchyma. The liver biopsy limitations have led the clinicians to use, also if highly imperfect, non-invasive methods to diagnose and stage NAFLD. In this editorial the main diagnostic controversies in pediatric NAFLD are examined.

  14. Diets containing traditional and novel green leafy vegetables improve liver fatty acid profiles of spontaneously hypertensive rats

    OpenAIRE

    Johnson, Melissa; Pace, Ralphenia D.; Dawkins, Norma L.; Willian, Kyle R

    2013-01-01

    Background The consumption of green leafy vegetables (GLVs) has been demonstrated to reduce the risks associated with cardiovascular and other diseases. However, no literature exists that examines the influence of traditional and novel GLVs on the liver fatty acid profile of an animal model genetically predisposed to developing hypertension. The aim of the present study was to examine the effects of diets containing 4% collard greens, purslane or sweet potato greens on the liver fatty acid pr...

  15. Three-dimensional perfused human in vitro model of non-alcoholic fatty liver disease

    Science.gov (United States)

    Kostrzewski, Tomasz; Cornforth, Terri; Snow, Sophie A; Ouro-Gnao, Larissa; Rowe, Cliff; Large, Emma M; Hughes, David J

    2017-01-01

    AIM To develop a human in vitro model of non-alcoholic fatty liver disease (NAFLD), utilising primary hepatocytes cultured in a three-dimensional (3D) perfused platform. METHODS Fat and lean culture media were developed to directly investigate the effects of fat loading on primary hepatocytes cultured in a 3D perfused culture system. Oil Red O staining was used to measure fat loading in the hepatocytes and the consumption of free fatty acids (FFA) from culture medium was monitored. Hepatic functions, gene expression profiles and adipokine release were compared for cells cultured in fat and lean conditions. To determine if fat loading in the system could be modulated hepatocytes were treated with known anti-steatotic compounds. RESULTS Hepatocytes cultured in fat medium were found to accumulate three times more fat than lean cells and fat uptake was continuous over a 14-d culture. Fat loading of hepatocytes did not cause any hepatotoxicity and significantly increased albumin production. Numerous adipokines were expressed by fatty cells and genes associated with NAFLD and liver disease were upregulated including: Insulin-like growth factor-binding protein 1, fatty acid-binding protein 3 and CYP7A1. The metabolic activity of hepatocytes cultured in fatty conditions was found to be impaired and the activities of CYP3A4 and CYP2C9 were significantly reduced, similar to observations made in NAFLD patients. The utility of the model for drug screening was demonstrated by measuring the effects of known anti-steatotic compounds. Hepatocytes, cultured under fatty conditions and treated with metformin, had a reduced cellular fat content compared to untreated controls and consumed less FFA from cell culture medium. CONCLUSION The 3D in vitro NAFLD model recapitulates many features of clinical NAFLD and is an ideal tool for analysing the efficacy of anti-steatotic compounds. PMID:28127194

  16. Hydrogen peroxide impairs autophagic flux in a cell model of nonalcoholic fatty liver disease

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Pengtao [National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing 100101 (China); University of Chinese Academy of Sciences, 19 Yuquan Road, Shijingshan District, Beijing 100049 (China); Huang, Zhen [Department of Abdominal Surgical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences, 17 Panjiayuan Nanli, Chaoyang District, Beijing 100021 (China); Zhao, Hong, E-mail: zhaohong9@sina.com [Department of Abdominal Surgical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences, 17 Panjiayuan Nanli, Chaoyang District, Beijing 100021 (China); Wei, Taotao, E-mail: weitt@moon.ibp.ac.cn [National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing 100101 (China)

    2013-04-19

    Highlights: •Free fatty acids exposure induces elevated autophagy. •H{sub 2}O{sub 2} inhibits autophagic flux through impairing the fusion between autophagosomes and lysosomes. •Inhibition of autophagy potentiates H{sub 2}O{sub 2}-induced cell death. -- Abstract: Nonalcoholic fatty liver disease (NAFLD) has become the leading cause of chronic liver disease, but the pathogenesis of NAFLD is not fully clear. The aim of this study was to determine whether autophagy plays a role in the pathogenesis of NAFLD. We found that the levels of autophagy were elevated in hepatoma cells upon exposure to free fatty acids, as confirmed by the increase in the number of autophagosomes. However, exposure of hepatoma cells to H{sub 2}O{sub 2} and TNF-α, two typical “second hit” factors, increased the initiation of autophagy but inhibited the autophagic flux. The inhibition of autophagy sensitized cells to pro-apoptotic stimuli. Taken together, our results suggest that autophagy acts as a protective mechanism in the pathogenesis of NAFLD and that impairment of autophagy might induce more severe lesions of the liver. These findings will be a benefit to the understanding of the pathogenesis of NAFLD and might suggest a strategy for the prevention and cure of NAFLD.

  17. The Effect of Weight Reduction on Ultrasonographic Findings of Nonalcoholic Fatty Liver

    Science.gov (United States)

    Tahaei, SA; Sedighi, N; Derogar, R; Aslani, A; Malekzadeh, R; Merat, S

    2010-01-01

    BACKGROUND Non-alcoholic fatty liver (NAFL) includes a spectrum of diseases ranging from simple hepatic steatosis to nonalcoholic steatohepatitis (NASH) and cirrhosis. NAFL is typically seen in association with obesity, diabetes and hypertriglyceridaemia. In order to seek the role of diet therapy in treatment of NAFL, we compared the ultrasonographic findings of patients with fatty liver disease before and after standard diet therapy. METHODS Twenty-three overweight or obese subjects with incidental fatty liver discovered during ultrasonography were included. Subjects underwent 3 months of diet therapy, and anthropometric data including weight, height, BMI, waist circumference, and hip circumference were measured. Ultrasonographic findings were graded from 0 to 3. Changes in ultrasonographic findings and anthropometric data were studied. RESULTS After three months of dieting, the ultrasonographic grade of all patients decreased by one or two grades. Fifteen patients decreased one grade while 8 others decreased by 2 grades. We observed a significant correlation between the decrease in ultrasonographic grade and the decrease in weight and BMI. CONCLUSION Our study indicates that standard diet therapy could be used as an effective treatment for NAFL patients. PMID:25197505

  18. Doppler waveforms of the hepatic veins in children with diffuse fatty infiltration of the liver

    Energy Technology Data Exchange (ETDEWEB)

