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Sample records for acid-induced fatty liver

  1. Fatty acid induced remodeling within the human liver fatty acid-binding protein.

    Science.gov (United States)

    Sharma, Ashwani; Sharma, Amit

    2011-09-01

    We crystallized human liver fatty acid-binding protein (LFABP) in apo, holo, and intermediate states of palmitic acid engagement. Structural snapshots of fatty acid recognition, entry, and docking within LFABP support a heads-in mechanism for ligand entry. Apo-LFABP undergoes structural remodeling, where the first palmitate ingress creates the atomic environment for placement of the second palmitate. These new mechanistic insights will facilitate development of pharmacological agents against LFABP. PMID:21757748

  2. Fatty Acid Induced Remodeling within the Human Liver Fatty Acid-binding Protein*

    OpenAIRE

    Sharma, Ashwani; Sharma, Amit

    2011-01-01

    We crystallized human liver fatty acid-binding protein (LFABP) in apo, holo, and intermediate states of palmitic acid engagement. Structural snapshots of fatty acid recognition, entry, and docking within LFABP support a heads-in mechanism for ligand entry. Apo-LFABP undergoes structural remodeling, where the first palmitate ingress creates the atomic environment for placement of the second palmitate. These new mechanistic insights will facilitate development of pharmacological agents against ...

  3. Long-term fatty liver-induced insulin resistance in orotic acid-induced nonalcoholic fatty liver rats.

    Science.gov (United States)

    Han, Xiuqing; Liu, Chunhua; Xue, Yong; Wang, Jingfeng; Xue, Changhu; Yanagita, Teruyoshi; Gao, Xiang; Wang, Yuming

    2016-01-01

    We investigated whether fatty liver preceded insulin resistance or vice versa using a long-term orotic acid (OA)-induced nonalcoholic fatty liver disease (NAFLD) model without the confounding effects of obesity and hyperlipidemia and explored the role of the liver in insulin resistance. Male Wistar rats were fed with or without OA supplementation for 30, 60, and 90 days. The NAFLD group showed increased liver lipid at 30, 60, and 90 days; glucose intolerance was noted at 60 and 90 days. Furthermore, partial liver proteins and gene expressions related to upstream signaling of insulin were decreased. However, the liver glycogen content was elevated, and gluconeogenesis genes expressions were obviously decreased at 90 days. The occurrence of fatty liver preceded insulin resistance in OA-induced NAFLD without the interference of obesity and hyperlipidemia, and hepatic insulin resistance may not play a conclusive role in insulin resistance in this model. PMID:26775542

  4. Fatty acid-induced insulin resistance

    DEFF Research Database (Denmark)

    Le Marchand-Brustel, Y; Gual, P; Grémeaux, T;

    2003-01-01

    Insulin resistance, when combined with impaired insulin secretion, contributes to the development of type 2 diabetes. Insulin resistance is characterized by a decrease in the insulin effect on glucose transport in muscle and adipose tissue. Tyrosine phosphorylation of IRS-1 (insulin receptor...... substrate 1) and its binding to PI 3-kinase (phosphoinositide 3-kinase) are critical events in the insulin signalling cascade leading to insulin-stimulated glucose transport. Various studies have implicated lipids as a cause of insulin resistance in muscle. Elevated plasma fatty acid concentrations...... are associated with reduced insulin-stimulated glucose transport activity as a consequence of altered insulin signalling through PI 3-kinase. Modification of IRS-1 by serine phosphorylation could be one of the mechanisms leading to a decrease in IRS-1 tyrosine phosphorylation, PI 3-kinase activity and glucose...

  5. 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...

  6. 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

  7. 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.

  8. 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...

  9. 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 ...

  10. 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.

  11. 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...

  12. 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...

  13. 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...

  14. Nonalcoholic fatty liver disease.

    Science.gov (United States)

    Brunt, Elizabeth M; Wong, Vincent W-S; Nobili, Valerio; Day, Christopher P; Sookoian, Silvia; Maher, Jacquelyn J; Bugianesi, Elisabetta; Sirlin, Claude B; Neuschwander-Tetri, Brent A; Rinella, Mary E

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) is a disorder characterized by excess accumulation of fat in hepatocytes (nonalcoholic fatty liver (NAFL)); in up to 40% of individuals, there are additional findings of portal and lobular inflammation and hepatocyte injury (which characterize nonalcoholic steatohepatitis (NASH)). A subset of patients will develop progressive fibrosis, which can progress to cirrhosis. Hepatocellular carcinoma and cardiovascular complications are life-threatening co-morbidities of both NAFL and NASH. NAFLD is closely associated with insulin resistance; obesity and metabolic syndrome are common underlying factors. As a consequence, the prevalence of NAFLD is estimated to be 10-40% in adults worldwide, and it is the most common liver disease in children and adolescents in developed countries. Mechanistic insights into fat accumulation, subsequent hepatocyte injury, the role of the immune system and fibrosis as well as the role of the gut microbiota are unfolding. Furthermore, genetic and epigenetic factors might explain the considerable interindividual variation in disease phenotype, severity and progression. To date, no effective medical interventions exist that completely reverse the disease other than lifestyle changes, dietary alterations and, possibly, bariatric surgery. However, several strategies that target pathophysiological processes such as an oversupply of fatty acids to the liver, cell injury and inflammation are currently under investigation. Diagnosis of NAFLD can be established by imaging, but detection of the lesions of NASH still depend on the gold-standard but invasive liver biopsy. Several non-invasive strategies are being evaluated to replace or complement biopsies, especially for follow-up monitoring. PMID:27188459

  15. 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

  16. 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

  17. 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.

  18. 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-

  19. 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-

  20. 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...

  1. Glycyrrhetinic acid-induced permeability transition in rat liver mitochondria.

    Science.gov (United States)

    Salvi, Mauro; Fiore, Cristina; Armanini, Decio; Toninello, Antonio

    2003-12-15

    Glycyrrhetinic acid, a hydrolysis product of one of the main constituents of licorice, the triterpene glycoside of glycyrrhizic acid, when added to rat liver mitochondria at micromolar concentrations induces swelling, loss of membrane potential, pyridine nucleotide oxidation, and release of cytochrome c and apoptosis inducing factor. These changes are Ca(2+) dependent and are prevented by cyclosporin A, bongkrekic acid, and N-ethylmaleimide. All these observations indicate that glycyrrhetinic acid is a potent inducer of mitochondrial permeability transition and can trigger the pro-apoptotic pathway. PMID:14637195

  2. 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

  3. 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

    2016-01-01

    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. PMID:27485440

  4. 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. PMID:23603006

  5. 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.

  6. Non-alcoholic fatty liver disease.

    Science.gov (United States)

    Pearce, Lynne

    2016-08-24

    Essential facts Non-alcoholic fatty liver disease (NAFLD) is an excess of fat in the liver that is not the result of excessive alcohol consumption or other secondary causes, such as hepatitis C. According to the National Institute for Health and Care Excellence, fatty liver - steatosis - affects between 20% and 30% of the population and its prevalence is increasing. PMID:27641564

  7. 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

  8. 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.

  9. 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.

  10. Lipotoxic effect of p21 on free fatty acid-induced steatosis in L02 cells.

    Directory of Open Access Journals (Sweden)

    Jie-wei Wang

    Full Text Available Nonalcoholic fatty liver disease (NAFLD is increasingly regarded as a hepatic manifestation of metabolic syndrome. Though with high prevalence, the mechanism is poorly understood. This study aimed to investigate the effects of p21 on free fatty acid (FFA-induced steatosis in L02 cells. We therefore analyzed the L02 cells with MG132 and siRNA treatment for different expression of p21 related to lipid accumulation and lipotoxicity. Cellular total lipid was stained by Oil Red O, while triglyceride content, cytotoxicity assays, lipid peroxidation markers and anti-oxidation levels were measured by enzymatic kits. Treatment with 1 mM FFA for 48 hr induced magnificent intracellular lipid accumulation and increased oxidative stress in p21 overload L02 cells compared to that in p21 knockdown L02 cells. By increasing oxidative stress and peroxidation, p21 accelerates FFA-induced lipotoxic effect in L02 cells and might provide information about potentially new targets for drug development and treatments of NAFLD.

  11. 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.

  12. 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.

  13. 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...

  14. 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

  15. 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

    2010-01-01

    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. PMID:20606731

  16. 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.

  17. 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

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

    Science.gov (United States)

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

    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. CONCLUSION: Sch B inhibits FFA-induced steatosis in L-02 cells by, at least in part, reversing the up-regulation of ADRP and SREBP-1. PMID:21633637

  19. 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.

  20. 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...

  1. Fatty acid-inducible ANGPTL4 governs lipid metabolic response to exercise

    OpenAIRE

    Catoire, Milène; Alex, Sheril; Paraskevopulos, Nicolas; Mattijssen, Frits; Evers-van Gogh, Inkie; Schaart, Gert; Jeppesen, Jacob; Kneppers, Anita; Mensink, Marco; Voshol, Peter J.; Olivecrona, Gunilla; Tan, Nguan Soon; Hesselink, Matthijs K. C.; Berbée, Jimmy F.; Rensen, Patrick C N

    2014-01-01

    Physical exercise causes profound changes in energy metabolism in humans. In this study we show that resting skeletal muscle has a crucial role in the metabolic response to acute exercise. During endurance exercise, selective induction of the protein angiopoietin-like 4 (ANGPTL4) in nonexercising muscle reduces local fatty acid uptake, presumably to prevent fat overload, while directing fatty acids to the active skeletal muscle as fuel. Our data thus suggest that nonexercising muscle has a ke...

  2. Polyunsaturated Branched-Chain Fatty Acid Geranylgeranoic Acid Induces Unfolded Protein Response in Human Hepatoma Cells.

    Directory of Open Access Journals (Sweden)

    Chieko Iwao

    Full Text Available The acyclic diterpenoid acid geranylgeranoic acid (GGA has been reported to induce autophagic cell death in several human hepatoma-derived cell lines; however, the molecular mechanism for this remains unknown. In the present study, several diterpenoids were examined for ability to induce XBP1 splicing and/or lipotoxicity for human hepatoma cell lines. Here we show that three groups of diterpenoids emerged: 1 GGA, 2,3-dihydro GGA and 9-cis retinoic acid induce cell death and XBP1 splicing; 2 all-trans retinoic acid induces XBP1 splicing but little cell death; and 3 phytanic acid, phytenic acid and geranylgeraniol induce neither cell death nor XBP1 splicing. GGA-induced ER stress/ unfolded protein response (UPR and its lipotoxicity were both blocked by co-treatment with oleic acid. The blocking activity of oleic acid for GGA-induced XBP1 splicing was not attenuated by methylation of oleic acid. These findings strongly suggest that GGA at micromolar concentrations induces the so-called lipid-induced ER stress response/UPR, which is oleate-suppressive, and shows its lipotoxicity in human hepatoma cells.

  3. 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.

  4. 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.

  5. Nutritional therapy for nonalcoholic fatty liver disease.

    Science.gov (United States)

    Dongiovanni, Paola; Lanti, Claudia; Riso, Patrizia; Valenti, Luca

    2016-03-01

    Following the epidemics of obesity, nonalcoholic fatty liver disease (NAFLD) has become the leading cause of liver disease in western countries. NAFLD is the hepatic manifestation of metabolic syndrome and may progress to cirrhosis and hepatocellular carcinoma. To date, there are no approved drugs for the treatment of NAFLD, and the main clinical recommendation is lifestyle modification, including increase of physical activity and the adoption of a healthy eating behavior. In this regard, studies aimed to elucidate the effect of dietary interventions and the mechanisms of action of specific food bioactives are urgently needed. The present review tries to summarize the most recent data evidencing the effects of nutrients and dietary bioactive compounds intake (i.e., long-chain PUFA, Vitamin E, Vitamin D, minerals and polyphenols) on the modulation of molecular mechanisms leading to fat accumulation, oxidative stress, inflammation and liver fibrosis in NAFLD patients. PMID:26895659

  6. 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.

  7. 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...

  8. 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

  9. 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.

  10. 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.

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

    Directory of Open Access Journals (Sweden)

    Ali Koskela

    2016-05-01

    Full Text Available 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.

  12. 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

    2016-01-01

    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. PMID:27187449

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

    International Nuclear Information System (INIS)

    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)

  14. 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)

  15. 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.

  16. 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

  17. 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...

  18. Trans fatty acids induce vascular inflammation and reduce vascular nitric oxide production in endothelial cells.

    Directory of Open Access Journals (Sweden)

    Naomi G Iwata

    Full Text Available Intake of trans fatty acids (TFA, which are consumed by eating foods made from partially hydrogenated vegetable oils, is associated with a higher risk of cardiovascular disease. This relation can be explained by many factors including TFA's negative effect on endothelial function and reduced nitric oxide (NO bioavailability. In this study we investigated the effects of three different TFA (2 common isomers of C18 found in partially hydrogenated vegetable oil and a C18 isomer found from ruminant-derived-dairy products and meat on endothelial NF-κB activation and nitric oxide (NO production. Human endothelial cells were treated with increasing concentrations of Elaidic (trans-C18:1 (9 trans, Linoelaidic (trans-C18:2 (9 trans, 12 trans, and Transvaccenic (trans-C18:1 (11 trans for 3 h. Both Elaidic and Linoelaidic acids were associated with increasing NF-κB activation as measured by IL-6 levels and phosphorylation of IκBα, and impairment of endothelial insulin signaling and NO production, whereas Transvaccenic acid was not associated with these responses. We also measured superoxide production, which has been hypothesized to be necessary in fatty acid-dependent activation of NF-κB. Both Elaidic acid and Linoelaidic acid are associated with increased superoxide production, whereas Transvaccenic acid (which did not induce inflammatory responses did not increase superoxide production. We observed differential activation of endothelial superoxide production, NF-κB activation, and reduction in NO production by different C18 isomers suggesting that the location and number of trans double bonds effect endothelial NF-κB activation.

  19. 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.

  20. 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

  1. 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

  2. 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.

  3. 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

  4. 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.

  5. 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.

  6. The effects of pantethine on fatty liver and fat distribution.

    Science.gov (United States)

    Osono, Y; Hirose, N; Nakajima, K; Hata, Y

    2000-01-01

    Although the prognosis of fatty liver depends on its causes, we feel from our clinical experience that fatty liver with hypertriglyceridemia has a good prognosis and responds well to treatment. In this study, 600 mg/day of pantethine was administered to 16 outpatients with fatty liver and hypertriglyceridemia for six months or longer to examine whether the drug improved fatty liver using abdominal plain computed tomography (CT). Nine of the 16-pantethine patients were no longer diagnosed as having fatty liver after the study period. An chi2 test indicated the significant disappearance of fatty liver. At the same time, the visceral fat calculated from the CT image passing the umbilical region was also significantly reduced. On the contrary, the subcutaneous fat area tended to increase, so the ratio of the visceral-to-subcutaneous fat area was reduced significantly. This indicates triglycerides may be pooled in the body as hepato-visceral fat and subcutaneous fat, and that pantethine may transfer fat from the liver and viscera to the subcutaneous tissue. This suggests that visceral fat deposition and fatty liver occurring with hypertriglyceridemia may have a common basis, probably excessive matrixes, and that pantethine may simultaneously improve the two conditions. PMID:11425046

  7. Liver Fatty acid binding protein (L-Fabp) modulates murine stellate cell activation and diet induced nonalcoholic fatty liver disease

    OpenAIRE

    Chen, Anping; Tang, Youcai; Davis, Victoria; Hsu, Fong-Fu; Kennedy, Susan M; Song, Haowei; Turk, John; Brunt, Elizabeth M.; Newberry, Elizabeth P.; Davidson, Nicholas O.

    2013-01-01

    Activation of hepatic stellate cells (HSCs) is crucial to the development of fibrosis in nonalcoholic fatty liver disease. Quiescent HSCs contain lipid droplets (LDs), whose depletion upon activation induces a fibrogenic gene program. Here we show that liver fatty acid-binding protein (L-Fabp), an abundant cytosolic protein that modulates fatty acid (FA) metabolism in enterocytes and hepatocytes also modulates HSC FA utilization and in turn regulates the fibrogenic program. L-Fabp expression ...

  8. Gut microbiome and nonalcoholic fatty liver diseases.

    Science.gov (United States)

    Zhu, Lixin; Baker, Robert D; Baker, Susan S

    2015-01-01

    We review recent findings and hypotheses on the roles of gut microbiome in the pathogenesis of nonalcoholic fatty liver diseases (NAFLD). Microbial metabolites and cell components contribute to the development of hepatic steatosis and inflammation, key components of nonalcoholic steatohepatitis (NASH), the severe form of NAFLD. Altered gut microbiome can independently cause obesity, the most important risk factor for NAFLD. This capability is attributed to short-chain fatty acids (SCFAs), major gut microbial fermentation products. SCFAs account for a large portion of caloric intake of the host, and they enhance intestinal absorption by activating GLP-2 signaling. However, elevated SCFAs may be an adaptive measure to suppress colitis, which could be a higher priority than imbalanced calorie intake. The microbiome of NASH patients features an elevated capacity for alcohol production. The pathomechanisms for alcoholic steatohepatitis may apply to NASH. NAFLD/NASH is associated with elevated Gram-negative microbiome and endotoxemia. However, many NASH patients exhibited normal serum endotoxin indicating that endotoxemia is not required for the pathogenesis of NASH. These observations suggest that microbial intervention may benefit NAFLD/NASH patients. However, very limited effects were observed using traditional probiotic species. Novel probiotic therapy based on NAFLD/NASH specific microbial composition represents a promising future direction. PMID:25310763

  9. 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

  10. 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

  11. 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.

  12. 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.

  13. 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...

  14. 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...

  15. 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.

  16. 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.

  17. 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

  18. 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

  19. Free fatty acid-induced PP2A hyperactivity selectively impairs hepatic insulin action on glucose metabolism.

    Directory of Open Access Journals (Sweden)

    Thomas Galbo

    Full Text Available In type 2 Diabetes (T2D free fatty acids (FFAs in plasma are increased and hepatic insulin resistance is "selective", in the sense that the insulin-mediated decrease of glucose production is blunted while insulin's effect on stimulating lipogenesis is maintained. We investigated the molecular mechanisms underlying this pathogenic paradox. Primary rat hepatocytes were exposed to palmitate for twenty hours. To establish the physiological relevance of the in vitro findings, we also studied insulin-resistant Zucker Diabetic Fatty (ZDF rats. While insulin-receptor phosphorylation was unaffected, activation of Akt and inactivation of the downstream targets Glycogen synthase kinase 3α (Gsk3α and Forkhead box O1 (FoxO1 was inhibited in palmitate-exposed cells. Accordingly, dose-response curves for insulin-mediated suppression of the FoxO1-induced gluconeogenic genes and for de novo glucose production were right shifted, and insulin-stimulated glucose oxidation and glycogen synthesis were impaired. In contrast, similar to findings in human T2D, the ability of insulin to induce triglyceride (TG accumulation and transcription of the enzymes that catalyze de novo lipogenesis and TG assembly was unaffected. Insulin-induction of these genes could, however, be blocked by inhibition of the atypical PKCs (aPKCs. The activity of the Akt-inactivating Protein Phosphatase 2A (PP2A was increased in the insulin-resistant cells. Furthermore, inhibition of PP2A by specific inhibitors increased insulin-stimulated activation of Akt and phosphorylation of FoxO1 and Gsk3α. Finally, PP2A mRNA levels were increased in liver, muscle and adipose tissue, while PP2A activity was increased in liver and muscle tissue in insulin-resistant ZDF rats. In conclusion, our findings indicate that FFAs may cause a selective impairment of insulin action upon hepatic glucose metabolism by increasing PP2A activity.

  20. 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.

  1. 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...

  2. 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...

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

    OpenAIRE

    Attar, Bashar M.; Van Thiel, David H.

    2013-01-01

    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) flu...

  4. 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

  5. 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

  6. Effect of Whole-Body X-Irradiation of the Synthesis of Individual Fatty Acids in Liver Slices from Normal and Fasted Rats

    DEFF Research Database (Denmark)

    Hansen, Heinz Johs. Max; Hansen, Lisbeth Grænge; Faber, M.

    1965-01-01

    (1) Using (2-14C) acetate and (1-14C) butyrate as precursors, rat-liver fatty acids were synthesized in vitro and assayed by paper chromatography. (2) Whole-body x-irradiation induced a change in the synthetic pattern of hepatic fatty acids towards a relatively enhanced synthesis of palmitic acid....... (3) X-irradiation and fasting seem to have opposite effects on fatty-acid synthesis. X-irradiation counteracts the drop in total synthesis and the relatively enhanced synthesis of palmitoleic acid induced by fasting. The relative enhancement of palmitic-acid synthesis mentioned under (2) stands...

  7. Liver Fatty Acid Binding Protein and Obesity

    OpenAIRE

    Atshaves, B.P.; Martin, G G; Hostetler, H.A.; McIntosh, A.L.; Kier, A B; Schroeder, F.

    2010-01-01

    While low levels of unesterified long chain fatty acids (LCFAs) are normal metabolic intermediates of dietary and endogenous fat, LCFAs are also potent regulators of key receptors/enzymes, and at high levels become toxic detergents within the cell. Elevated levels of LCFAs are associated with diabetes, obesity, and metabolic syndrome. Consequently, mammals evolved fatty acid binding proteins (FABPs) that bind/sequester these potentially toxic free fatty acids in the cytosol and present them f...

  8. Mitochondrial genome depletion in human liver cells abolishes bile acid-induced apoptosis: role of the Akt/mTOR survival pathway and Bcl-2 family proteins.

    Science.gov (United States)

    Marin, Jose J G; Hernandez, Alicia; Revuelta, Isabel E; Gonzalez-Sanchez, Ester; Gonzalez-Buitrago, Jose M; Perez, Maria J

    2013-08-01

    Acute accumulation of bile acids in hepatocytes may cause cell death. However, during long-term exposure due to prolonged cholestasis, hepatocytes may develop a certain degree of chemoresistance to these compounds. Because mitochondrial adaptation to persistent oxidative stress may be involved in this process, here we have investigated the effects of complete mitochondrial genome depletion on the response to bile acid-induced hepatocellular injury. A subline (Rho) of human hepatoma SK-Hep-1 cells totally depleted of mitochondrial DNA (mtDNA) was obtained, and bile acid-induced concentration-dependent activation of apoptosis/necrosis and survival signaling pathways was studied. In the absence of changes in intracellular ATP content, Rho cells were highly resistant to bile acid-induced apoptosis and partially resistant to bile acid-induced necrosis. In Rho cells, both basal and bile acid-induced generation of reactive oxygen species (ROS), such as hydrogen peroxide and superoxide anion, was decreased. Bile acid-induced proapoptotic signals were also decreased, as evidenced by a reduction in the expression ratios Bax-α/Bcl-2, Bcl-xS/Bcl-2, and Bcl-xS/Bcl-xL. This was mainly due to a downregulation of Bax-α and Bcl-xS. Moreover, in these cells the Akt/mTOR pathway was constitutively activated in a ROS-independent manner and remained similarly activated in the presence of bile acid treatment. In contrast, ERK1/2 activation was constitutively reduced and was not activated by incubation with bile acids. In conclusion, these results suggest that impaired mitochondrial function associated with mtDNA alterations, which may occur in liver cells during prolonged cholestasis, may activate mechanisms of cell survival accounting for an enhanced resistance of hepatocytes to bile acid-induced apoptosis. PMID:23597504

  9. 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.

  10. 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

  11. Computed tomography in the diagnosis of fatty liver

    International Nuclear Information System (INIS)

    Fifty-three histologically proved cases of various diffuse liver diseases were studied on their computed tomography numbers (CTN). The machine used was the Ohio Nuclear's Delta Scanner 50 FS type and CTN was expressed by the Hounsfield unit (H). The mean was 66.6 +- 2.6 H for normal control (N), 63.3 +- 6.0 H for chronic hepatitis (CH), 61.8 +- 7.0 H for liver cirrhosis (LC), 44.4 +- 10.6 H for fatty infiltration (FI). There were no significant differences among them except FI group. As N group were all above 60 H and CH and LC groups were all above 50 H, CTN below 60 H could suggest chronic liver disease or fatty infiltration and CTN below 50 H could strongly suggest fatty infiltration. In eleven cases where total lipid content of the liver could be biochemically determined by the sulfophospho-vanillin reagent, a relation of total lipid content to CTN was studied. As a result, a significant correlation existed between them (r = -0.89; p < 0.001). If the diagnostic criterion for the fatty liver was set at total lipid content above 100 mg/g wet liver, CT criterion was estimated at CTN below 48 H from the regression formula. (author)

  12. 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...

  13. 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

  14. 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.

  15. 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. PMID:27063268

  16. 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.

  17. Mechanisms of disease progression in nonalcoholic fatty liver disease.

    Science.gov (United States)

    Jou, Janice; Choi, Steve S; Diehl, Anna Mae

    2008-11-01

    Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of hepatic pathology, ranging from simple steatosis (also called nonalcoholic fatty liver or NAFL) in its most benign form, to cirrhosis in its most advanced form. Nonalcoholic steatohepatitis (NASH) is an intermediate level of hepatic pathology. Hepatocyte accumulation of triglyceride is a hallmark of NAFL and NASH, but this sometimes subsides once cirrhosis has developed. Triglyceride storage per se is not hepatotoxic. Rather, it is a marker of increased exposure of hepatocytes to potentially toxic fatty acids. NAFL progresses to NASH when adaptive mechanisms that protect hepatocytes from fatty acid-mediated lipotoxicity become overwhelmed and rates of hepatocyte death begin to outstrip mechanisms that normally regenerate dead hepatocytes. This triggers repair responses that involve activation of hepatic stellate cells to myofibroblasts. The myofibroblasts generate excessive matrix and produce factors that stimulate expansion of liver progenitor populations. The progenitor cells produce chemokines to attract various kinds of inflammatory cells to the liver. They also differentiate to replace the dead hepatocytes. The intensity of these repair responses generally parallel the degree of hepatocyte death, resulting in variable distortion of the hepatic architecture with fibrosis, infiltrating immune cells, and regenerating epithelial nodules. As in other types of chronic liver injury, cirrhosis ensues in patients with NAFLD when repair is extreme and sustained, but ultimately unsuccessful, at reconstituting healthy hepatic epithelia. PMID:18956293

  18. 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

  19. 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....

  20. 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.

  1. 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. PMID:26620035

  2. 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.

  3. 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.

  4. 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.

  5. Computer image analysis of toxic fatty degeneration in rat liver.

    Science.gov (United States)

    Stetkiewicz, J; Zieliński, K; Stetkiewicz, I; Koktysz, R

    1989-01-01

    Fatty degeneration of the liver is one of the most frequently observed pathological changes in the experimental estimation of the toxicity of chemical compounds. The intensity of this kind of damage is most often detected by means of a generally accepted scale of points, whereas the classification is performed according to the subjective "feeling" of the pathologist. In modern pathological diagnostics, computer analysis of images is used to perform an objective estimation of the degree of damage to various organs. In order to check the usefulness of this kind of method, comparative biochemical and morphometrical studies were undertaken in trichloroethylene (TRI)-induced fatty degeneration of the liver. TRI was administered to rats intragastrically, in single doses: 1/2; 1/3; 1/4; 1/6 and 1/18 DL50. 24 hours after the administration, the animals were sacrificed. The content of triglycerides in the liver was determined according to Folch et al. (1956). Simple lipids in the histochemical samples were detected by means of staining with a lipotropic, Fat Red 7B. The area of fatty degeneration was estimated in the microscopic samples by the use of an automatic image analyser IBAS 2000 (Kontron). The morphometrical data concerning the area of fatty degeneration in the liver amplified a high degree of correlation with the content of triglycerides (r = 0.89) and the dose of TRI (r = 0.96). The degree of correlation between the biochemical data and the dose of TRI was 0.88. The morphometrical studies performed have proved to be of great use in estimating the degree of fatty degeneration in the liver. This method enables precise, quantitative measuring of this sort of liver damage in the material prepared for routine histopathological analysis. It requires, however, the application of a specialized device for quantitative image analysis.

  6. Hepatic Glucagon Action Is Essential for Exercise-Induced Reversal of Mouse Fatty Liver

    OpenAIRE

    Berglund, Eric D.; Lustig, Daniel G.; Baheza, Richard A.; Hasenour, Clinton M.; Lee-Young, Robert S.; Donahue, E. Patrick; Lynes, Sara E.; Swift, Larry L.; Charron, Maureen J; Damon, Bruce M.; Wasserman, David H

    2011-01-01

    OBJECTIVE Exercise is an effective intervention to treat fatty liver. However, the mechanism(s) that underlie exercise-induced reductions in fatty liver are unclear. Here we tested the hypothesis that exercise requires hepatic glucagon action to reduce fatty liver. RESEARCH DESIGN AND METHODS C57BL/6 mice were fed high-fat diet (HFD) and assessed using magnetic resonance, biochemical, and histological techniques to establish a timeline for fatty liver development over 20 weeks. Glucagon recep...

  7. Fatty liver and medium chain triglyceride (MCT) diet.

    OpenAIRE

    Beverley, D; Arthur, R.

    1988-01-01

    A 12 year old boy with intractable epilepsy developed fatty infiltration of the liver after three years' treatment on the medium chain triglyceride (MCT) diet. This was not associated with any hepatic dysfunction and resolved after discontinuing the diet. Three of four other patients on the same diet had evidence of hepatic steatosis.

  8. 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…

  9. 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.

  10. 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.

  11. 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.

  12. 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...... up time was 16.7 (0.2-21.9) years in the non-alcoholic and 9.2 (0.6-23.1) years in the alcoholic group. Systematic data collection was carried out by review of all medical records. All members of the study cohort were linked through their unique personal identification number to the National Registry...... 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...

  13. Role of scintigraphy in focally abnormal sonograms of fatty livers

    Energy Technology Data Exchange (ETDEWEB)

    Lisbona, R.; Mishkin, S.; Derbekyan, V.; Novales-Diaz, J.A.; Roy, A.; Sanders, L.

    1988-06-01

    Fatty infiltration of the liver may cause a range of focal abnormalities on hepatic sonography which may simulate hepatic nodular lesions. Discrete deposits of fat or islands of normal tissue which are uninvolved by fatty infiltration may stand out as potential space-occupying lesions on the sonograms. Twelve patients with such focally abnormal ultrasound images were referred for liver scintigraphy with /sup 133/Xe and /sup 99m/Tc colloidal SPECT studies to clarify the issue. These examinations helped identify, in nine of 12 patients, the innocent nature of the sonographic abnormalities which were simply related to the fat deposition process. Further, (/sup 99m/Tc)RBC scans defined the additional pathologic process in three patients in whom actual space-occupying lesions were indeed present in the liver. Scintigraphy has an important role to play in the understanding of focal hepatic ultrasound abnormalities particularly in unsuspected hepatic steatosis.

  14. 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.

  15. 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...

  16. 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

  17. 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.

  18. 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

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

    International Nuclear Information System (INIS)

    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 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.

  20. 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.

  1. 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.

  2. Nonalcoholic Fatty Liver Disease: Lipids and Insulin Resistance.

    Science.gov (United States)

    Berk, Paul D; Verna, Elizabeth C

    2016-05-01

    Obesity and its major comorbidities, including type 2 diabetes mellitus, nonalcoholic fatty liver disease (NAFLD), obesity cardiomyopathy, and certain cancers, have caused life expectancy in the United States to decline in recent years. Obesity is the increased accumulation of triglycerides (TG), which are synthesized from glycerol and long-chain fatty acids (LCFA) throughout the body. LCFA enter adipocytes, hepatocytes, and cardiomyocytes via specific, facilitated transport processes. Metabolism of increased cellular TG content in obesity may lead to comorbidities such as NAFLD and cardiomyopathy. Better understanding of LCFA transport processes may lead to successful treatment of obesity and NAFLD. PMID:27063267

  3. 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.