    Uzun, Hakan [Duzce University School of Medicine, Department of Pediatrics, Konuralp, Duzce 81620 (Turkey); Yazici, Burhan [Duzce University School of Medicine, Department of Radiology, Konuralp, Duzce 81620 (Turkey)], E-mail: dryazici@yahoo.com; Erdogmus, Besir [Duzce University School of Medicine, Department of Radiology, Konuralp, Duzce 81620 (Turkey); Kocabay, Kenan [Duzce University School of Medicine, Department of Pediatrics, Konuralp, Duzce 81620 (Turkey); Buyukkaya, Ramazan; Buyukkaya, Ayla; Yazgan, Omer [Duzce University School of Medicine, Department of Radiology, Konuralp, Duzce 81620 (Turkey)

    2009-09-15

    Objective: The aim of this study was to investigate the effect of fatty infiltration of the liver (FIL) on the Doppler waveform pattern in the hepatic veins of obese children. Methods: In this prospective study, 59 patients with diffuse FIL and 45 normal healthy children who served as control group underwent hepatic vein B-mod and duplex Doppler sonography. The Doppler sonography spectrum of the right hepatic vein was classified into three groups: triphasic waveform, biphasic waveform, and monophasic or flat waveform. Results: There was a statistically significant difference in the phasicity of hepatic venous flow between patients and control subjects (p < 0.001). The Doppler flow pattern in the right hepatic vein was triphasic in 28 (47.5%), biphasic in 28 (47.5%), and monophasic in 3 (5%) children with fatty liver, while it was triphasic in 43 (95.6%) and biphasic in 2 (4.4%) control subjects. There was an inverse correlation between the sonographic grade of fatty infiltration of the liver and the phasicity of hepatic venous flow (r = -0.479, p < 0.001). Conclusions: Abnormal right hepatic vein Doppler waveform, biphasic as well as monophasic, can be seen in healthy obese children with diffuse FIL.

  19. Clinical significance of serum alanine aminotransferase and lifestyle intervention in children with nonalcoholic fatty liver disease

    Science.gov (United States)

    Kwon, Kyoung Ah; Chun, Peter

    2016-01-01

    Purpose This study aimed to investigate the clinical significance of serum alanine aminotransferase (ALT) levels in children with nonalcoholic fatty liver disease (NAFLD) and the effect of lifestyle intervention on NAFLD. Methods The clinical data of 86 children diagnosed with NAFLD were reviewed retrospectively. Forty-six patients belonged to the elevated ALT group and 40 to the normal ALT group. The clinical parameters of patients with NAFLD were also compared based on the status of ALT levels after lifestyle intervention. Results Patients with elevated ALT had significantly higher body mass index (BMI) scores than those with normal ALT (P<0.05). Of all the patients with elevated ALT, 89% exhibited moderate or severe degree of fatty change in the liver on ultrasonographic examination, whereas most patients with normal ALT exhibited mild or moderate degree changes. Liver biopsy was performed in 15 children with elevated ALT and all showed mild histological changes. Of all patients with elevated ALT, 49% achieved normal ALT levels after lifestyle intervention. Those with more severe histological changes tended to have continuously increasing ALT levels. There was no correlation between the normalization of posttreatment ALT level and BMI, as well as ultrasonographic findings at diagnosis. Conclusion ALT elevation in NAFLD is highly associated with higher BMI scores and more severe degree of fatty changes on ultrasonographic examination. Lifestyle intervention can significantly improve ALT in children with NAFLD. The degree of histologic changes appears to be a predictor of the treatment response to NAFLD.

  20. Role of diet on non-alcoholic fatty liver disease: An updatednarrative review

    Institute of Scientific and Technical Information of China (English)

    Dimitrios Papandreou; Eleni Andreou

    2015-01-01

    The purpose of this article review is to update whatis known about the role of diet on non-alcoholic fattyliver disease (NAFLD). NAFLD is the most commoncause of chronic liver disease in the developed worldand is considered to be a spectrum, ranging from fattyinfiltration of the liver alone (steatosis), which may leadto fatty infiltration with inflammation known as nonalcoholic steatohepatitis While the majority of individualswith risk factors like obesity and insulin resistance havesteatosis, only few people may develop steatohepatitis.Current treatment relies on weight loss and exercise,although various insulin-sensitizing medications appearpromising. Weight loss alone by dietary changeshas been shown to lead to histological improvementin fatty liver making nutrition therapy to become acornerstone of treatment for NAFLD. Supplementationof vitamin E, C and omega 3 fatty acids are underconsideration with some conflicting data. Moreover,research has been showed that saturated fat, trans-fattyacid, carbohydrate, and simple sugars (fructose andsucrose) may play significant role in the intrahepatic fataccumulation. However, true associations with specificnutrients yet to be clarified.

  1. 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

  2. [A Future Perspective on the Involvement of n-3 Polyunsaturated Fatty Acid in the Development of Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis].

    Science.gov (United States)

    Nakamoto, Kazuo; Obata, Tokio; Hirasawa, Akira; Kim, Ke Ih; Kim, Soo Ryang; Tokuyama, Shogo

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) is characterized by the pathological accumulation of fat in the liver in the absence of any other disease related to liver steatosis, which includes a wide spectrum of liver diseases ranging from mild asymptomatic fatty liver to nonalcoholic steatohepatitis (NASH) and cirrhosis. Recently, it was reported that NAFLD is characterized by the impaired bioavailability of liver n-6 and n-3 long-chain polyunsaturated fatty acids (PUFAs). That is, compared with healthy individuals, steatosis and steatohepatitis patients have higher n-6/n-3 PUFA ratios. Furthermore, per recent research, decreasing the intake of total fats and increasing the intake of n-3 PUFAs may be beneficial in the treatment of NAFLD. In contrast, some reports describe that NASH patients have more metabolic abnormalities than NAFLD patients; however, these are not influenced by dietary fatty acids. Thus, at present, various opinions exist regarding the efficacy of n-3 PUFA in the treatment of NAFLD. In this review, we discuss the considerable interest n-3 PUFA has attracted as a potential treatment for NAFLD.

  3. The Effect of Green Tea Extract Supplementation on Liver Enzymes in Patients with Nonalcoholic Fatty Liver Disease

    Science.gov (United States)

    Pezeshki, Ali; Safi, Sara; Feizi, Awat; Askari, Gholamreza; Karami, Fatemeh

    2016-01-01

    Background: Green tea is one of the most popular beverages in the world. It is believed to have beneficial effects in the prevention and treatment of many diseases, one of which is nonalcoholic fatty liver disease (NAFLD). The present study investigated the effects of consumption of green tea in NAFLD patients. Methods: This study was a double-blind, placebo-controlled, randomized clinical trial. Ultrasonography was used to diagnose fatty liver in patients with alanine aminotransferase (ALT) >31 mg/dl and 41 mg/dl and aspartate aminotransferase (AST) >31 mg/dl and 47 g/dl in women and men, respectively and without other hepatic diseases. A total of 80 participants (20–50 years) with NAFLD were randomly allocated into two groups to receive either green tea extract (GTE) supplement (500 mg GTE tablet per day) or placebo for 90 days. At baseline and at the end of the intervention weight, serum ALT, AST, and alkaline phosphatase (ALP) were measured in fasting state, and dietary data were collected at baseline and end of the study. Results: Green tea group showed significant reductions in ALT and AST levels after 12 weeks period (P < 0.001). The placebo group showed a reduction in ALT and AST levels at the end of the study, but it was no significant. ALP levels showed significant reductions in both groups after 12 weeks period (P < 0.001). Conclusions: According to the findings of this study, GTE supplementation decrease liver enzymes in patients with NAFLD. It can be claimed that GTE prescribed can be considered as a treatment to improve serum levels of liver enzymes in NAFLD patients. PMID:26955458

  4. Sonographic fatty liver and hepatitis B virus carrier status: Synergistic effect on liver damage in Taiwanese adults

    Institute of Scientific and Technical Information of China (English)

    Yu-Cheng Lin; Shu-Tin Hsiao; Jong-Dar Chen

    2007-01-01

    AIM:To examine the epidemiology of hepatitis B virus carrier status (HBVC) and Sonographic fatty liver (SFL) in Taiwanese adults,and to evaluate their possible interaction in inducing liver damage (LD). From an epidemiological viewpoint,we analyzed previous studies which indicated that fatty liver sensitizes host immune response to HBV infection and enhances liver damage.METHODS:A cross-sectional retrospective analysis of health records including medical history,physical examination,abdominal sonogram,blood biochemistry and hepatic virological tests. We utilized the Student's f-test,chi-square,multivariate logistic regression and synergy index to assess risks for LD.RESULTS:Among a total of 5406 Taiwanese adults (mean age 46.2 years,51.5% males),the prevalence of LD,HBVC and SFL were 12.3%,15.1% and 33.4%,respectively; 5.1% of participants had SFL plus HBVC. Muifivariate logistic regression analysis demonstrated that male gender (odds ratio (OR) = 2.8,95% confidence interval (CI):2.3-3.5),overweight state (OR = 1.6,95% CI:1.3-2.0),HBVC (OR = 2.5,95% CI:2.0-3.1) and SFL (OR = 4.2,95% CI:2.2-5.3) were independently associated with LD. Synergism analysis showed that the adjusted OR for LD in adults with HBVC-alone was 3.3 (95% CI:2.4-4.6),SFL-alone,4.7 (95% CI:3.7-6.1) and combined HBVC and SFL,9.5 (95% CI:6.8-13.3); the synergy index was 1.4 (95% CI:1.001-2.0).CONCLUSION:In Taiwanese adults,SFL plus HBVC have a significant Synergistic association with LD.

  5. Epidemiology of fatty liver in an islander population of China:a population-based case-control study

    Institute of Scientific and Technical Information of China (English)

    Hui-Fen Dai; Zhe Shen; Chao-Hui Yu; Xi-Cheng Zhang; You-Ming Li

    2008-01-01

    BACKGROUND: Because of dififculty in evaluating fatty liver disease in islander populations, we conducted a cross-sectional study to investigate the prevalence of fatty liver and its risk factors in an islander population of East China. METHODS: Randomized multistage stratiifed cluster sampling from the islander population was used in a population-based case-control study. Then interview, physical examination, and ultrasonography were done. RESULTS: Univariate logistic-regression analysis showed that male gender, smoking, daily alcohol intake ≥20 g, duration of drinking≥5 years, total alcohol intake≥36.5 kg, hypertension and obesity were closely related to fatty liver (all P CONCLUSIONS: The duration of drinking≥5 years and obesity were two important risk factors for fatty liver in the islander population of East China. The prevalence of fatty liver in this population was high. An alcoholic threshold effect may be more important than a dose-response effect on the morbidity of fatty liver.

  6. The adaptive endoplasmic reticulum stress response to lipotoxicity in progressive human nonalcoholic fatty liver disease.

    Science.gov (United States)

    Lake, April D; Novak, Petr; Hardwick, Rhiannon N; Flores-Keown, Brieanna; Zhao, Fei; Klimecki, Walter T; Cherrington, Nathan J

    2014-01-01

    Nonalcoholic fatty liver disease (NAFLD) may progress from simple steatosis to severe, nonalcoholic steatohepatitis (NASH) in 7%-14% of the U.S. population through a second "hit" in the form of increased oxidative stress and inflammation. Endoplasmic reticulum (ER) stress signaling and the unfolded protein response (UPR) are triggered when high levels of lipids and misfolded proteins alter ER homeostasis creating a lipotoxic environment within NAFLD livers. The objective of this study was to determine the coordinate regulation of ER stress-associated genes in the progressive stages of human NAFLD. Human liver samples categorized as normal, steatosis, NASH (Fatty), and NASH (Not Fatty) were analyzed by individual Affymetrix GeneChip Human 1.0 ST microarrays, immunoblots, and immunohistochemistry. A gene set enrichment analysis was performed on autophagy, apoptosis, lipogenesis, and ER stress/UPR gene categories. An enrichment of downregulated genes in the ER stress-associated lipogenesis and ER stress/UPR gene categories was observed in NASH. Conversely, an enrichment of upregulated ER stress-associated genes for autophagy and apoptosis gene categories was observed in NASH. Protein expression of the adaptive liver response protein STC2 and the transcription factor X-box binding protein 1 spliced (XBP-1s) were significantly elevated among NASH samples, whereas other downstream ER stress proteins including CHOP, ATF4, and phosphorylated JNK and eIF2α were not significantly changed in disease progression. Increased nuclear accumulation of total XBP-1 protein was observed in steatosis and NASH livers. The findings reveal the presence of a coordinated, adaptive transcriptional response to hepatic ER stress in human NAFLD.

  7. Metformin protects rat hepatocytes against bile acid-induced apoptosis.

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    Titia E Woudenberg-Vrenken

    Full Text Available BACKGROUND: Metformin is used in the treatment of Diabetes Mellitus type II and improves liver function in patients with non-alcoholic fatty liver disease (NAFLD. Metformin activates AMP-activated protein kinase (AMPK, the cellular energy sensor that is sensitive to changes in the AMP/ATP-ratio. AMPK is an inhibitor of mammalian target of rapamycin (mTOR. Both AMPK and mTOR are able to modulate cell death. AIM: To evaluate the effects of metformin on hepatocyte cell death. METHODS: Apoptotic cell death was induced in primary rat hepatocytes using either the bile acid glycochenodeoxycholic acid (GCDCA or TNFα in combination with actinomycin D (actD. AMPK, mTOR and phosphoinositide-3 kinase (PI3K/Akt were inhibited using pharmacological inhibitors. Apoptosis and necrosis were quantified by caspase activation, acridine orange staining and Sytox green staining respectively. RESULTS: Metformin dose-dependently reduces GCDCA-induced apoptosis, even when added 2 hours after GCDCA, without increasing necrotic cell death. Metformin does not protect against TNFα/ActD-induced apoptosis. The protective effect of metformin is dependent on an intact PI3-kinase/Akt pathway, but does not require AMPK/mTOR-signaling. Metformin does not inhibit NF-κB activation. CONCLUSION: Metformin protects against bile acid-induced apoptosis and could be considered in the treatment of chronic liver diseases accompanied by inflammation.