  4. 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

  5. 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

  6. 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.

  7. 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.)

  8. 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; Zheng, Yuanyuan; Wang, Fan; Xia, Yujing; Chen, Kan; Liu, Tong; Lu, Jie; Zhou, Yingqun; Guo, Chuanyong

    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

  9. 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

  10. 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).

  11. 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.

  12. 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

  13. Ketogenic Diet, but Not Polyunsaturated Fatty Acid Diet, Reduces Spontaneous Seizures in Juvenile Rats with Kainic Acid-induced Epilepsy

    OpenAIRE

    Dustin, Simone M.; Stafstrom, Carl E

    2016-01-01

    Background and Purpose: The high-fat, low-carbohydrate ketogenic diet (KD) is effective in many cases of drug-resistant epilepsy, particularly in children. In the classic KD, fats consist primarily of long-chain saturated triglycerides. Polyunsaturated fatty acids (PUFAs), especially the n-3 type, decrease neuronal excitability and provide neuroprotection; pilot human studies have raised the possibility of using PUFAs to control seizures in patients. Methods: To determine the relative roles o...

  14. Role and mechanism of uncoupling protein 2 on the fatty acid-induced dysfunction of pancreatic alpha cells in vitro

    Institute of Scientific and Technical Information of China (English)

    SU Jie-ying; LI Hong-liang; YANG Wen-ying; XIAO Jian-zhong; DU Rui-qin; SHEN Xiao-xia; CAI Zhe; ZHANG Lan; SHU Jun

    2010-01-01

    Background Uncoupling protein (UCP) 2 is related to the dysfunction of beta cells induced by fatty acids. However,whether UCP2 has similar effects on alpha cell is still not clear. This study aimed to investigate the effects of UCP2 and its possible mechanisms in lipotoxicity-induced dysfunction of pancreatic alpha cells.Methods The alpha TC1-6 cells were used in this study to evaluate the effects of palmitate and/or UCP2 inhibit factors on the glucagon secretory function, glucagon content, the glucagon mRNA level and the nitrotyrosine level in the supernatant. Meantime, the expression levels of UCP2 and peroxisome proliferator-activated receptor-γ coactivator-1 alpha (PGC-1 alpha) were measured by real-time reverse transcription polymerase chain reaction (RT-PCR) and Western blotting. Furthermore, the possible relationship between UCP2 and insulin signal transduction pathway was analyzed.Results Palmitate stimulated alpha cell glucagon secretion and the expression of UCP2 and PGC-1 alpha, which could be partially decreased by the inhibition of UCP2. Palmitate increased nitrotyrosine level and suppressed insulin signal transduction pathway in alpha cells. Inhibition of UCP2 influenced the effects of free fatty acid on alpha cells and may relate to glucagon secretion.Conclusion UCP2 played an important role on alpha cell dysfunction induced by free fatty acid in vitro, which may be related to its effects on oxidative stress and insulin signal transduction pathway.

  15. Dyslipidemia in Patients with Nonalcoholic Fatty Liver Disease

    OpenAIRE

    Chatrath, Hemant; Vuppalanchi, Raj; Chalasani, Naga

    2012-01-01

    Patients with nonalcoholic fatty liver disease (NAFLD) often have dyslipidemia along with other features of metabolic syndrome such as obesity, diabetes mellitus, and hypertension. The dyslipidemia in NAFLD is characterized by increased serum triglycerides, increased small, dense low-density lipoprotein (LDL nontype A) particles, and low high-density lipoprotein (HDL) cholesterol. The pathogenesis of dyslipidemia in NAFLD is not well understood, but it is likely related to hepatic overproduct...

  16. 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...... 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....

  17. 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.

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

    Science.gov (United States)

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

    2015-10-28

    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. PMID:26523205

  19. 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.

  20. 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...

  1. 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.

  2. 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).

  3. 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.

  4. 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.

  5. 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.

  6. Fatty Acid Binding Protein 5 Modulates Docosahexaenoic Acid-Induced Recovery in Rats Undergoing Spinal Cord Injury.

    Science.gov (United States)

    Figueroa, Johnny D; Serrano-Illan, Miguel; Licero, Jenniffer; Cordero, Kathia; Miranda, Jorge D; De Leon, Marino

    2016-08-01

    Omega-3 polyunsaturated fatty acids (n-3 PUFAs) promote functional recovery in rats undergoing spinal cord injury (SCI). However, the precise molecular mechanism coupling n-3 PUFAs to neurorestorative responses is not well understood. The aim of the present study was to determine the spatiotemporal expression of fatty acid binding protein 5 (FABP5) after contusive SCI and to investigate whether this protein plays a role in n-3 PUFA-mediated functional recovery post-SCI. We found that SCI resulted in a robust spinal cord up-regulation in FABP5 mRNA levels (556 ± 187%) and protein expression (518 ± 195%), when compared to sham-operated rats, at 7 days post-injury (dpi). This upregulation coincided with significant alterations in the metabolism of fatty acids in the injured spinal cord, as revealed by metabolomics-based lipid analyses. In particular, we found increased levels of the n-3 series PUFAs, particularly docosahexaenoic acid (DHA; 22:6 n-3) and eicosapentaenoic acid (EPA; 20:5 n-3) at 7 dpi. Animals consuming a diet rich in DHA and EPA exhibited a significant upregulation in FABP5 mRNA levels at 7 dpi. Immunofluorescence showed low basal FABP5 immunoreactivity in spinal cord ventral gray matter NeuN(+) neurons of sham-operated rats. SCI resulted in a robust induction of FABP5 in glial (GFAP(+), APC(+), and NG2(+)) and precursor cells (DCX(+), nestin(+)). We found that continuous intrathecal administration of FABP5 silencing with small interfering RNA (2 μg) impaired spontaneous open-field locomotion post-SCI. Further, FABP5 siRNA administration hindered the beneficial effects of DHA to ameliorate functional recovery at 7 dpi. Altogether, our findings suggest that FABP5 may be an important player in the promotion of cellular uptake, transport, and/or metabolism of DHA post-SCI. Given the beneficial roles of n-3 PUFAs in ameliorating functional recovery, we propose that FABP5 is an important contributor to basic repair mechanisms in the

  7. 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.

  8. Grape seed extract to improve liver function in patients with nonalcoholic fatty liver change

    Directory of Open Access Journals (Sweden)

    Khoshbaten Manouchehr

    2010-01-01

    Full Text Available Background/Aim: Therapeutic interventions in nonalcoholic fatty liver disease are limited, while anti-oxidative materials have shown benefits in animal models. This study aimed to evaluate grape seed extract as an anti-oxidative material in this process. Therapeutic effects of grape seed extract were evaluated in comparison to vitamin C in a double-blind setting. Materials and Methods: Fifteen patients were enrolled in each group. Liver function tests were done; also, grade of steatosis and pattern of echogenicity of the liver were determined. Patients were followed up by the same evaluation repeated in first, second and third months. Results: Mean age ± standard deviation was 43.2 ± 10.3 years. Grape seed extract (GSE significantly improved the grade of fatty liver change; and resulted in significant decrease in alanine aminotransferase in patients receiving the concentrate compared to those receiving vitamin C independently, from the initial grade of steatosis. Conclusions: This study describes the beneficial effect of using grape seed extract for three months in patients with nonalcoholic fatty liver disease. These results may improve with a longer period of follow-up.

  9. Nonalcoholic fatty liver disease: Synopsis of current developments.

    Science.gov (United States)

    Onyekwere, C A; Ogbera, A O; Samaila, A A; Balogun, B O; Abdulkareem, F B

    2015-01-01

    Non-alcoholic fatty liver disease (NAFLD) which is defined as the accumulation of fat>5% of liver weight is increasingly becoming an important cause of chronic liver disease. This article tries to chronicle advances that have occurred in the understanding of the pathogenesis, pathology as well as the management of this disease. We have done a Medline search on published work on the subject and reviewed major conference proceedings in the preceding years. The Pathogenesis involves a multi-hit process in which increased accumulation of triglycerides in face of insulin resistance results in increased susceptibility to inflammatory damage mediated by increased expression of inflammatory cytokines and adipokines, oxidative stress and mitochondrial dysfunction, endoplasmic reticulum stress and gut derived endotoxemia. An interplay of multiple metabolic genetic expression and environmental factors however determine which patient with NAFLD will progress from simple steatosis to non-alcoholic steatohepatitis (NASH) and liver cirrhosis. The minimum criteria for diagnosis of NASH are steatosis, ballooning and lobular inflammation; fibrosis is not required. The NASH Clinical Research Network (CRN), histological scoring system is used to grade and stage the disease for standardization. The management of NAFLD consists of treating liver disease as well as associated metabolic co-morbidities such as obesity, hyperlipidaemia, insulin resistance and type 2 diabetes mellitus (T2DM). Patient education is important as their insight and commitment is pivotal, and lifestyle modification is the first line of treatment. Improvement in liver histology in non-diabetic NASH patients has been reported with use of Vitamin E. Other liver-related therapies under investigations include pentoxyfiylins, Caspar inhibitors, Resveratrol as well as probiotics. The prognosis (both overall and liver-related mortality) for simple steatosis is not different from that of the general population however

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

    Directory of Open Access Journals (Sweden)

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  12. Relationship between Chemotherapy and Tamoxifen with Incidence of Fatty Liver in Women with Breast Cancer

    Directory of Open Access Journals (Sweden)

    Sh Keyhanian

    2013-08-01

    Full Text Available Introduction: Fatty liver disease is characterized by deposition of fat droplets in the liver of patients. According to some epidemiological studies; BMI, amount of fat intake from foods and high central fat are risk factors of breast cancer. This issue is one of the factors that cause high incidence of fatty liver in patients with breast cancer. Methods: In this cross-sectional descriptive study, all patients with breast cancer were evaluated who referred to Imam Sajjad hospital of Ramsar during 2008 - 2011. After initial review, 100 patients were enrolled. Those who were treated by chemotherapy underwent abdominal Sonography for evaluation of fatty liver. Also, those patients who also received tamoxifen in addition to chemotherapy, underwent abdominal ultrasonography 6 months after taking tamoxifen. After that, relationship between treatment of breast cancer and fatty liver in studied patients was evaluated based on obtained information. Results: The study results revealed that after chemotherapy, 30 (30% patients were reported to have fatty liver. Out of 70 people that after chemotherapy did not have fatty liver, 62 patients received tamoxifen; and after taking tamoxifen, 45.2% developed fatty liver. Using Chi Square test, there was a significant relationship between fatty liver after receiving tamoxifen, hyperlipidemia (p=0.011 and getting overweight (P =0.017. Conclusion: As the findings indicated, treatment of breast cancer especially with tamoxifen is associated with increased risk of fatty liver, especially in women who have hyperlipidemia and are overweight.

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

    Energy Technology Data Exchange (ETDEWEB)

    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

    Energy Technology Data Exchange (ETDEWEB)

    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. 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.

  17. Molecular classification of fatty liver by high-throughput profiling of protein post-translational modifications.

    Science.gov (United States)

    Urasaki, Yasuyo; Fiscus, Ronald R; Le, Thuc T

    2016-04-01

    We describe an alternative approach to classifying fatty liver by profiling protein post-translational modifications (PTMs) with high-throughput capillary isoelectric focusing (cIEF) immunoassays. Four strains of mice were studied, with fatty livers induced by different causes, such as ageing, genetic mutation, acute drug usage, and high-fat diet. Nutrient-sensitive PTMs of a panel of 12 liver metabolic and signalling proteins were simultaneously evaluated with cIEF immunoassays, using nanograms of total cellular protein per assay. Changes to liver protein acetylation, phosphorylation, and O-N-acetylglucosamine glycosylation were quantified and compared between normal and diseased states. Fatty liver tissues could be distinguished from one another by distinctive protein PTM profiles. Fatty liver is currently classified by morphological assessment of lipid droplets, without identifying the underlying molecular causes. In contrast, high-throughput profiling of protein PTMs has the potential to provide molecular classification of fatty liver.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  20. Chronically Elevated Levels of Short-Chain Fatty Acids Induce T Cell-Mediated Ureteritis and Hydronephrosis.

    Science.gov (United States)

    Park, Jeongho; Goergen, Craig J; HogenEsch, Harm; Kim, Chang H

    2016-03-01

    Short-chain fatty acids (SCFAs) are major products of gut microbial fermentation and profoundly affect host health and disease. SCFAs generate IL-10(+) regulatory T cells, which may promote immune tolerance. However, SCFAs can also induce Th1 and Th17 cells upon immunological challenges and, therefore, also have the potential to induce inflammatory responses. Because of the seemingly paradoxical SCFA activities in regulating T cells, we investigated, in depth, the impact of elevated SCFA levels on T cells and tissue inflammation in mice. Orally administered SCFAs induced effector (Th1 and Th17) and regulatory T cells in ureter and kidney tissues, and they induced T cell-mediated ureteritis, leading to kidney hydronephrosis (hereafter called acetate-induced renal disease, or C2RD). Kidney hydronephrosis in C2RD was caused by ureteral obstruction, which was, in turn, induced by SCFA-induced inflammation in the ureteropelvic junction and proximal ureter. Oral administration of all major SCFAs, such as acetate, propionate, and butyrate, induced the disease. We found that C2RD development is dependent on mammalian target of rapamycin activation, T cell-derived inflammatory cytokines such as IFN-γ and IL-17, and gut microbiota. Young or male animals were more susceptible than old or female animals, respectively. However, SCFA receptor (GPR41 or GPR43) deficiency did not affect C2RD development. Thus, SCFAs, when systemically administered at levels higher than physiological levels, cause dysregulated T cell responses and tissue inflammation in the renal system. The results provide insights into the immunological and pathological effects of chronically elevated SCFAs. PMID:26819206

  1. Nonesterified Fatty Acid-Induced Endoplasmic Reticulum Stress in Cattle Cumulus Oocyte Complexes Alters Cell Metabolism and Developmental Competence.

    Science.gov (United States)

    Sutton-McDowall, Melanie L; Wu, Linda L Y; Purdey, Malcolm; Abell, Andrew D; Goldys, Ewa M; MacMillan, Keith L; Thompson, Jeremy G; Robker, Rebecca L

    2016-01-01

    Reduced oocyte quality has been associated with poor fertility of high-performance dairy cows during peak lactation, due to negative energy balance. We examined the role of nonesterified fatty acids (NEFAs), known to accumulate within follicular fluid during under- and overnutrition scenarios, in causing endoplasmic reticulum (ER) stress of in vitro maturated cattle cumulus-oocyte complexes (COCs). NEFA concentrations were: palmitic acid (150 μM), oleic acid (200 μM), and steric acid (75 μM). Abattoir-derived COCs were randomly matured for 24 h in the presence of NEFAs and/or an ER stress inhibitor, salubrinal. Total and hatched blastocyst yields were negatively impacted by NEFA treatment compared with controls, but this was reversed by salubrinal. ER stress markers, activating transcription factor 4 (Atf4) and heat shock protein 5 (Hspa5), but not Atf6, were significantly up-regulated by NEFA treatment within whole COCs but reversed by coincubation with salubrinal. Likewise, glucose uptake and lactate production, measured in spent medium samples, showed a similar pattern, suggesting that cumulus cell metabolism is sensitive to NEFAs via an ER stress-mediated process. In contrast, while mitochondrial DNA copy number was recovered in NEFA-treated oocytes, oocyte autofluorescence of the respiratory chain cofactor, FAD, was lower following NEFA treatment of COCs, and this was not reversed by salubrinal, suggesting the negative impact was via reduced mitochondrial function. These results reveal the significance of NEFA-induced ER stress on bovine COC developmental competence, revealing a potential therapeutic target for improving oocyte quality during peak lactation. PMID:26658709

  2. 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.