  8. Reducing Liver Fat by Low Carbohydrate Caloric Restriction Targets Hepatic Glucose Production in Non-Diabetic Obese Adults with Non-Alcoholic Fatty Liver Disease

    OpenAIRE

    Haoyong Yu; Weiping Jia; ZengKui Guo

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) impairs liver functions, the organ responsible for the regulation of endogenous glucose production and thus plays a key role in glycemic homeostasis. Therefore, interventions designed to normalize liver fat content are needed to improve glucose metabolism in patients affected by NAFLD such as obesity. Objective: this investigation is designed to determine the effects of caloric restriction on hepatic and peripheral glucose metabolism in obese humans w...

  9. Nonalcoholic fatty liver disease progression in rats is accelerated by splenic regulation of liver PTEN/AKT

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    Ziming Wang

    2015-01-01

    Full Text Available Background/Aim: The spleen has been reported to participate in the development of nonalcoholic fatty liver disease (NAFLD, but the mechanism has not been fully characterized. This study aims to elucidate how the spleen affects the development of NAFLD in a rat model. Materials and Methods: Following either splenectomy or sham operation, male Sprague–Dawley (SD rats were fed a high-fat diet to drive the development of NAFLD; animals fed a normal diet were used as controls. Two months after surgery, livers and blood samples were collected. Serum lipids were measured; liver histology, phosphatase and tensin homologue deleted on chromosome 10 (PTEN gene expression, and the ratio of pAkt/Akt were determined. Results: Splenectomy increased serum lipids, except triglyceride (TG and high-density lipoprotein (HDL, in animals fed either a high-fat or normal diet. Furthermore, splenectomy significantly accelerated hepatic steatosis. Western blot analysis and real-time polymerase chain reaction showed splenectomy induced significant downregulation of PTEN expression and a high ratio of pAkt/Akt in the livers. Conclusions: The spleen appears to play a role in the development of NAFLD, via a mechanism involving downregulation of hepatic PTEN expression.

  10. Liver transcriptome profile in pigs with extreme phenotypes of intramuscular fatty acid composition

    Directory of Open Access Journals (Sweden)

    Ramayo-Caldas Yuliaxis

    2012-10-01

    Full Text Available Abstract Background New advances in high-throughput technologies have allowed for the massive analysis of genomic data, providing new opportunities for the characterization of the transcriptome architectures. Recent studies in pigs have employed RNA-Seq to explore the transcriptome of different tissues in a reduced number of animals. The main goal of this study was the identification of differentially-expressed genes in the liver of Iberian x Landrace crossbred pigs showing extreme phenotypes for intramuscular fatty acid composition using RNA-Seq. Results The liver transcriptomes of two female groups (H and L with phenotypically extreme intramuscular fatty acid composition were sequenced using RNA-Seq. A total of 146 and 180 unannotated protein-coding genes were identified in intergenic regions for the L and H groups, respectively. In addition, a range of 5.8 to 7.3% of repetitive elements was found, with SINEs being the most abundant elements. The expression in liver of 186 (L and 270 (H lncRNAs was also detected. The higher reproducibility of the RNA-Seq data was validated by RT-qPCR and porcine expression microarrays, therefore showing a strong correlation between RT-qPCR and RNA-Seq data (ranking from 0.79 to 0.96, as well as between microarrays and RNA-Seq (r=0.72. A differential expression analysis between H and L animals identified 55 genes differentially-expressed between groups. Pathways analysis revealed that these genes belong to biological functions, canonical pathways and three gene networks related to lipid and fatty acid metabolism. In concordance with the phenotypic classification, the pathways analysis inferred that linolenic and arachidonic acids metabolism was altered between extreme individuals. In addition, a connection was observed among the top three networks, hence suggesting that these genes are interconnected and play an important role in lipid and fatty acid metabolism. Conclusions In the present study RNA-Seq was used

  11. The role of endocannabinoids system in fatty liver disease and therapeutic potentials.

    Science.gov (United States)

    Alswat, Khalid A

    2013-01-01

    Non-alcoholic fatty liver disease (NAFLD) is a major cause of liver morbidity and mortality with no proven effective therapy as of yet. Its prevalence is increasing globally in parallel with obesity and metabolic syndrome pandemic. The endocannabinoid (EC) system has been implicated in the pathogenesis of several diseases, including fatty liver diseases. This system refers to the cannabinoid receptors type 1 (CB1) and type 2 (CB2), with both their endogenous ligands and machinery dedicated to EC synthesis and degradation. There is accumulating evidence on the role CB1 as a key mediator of insulin resistance and liver lipogenesis in both animals and humans. On the other hand, CB2 receptors have been shown to promote inflammation with anti-fibrogenic properties. The pharmacological modulation of the EC system activity for the treatment of metabolic syndrome and NAFLD are promising yet premature. The initial limited success due to deleterious central nervous system side-effects are likely to be bypassed with the use of peripherally restricted drugs.

  12. The role of endocannabinoids system in fatty liver disease and therapeutic potentials

    Directory of Open Access Journals (Sweden)

    Khalid A Alswat

    2013-01-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD is a major cause of liver morbidity and mortality with no proven effective therapy as of yet. Its prevalence is increasing globally in parallel with obesity and metabolic syndrome pandemic. The endocannabinoid (EC system has been implicated in the pathogenesis of several diseases, including fatty liver diseases. This system refers to the cannabinoid receptors type 1 (CB1 and type 2 (CB2, with both their endogenous ligands and machinery dedicated to EC synthesis and degradation. There is accumulating evidence on the role CB1 as a key mediator of insulin resistance and liver lipogenesis in both animals and humans. On the other hand, CB2 receptors have been shown to promote inflammation with anti-fibrogenic properties. The pharmacological modulation of the EC system activity for the treatment of metabolic syndrome and NAFLD are promising yet premature. The initial limited success due to deleterious central nervous system side-effects are likely to be bypassed with the use of peripherally restricted drugs.

  13. Autofluorescence discrimination of metabolic fingerprint in nutritional and genetic fatty liver models.

    Science.gov (United States)

    Croce, Anna C; Ferrigno, Andrea; Di Pasqua, Laura G; Berardo, Clarissa; Piccolini, Valeria Maria; Bertone, Vittorio; Bottiroli, Giovanni; Vairetti, Mariapia

    2016-11-01

    Liver tissue autofluorescence (AF) has been characterized in two models with a different potential to undergo disease progression to steatohepatitis: Wistar rats, administered with a methionine, choline deficient diet (MCD), and Zucker (fa/fa) rats, homozygous for a spontaneous mutation of leptin receptor. AF spectra were recorded from liver tissue cryostatic sections by microspectrofluorometry, under 366nm excitation. Curve fitting analysis was used to estimate the contribution of different endogenous fluorophores (EFs) to the overall AF emission: i) fluorescing fatty acids, a fraction of liver lipids up to now poorly considered and complicated to detect by conventional procedures; ii) lipofuscin-like lipopigments, biomarkers of oxidizing events; iii) NAD(P)H and flavins, biomarkers of energy metabolism and tissue redox state. AF data and biochemical correlates of hepatocellular injury resulted to depend more on rat strain than on intratissue bulk lipid or ROS levels, reflecting a different metabolic ability of the two models to counteract potentially harmful agents. AF analysis can thus be proposed for extensive applications ranging from experimental hepatology to the clinics. AF based diagnostic procedures are expected to help both the prediction of the risk of fatty liver disease progression and the prescreening of marginal organs to be recruited as donors for transplantation. A support is also foreseen in the advancement and personalization of strategies to ameliorate the donor organ preservation outcome and the follow up of therapeutic interventions.

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

    Science.gov (United States)

    2016-01-01

    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. PMID:27847552

  15. Evaluation of atherosclerotic findings in patients with nonalcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    Mohammadi A

    2011-10-01

    Full Text Available Afshin Mohammadi1, Ali Bazazi2, Mohammad Ghasemi-rad21Department of Radiology, Urmia University of Medical Sciences, Urmia, West-Azerbaijan, Iran; 2Student Research Committee, Urmia University of Medical Sciences, Urmia, West-Azerbaijan, IranBackground: Nonalcoholic fatty liver disease (NAFLD, a highly prevalent condition, is a feature of metabolic syndrome and is characterized by excessive accumulation of fat in the liver cells. The purpose of this study was to investigate the association between NAFLD and carotid intima-media thickness (CIMT as an independent risk factor for atherosclerosis.Methods: We examined 250 consecutive patients with ultrasonographically confirmed NAFLD and 85 age-matched and gender-matched controls with normal parenchymal liver echogenicity for determination of CIMT and presence of carotid atherosclerotic plaque.Results: Compared with control subjects, patients with NAFLD showed an increased mean CIMT (0.81 ± 0.14 mm compared with control subjects (0.58 ± 0.15 mm. This difference was statistically significant (P = 0.001. After performing multivariate analysis, the presence of NAFLD was associated with abnormal CIMT independent of other atherogenic risk factors or its association with metabolic syndrome.Conclusion: NAFLD can be an independent risk factor for developing atherosclerosis. Therefore, NAFLD with and without metabolic syndrome can be associated with increased CIMT and increased risk of cardiovascular events in patients with NAFLD incidentally diagnosed on abdominal ultrasonography.Keywords: nonalcoholic fatty liver disease, metabolic syndrome, atherosclerosis, carotid intima media thickness, risk factor

  16. Current pharmacological therapies for nonalcoholic fatty liver disease/nonalcoholic steatohepatitis.

    Science.gov (United States)

    Takahashi, Yoshihisa; Sugimoto, Keiichiro; Inui, Hiroshi; Fukusato, Toshio

    2015-04-07

    Nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) is considered to be a hepatic manifestation of metabolic syndrome, and its incidence is rapidly increasing worldwide. It is currently the most common chronic liver disease. NASH can progress to liver cirrhosis and hepatocellular carcinoma, and may result in liver-related death. Currently, the principal treatment for NAFLD/NASH is lifestyle modification by diet and exercise. However, pharmacological therapy is indispensable because obese patients with NAFLD often have difficulty maintaining improved lifestyles. The pathogenesis of NAFLD/NASH has not been completely elucidated. However, insulin resistance, inflammatory cytokines, and oxidative stress are thought to be important in the development and/or progression of the disease. Currently, insulin sensitizers (thiazolidinediones) and antioxidants (vitamin E) seem to be the most promising therapeutic agents for NAFLD/NASH, and lipid-lowering drugs, pentoxifylline, angiotensin receptor blockers, and n-3 polyunsaturated fatty acids also have promise. However, there is a lack of consensus regarding the most effective and appropriate pharmacotherapy for NAFLD/NASH. Animal experiments suggest that herbal medicines and natural products may be promising therapeutic agents for NAFLD/NASH, but their efficacy and safety are yet to be investigated in human studies. In this paper, we review the existing and potential pharmacological therapies for NAFLD/NASH.

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

    Directory of Open Access Journals (Sweden)

    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.

  18. Experimental models of non-alcoholic fatty liver disease in rats.

    Science.gov (United States)

    Kucera, Otto; Cervinkova, Zuzana

    2014-07-14

    Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the Western world, and it persists at a high prevalence. NAFLD is characterised by the accumulation of triglycerides in the liver and includes a spectrum of histopathological findings, ranging from simple fatty liver through non-alcoholic steatohepatitis (NASH) to fibrosis and ultimately cirrhosis, which may progress to hepatocellular carcinoma. The pathogenesis of NAFLD is closely related to the metabolic syndrome and insulin resistance. Understanding the pathophysiology and treatment of NAFLD in humans has currently been limited by the lack of satisfactory animal models. The ideal animal model for NAFLD should reflect all aspects of the intricate etiopathogenesis of human NAFLD and the typical histological findings of its different stages. Within the past several years, great emphasis has been placed on the development of an appropriate model for human NASH. This paper reviews the widely used experimental models of NAFLD in rats. We discuss nutritional, genetic and combined models of NAFLD and their pros and cons. The choice of a suitable animal model for this disease while respecting its limitations may help to improve the understanding of its complex pathogenesis and to discover appropriate therapeutic strategies. Considering the legislative, ethical, economical and health factors of NAFLD, animal models are essential tools for the research of this disease.