  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. 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

  5. Clinical usefulness of biochemical markers of liver fibrosis in patients with nonalcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    Hiroshi Sakugawa; Fukunori Kinjo; Atsushi Saito; Tomofumi Nakayoshi; Kasen Kobashigawa; Tsuyoshi Yamashiro; Tatsuji Maeshiro; Satoru Miyagi; Joji Shiroma; Akiyo Toyama; Tomokuni Nakayoshi

    2005-01-01

    AIM: Nonalcoholic steatohepatitis (NASH) is a severe form of nonalcoholic fatty liver disease (NAFLD), and progresses to the end stage of liver disease. Biochemical markers of liver fibrosis are strongly associated with the degree of histological liver fibrosis in patients with chronic liver disease.However, data are few on the usefulness of markers in NAFLD patients. The aim of this study was to identify better noninvasive predictors of hepatic fibrosis, with special focus on markers of liver fibrosis, type Ⅵ collagen 7S domain and hyaluronic acid.METHODS: One hundred and twelve patients with histologically proven NAFLD were studied.RESULTS: The histological stage of NAFLD correlated with several clinical and biochemical variables, the extent of hepatic fibrosis and the markers of liver fibrosis were relatively strong associated. The best cutoff values to detect NASH were assessed by using receiver operating characteristic analysis: type Ⅵ collagen 7S domain ≥5.0 ng/mL, hyaluronic acid ≥43 ng/mL. Both markers had a high positive predictive value: type Ⅵ collagen 7S domain, 86% and hyaluronic acid,92%. Diagnostic accuracies of these markers were evaluated to detect severe fibrosis. Both markers showed high negative predictive values: type Ⅵ collagen 7S domain (≥5.0 ng/mL),84% and hyaluronic acid (≥50 ng/mL), 78%, and were significantly and independently associated with the presence of NASH or severe fibrosis by logistic regression analysis.CONCLUSION: Both markers of liver fibrosis are useful in discriminating NASH from fatty liver alone or patients with severe fibrosis from patients with non-severe fibrosis.

  6. Association between retinal artery lesions and nonalcoholic fatty liver disease

    OpenAIRE

    Yang, Wen; Xu, Hongtao; Yu, Xiaohong; Wang, Yuzhu

    2015-01-01

    Objective Retinal artery lesions have been reported to be a risk marker of morbidity and mortality for cardiovascular and cerebrovascular diseases in various study populations. Nonalcoholic fatty liver disease (NAFLD) is also a risk factor for cardiovascular disease. However, the relationship between retinal artery lesions and NAFLD is less certain. Methods Data were obtained from 2,454 patients who attended their annual health examination (2,143 males and 311 females, aged 62.34 ± 10.03 year...

  7. Update on Berberine in Nonalcoholic Fatty Liver Disease

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    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.

  8. Current Pharmacologic Therapy for Nonalcoholic Fatty Liver Disease.

    Science.gov (United States)

    Ganesh, Swaytha; Rustgi, Vinod K

    2016-05-01

    Weight loss, regular exercise, and diet composition modification seem to improve biochemical and histologic abnormalities. Other therapies directed at insulin resistance, oxidative stress, cytoprotection, and fibrosis may also offer benefits. Insulin sensitizers and vitamin E seem to be the most promising; however, they cause side effects. A multifaceted approach of lifestyle modifications, weight loss, and pharmacotherapy can be used in combination, but no single treatment approach has proved universally applicable to the general population with nonalcoholic steatohepatitis (NASH). Continuous clinical and preclinical studies on existing and potential drugs are needed to improve treatment of nonalcoholic fatty liver disease/NASH. PMID:27063274

  9. Non-alcoholic fatty liver disease and type 2 diabetes mellitus: The liver disease of our age?

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    Firneisz, Gábor

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease that might affect up to one-third of the adult population in industrialised countries. NAFLD incorporates histologically and clinically different non-alcoholic entities; fatty liver (NAFL, steatosis hepatis) and steatohepatitis (NASH-characterised by hepatocyte ballooning and lobular inflammation ± fibrosis) might progress to cirrhosis and rarely to hepatocellular cancer. NAFL increasingly affects children (paediatric preval...

  10. 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.

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

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    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

  12. 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.

  13. 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.

  14. Treatment of Non-Alcoholic Fatty Liver Disease.

    Science.gov (United States)

    Scherer, Antonia; Dufour, Jean-François

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of conditions from steatosis to cirrhosis and hepatocellular carcinoma. Steatosis is a benign reversible condition, which does not need treatment. Cirrhosis and hepatocellular carcinoma are the end stages of any chronic liver disease and do not have etiology-specific treatments. In this chapter, we will review treatment options for non-alcoholic steatohepatitis, which is the progressive form of NAFLD. Basically there are 2 strategies, the first of which is to address lifestyle and the second to use medication. The first approach is the most physiologic, the least expensive, but is also the most difficult to implement. The second approach, which should help patients who failed the first approach, is at the advanced clinical research stage. PMID:27548081

  15. [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.

  16. Autophagy and Non-Alcoholic Fatty Liver Disease

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    Vanessa J. Lavallard

    2014-01-01

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

  17. Essential phospholipids in fatty liver: a scientific update

    Science.gov (United States)

    Gundermann, Karl-Josef; Gundermann, Simon; Drozdzik, Marek; Mohan Prasad, VG

    2016-01-01

    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-phosphatidyl)choline 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, anti apoptotic, 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. PMID:27217791

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

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    Luca Valenti

    2013-01-01

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

  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. 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.

  1. 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.

  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. PMID:26345909

  3. 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.

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

    Directory of Open Access Journals (Sweden)

    Bashar M. Attar

    2013-01-01

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

  5. Current concepts and management approaches in nonalcoholic fatty liver disease.

    Science.gov (United States)

    Attar, Bashar M; Van Thiel, David H

    2013-01-01

    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. PMID:23576902

  6. 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. PMID:25851235

  7. Effect of curcuma longa L. on fatty liver induced by oxytetracycline in albino rats.

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    Eman G.E. Helal , Samia M. Abd El-Wahab and Ghada A. Zedan

    2011-04-01

    Full Text Available Background: Curcuma longa has been shown to be a potent anti-inflammatory, antioxidant and anticarcinogenic agent. The present investigation aimed at examining the possible potential protective effect of curcuma 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 resulting in steatosis and c curcuma treated group; which was treated with curcuma ( 0.4 % of diet 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 and c drug protection group; which received curcuma 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, ALT, AST, GGT, LDH, total protein, albumin, globulin, urea and creatinine while HDL cholesterol and A/G ratio were significantly decreased compared to control group. Histopathological changes were detected in liver tissue of fatty liver rats. The treatment with curcuma ameliorated the biochemical parameters and histological changes. The pre-treatment with curcuma before the induction of fatty liver also ameliorated the results but they did not turn back to the normal values. Conclusion: It is recommend to using curcuma as diet additive for fatty liver patients or those people who have hyperlipidemic family history.

  8. Gut-liver axis and probiotics: Their role in non-alcoholic fatty liver disease

    OpenAIRE

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

    2014-01-01

    The incidence of obesity and its related conditions, including non-alcoholic fatty liver disease (NAFLD), has dramatically increased in all age groups worldwide. Given the health consequences of these conditions, and the subsequent economic burden on healthcare systems, their prevention and treatment have become major priorities. Because standard dietary and lifestyle changes and pathogenically-oriented therapies (e.g., antioxidants, oral hypoglycemic agents, and lipid-lowering agents) often ...

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

    Science.gov (United States)

    Stål, Per

    2015-10-21

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

  10. 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. 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.

  12. Histopathological differences utilizing the nonalcoholic fatty liver disease activity score criteria in diabetic (type 2 diabetes mellitus) and non-diabetic patients with nonalcoholic fatty liver disease

    OpenAIRE

    Puchakayala, Bharat K; Verma, Siddharth; Kanwar, Pushpjeet; Hart, John; Sanivarapu, Raghavendra R; Mohanty, Smruti R

    2015-01-01

    AIM: To study clinical and histopathological features of nonalcoholic fatty liver disease (NAFLD) in patients with and without type 2 diabetes mellitus (T2DM) using updated nonalcoholic steatohepatitis clinical research network (NASH-CRN) grading system.

  13. 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.

  14. 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).

  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. 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.

  17. Nonalcoholic fatty liver disease and obstructive sleep apnea.

    Science.gov (United States)

    Aron-Wisnewsky, Judith; Clement, Karine; Pépin, Jean-Louis

    2016-08-01

    Obstructive sleep apnea (OSA) and more importantly its hallmark, chronic intermittent hypoxia (CIH), are established factors in the pathogenesis and exacerbation of nonalcoholic fatty liver disease (NAFLD). This has been clearly demonstrated in rodent models exposed to intermittent hypoxia, and strong evidence now also exists in both paediatric and adult human populations. OSA and CIH induce insulin-resistance and dyslipidemia which are involved in NAFLD physiopathogenesis. CIH increases the expression of the hypoxia inducible transcription factor HIF1α and that of downstream genes involved in lipogenesis, thereby increasing β-oxidation and consequently exacerbating liver oxidative stress. OSA also disrupts the gut liver axis, increasing intestinal permeability and with a possible role of gut microbiota in the link between OSA and NAFLD. OSA patients should be screened for NAFLD and vice versa those with NAFLD for OSA. To date there is no evidence that treating OSA with continuous positive airway pressure (CPAP) will improve NAFLD but it might at least stabilize and slow its progression. Nevertheless, these multimorbid patients should be efficiently treated for all their metabolic co-morbidities and be encouraged to follow weight stabilization or weight loss programs and physical activity life style interventions. PMID:27324067

  18. 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.

  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. 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. PMID:26151226

  1. 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

  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. 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.

  5. 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.

  6. 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

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

    Science.gov (United States)

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

    2015-01-01

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

  8. 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.

  9. 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.

  10. 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.

  11. Liver fatty acid-binding protein binds monoacylglycerol in vitro and in mouse liver cytosol.

    Science.gov (United States)

    Lagakos, William S; Guan, Xudong; Ho, Shiu-Ying; Sawicki, Luciana Rodriguez; Corsico, Betina; Kodukula, Sarala; Murota, Kaeko; Stark, Ruth E; Storch, Judith

    2013-07-01

    Liver fatty acid-binding protein (LFABP; FABP1) is expressed both in liver and intestinal mucosa. Mice null for LFABP were recently shown to have altered metabolism of not only fatty acids but also monoacylglycerol, the two major products of dietary triacylglycerol hydrolysis (Lagakos, W. S., Gajda, A. M., Agellon, L., Binas, B., Choi, V., Mandap, B., Russnak, T., Zhou, Y. X., and Storch, J. (2011) Am. J. Physiol. Gastrointest. Liver Physiol. 300, G803-G814). Nevertheless, the binding and transport of monoacylglycerol (MG) by LFABP are uncertain, with conflicting reports in the literature as to whether this single chain amphiphile is in fact bound by LFABP. In the present studies, gel filtration chromatography of liver cytosol from LFABP(-/-) mice shows the absence of the low molecular weight peak of radiolabeled monoolein present in the fractions that contain LFABP in cytosol from wild type mice, indicating that LFABP binds sn-2 MG in vivo. Furthermore, solution-state NMR spectroscopy demonstrates two molecules of sn-2 monoolein bound in the LFABP binding pocket in positions similar to those found for oleate binding. Equilibrium binding affinities are ∼2-fold lower for MG compared with fatty acid. Finally, kinetic studies examining the transfer of a fluorescent MG analog show that the rate of transfer of MG is 7-fold faster from LFABP to phospholipid membranes than from membranes to membranes and occurs by an aqueous diffusion mechanism. These results provide strong support for monoacylglycerol as a physiological ligand for LFABP and further suggest that LFABP functions in the efficient intracellular transport of MG. PMID:23658011

  12. Liver Fatty Acid-binding Protein Binds Monoacylglycerol in Vitro and in Mouse Liver Cytosol*

    Science.gov (United States)

    Lagakos, William S.; Guan, Xudong; Ho, Shiu-Ying; Sawicki, Luciana Rodriguez; Corsico, Betina; Kodukula, Sarala; Murota, Kaeko; Stark, Ruth E.; Storch, Judith

    2013-01-01

    Liver fatty acid-binding protein (LFABP; FABP1) is expressed both in liver and intestinal mucosa. Mice null for LFABP were recently shown to have altered metabolism of not only fatty acids but also monoacylglycerol, the two major products of dietary triacylglycerol hydrolysis (Lagakos, W. S., Gajda, A. M., Agellon, L., Binas, B., Choi, V., Mandap, B., Russnak, T., Zhou, Y. X., and Storch, J. (2011) Am. J. Physiol. Gastrointest. Liver Physiol. 300, G803–G814). Nevertheless, the binding and transport of monoacylglycerol (MG) by LFABP are uncertain, with conflicting reports in the literature as to whether this single chain amphiphile is in fact bound by LFABP. In the present studies, gel filtration chromatography of liver cytosol from LFABP−/− mice shows the absence of the low molecular weight peak of radiolabeled monoolein present in the fractions that contain LFABP in cytosol from wild type mice, indicating that LFABP binds sn-2 MG in vivo. Furthermore, solution-state NMR spectroscopy demonstrates two molecules of sn-2 monoolein bound in the LFABP binding pocket in positions similar to those found for oleate binding. Equilibrium binding affinities are ∼2-fold lower for MG compared with fatty acid. Finally, kinetic studies examining the transfer of a fluorescent MG analog show that the rate of transfer of MG is 7-fold faster from LFABP to phospholipid membranes than from membranes to membranes and occurs by an aqueous diffusion mechanism. These results provide strong support for monoacylglycerol as a physiological ligand for LFABP and further suggest that LFABP functions in the efficient intracellular transport of MG. PMID:23658011

  13. Hormesis in Cholestatic Liver Disease; Preconditioning with Low Bile Acid Concentrations Protects against Bile Acid-Induced Toxicity

    OpenAIRE

    Verhaag, Esther M.; Manon Buist-Homan; Martijn Koehorst; Groen, Albert K; Han Moshage; Klaas Nico Faber

    2016-01-01

    Introduction Cholestasis is characterized by accumulation of bile acids and inflammation, causing hepatocellular damage. Still, liver damage markers are highest in acute cholestasis and drop when this condition becomes chronic, indicating that hepatocytes adapt towards the hostile environment. This may be explained by a hormetic response in hepatocytes that limits cell death during cholestasis. Aim To investigate the mechanisms that underlie the hormetic response that protect hepatocytes agai...

  14. Preventive Effects of Dexmedetomidine on the Liver in a Rat Model of Acid-Induced Acute Lung Injury

    Directory of Open Access Journals (Sweden)

    Velat Şen

    2014-01-01

    Full Text Available The aim of this study was to examine whether dexmedetomidine improves acute liver injury in a rat model. Twenty-eight male Wistar albino rats weighing 300–350 g were allocated randomly to four groups. In group 1, normal saline (NS was injected into the lungs and rats were allowed to breathe spontaneously. In group 2, rats received standard ventilation (SV in addition to NS. In group 3, hydrochloric acid was injected into the lungs and rats received SV. In group 4, rats received SV and 100 µg/kg intraperitoneal dexmedetomidine before intratracheal HCl instillation. Blood samples and liver tissue specimens were examined by biochemical, histopathological, and immunohistochemical methods. Acute lung injury (ALI was found to be associated with increased malondialdehyde (MDA, total oxidant activity (TOA, oxidative stress index (OSI, and decreased total antioxidant capacity (TAC. Significantly decreased MDA, TOA, and OSI levels and significantly increased TAC levels were found with dexmedetomidine injection in group 4 (P<0.05. The highest histologic injury scores were detected in group 3. Enhanced hepatic vascular endothelial growth factor (VEGF expression and reduced CD68 expression were found in dexmedetomidine group compared with the group 3. In conclusion, the presented data provide the first evidence that dexmedetomidine has a protective effect on experimental liver injury induced by ALI.