  19. Nonalcoholic fatty liver disease and the heart in children and adolescents.

    Science.gov (United States)

    Pacifico, Lucia; Chiesa, Claudio; Anania, Caterina; De Merulis, Antonio; Osborn, John Frederick; Romaggioli, Sara; Gaudio, Eugenio

    2014-07-21

    Over the last two decades, the rise in the prevalence rates of overweight and obesity explains the emergence of nonalcoholic fatty liver disease (NAFLD) as the leading cause of chronic liver disease worldwide. As described in adults, children and adolescents with fatty liver display insulin resistance, glucose intolerance, and dyslipidemia. Thus NAFLD has emerged as the hepatic component of the metabolic syndrome (MetS) and a strong cardiovascular risk factor even at a very early age. Several studies, including pediatric populations, have reported independent associations between NAFLD and markers of subclinical atherosclerosis including impaired flow-mediated vasodilation, increased carotid artery intima-media thickness, and arterial stiffness, after adjusting for cardiovascular risk factors and MetS. Also, it has been shown that NAFLD is associated with cardiac alterations, including abnormal left ventricular structure and impaired diastolic function. The duration of these subclinical abnormalities may be important, because treatment to reverse the process is most likely to be effective earlier in the disease. In the present review, we examine the current evidence on the association between NAFLD and atherosclerosis as well as between NAFLD and cardiac dysfunction in the pediatric population, and discuss briefly the possible biological mechanisms linking NAFLD and cardiovascular changes. We also address the approach to treatment for this increasingly prevalent disease, which is likely to have an important future global impact on the burden of ill health, to prevent not only end-stage liver disease but also cardiovascular disease.

  20. EFFECTS OF HIGH DIETARY FAT ON SERUM CHOLESTEROL AND FATTY LIVER SYNDROME IN BROILERS

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    I. A. Qureshi, S.A. Khan, Z. I. Chaudhry, N. A. Mian1, M. Y. Tipu and M. F. Rai

    2004-10-01

    Full Text Available The present study was designed to evaluate the effects of high dietary fat on serum cholesterol and fatty liver syndrome in broilers. For this purpose, 90 day-old chicks were divided into three equal groups A, B and C. Group A acted as control. The birds of group B were fed on diet containing vegetable fat while birds of group C were fed on diet containing animal fat. It was observed that the serum cholestrol values in chicks of groups B and C were higher than those of the control group. Furthermore, the serum cholesterol value was higher in birds of group C than group B. Grossly, the livers of birds of groups B and C were enlarged, pale in colour, soft in consistency and were having petechial haemorrhages with fat and fibrin deposits. Histopathologically, livers of groups B and C showed fatty infiltration, haemorrhages and mass of eosinophilic materials. The vacuoles coalesced to create clear space that displaced the nucleus to the periphery of the cell. It was concluded that addition of dietary fat from animal and vegetable sources in the diet of broiler chicks not only resulted in increase in serum cholesterol but also in marked macroscopic and microscopic changes in liver.

  1. Fatty liver disease induced by perfluorooctane sulfonate: Novel insight from transcriptome analysis.

    Science.gov (United States)

    Fai Tse, William Ka; Li, Jing Woei; Kwan Tse, Anna Chung; Chan, Ting Fung; Hin Ho, Jeff Cheuk; Sun Wu, Rudolf Shiu; Chu Wong, Chris Kong; Lai, Keng Po

    2016-09-01

    Perfluorooctane sulfonate (PFOS), a hepato-toxicant and potential non-genotoxic carcinogen, was widely used in industrial and commercial products. Recent studies have revealed the ubiquitous occurrence of PFOS in the environment and in humans worldwide. The widespread contamination of PFOS in human serum raised concerns about its long-term toxic effects and its potential risks to human health. Using fatty liver mutant foie gras (fgr(-/-))/transport protein particle complex 11 (trappc11(-/-)) and PFOS-exposed wild-type zebrafish embryos as the study model, together with RNA sequencing and comparative transcriptomic analysis, we identified 499 and 1414 differential expressed genes (DEGs) in PFOS-exposed wild-type and trappc11 mutant zebrafish, respectively. Also, the gene ontology analysis on common deregulated genes was found to be associated with different metabolic processes such as the carbohydrate metabolic process, glycerol ether metabolic process, mannose biosynthetic process, de novo' (Guanosine diphosphate) GDP-l-fucose biosynthetic process, GDP-mannose metabolic process and galactose metabolic process. Ingenuity Pathway Analysis further highlighted that these deregulated gene clusters are closely related to hepatitis, inflammation, fibrosis and cirrhosis of liver cells, suggesting that PFOS can cause liver pathogenesis and non-alcoholic fatty liver disease in zebrafish. The transcriptomic alterations revealed may serve as biomarkers for the hepatotoxic effect of PFOS.

  2. Sex Differences in Long Chain Fatty Acid Utilization and Fatty Acid Binding Protein Concentration in Rat Liver

    Science.gov (United States)

    Ockner, Robert K.; Burnett, David A.; Lysenko, Nina; Manning, Joan A.

    1979-01-01

    those of male FABP. In contrast, the concentration of FABP, per milligram cytosolic protein, was 44% greater in female liver than in male, as indicated by measurement of [14C]oleate binding and of 280 nm OD in the FABP fraction of 105,000 g supernate after gel filtration chromatography. These experiments demonstrate profound sex differences in hepatocyte utilization of long chain fatty acids at concentrations within and below the physiological range, and suggest that these are attributable at least in part to corresponding differences in cytosolic FABP concentration. At higher FFA concentrations, sex differences in hepatocyte FFA utilization are virtually eliminated, suggesting that under these conditions, differences in FABP concentration are not rate determining. Sex differences in hepatic lipoprotein production may largely reflect these important differences in the initial stages of hepatocyte FFA utilization. PMID:447853

  3. Late nonalcoholic fatty liver disease with cirrhosis: a pathologic case of lost or mistaken identity.

    Science.gov (United States)

    Lefkowitch, Jay H; Morawski, John L

    2012-02-01

    Late-stage nonalcoholic fatty liver disease (NAFLD) may present clinically and/or pathologically as cryptogenic cirrhosis. The subject of this report, a middle-aged obese man with diabetes, underwent liver biopsy at the time of laparoscopic cholecystectomy because the liver surface appeared nodular and thickened. The biopsy showed relatively nondescript cirrhosis at initial low-power microscopic inspection, but glycogenated hepatocyte nuclei (consistent with diabetes), sparse macrovesicular fat, and very rare foci of residual mild steatohepatitis were later found. Slender fibrous septa (without significant inflammation and often enclosing microvessels) were present and interconnected to portal tracts. Immunostains for cytokeratin 7, ubiquitin, and glutamine synthetase provided additional histologic data supporting NAFLD as the cause of the cirrhosis in this case. A strategic pathologic approach is discussed, which can be utilized for the pathologic assessment of cirrhosis of unknown cause, particularly when late NAFLD is suspected.

  4. Breath biomarkers and non-alcoholic fatty liver disease: preliminary observations.

    Science.gov (United States)

    Solga, S F; Alkhuraishe, A; Cope, K; Tabesh, A; Clark, J M; Torbenson, M; Schwartz, P; Magnuson, T; Diehl, A M; Risby, T H

    2006-01-01

    Breath biomarkers have the potential to offer information that is similar to conventional clinical tests or they are entirely unique. Preliminary data support the use of breath biomarkers in the study of liver disease, in particular non-alcoholic fatty liver disease (NAFLD). It was evaluated whether breath ethanol, ethane, sulfur compounds and acetone would be associated with hepatic histopathology amongst morbidly obese patients presenting for bariatric surgery. Breath samples were collected during a preoperative visit and compared with liver biopsies obtained during the surgery. A Student's two-tailed t-test was used to compare differences between the two groups. Linear regression was used to analyse associations between the concentrations of breath molecules and independent predictor variables. It was found that breath ethanol, ethane and acetone can be useful biomarkers in patients with NAFLD. In particular, breath ethanol can be associated with hepatic steatosis, and breath acetone can be associated with non-alcoholic steatohepatitis.

  5. Management of dyslipidemia as a cardiovascular risk factor in individuals with nonalcoholic fatty liver disease.

    Science.gov (United States)

    Corey, Kathleen E; Chalasani, Naga

    2014-07-01

    Nonalcoholic fatty liver disease (NAFLD) is the most frequent cause of liver disease in the United States and is associated with an increased risk of cardiovascular disease (CVD) and cardiovascular (CV) mortality, independent of traditional cardiovascular risk factors. CVD is one of the most common causes of death among individuals with NAFLD and management of NAFLD must extend beyond liver disease to include CVD risk modification. Clinicians should assess CVD risk with the Framingham Risk Score and screen for CVD risk factors including dyslipidemia, diabetes mellitus, hypertension, tobacco use, and the metabolic syndrome. CVD risk factors, particularly dyslipidemia, require aggressive medical management to reduce the high risk of CVD events and death in individuals with NAFLD.

  6. 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.

  7. Pathogenesis of hepatocarcinogenesis in non-cirrhotic nonalcoholic fatty liver disease:Potential mechanistic pathways

    Institute of Scientific and Technical Information of China (English)

    Ryan; B; Perumpail; Andy; Liu; Robert; J; Wong; Aijaz; Ahmed; Stephen; A; Harrison

    2015-01-01

    Although hepatocellular carcinoma(HCC) primarily arises in the background of liver cirrhosis,the development of HCC in nonalcoholic fatty liver disease(NAFLD) without cirrhosis is increasingly recognized. The pathogenesis of NAFLD associated non-cirrhotic HCC is distinct from that of cirrhotic HCC because the metabolic syndrome(MS) along with obesity and insulin resistance(IR) underlie several unique mechanisms that promote tumorigenesis. IR associated with MS,NAFLD,and type 2 diabetes mellitus lead to the release of multiple pro-inflammatory cytokines,including tumor necrosis factor alpha,interleukin-6,leptin and resistin,as well as decreased amounts of adiponectin. These processes favor the development of hepatic steatosis and inflammation within the liver,which precede HCC development. Nevertheless,further investigation is necessary to elucidate the determinants for development of HCC in patients with NAFLD in the absence of cirrhosis.

  8. Chronic intermittent hypoxia causes hepatitis in a mouse model of diet-induced fatty liver.

    Science.gov (United States)

    Savransky, Vladimir; Bevans, Shannon; Nanayakkara, Ashika; Li, Jianguo; Smith, Philip L; Torbenson, Michael S; Polotsky, Vsevolod Y

    2007-10-01

    Obstructive sleep apnea (OSA) causes chronic intermittent hypoxia (CIH) during sleep. OSA is associated with nonalcoholic steatohepatitis (NASH) in obese individuals and may contribute to progression of nonalcoholic fatty liver disease from steatosis to NASH. The purpose of this study was to examine whether CIH induces inflammatory changes in the liver in mice with diet-induced hepatic steatosis. C57BL/6J mice (n = 8) on a high-fat, high-cholesterol diet were exposed to CIH for 6 mo and were compared with mice on the same diet exposed to intermittent air (control; n = 8). CIH caused liver injury with an increase in serum ALT (461 +/- 58 U/l vs. 103 +/- 16 U/l in the control group; P diet.

  9. Liver fatty acid binding protein (L-Fabp) modifies intestinal fatty acid composition and adenoma formation in ApcMin/+ mice

    OpenAIRE

    Dharmarajan, Sekhar; Newberry, Elizabeth P.; Montenegro, Grace; Nalbantoglu, ILKe; Davis, Victoria R.; Clanahan, Michael J.; Blanc, Valerie; Xie, Yan; Luo, Jianyang; Fleshman, James W.; Kennedy, Susan; Davidson, Nicholas O.

    2013-01-01

    Evidence suggests a relationship between dietary fat intake, obesity and colorectal cancer, implying a role for fatty acid (FA) metabolism in intestinal tumorigenesis that is incompletely understood. Liver fatty acid binding protein (L-Fabp), a dominant intestinal FA binding protein, regulates intestinal FA trafficking and metabolism and L-Fabp deletion attenuates diet-induced obesity. Here we examined whether changes in intestinal FA metabolism following L-Fabp deletion modify adenoma develo...

  10. 4Ps medicine of the fatty liver: the research model of predictive, preventive, personalized and participatory medicine-recommendations for facing obesity, fatty liver and fibrosis epidemics.

    Science.gov (United States)

    Trovato, Francesca Maria; Catalano, Daniela; Musumeci, Giuseppe; Trovato, Guglielmo M

    2014-01-01

    Relationship between adipose tissue and fatty liver, and its possible evolution in fibrosis, is supported by clinical and research experience. Given the multifactorial pathogenesis of non-alcoholic fatty liver disease (NAFLD), treatments for various contributory risk factors have been proposed; however, there is no single validated therapy or drug association recommended for all cases which can stand alone. Mechanisms, diagnostics, prevention and treatment of obesity, fatty liver and insulin resistance are displayed along with recommendations and position points. Evidences and practice can get sustainable and cost-benefit valuable outcomes by participatory interventions. These recommendations can be enhanced by comprehensive research projects, addressed to societal issues and innovation, market appeal and industry development, cultural acceptance and sustainability. The basis of participatory medicine is a greater widespread awareness of a condition which is both a disease and an easy documented and inclusive clue for associated diseases and unhealthy lifestyle. This model is suitable for addressing prevention and useful for monitoring improvement, worsening and adherence with non-invasive imaging tools which allow targeted approaches. The latter include health psychology and nutritional and physical exercise prescription expertise disseminated by continuous medical education but, more important, by concrete curricula for training undergraduate and postgraduate students. It is possible and recommended to do it by early formal teaching of ultrasound imaging procedures and of practical lifestyle intervention strategies, including approaches aimed to healthier fashion suggestions. Guidelines and requirements of research project funding calls should be addressed also to NAFLD and allied conditions and should encompass the goal of training by research and the inclusion of participatory medicine topics. A deeper awareness of ethics of competences in health professionals