  15. Preventive effects of dexmedetomidine on the liver in a rat model of acid-induced acute lung injury.

    Science.gov (United States)

    Sen, Velat; Güzel, Abdulmenap; Şen, Hadice Selimoğlu; Ece, Aydın; Uluca, Unal; Söker, Sevda; Doğan, Erdal; Kaplan, İbrahim; Deveci, Engin

    2014-01-01

    The aim of this study was to examine whether dexmedetomidine improves acute liver injury in a rat model. Twenty-eight male Wistar albino rats weighing 300-350 g were allocated randomly to four groups. In group 1, normal saline (NS) was injected into the lungs and rats were allowed to breathe spontaneously. In group 2, rats received standard ventilation (SV) in addition to NS. In group 3, hydrochloric acid was injected into the lungs and rats received SV. In group 4, rats received SV and 100 µg/kg intraperitoneal dexmedetomidine before intratracheal HCl instillation. Blood samples and liver tissue specimens were examined by biochemical, histopathological, and immunohistochemical methods. Acute lung injury (ALI) was found to be associated with increased malondialdehyde (MDA), total oxidant activity (TOA), oxidative stress index (OSI), and decreased total antioxidant capacity (TAC). Significantly decreased MDA, TOA, and OSI levels and significantly increased TAC levels were found with dexmedetomidine injection in group 4 (P < 0.05). The highest histologic injury scores were detected in group 3. Enhanced hepatic vascular endothelial growth factor (VEGF) expression and reduced CD68 expression were found in dexmedetomidine group compared with the group 3. In conclusion, the presented data provide the first evidence that dexmedetomidine has a protective effect on experimental liver injury induced by ALI. PMID:25165710

  16. The Severity of Fatty Liver Disease Relating to Metabolic Abnormalities Independently Predicts Coronary Calcification

    OpenAIRE

    Ying-Hsiang Lee; Yih-Jer Wu; Chuan-Chuan Liu; Charles Jia-Yin Hou; Hung-I Yeh; Cheng-Ho Tsai; Shou-Chuan Shih; Chung-Lieh Hung

    2011-01-01

    Background. Nonalcoholic fatty liver disease (NAFLD) is one of the metabolic disorders presented in liver. The relationship between severity of NAFLD and coronary atherosclerotic burden remains largely unknown. Methods and Materials. We analyzed subjects undergoing coronary calcium score evaluation by computed tomography (MDCT) and fatty liver assessment using abdominal ultrasonography. Framingham risk score (FRS) and metabolic risk score (MRS) were obtained in all subjects. A graded, semiqua...

  17. Resveratrol inhibits nonalcoholic fatty liver disease in rats

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    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.

  18. Oxidative Stress and Oval Cell Accumulation in Mice and Humans with Alcoholic and Nonalcoholic Fatty Liver Disease

    OpenAIRE

    Roskams, Tania; Yang, Shi Qi; Koteish, Aymen; Durnez, Anne; DeVos, Rita; Huang, Xiawen; Achten, Ruth; Verslype, Chris; Diehl, Anna Mae

    2003-01-01

    In animals, the combination of oxidative liver damage and inhibited hepatocyte proliferation increases the numbers of hepatic progenitors (oval cells). We studied different murine models of fatty liver disease and patients with nonalcoholic fatty liver disease or alcoholic liver disease to determine whether oval cells increase in fatty livers and to clarify the mechanisms for this response. To varying degrees, all mouse models exhibit excessive hepatic mitochondrial production of H2O2, a know...

  19. 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

  20. OSAS-related inflammatory mechanisms of liver injury in nonalcoholic fatty liver disease.

    Science.gov (United States)

    Paschetta, Elena; Belci, Paola; Alisi, Anna; Liccardo, Daniela; Cutrera, Renato; Musso, Giovanni; Nobili, Valerio

    2015-01-01

    Obstructive sleep apnoea syndrome (OSAS) is a common sleep disorder, affecting over 4% of the general population, and is associated with metabolic syndrome and cardiovascular disease, independent of obesity and traditional risk factors. OSAS has been recently connected to nonalcoholic fatty liver disease (NAFLD), the most common chronic liver disease in the world, which can be found in 30% of the general adult population. Several studies suggest that the chronic intermittent hypoxia (CIH) of OSAS patients may per se trigger liver injury, inflammation, and fibrogenesis, promoting NAFLD development and the progression from steatosis to steatohepatitis, cirrhosis, and hepatocellular carcinoma. In NAFLD patients, liver disease may be caused by hypoxia both indirectly by promoting inflammation and insulin resistance and directly by enhancing proinflammatory cytokine production and metabolic dysregulation in liver cells. In this review, we focus on molecular mechanisms linking OSAS to NAFLD, including hypoxia inducible factor (HIF), nuclear factor kappa B (NF-κB), YKL-40, unfolded protein response, and hypoxic adipose tissue inflammation, which all could provide novel potential therapeutic approaches for the management of NAFLD patients with OSAS. PMID:25873773

  1. OSAS-Related Inflammatory Mechanisms of Liver Injury in Nonalcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Elena Paschetta

    2015-01-01

    Full Text Available Obstructive sleep apnoea syndrome (OSAS is a common sleep disorder, affecting over 4% of the general population, and is associated with metabolic syndrome and cardiovascular disease, independent of obesity and traditional risk factors. OSAS has been recently connected to nonalcoholic fatty liver disease (NAFLD, the most common chronic liver disease in the world, which can be found in 30% of the general adult population. Several studies suggest that the chronic intermittent hypoxia (CIH of OSAS patients may per se trigger liver injury, inflammation, and fibrogenesis, promoting NAFLD development and the progression from steatosis to steatohepatitis, cirrhosis, and hepatocellular carcinoma. In NAFLD patients, liver disease may be caused by hypoxia both indirectly by promoting inflammation and insulin resistance and directly by enhancing proinflammatory cytokine production and metabolic dysregulation in liver cells. In this review, we focus on molecular mechanisms linking OSAS to NAFLD, including hypoxia inducible factor (HIF, nuclear factor kappa B (NF-κB, YKL-40, unfolded protein response, and hypoxic adipose tissue inflammation, which all could provide novel potential therapeutic approaches for the management of NAFLD patients with OSAS.

  2. 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

  3. 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.

  4. 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.

  5. 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

    2016-08-21

    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

  6. Pathophysiology and Mechanisms of Nonalcoholic Fatty Liver Disease.

    Science.gov (United States)

    Haas, Joel T; Francque, Sven; Staels, Bart

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of liver disorders characterized by abnormal hepatic fat accumulation, inflammation, and hepatocyte dysfunction. Importantly, it is also closely linked to obesity and the metabolic syndrome. NAFLD predisposes susceptible individuals to cirrhosis, hepatocellular carcinoma, and cardiovascular disease. Although the precise signals remain poorly understood, NAFLD pathogenesis likely involves actions of the different hepatic cell types and multiple extrahepatic signals. The complexity of this disease has been a major impediment to the development of appropriate metrics of its progression and effective therapies. Recent clinical data place increasing importance on identifying fibrosis, as it is a strong indicator of hepatic disease-related mortality. Preclinical modeling of the fibrotic process remains challenging, particularly in the contexts of obesity and the metabolic syndrome. Future studies are needed to define the molecular pathways determining the natural progression of NAFLD, including key determinants of fibrosis and disease-related outcomes. This review covers the evolving concepts of NAFLD from both human and animal studies. We discuss recent clinical and diagnostic methods assessing NAFLD diagnosis, progression, and outcomes; compare the features of genetic and dietary animal models of NAFLD; and highlight pharmacological approaches for disease treatment. PMID:26667070

  7. 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.

  8. 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

  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. '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

  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. Effect of Cichorium intybus L. 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**

    2011-10-01

    Full Text Available Background: Fatty liver is now one of the most common diseases in Egypt. 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.The current investigation was carried out to examine the possible potential therapeutic and protective effects of Cichorium intybus (chicory 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 resulting in steatosis and c chicory treated group; which was treated with chicory water extract (70 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 (120mg/kg for three consecutive days and c drug protection group; which received chicory 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 with chicory ameliorated most of the evaluated biochemical parameters and improved the

  14. 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.

  15. (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. PMID:26732447

  16. (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.

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

    International Nuclear Information System (INIS)

    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.

  18. 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.

  19. 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

  20. Coffee consumption and nonalcoholic fatty liver onset: a prospective study in the general population.

    Science.gov (United States)

    Zelber-Sagi, Shira; Salomone, Federico; Webb, Muriel; Lotan, Roni; Yeshua, Hanny; Halpern, Zamir; Santo, Erwin; Oren, Ran; Shibolet, Oren

    2015-03-01

    Retrospective studies suggest that coffee consumption may exert beneficial effects in patients with nonalcoholic fatty liver; however, prospective data supporting a protective role on liver steatosis development are lacking. In this study, we aimed to evaluate the association between coffee consumption and fatty liver onset in the general population. The analysis was performed both in a cross-sectional cohort (n = 347) and, prospectively, in a subcohort of patients without fatty liver at baseline and followed-up for 7 years (n = 147). Fatty liver was diagnosed with abdominal ultrasound and liver steatosis was quantified noninvasively by hepatorenal index (HRI) and SteatoTest, whereas FibroTest was used to assess fibrosis degree. A structured questionnaire on coffee consumption was administrated during a face-to-face interview. Neither the incidence nor the prevalence of fatty liver according to ultrasonography, SteatoTest, and the HRI was associated with coffee consumption. In the cross-sectional study, high coffee consumption was associated with a lower proportion of clinically significant fibrosis ≥ F2 (8.8% vs 16.3%; P = 0.038); consistently, in multivariate logistic regression analysis, high coffee consumption was associated with lower odds for significant fibrosis (odds ratio = 0.49, 95% confidence interval, 0.25-0.97; P = 0.041) and was the strongest predictor for significant fibrosis. No association was demonstrated between coffee consumption and the new onset of nonalcoholic fatty liver, but coffee intake may exert beneficial effects on fibrosis progression. PMID:25468486

  1. 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...

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

    International Nuclear Information System (INIS)

    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 (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, but it has a tendency to underestimate compared to the

  3. 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

  4. Fatty Liver Index Associates with Relative Sarcopenia and GH/ IGF- 1 Status in Obese Subjects

    OpenAIRE

    Eleonora Poggiogalle; Carla Lubrano; Lucio Gnessi; Stefania Mariani; Andrea Lenzi; Lorenzo Maria Donini

    2016-01-01

    Introduction Recently the association between hepatic steatosis and sarcopenia has been described. GH/IGF-1 axis has been postulated to play a role in linking fatty liver and low muscle mass. The aim of our study was to explore the association between fatty liver index, sarcopenic obesity, insulin sensitivity, and GH/IGF-1 status. Methods 427 subjects [age: 45.65±13.94 years, BMI: 36.92±6.43 kg/m2] were enrolled. Participants were divided into three groups: fatty liver index (FLI)

  5. Phenotype, Body Composition, and Prediction Equations (Indian Fatty Liver Index for Non-Alcoholic Fatty Liver Disease in Non-Diabetic Asian Indians: A Case-Control Study.

    Directory of Open Access Journals (Sweden)

    Surya Prakash Bhatt

    Full Text Available In this study, we have attempted comparison of detailed body composition phenotype of Asian Indians with non-alcoholic fatty liver disease (NAFLD vs. those without, in a case controlled manner. We also aim to analyse prediction equations for NAFLD for non-diabetic Asian Indians, and compare performance of these with published prediction equations researched from other populations.In this case-control study, 162 cases and 173 age-and sex-matched controls were recruited. Clinical, anthropometric, metabolic, and body composition profiles, and liver ultrasound were done. Fasting insulin levels, value of homeostasis model assessment of insulin resistance (HOMA-IR, and serum high sensitive C-reactive protein (hs-CRP levels were evaluated. Multivariate logistic and linear regression analyses were used to arrive at prediction equations for fatty liver [Indian fatty liver index (IFLI].As compared to those without fatty liver, those with fatty liver exhibited the following; Excess dorsocervical fat ('Buffalo hump', skin tags, xanthelasma, 'double chin', arcus; excess total, abdominal and subcutaneous adiposity, and high blood pressure, blood glucose, measures of insulin resistance (fasting insulin and HOMA-IR values, lipids and hs-CRP levels. Two prediction equations were developed; Clinical [Indian Fatty Liver Index-Clinical; IFLI-C]: 1(double chin +15.5 (systolic blood pressure +13.8 (buffalo hump; and IFLI-Clinical and Biochemical (CB: serum triglycerides+12 (insulin+1(systolic blood pressure +18 (buffalo hump. On ROC Curve analysis, IFLI performed better than all published prediction equations, except one.Non-diabetic Asian Indians with NAFLD researched by us were overweight/obese, had excess abdominal and subcutaneous fat, multiple other phenotypic markers, had higher insulin resistance, glycemia, dyslipidemia and subclinical inflammation than those without. Prediction score developed by us for NAFLD; IFLI-C and IFLI-CB, should be useful for

  6. 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. PMID:25639618

  7. 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.

  8. 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.

  9. Current pharmacological therapies for nonalcoholic fatty liver disease/nonalcoholic steatohepatitis

    OpenAIRE

    Takahashi, Yoshihisa; Sugimoto, Keiichiro; INUI, Hiroshi; Fukusato, Toshio

    2015-01-01

    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 indispe...

  10. 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.

  11. 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.

  12. Hormesis in Cholestatic Liver Disease; Preconditioning with Low Bile Acid Concentrations Protects against Bile Acid-Induced Toxicity.

    Directory of Open Access Journals (Sweden)

    Esther M Verhaag

    Full Text Available Cholestasis is characterized by accumulation of bile acids and inflammation, causing hepatocellular damage. Still, liver damage markers are highest in acute cholestasis and drop when this condition becomes chronic, indicating that hepatocytes adapt towards the hostile environment. This may be explained by a hormetic response in hepatocytes that limits cell death during cholestasis.To investigate the mechanisms that underlie the hormetic response that protect hepatocytes against experimental cholestatic conditions.HepG2.rNtcp cells were preconditioned (24 h with sub-apoptotic concentrations (0.1-50 μM of various bile acids, the superoxide donor menadione, TNF-α or the Farsenoid X Receptor agonist GW4064, followed by a challenge with the apoptosis-inducing bile acid glycochenodeoxycholic acid (GCDCA; 200 μM for 4 h, menadione (50 μM, 6 h or cytokine mixture (CM; 6 h. Levels of apoptotic and necrotic cell death, mRNA expression of the bile salt export pump (ABCB11 and bile acid sensors, as well as intracellular GCDCA levels were analyzed.Preconditioning with the pro-apoptotic bile acids GCDCA, taurocholic acid, or the protective bile acids (tauroursodeoxycholic acid reduced GCDCA-induced caspase-3/7 activity in HepG2.rNtcp cells. Bile acid preconditioning did not induce significant levels of necrosis in GCDCA-challenged HepG2.rNtcp cells. In contrast, preconditioning with cholic acid, menadione or TNF-α potentiated GCDCA-induced apoptosis. GCDCA preconditioning specifically reduced GCDCA-induced cell death and not CM- or menadione-induced apoptosis. The hormetic effect of GCDCA preconditioning was concentration- and time-dependent. GCDCA-, CDCA- and GW4064- preconditioning enhanced ABCB11 mRNA levels, but in contrast to the bile acids, GW4064 did not significantly reduce GCDCA-induced caspase-3/7 activity. The GCDCA challenge strongly increased intracellular levels of this bile acid, which was not lowered by GCDCA

  13. 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.

  14. 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.

  15. 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

  16. [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.

  17. 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.

  18. 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.

  19. 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

  20. Detection of differentially expressed candidate genes for a fatty liver QTL on mouse chromosome 12

    OpenAIRE

    Kobayashi, Misato; Suzuki, Miyako; Ohno, Tamio; Tsuzuki, Kana; Taguchi, Chie; Tateishi, Soushi; Kawada, Teruo; Kim, Young-Il; Murai, Atsushi; Horio, Fumihiko

    2016-01-01

    Background The SMXA-5 mouse is an animal model of high-fat diet-induced fatty liver. The major QTL for fatty liver, Fl1sa on chromosome 12, was identified in a SM/J × SMXA-5 intercross. The SMXA-5 genome consists of the SM/J and A/J genomes, and the A/J allele of Fl1sa is a fatty liver-susceptibility allele. The existence of the responsible genes for fatty liver within Fl1sa was confirmed in A/J-12SM consomic mice. The aim of this study was to identify candidate genes for Fl1sa, and to invest...

  1. 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.

  2. Effects of fatty acids and growth hormone on liver fatty acid binding protein and PPARalpha in rat liver.

    Science.gov (United States)

    Carlsson, L; Lindén, D; Jalouli, M; Oscarsson, J

    2001-10-01

    The aim of this study was to investigate the interaction between long-chain fatty acids (LCFA) and growth hormone (GH) in the regulation of liver fatty acid binding protein (LFABP) and peroxisome proliferator-activated receptor-alpha (PPARalpha). Cultured rat hepatocytes were given oleic acid (OA; 500 microM) and GH (100 ng/ml) for 3 days. LFABP mRNA increased 3.6-fold by GH and 5.7-fold by OA, and combined incubation with GH and OA increased LFABP mRNA 17.6-fold. PPARalpha mRNA was decreased 50% by GH, but OA had no effect. Hypophysectomized (Hx) female rats were treated with L-thyroxine, cortisol, GH, and dietary fat for 7 days. PPARalpha mRNA levels were three- to fourfold higher in Hx than in normal female rats. GH decreased PPARalpha mRNA 50% in Hx rats. Dietary triglycerides (10% corn oil) increased LFABP mRNA and cytosolic LFABP about twofold but had no effect on PPARalpha mRNA in Hx rats. GH and dietary triglycerides had an additive effect on LFABP expression. Dietary triglycerides increased mitochondrial hydroxymethylglutaryl-CoA synthase mRNA only in the presence of GH. The diet increased serum triglycerides in Hx rats, and GH treatment prevented this increase. Addition of cholesterol to the diet did not influence LFABP levels but mitigated increased hepatic triglyceride content. In summary, these studies show that GH regulates LFABP expression independently of PPARalpha. Moreover, GH has different effects on PPARalpha-responsive genes and does not counteract the effect of LCFA on the expression of these gene products. PMID:11551854

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

    OpenAIRE

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

    2007-01-01

    Nonalcoholic fatty liver disease (NAFLD) has, although it is a very common disorder, only relatively recently gained broader interest among physicians and scientists. Fatty liver has been documented in up to 10 to 15 percent of normal individuals and 70 to 80 percent of obese individuals. Although the pathophysiology of NAFLD is still subject to intensive research, several players and mechanisms have been suggested based on the substantial evidence. Excessive hepatocyte triglyceride accumulat...

  4. Uric Acid Stimulates Fructokinase and Accelerates Fructose Metabolism in the Development of Fatty Liver

    OpenAIRE

    Lanaspa, Miguel A.; Sanchez-Lozada, Laura G.; Christina Cicerchi; Nanxing Li; Roncal-Jimenez, Carlos A.; Takuji Ishimoto; Myphuong Le; Garcia, Gabriela E.; Thomas, Jeffrey B.; Rivard, Christopher J.; Ana Andres-Hernando; Brandi Hunter; George Schreiner; Bernardo Rodriguez-Iturbe; Sautin, Yuri Y.

    2012-01-01

    Excessive dietary fructose intake may have an important role in the current epidemics of fatty liver, obesity and diabetes as its intake parallels the development of these syndromes and because it can induce features of metabolic syndrome. The effects of fructose to induce fatty liver, hypertriglyceridemia and insulin resistance, however, vary dramatically among individuals. The first step in fructose metabolism is mediated by fructokinase (KHK), which phosphorylates fructose to fructose-1-ph...

  5. 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.

  6. 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

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

    Science.gov (United States)

    Lin, Pei; Lu, Jianmei; Wang, Yanfang; Gu, Wen; Yu, Jie; Zhao, Ronghua

    2015-01-01

    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. PMID:26474417

  8. 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.

  9. Enterocyte Fatty Acid Binding Proteins (FABPs): Different Functions of Liver- and Intestinal- FABPs in the Intestine

    OpenAIRE

    Gajda, Angela M.; Storch, Judith

    2014-01-01

    Fatty acid binding proteins (FABP) are highly abundant cytosolic proteins that are expressed in most mammalian tissues. In the intestinal enterocyte, both Liver- (LFABP; FABP1) and Intestinal-fatty acid binding proteins (IFABP; FABP2) are expressed. These proteins display high affinity binding for long chain fatty acids (FA) and other hydrophobic ligands, thus they are believed to be involved with uptake and trafficking of lipids in the intestine. In vitro studies have identified differences ...

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

    OpenAIRE

    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 extrac...

  11. 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.

  12. 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.

  13. 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. PMID:26440324

  14. 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...

  15. Trivalent chromium alleviates oleic acid induced steatosis in SMMC-7721 cells by decreasing fatty acid uptake and triglyceride synthesis.

    Science.gov (United States)

    Wang, Song; Wang, Jian; Zhang, Xiaonan; Hu, Linlin; Fang, Zhijia; Huang, Zhiwei; Shi, Ping

    2016-10-01

    Trivalent chromium [Cr(III)] has been shown as an essential trace element for human health. Previous studies depict that Cr(III) plays important roles in maintaining normal glucose and lipid metabolism, whereas its effect on the hepatic lipid metabolism is still unknown. In the present study, we investigated the effects and underlying mechanisms of Cr on hepatic steatosis induced by oleic acid (OA) in human hepatoma SMMC-7721 cells. Hepatic steatosis model was co-administered with Cr. Indexes of lipid accumulation were determined and associated genes expression were analyzed. The data showed that OA could induce lipid accumulation and triglyceride (TG) content in SMMC-7721 cells, and significantly increase the expression of cluster of differentiation 36 (CD36) and diacylglycerol acyltransferase 2 (DGAT2). This steatosis effect of OA was ameliorated by Cr. The TG accumulation and up-regulation of CD36 and DGAT2 genes followed steatosis induction were inhibited by Cr. After the treatment of Cr, excessive intracellular OA content was also attenuated. Furthermore, Cr still performed inhibitory effect of DGAT2 expression at the presence of DGAT2 agonist or inhibitor, which indicated that the inhibitory effect of Cr on lipogenesis is associated with the downregulation of DGAT2 expression. These findings demonstrate that Cr alleviates hepatic steatosis via suppressing CD36 expression to prevent fatty acid uptake, as well as suppressing DGAT2 expression to inhibit TG synthesis. It suggests that CD36 and DGAT2 might become the novel drug targets for their properties in hepatic steatosis. Most importantly, Cr may be a potential anti-steatosis candidate to offer protective effects against liver damage. PMID:27497686

  16. Non-alcoholic fatty liver disease in HIV infection associated with altered hepatic fatty acid composition.

    Science.gov (United States)

    Arendt, Bianca M; Mohammed, Saira S; Ma, David W L; Aghdassi, Elaheh; Salit, Irving E; Wong, David K H; Guindi, Maha; Sherman, Morris; Heathcote, E Jenny; Allard, Johane P

    2011-03-01

    Hepatic fatty acid (FA) composition, especially a reduction in n-3 polyunsaturated FA (PUFA) may contribute to the pathogenesis of non-alcoholic fatty liver disease (NAFLD), which is common in HIV-infection.. In a cross-sectional study we compared hepatic FA composition between 20 HIV-infected men with NAFLD (HIV/NAFLD), 21 HIV-negative men with NAFLD (NAFLD), and 7 healthy controls. Within HIV/NAFLD we compared simple steatosis (HIV/SS) to steatohepatitis (HIV/NASH). FA composition in liver and erythrocytes, oxidative stress, diet, and exercise were assessed. Major findings (P<0.05) were: 1) higher hepatic n-6/n-3 ratio in HIV/NAFLD [median (range)] [8.08 (1.08-21.52)] compared to controls [5.83 (3.58-6.93)] and NAFLD [5.97 (1.46-10.40)], with higher n-6 PUFA in HIV/NAFLD compared to NAFLD; 2) lower n-3 PUFA in erythrocytes (mol%), a marker for dietary intake, in HIV/NAFLD [5.26 (1.04-11.75)] compared to controls [8.92 (4.79-12.67)]; 3) the ratios of long-chain PUFA products to essential FA precursors of the n-6 and n-3 series were lower in HIV/NAFLD and NAFLD compared to controls. In contrast, the ratio of oleic/stearic acid was higher in HIV/NAFLD compared to the other groups. These ratios are indirect markers of enzymatic FA desaturation and elongation. Hepatic PUFA, especially biologically active long-chain PUFA, were also lower in HIV/NASH compared to HIV/SS. Oxidative stress was not different among the groups. We conclude that HIV/NAFLD is associated with altered hepatic FA composition. Changes may be due to impaired FA metabolism or suboptimal n-3 PUFA intake. The potential role of n-3 PUFA (e.g. fish oil) to treat or prevent HIV/NAFLD warrants further investigation. PMID:21434863

  17. 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

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

    Science.gov (United States)

    Vitins, Alexa P; Kienhuis, Anne S; Speksnijder, Ewoud N; Roodbergen, Marianne; Luijten, Mirjam; van der Ven, Leo T M

    2014-08-01

    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 reflective of disease. Therefore, an in vivo mouse toxicogenomics study was completed to identify common pathways, nuclear receptor (NR) binding sites, and genes regulated by three known human steatosis-inducing compounds, amiodarone (AMD), valproic acid (VPA), and tetracycline (TET). Over 1, 4, and 11 days of treatment, AMD induced changes in clinical chemistry parameters and histopathology consistent with steatosis. Common processes and NR binding sites involved in lipid, retinol, and drug metabolism were found for AMD and VPA, but not for TET, which showed no response. Interestingly, the pattern of enrichment of these common pathways and NR binding sites over time was unique to each compound. Eleven biomarkers of steatosis were identified as dose responsive and time sensitive to toxicity for AMD and VPA. Finally, this in vivo mouse study was compared to an AMD rat in vivo, an AMD mouse primary hepatocyte, and a VPA human primary hepatocyte study to identify concordance for steatosis. We conclude that concordance is found on the process level independent of species, model or dose*time point. PMID:24535564

  19. 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.

  20. Expression of liver fatty acid binding protein in hepatocellular carcinoma.

    Science.gov (United States)

    Cho, Soo-Jin; Ferrell, Linda D; Gill, Ryan M

    2016-04-01

    Loss of expression of liver fatty acid binding protein (LFABP) by immunohistochemistry has been shown to be characteristic of a subset of hepatocellular adenomas (HCAs) in which HNF1A is inactivated. Transformation to hepatocellular carcinoma is thought to be a very rare phenomenon in the HNF1A-inactivated variant of HCA. However, we recently observed 2 cases at our institution, 1 definite hepatocellular carcinoma and 1 possible hepatocellular carcinoma, with loss of LFABP staining, raising the possibility that LFABP down-regulation may be associated with hepatocellular carcinogenesis. Our aim was to evaluate hepatocellular carcinomas arising in various backgrounds and with varying degrees of differentiation for loss of LFABP staining. Twenty total cases of hepatocellular carcinoma were examined. Thirteen cases arose in a background of cirrhosis due to hepatitis C (n = 8) or steatohepatitis (n = 5); 7 cases arose in a noncirrhotic background, with 2 cases arising within HNF1A-inactivated variant HCA and 2 cases arising within inflammatory variant HCA. Complete loss of expression of LFABP was seen in 6 of 20 cases, including 2 cases of hepatocellular carcinoma arising within HNF1A-inactivated variant HCA. Thus, loss of staining for LFABP appears to be common in hepatocellular carcinoma and may be seen in well-differentiated hepatocellular carcinoma. Therefore, LFABP loss should not be interpreted as evidence for hepatocellular adenoma over carcinoma, when other features support a diagnosis of hepatocellular carcinoma. The findings raise consideration for a role of HNF1A inactivation in hepatocellular carcinogenesis, particularly in less differentiated tumors. PMID:26997447

  1. 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

  2. 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.

  3. 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. PMID:26698409

  4. 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.

  5. 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.

  6. Protective effect of whey proteins against nonalcoholic fatty liver in rats

    OpenAIRE

    Sitohy Mahmoud Z; Abou Dawood Abdel-Gawad I; Taha Soad H; Hamad Essam M; Abdel-Hamid Mahmoud

    2011-01-01

    Abstract Background Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome and can vary from hepatic steatosis to end-stage liver disease. It is the most common liver disease and its prevalence is increasing worldwide. In the present study, the effect of whey proteins on some parameters of NAFLD was investigated. Results Oral administration of the studied whey proteins products reduced the final body weight of rats. There was a significant reduction ef...

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

    OpenAIRE

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

    2015-01-01

    Non-alcoholic fatty liver disease (NAFLD) is the main cause of liver disease worldwide. NAFLD is linked to circumstances such as type 2 diabetes, insulin resistance, obesity, hyperlipidemia, and hypertension. Since the obesity figures and related comorbidities are increasing, NAFLD has turned into a liver problem that has become progressively more common. Currently, there is no effective drug therapy for NAFLD; therefore, interventions in lifestyles remain the first line of treatment. Bearing...

  8. 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.

  9. 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.

  10. Insights from Genome-Wide Association Analyses of Nonalcoholic Fatty Liver Disease

    Science.gov (United States)

    Kahali, Bratati; Halligan, Brian; Speliotes, Elizabeth K.

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) is caused by hepatic steatosis, which can progress to nonalcoholic steatohepatitis, fibrosis/cirrhosis, and hepatocellular carcinoma in the absence of excessive alcohol consumption. Nonalcoholic fatty liver disease will become the number one cause of liver disease worldwide by 2020. Nonalcoholic fatty liver disease is correlated albeit imperfectly with obesity and other metabolic diseases such as diabetes, hyperlipidemia, and cardiovascular disease, but exactly how having one of these diseases contributes to the development of other metabolic diseases is only now being elucidated. Development of NAFLD and related metabolic diseases is genetically influenced in the population, and recent genome-wide association studies (GWASs) have discovered genetic variants that associate with these diseases. These GWAS-associated variants cannot only help us to identify individuals at high risk of developing NAFLD, but also to better understand its pathophysiology so that we can develop more effective treatments for this disease and related metabolic diseases in the future. PMID:26676813

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. Hepatic Oxidative Stress in Fructose-Induced Fatty Liver Is Not Caused by Sulfur Amino Acid Insufficiency

    OpenAIRE

    Jones, Dean P.; Youngja Park; Ziegler, Thomas R; Orr, Michael L.; Young-Mi Go; Vos, Miriam B.; James R. Roede; Kunde, Sachin S.

    2011-01-01

    Fructose-sweetened liquid consumption is associated with fatty liver and oxidative stress. In rodent models of fructose-mediated fatty liver, protein consumption is decreased. Additionally, decreased sulfur amino acid intake is known to cause oxidative stress. Studies were designed to test whether oxidative stress in fructose-sweetened liquid-induced fatty liver is caused by decreased ad libitum solid food intake with associated inadequate sulfur amino acid intake. C57BL6 mice were grouped as...

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

    International Nuclear Information System (INIS)

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

  19. 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....... A wide range (C4:0–C18:0) of fatty acids was synthesised and the proportions were modified by substrate concentrations in the same manner as for purified rabbit mammary gland fatty acid synthetase. - 3. The relative amount of radioactivity incorporated from added acetyl-CoA and malonyl-CoA depended...... on the substrate concentrations used. At excess acetyl-CoA to malonyl-CoA, greater amounts of acetyl-CoA were incorporated than theoretically expected from the malonyl-CoA pathway. At excess malonyl-CoA, less acetyl-CoA was incorporated than theoretically expected. - 4. An increase in the chain-length of fatty...

  20. 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.

  1. 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

  2. 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.

  3. 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...