  11. Effect of orlistat on periostin, adiponectin, inflammatory markers and ultrasound grades of fatty liver in obese NAFLD patients

    Science.gov (United States)

    Ali Khan, Rashid; Kapur, Prem; Jain, Abhinav; Farah, Farrukh; Bhandari, Uma

    2017-01-01

    Orlistat is recommended in the treatment of obesity, which is an independent risk factor for nonalcoholic fatty liver disease (NAFLD). The reported findings of orlistat in NAFLD are divisive. Recently, periostin is identified as an important regulatory molecule in the pathogenesis of obesity-induced fatty liver. Therefore, this study aimed to evaluate the potential effects of orlistat in the treatment of NAFLD. A 16-week prospective observational study was conducted, with obese NAFLD patient (n=77) receiving orlistat (120 mg capsules, three times a day) with hypocaloric diet or hypocaloric diet only. Grades of fatty liver were determined using ultrasound (US) echogenicity of liver; serum levels of periostin, adiponectin, tumor necrosis factor (TNF)-α and interleukin-6 were determined using ELISA kits at 0 and 16 weeks. Correlations of US grades of fatty liver with these biomarkers were also determined. Orlistat significantly reversed the US grades of fatty liver (P=0.016), decreased serum levels of periostin (P=0.030) and TNF-α (P=0.040), and increased serum adiponectin levels (P<0.001) when compared with hypocaloric diet only. Serum interleukin-6 levels were not found to be significantly different in both groups after the treatment. In the orlistat group, the degree of reduction in grades of fatty liver was found to be positively correlated with the changes in serum levels of periostin (rs=0.306, P=0.041) and adiponectin (rs=0.314, P=0.036), whereas the associations were insignificant with the change in serum levels of TNF-α (rs=0.053, P=0.729). Mild gastrointestinal side effects (20%) were reported in the orlistat group. In conclusion, orlistat is effective in the treatment of NAFLD patients without fibrosis. This study demonstrated a positive association between the reduction of fatty infiltration in the liver and the changes in serum levels of periostin and adiponectin in obese NAFLD patients. PMID:28260907

  12. 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;

    2016-01-01

    . 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.......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...

  13. Circulating sCD36 levels in patients with non-alcoholic fatty liver disease and controls

    DEFF Research Database (Denmark)

    Heebøll, Sara; Poulsen, Marianne Kjær; Ørnstrup, Marie Juul

    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....

  14. Effect of maternal micronutrients (folic acid, vitamin B12) and omega 3 fatty acids on liver fatty acid desaturases and transport proteins in Wistar rats.

    Science.gov (United States)

    Wadhwani, Nisha S; Manglekar, Rupali R; Dangat, Kamini D; Kulkarni, Asmita V; Joshi, Sadhana R

    2012-01-01

    A disturbed fatty acid metabolism increases the risk of adult non-communicable diseases. This study examines the effect of maternal micronutrients on the fatty acid composition, desaturase activity, mRNA levels of fatty acid desaturases and transport proteins in the liver. Pregnant female rats were divided into 6 groups at 2 levels of folic acid both in the presence and absence of vitamin B(12). The vitamin B(12) deficient groups were supplemented with omega 3 fatty acid. An imbalance of maternal micronutrients reduces liver docosahexaenoic acid, increases Δ5 desaturase activity but decreases mRNA levels, decreases Δ6 desaturase activity but not mRNA levels as compared to control. mRNA level of Δ5 desaturase reverts back to the levels of the control group as a result of omega 3 fatty acid supplementation. Our data for the first time indicates that maternal micronutrients differentially alter the activity and expression of fatty acid desaturases in the liver.

  15. Peroxisome proliferator activated receptor-γ in pathogenesis of experimental fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    Cai-Yan Zhao; Ling-Ling Jiang; Li Li; Zhuo-Jun Deng; Bao-Li Liang; Jian-Mei Li

    2004-01-01

    AIM: To study the expression of peroxisome proliferator activated receptor-γ (PPARγ) in the liver of rats with fatty liver disease (FLD) and to explore the role of PPARγ in the pathogenesis of FLD to provide the basis for using PPARγligand to treat patients with FLD.METHODS: Forty Wistar rats were divided into 4 groups of ten rats each randomly: normal group (group A), alcohol group (group B), fat-rich diet group (group C), alcohol and fat-rich diet group (group D). The rats were sacrificed at the end of the 16th week from the feeding day. Alanine aminotransferase (ALT), tumor necrosis factor-alfa (TNFα)in serum and malondialdehyde (MDA) in liver homogenate were determined; livers were collected for observing pathologic changes by HE, Sudan Ⅳ, Masson stain under microscope. The morphologic results were analyzed by picture quantitative analysis technique. The changes of ultrastructure were also examined under electron microscope.The expression of PPARγ in liver was detected by immunohistochemistry and RT-PCR. The correlations between the expression of PPARγ and biochemical indexes, and liver histology were analyzed.RESULTS: The steatosis, inflammation, necrosis and fibrosis were present in livers of different experimental groups,especially in livers of alcohol and fat-rich diet group. The content of immunodetectable PPARγ was decreasedremarkably in the livers of model rats (group B-D); the level in alcohol and fat-rich diet group (3.43±1.48) was significantly lower than that in normal group (18.34±3.73), alcohol group (8.82±2.52) and fat-rich diet group (11.73±2.51) (all P<0.01).The level of PPARγ mRNA was also lower in the livers of model rats (group B-D) than in'livers of controls. The expression of PPARγ in rat liver correlated negatively with the degree of its inflammation, necrosis and fibrosis, as well as the level of serum TNFα and the content of MDA in liver homogenates, but not with steatosis or serum ALT.CONCLUSION: Decreased expression

  16. Non-Alcoholic Fatty Liver Disease and Metabolic Syndrome after Liver Transplant.

    Science.gov (United States)

    Gitto, Stefano; Villa, Erica

    2016-04-02

    Liver transplant is the unique curative therapy for patients with acute liver failure or end-stage liver disease, with or without hepatocellular carcinoma. Increase of body weight,