  4. Protective effect of bicyclol on tetracycline-induced fatty liver in mice

    International Nuclear Information System (INIS)

    Peroxisome proliferators-activated receptor α (PPARα) and oxidative stress are two important pathological factors in non-alcoholic fatty liver disease (NAFLD). Tetracycline-induced fatty liver was partly due to the disturbance of mitochondrial fatty acids β-oxidation regulated by PPARα. Bicyclol was found to protect against high fat diet-induced fatty liver through modulating PPARα and clearing reactive oxygen species (ROS). The present study was performed to further investigate the effect of bicyclol on tetracycline-induced fatty liver and related mechanism in mice. Bicyclol (75, 150, 300 mg/kg) was given orally three times in two consecutive days. Tetracycline (200 mg/kg) was injected intraperitoneally 1 h after the last administration of bicyclol. Oxidative stress, mitochondrial function, PPARα and its target genes were evaluated by biochemical and RT-PCR analysis. The activity of CYP4A was assessed by liquid chromatography/mass spectrometry (LC/MS) method. Bicyclol significantly protected against tetracycline-induced fatty liver by reducing the accumulation of hepatic lipids and elevation of serum aminotransferase. In addition, bicyclol remarkably alleviated the over-production of thiobarbituric acid-reactive substance. The reduced activity of mitochondrial respiratory chain (MRC) complexes I and IV and mitochondrial permeability transition (MPT) were also improved by bicyclol. Furthermore, bicyclol inhibited the decrease of PPARα expression and its target genes, including long-chain acyl CoA dehydrogenase (LCAD), acetyl CoA oxidase (AOX) and CYP4A at mRNA and enzyme activity level. Bicyclol protected against tetracycline-induced fatty liver mainly through modulating the disturbance of PPARα pathway and ameliorating mitochondrial function.

  5. 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.

  6. 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.)

  7. [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.

  8. 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.

  9. 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.

  10. 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.

  11. 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).

  12. 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

  13. 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.

  14. 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.

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

    Science.gov (United States)

    White, Heather M

    2015-01-01

    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. PMID:26479386

  16. 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

  17. Interactions between Human Liver Fatty Acid Binding Protein and Peroxisome Proliferator Activated Receptor Selective Drugs

    OpenAIRE

    Tony Velkov

    2013-01-01

    Fatty acid binding proteins (FABPs) act as intracellular shuttles for fatty acids as well as lipophilic xenobiotics to the nucleus, where these ligands are released to a group of nuclear receptors called the peroxisome proliferator activated receptors (PPARs). PPAR mediated gene activation is ultimately involved in maintenance of cellular homeostasis through the transcriptional regulation of metabolic enzymes and transporters that target the activating ligand. Here we show that liver- (L-) FA...

  18. Effect of dietary monosodium glutamate on trans fat-induced nonalcoholic fatty liver disease

    OpenAIRE

    Collison, Kate S; Maqbool, Zakia; Saleh, Soad M; Inglis, Angela; Makhoul, Nadine J; Bakheet, Razan; Al-Johi, Mohammed; Al-Rabiah, Rana; Zaidi, Marya Z; Al-Mohanna, Futwan A.

    2009-01-01

    The effects of dietary monosodium glutamate (MSG) on trans-fatty acid (TFA)-induced nonalcoholic fatty liver disease (NAFLD) are addressed in an animal model. We used Affymetrix microarray analysis to investigate hepatic gene expression and the contribution of visceral white adipose tissue (WAT) to diet-induced NAFLD. Trans-fat feeding increased serum leptin, FFA, HDL-cholesterol (HDL-C), and total cholesterol (T-CHOL) levels, while robustly elevating the expression of genes involved in hepat...

  19. 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...

  20. 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

  1. Defining hepatic dysfunction parameters in two models of fatty liver disease in zebrafish larvae.

    Science.gov (United States)

    Howarth, Deanna L; Yin, Chunyue; Yeh, Karen; Sadler, Kirsten C

    2013-06-01

    Fatty liver disease in humans can progress from steatosis to hepatocellular injury, fibrosis, cirrhosis, and liver failure. We developed a series of straightforward assays to determine whether zebrafish larvae with either tunicamycin- or ethanol-induced steatosis develop hepatic dysfunction. We found altered expression of genes involved in acute phase response and hepatic function, and impaired hepatocyte secretion and disruption of canaliculi in both models, but glycogen deficiency in hepatocytes and dilation of hepatic vasculature occurred only in ethanol-treated larvae. Hepatic stellate cells (HSCs) become activated during liver injury and HSC numbers increased in both models. Whether the excess lipids in hepatocytes are a direct cause of hepatocyte dysfunction in fatty liver disease has not been defined. We prevented ethanol-induced steatosis by blocking activation of the sterol response element binding proteins (Srebps) using gonzo(mbtps1) mutants and scap morphants and found that hepatocyte dysfunction persisted even in the absence of lipid accumulation. This suggests that lipotoxicity is not the primary cause of hepatic injury in these models of fatty liver disease. This study provides a panel of parameters to assess liver disease that can be easily applied to zebrafish mutants, transgenics, and for drug screening in which liver function is an important consideration. PMID:23697887

  2. 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.

  3. Circulating lipocalin 2 is neither related to liver steatosis in patients with non-alcoholic fatty liver disease nor to residual liver function in cirrhosis.

    Science.gov (United States)

    Meier, Elisabeth M; Pohl, Rebekka; Rein-Fischboeck, Lisa; Schacherer, Doris; Eisinger, Kristina; Wiest, Reiner; Krautbauer, Sabrina; Buechler, Christa

    2016-09-01

    Lipocalin 2 (LCN2) is induced in the injured liver and associated with inflammation. Aim of the present study was to evaluate whether serum LCN2 is a non-invasive marker to assess hepatic steatosis in patients with non-alcoholic fatty liver disease (NAFLD) or residual liver function in patients with liver cirrhosis. Therefore, LCN2 was measured by ELISA in serum of 32 randomly selected patients without fatty liver (controls), 24 patients with ultrasound diagnosed NAFLD and 42 patients with liver cirrhosis mainly due to alcohol. Systemic LCN2 was comparable in patients with liver steatosis, those with liver cirrhosis and controls. LCN2 negatively correlated with bilirubin in both cohorts. In cirrhosis, LCN2 was not associated with more advanced liver injury defined by the CHILD-PUGH score and model for end-stage liver disease score. Resistin but not C-reactive protein or chemerin positively correlated with LCN2. LCN2 levels were not increased in patients with ascites or patients with esophageal varices. Consequently, reduction of portal pressure by transjugular intrahepatic portosystemic shunt did not affect LCN2 levels. Hepatic venous blood (HVS), portal venous blood and systemic venous blood levels of LCN2 were similar. HVS LCN2 was unchanged in patients with end-stage liver cirrhosis compared to those with well-compensated disease arguing against increased hepatic release. Current data exclude that serum LCN2 is of any value as steatosis marker in patients with NAFLD and indicator of liver function in patients with alcoholic liver cirrhosis. PMID:27288631

  4. Supplementing dietary sugar promotes endoplasmic reticulum stress-independent insulin resistance and fatty liver in goose.

    Science.gov (United States)

    Geng, Tuoyu; Zhao, Xing; Xia, Lili; Liu, Long; Li, Fuyuan; Yang, Biao; Wang, Qianqian; Montgomery, Sean; Cui, Hengmi; Gong, Daoqing

    2016-08-01

    It is known that endoplasmic reticulum stress (ERS) contributes to insulin resistance (IR) and non-alcoholic fatty liver disease (NAFLD) in mammals. However, we recently demonstrated that overfeeding with a traditional diet (mainly consisting of cooked maize) does not induce ERS in goose. As cellular studies show that high glucose and palmitate can trigger ERS in mammalian cells, we hypothesized that supplementing sugar to the traditional diet could induce ERS, thus promoting insulin resistance and fatty liver. To test the hypothesis, we first treated goose primary hepatocytes with high glucose (25 mM and 50 mM) and palmitate (0.5 mM) supplemented with or without 0.25 mM oleate. Data indicated that, as in mammalian cells, high glucose and palmitate indeed induced ERS in goose primary hepatocytes, and palmitate-induced ERS was suppressed by supplemental 0.25 mM oleate. We then tested the hypothesis with an in vivo study, in which Landes geese overfed with traditional or novel diets (i.e., the traditional diet supplemented with sugar) were compared with control geese (normally fed with cooked maize) for ERS, IR and fatty liver. The differences in glucose tolerance, insulin tolerance and postprandial blood glucose between the geese overfed with traditional and novel diets suggested that supplementing dietary sugar promoted IR. This promotion was accompanied with an increasing trend of liver weight and abdominal fat weight relative to body weight. Surprisingly, compared to overfeeding with the traditional diet, overfeeding with the novel diet did not induce ERS, even further suppressed ERS in goose fatty liver. Together, our findings suggest that supplementing dietary sugar promotes ERS-independent IR and fatty liver in goose. It is intriguing to discover the factor(s) protecting goose liver from ERS as well as the non-ERS mechanism underlying IR. PMID:27246737

  5. Phenotype, Body Composition, and Prediction Equations (Indian Fatty Liver Index) for Non-Alcoholic Fatty Liver Disease in Non-Diabetic Asian Indians: A Case-Control Study

    OpenAIRE

    Surya Prakash Bhatt; Anoop Misra; Priyanka Nigam; Randeep Guleria; M A Qadar Pasha

    2015-01-01

    Objective In this study, we have attempted comparison of detailed body composition phenotype of Asian Indians with non-alcoholic fatty liver disease (NAFLD) vs. those without, in a case controlled manner. We also aim to analyse prediction equations for NAFLD for non-diabetic Asian Indians, and compare performance of these with published prediction equations researched from other populations. Methods In this case-control study, 162 cases and 173 age-and sex-matched controls were recruited. Cli...

  6. 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).

  7. 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.

  8. 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.

  9. Role of diet and lifestyle changes in nonalcoholic fatty liver disease

    OpenAIRE

    Nseir, William; Hellou, Elias; Assy, Nimer

    2014-01-01

    Nonalcoholic fatty liver disease (NAFLD) has become one of the most common causes of liver disease worldwide and has been recognized as a major health burden. The prevalence of NAFLD has grown proportionally with the rise in obesity, sedentary lifestyle, unhealthy dietary pattern, and metabolic syndrome. Currently, there is no drug therapy that can be formulated for treating NAFLD. A combination of dietary modifications and increased physical activity remains the mainstay of NAFLD management....

  10. Increased Selenoprotein P Levels in Subjects with Visceral Obesity and Nonalcoholic Fatty Liver Disease

    OpenAIRE

    Hae Yoon Choi; Soon Young Hwang; Chang Hee Lee; Ho Cheol Hong; Sae Jeong Yang; Hye Jin Yoo; Ji A Seo; Sin Gon Kim; Nan Hee Kim; Sei Hyun Baik; Dong Seop Choi; Kyung Mook Choi

    2013-01-01

    Background Selenoprotein P (SeP) has recently been reported as a novel hepatokine that regulates insulin resistance and systemic energy metabolism in rodents and humans. We explored the associations among SeP, visceral obesity, and nonalcoholic fatty liver disease (NAFLD). Methods We examined serum SeP concentrations in subjects with increased visceral fat area (VFA) or liver fat accumulation measured with computed tomography. Our study subjects included 120 nondiabetic individuals selected f...

  11. Nonalcoholic Fatty Liver Disease: Pathogenesis and Therapeutics from a Mitochondria-Centric Perspective

    OpenAIRE

    Gusdon, Aaron M.; Ke-xiu Song; Shen Qu

    2014-01-01

    Nonalcoholic fatty liver disease (NAFLD) describes a spectrum of disorders characterized by the accumulation of triglycerides within the liver. The global prevalence of NAFLD has been increasing as the obesity epidemic shows no sign of relenting. Mitochondria play a central role in hepatic lipid metabolism and also are affected by upstream signaling pathways involved in hepatic metabolism. This review will focus on the role of mitochondria in the pathophysiology of NAFLD and touch on some of ...

  12. 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.

  13. Defining Hepatic Dysfunction Parameters in Two Models of Fatty Liver Disease in Zebrafish Larvae

    OpenAIRE

    Howarth, Deanna L.; Yin, Chunyue; Yeh, Karen; Kirsten C. Sadler

    2013-01-01

    Fatty liver disease in humans can progress from steatosis to hepatocellular injury, fibrosis, cirrhosis, and liver failure. We developed a series of straightforward assays to determine whether zebrafish larvae with either tunicamycin- or ethanol-induced steatosis develop hepatic dysfunction. We found altered expression of genes involved in acute phase response and hepatic function, and impaired hepatocyte secretion and disruption of canaliculi in both models, but glycogen deficiency in hepato...

  14. 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-

  15. 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.

  16. 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

  17. 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

  18. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  20. 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. PMID:25729971

  1. 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.

  2. 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

  3. 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

  4. MyD88 signaling in the CNS is required for development of fatty acid induced leptin resistance and diet-induced obesity

    OpenAIRE

    Kleinridders, Andre; Schenten, Dominik; Mauer, Jan; Wunderlich, F. Thomas; Okamura, Tomoo; Koenner, A. Christine; Belgardt, Bengt F.; Bruening, Jens C.; Medzhitov, Ruslan

    2009-01-01

    Obesity-associated activation of inflammatory pathways represents a key step in the development of insulin resistance in peripheral organs, partially via activation of TLR-4 signaling by fatty acids. Here we demonstrate that palmitate acting in the central nervous system (CNS) inhibits leptin-induced anorexia and Stat-3 activation. To determine the functional significance of TLR signaling in the CNS in the development of leptin resistance and diet-induced obesity in vivo, we have characterize...

  5. Role of autophagy in the ω-3 long chain polyunsaturated fatty acid-induced death of lung cancer A549 cells

    OpenAIRE

    Yao, Qinghua; Fu, Ting; Wang, Lu; LAI, YUEBIAO; Wang, Yuqi; Xu, Chao; Huang, Lulu; Guo, Yong

    2015-01-01

    The present study identified that ω-3 long chain polyunsaturated fatty acids (ω-3 PUFAs), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) demonstrate anti-proliferative effects in lung cancer A549 cells. MTS and cytotoxicity assays were conducted to confirm that ω-3 PUFAs induced cell death. Autophagy-associated gene and signaling pathways were also detected. Microtubule-associated protein light chain 3 (LC3) expression was found to be increased subsequent to treatment with DHA and...

  6. 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

  7. 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...

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

    Directory of Open Access Journals (Sweden)

    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.

  9. 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...

  10. 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

  11. 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

  12. 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

  13. 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.

  14. Recurrent hepatitis C and non-alcoholic fatty liver disease in transplanted patients: a review.

    Science.gov (United States)

    Testino, G; Sumberaz, A; Leone, S; Borro, P

    2013-04-01

    Non-alcoholic fatty liver disease (NAFLD) is a common occurrence after orthotopic liver transplantation (OLT). The association steatosis/HCV determines important implications for clinical practice: steatosis accelerates the progression of fibrosis and reduces the likelihood of obtaining a sustained virological response (SVR) with antiviral therapy. In post-transplant HCV patients we have evidenced a strong correlation between body mass index (BMI), cholesterol, triglycerides (TGC) and hepatic percentage of steatosis. In subjects with BMI hepatitis C and how the management of dismetabolism, diet and exercise therapy can improve BMI, liver histology and the response to antiviral therapy. PMID:23514999

  15. 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

  16. 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 Violetlow) 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. PMID:26619195

  17. Pretreatment by low-dose fibrates protects against acute free fatty acid-induced renal tubule toxicity by counteracting PPARα deterioration

    International Nuclear Information System (INIS)

    Development of a preventive strategy against tubular damage associated with proteinuria is of great importance. Recently, free fatty acid (FFA) toxicities accompanying proteinuria were found to be a main cause of tubular damage, which was aggravated by insufficiency of peroxisome proliferator-activated receptor alpha (PPARα), suggesting the benefit of PPARα activation. However, an earlier study using a murine acute tubular injury model, FFA-overload nephropathy, demonstrated that high-dose treatment of PPARα agonist (0.5% clofibrate diet) aggravated the tubular damage as a consequence of excess serum accumulation of clofibrate metabolites due to decreased kidney elimination. To induce the renoprotective effects of PPARα agonists without drug accumulation, we tried a pretreatment study using low-dose clofibrate (0.1% clofibrate diet) using the same murine model. Low-dose clofibrate pretreatment prevented acute tubular injuries without accumulation of its metabolites. The tubular protective effects appeared to be associated with the counteraction of PPARα deterioration, resulting in the decrease of FFAs influx to the kidney, maintenance of fatty acid oxidation, diminution of intracellular accumulation of undigested FFAs, and attenuation of disease developmental factors including oxidative stress, apoptosis, and NFκB activation. These effects are common to other fibrates and dependent on PPARα function. Interestingly, however, clofibrate pretreatment also exerted PPARα-independent tubular toxicities in PPARα-null mice with FFA-overload nephropathy. The favorable properties of fibrates are evident when PPARα-dependent tubular protective effects outweigh their PPARα-independent tubular toxicities. This delicate balance seems to be easily affected by the drug dose. It will be important to establish the appropriate dosage of fibrates for treatment against kidney disease and to develop a novel PPARα activator that has a steady serum concentration regardless of

  18. 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.

  19. 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

  20. 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

  1. 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.

  2. Osthole improves alcohol-induced fatty liver in mice by reduction of hepatic oxidative stress.

    Science.gov (United States)

    Zhang, Jianjun; Xue, Jie; Wang, Hengbin; Zhang, Yan; Xie, Meilin

    2011-05-01

    The aim of our study was to examine the therapeutic effect of osthole, an active constituent isolated from the fruit of Cnidium monnieri (L.) Cusson, on alcohol-induced fatty liver in mice and investigate its potential mechanisms of treatment. A mouse alcoholic fatty liver model was established by feeding 52% alcohol for 4 weeks. These experimental mice were then treated with osthole 10, 20 and 40 mg/kg for 6 weeks. The levels of serum total cholesterol (TC), triglyceride (TG), low density lipoprotein-cholesterol (LDL-C) and hepatic tissue contents of TC, TG and malondialdehyde (MDA) in osthole-treated groups were significantly decreased, while the level of superoxide dismutase (SOD) was significantly increased compared with the model group. Moreover, the cytochrome P450 (CYP) 2E1 and diacylglycerol acyltransferase (DGAT) mRNA expressions in mouse liver were significantly decreased, and the carnitine palmitoyltransferase (CPT) 1A mRNA expression was increased by osthole treatment. Importantly, the histological evaluation of liver demonstrated that osthole dramatically decreased lipid accumulation. It was concluded that osthole was effective in treating mouse alcoholic fatty liver, and its main mechanisms might be related to reduction of hepatic oxidative stress, including the inhibition of reactive oxygen species (ROS) production, enhancement of antioxidative enzyme activity, and reduction of lipid accumulation and peroxidation. PMID:20981870

  3. 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).

  4. Short chain fatty acids induce both effector and regulatory T cells by suppression of histone deacetylases and regulation of the mTOR-S6K pathway

    OpenAIRE

    Park, Jeongho; Kim, Myunghoo; Kang, Seung G; Jannasch, Amber Hopf; Cooper, Bruce; Patterson, John; Chang H Kim

    2014-01-01

    Microbial metabolites such as short chain fatty acids (SCFAs) are highly produced in the intestine and potentially regulate the immune system. We studied the function of SCFAs in regulation of T cell differentiation into effector and regulatory T cells. We report that SCFAs can directly promote T cell differentiation into T cells producing IL-17, IFN-γ, and/or IL-10 depending on cytokine milieu. This effect of SCFAs on T cells is independent of GPR41- or GPR43 but dependent on direct histone ...

  5. In vivo incorporation of labeled fatty acids in rat liver lipids after oral administration

    International Nuclear Information System (INIS)

    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

  6. 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.

  7. Oxysterols induce mitochondrial impairment and hepatocellular toxicity in non-alcoholic fatty liver disease.

    Science.gov (United States)

    Bellanti, Francesco; Mitarotonda, Domenica; Tamborra, Rosanna; Blonda, Maria; Iannelli, Giuseppina; Petrella, Antonio; Sanginario, Vittorio; Iuliano, Luigi; Vendemiale, Gianluigi; Serviddio, Gaetano

    2014-10-01

    Non-alcoholic fatty liver disease (NAFLD) is a chronic hepatic disorder affecting up to 25% of the general population. Several intracellular events leading to NAFLD and progression to non-alcoholic steatohepatitis (NASH) have been identified, including lipid accumulation, mitochondrial dysfunction and oxidative stress. Emerging evidence links both hepatic free fatty acids (FFAs) and cholesterol (FC) accumulation in NAFLD development; in particular oxysterols, the oxidative products of cholesterol, may contribute to liver injury. We performed a targeted lipidomic analysis of oxysterols in the liver of male Wistar rats fed a high-fat (HF), high-cholesterol (HC) or high-fat/high-cholesterol (HF/HC) diet. Both HF and HC diets caused liver steatosis, but the HF/HC diet resulted in steatohepatitis with associated mitochondrial dysfunction. Above all, the oxysterol cholestane-3beta,5alpha,6beta-triol (triol) was particularly increased in the liver of rats fed diets rich in cholesterol. To verify the molecular mechanism involved in mitochondrial dysfunction and hepatocellular toxicity, Huh7 and primary rat hepatocytes were exposed to palmitic acid (PA) and/or oleic acid (OA), with or without triol. This compound induced apoptosis in cells co-exposed to both PA and OA, and this was associated with impaired mitochondrial respiration as well as down-regulation of PGC1-alpha, mTFA and NRF1.In conclusion, our data show that hepatic free fatty acid or oxysterols accumulation per se induce low hepatocellular toxicity. On the contrary, hepatic accumulation of both fatty acids and toxic oxysterols such as triol are determinant in the impairment of mitochondrial function and biogenesis, contributing to liver pathology in NAFLD. PMID:26461297

  8. 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.

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

    International Nuclear Information System (INIS)

    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

  10. Omega-3 fatty acid deficiency selectively up-regulates delta6-desaturase expression and activity indices in rat liver: prevention by normalization of omega-3 fatty acid status.

    Science.gov (United States)

    Hofacer, Rylon; Jandacek, Ronald; Rider, Therese; Tso, Patrick; Magrisso, I Jack; Benoit, Stephen C; McNamara, Robert K

    2011-09-01

    This study investigated the effects of perinatal dietary omega-3 (n-3) fatty acid depletion and subsequent repletion on the expression of genes that regulate long-chain (LC) polyunsaturated fatty acid biosynthesis in rat liver and brain. It was hypothesized that chronic n-3 fatty acid deficiency would increase liver Fads1 and Fads2 messenger RNA (mRNA) expression/activity and that n-3 fatty acid repletion would normalize this response. Adult rats fed the n-3-free diet during perinatal development exhibited significantly lower erythrocyte, liver, and frontal cortex LCn-3 fatty acid composition and reciprocal elevations in LC omega-6 (n-6) fatty acid composition compared with controls (CONs) and repleted rats. Liver Fads2, but not Fads1, Elovl2, or Elovl5, mRNA expression was significantly greater in n-3-deficient (DEF) rats compared with CONs and was partially normalized in repleted rats. The liver 18:3n-6/18:2n-6 ratio, an index of delta6-desturase activity, was significantly greater in DEF rats compared with CON and repleted rats and was positively correlated with Fads2 mRNA expression among all rats. The liver 18:3n-6/18:2n-6 ratio, but not Fads2 mRNA expression, was also positively correlated with erythrocyte and frontal cortex LCn-6 fatty acid compositions. Neither Fads1 or Fads2 mRNA expression was altered in brain cortex of DEF rats. These results confirm previous findings that liver, but not brain, delta6-desaturase expression and activity indices are negatively regulated by dietary n-3 fatty acids. PMID:22024496

  11. Non-Alcoholic Fatty Liver Disease and Metabolic Syndrome after Liver Transplant

    OpenAIRE

    Stefano Gitto; Erica Villa

    2016-01-01

    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, onset of insulin resistance and drug-induced alterations of metabolism are reported in liver transplant recipients. In this context, post-transplant diabetes mellitus, hyperlipidemia, and arterial hypertension can be often diagnosed. Multifactorial illnesses occurring in the post-transplant period represent signifi...

  12. A Comparison of the Abdominal Fat Distribution and Coronary Risk Markers in Body Mass Index-matched Subjects with and without Fatty Liver.

    Science.gov (United States)

    Shiina, Yutaka; Homma, Koichiro; Ozawa, Hideki; Yoshizawa, Joe; Kobayashi, Takako; Igarashi, Mihoko; Aikawa, Minoru; Shibata, Takeo; Homma, Yasuhiko

    2016-01-01

    Objective The close relationship between fatty liver and metabolic syndrome suggests that individuals with fatty liver may have multiple coronary risk factors. In the present study, we investigated the relationships among fatty liver, abdominal fat distribution, and coronary risk markers. Methods and Results Eighty-seven pairs of men and 42 pairs of women who were matched for age and body mass index were enrolled in the present study. The obesity-related markers, abdominal fat distribution (examined by CT), and coronary risk markers were compared in subjects with and without fatty liver. The visceral fat area was significantly larger in the men with fatty liver than in the men without fatty liver. The plasma levels of triglyceride and low-density lipoprotein cholesterol (LDL-C), as well as the homeostasis model assessment-insulin resistance level, were higher in both males and females with fatty liver than in those without fatty liver, while the plasma levels of high-density lipoprotein cholesterol (HDL-C) and adiponectin were lower in the males and females with fatty liver. The plasma levels of apolipoprotein B, remnant-like particle cholesterol (RLP-C), and oxidized LDL were higher in men with fatty liver, but not in women with fatty liver. Conclusion Both males and females with fatty liver had lower insulin sensitivity, lower plasma levels of HDL-C and adiponectin, and higher triglyceride and LDL-C levels. However, the plasma levels of apolipoprotein B, RLP-C, and oxidized LDL were only higher and closely associated with fatty liver in men. Men with fatty liver had a higher risk of coronary disease than women with fatty liver. PMID:27629946

  13. Natural ligand binding and transfer from liver fatty acid binding protein (LFABP) to membranes.

    Science.gov (United States)

    De Gerónimo, Eduardo; Hagan, Robert M; Wilton, David C; Córsico, Betina

    2010-09-01

    Liver fatty acid-binding protein (LFABP) is distinctive among fatty acid-binding proteins because it binds more than one molecule of long-chain fatty acid and a variety of diverse ligands. Also, the transfer of fluorescent fatty acid analogues to model membranes under physiological ionic strength follows a different mechanism compared to most of the members of this family of intracellular lipid binding proteins. Tryptophan insertion mutants sensitive to ligand binding have allowed us to directly measure the binding affinity, ligand partitioning and transfer to model membranes of natural ligands. Binding of fatty acids shows a cooperative mechanism, while acyl-CoAs binding presents a hyperbolic behavior. Saturated fatty acids seem to have a stronger partition to protein vs. membranes, compared to unsaturated fatty acids. Natural ligand transfer rates are more than 200-fold higher compared to fluorescently-labeled analogues. Interestingly, oleoyl-CoA presents a markedly different transfer behavior compared to the rest of the ligands tested, probably indicating the possibility of specific targeting of ligands to different metabolic fates. PMID:20541621

  14. Modulatory effects of unsaturated fatty acids on the binding of glucocorticoids to rat liver glucocorticoid receptors.

    Science.gov (United States)

    Vallette, G; Vanet, A; Sumida, C; Nunez, E A

    1991-09-01

    Binding of the synthetic glucocorticoid dexamethasone to the rat liver cytosol glucocorticoid receptor was inhibited by physiological concentrations of nonesterified fatty acids as a function of increasing dose, degree of unsaturation, and chain length of the fatty acid. Polyunsaturated fatty acids were the most potent inhibitors. Scatchard analysis and Line-weaver-Burk plots of the binding data revealed that both the association constants and number of binding sites decreased and that polyunsaturated fatty acids inhibition was of a mixed non-competitive type. The dissociation rate constant of [3H]dexamethasone from glucocorticoid receptors was increased by up to 10 times in the presence of docosahexaenoic acid, whereas a competitive inhibitor like the glucocorticoid antagonist RU 38486 had no effect. Moreover, sucrose density gradient analysis showed that docosahexaenoic acid inhibited the binding of [3H] dexamethasone to both the 8.8S and 4S forms. The results strongly suggest that unsaturated fatty acids are interacting at a site on the receptor different from the hormone binding site and the heat shock protein and that by binding to a second site unsaturated fatty acids greatly change the conformation of the hormone binding site to reduce its affinity for the hormone, either partially or completely depending on the concentration and the class of the fatty acid. PMID:1874175

  15. Large-scale analysis of factors influencing nonalcoholic fatty liver disease and its relationship with liver enzymes.

    Science.gov (United States)

    Bi, W R; Yang, C Q; Shi, Q; Xu, Y; Cao, C P; Ling, J; Wang, X Y

    2014-01-01

    Serum liver enzyme levels are often used effectively for the evaluation of nonalcoholic fatty liver disease (NAFLD). We aimed to investigate the associations between serum liver enzyme levels and risks for NAFLD in over 8000 cases in a large-scale analysis. A cross-sectional survey with multiple stages and random samplings was performed from May 2007 to May 2009 on 8102 workers at Tongji University. A questionnaire was given, assessments of physical measurements, plasma glucose, lipid profiles, and liver enzymes were made, and real-time liver ultrasounds conducted. The prevalence of NAFLD in Tongji University was 22.2%. It was higher in males than in females (P = 0.0023). The body mass index, waist-to-hip ratio, serum total triglycerides, serum total cholesterol, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT) values were all higher in the NAFLD group than in the control group. For moderate and severe NAFLD patients, the ALT, AST and GGT values were significantly increased, high density lipoprotein cholesterol was decreased, and drinking much, heavy entertainment and less exercise were more prevalent (P < 0.001). There were strong correlations between serum liver enzyme levels and NAFLD (P < 0.001), with GGT being a more sensitive marker for NAFLD than ALT or AST. ALT and GGT were independent predictors for NAFLD, and GGT was a better predictor than ALT for NAFLD. PMID:25117346

  16. 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).

  17. 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

  18. 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...... concentrations (2,123 +/- 261 vs. 1,764 +/- 194 micromol/l, P body FFA(ox) was improved in both groups at rest and during...

  19. 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. PMID:27258290

  20. 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.

  1. 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.

  2. Does Lysosomial Acid Lipase Reduction Play a Role in Adult Non-Alcoholic Fatty Liver Disease?

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    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.

  3. Modeling the relationships between quality and biochemical composition of fatty liver in mule ducks.

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    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.

  4. 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.

  5. 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.

  6. Macrophage Activation in Pediatric Nonalcoholic Fatty Liver Disease (NAFLD) Correlates with Hepatic Progenitor Cell Response via Wnt3a Pathway

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    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

  7. Liver Fatty Acid Binding Protein Gene Ablation Enhances Age-Dependent Weight Gain in Male Mice

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    Martin, Gregory G.; Atshaves, Barbara P.; McIntosh, Avery L.; Payne, H. Ross; Mackie, John T.; Kier, Ann B.; Schroeder, Friedhelm

    2008-01-01

    Although studies performed in vitro and with transfected cells in culture suggest a role for liver fatty acid binding protein (L-FABP) in regulating fatty acid oxidation and fat deposition, the physiological significance of this possibility is not completely clear. To begin to address this question, the effect of L-FABP gene ablation on phenotype of standard rodent chow-fed male mice was examined with increasing age up to 18 mo. While young (2-3 mo) L-FABP null mice displayed no visually obvi...

  8. Liver-Type Fatty Acid-Binding Protein Attenuates Renal Injury Induced by Unilateral Ureteral Obstruction

    OpenAIRE

    Kamijo-Ikemori, Atsuko; Sugaya, Takeshi; Obama, Ayako; Hiroi, Junya; Miura, Hiroshi; WATANABE, Minoru; Kumai, Toshio; Ohtani-Kaneko, Ritsuko; Hirata, Kazuaki; Kimura, Kenjiro

    2006-01-01

    Liver-type fatty-acid-binding protein (L-FABP), which has high affinity for long-chain fatty acid oxidation products, may be an effective endogenous antioxidant. To examine the role of L-FABP in tubulointerstitial damage, we used a unilateral ureteral obstruction (UUO) model. We established human L-FABP (hL-FABP) gene transgenic (Tg) mice and compared the tubulointerstitial pathology of the Tg mice (n = 23) with that of the wild-type (WT) mice (n = 23). Mice were sacrificed on days 2, 4, 5, o...

  9. 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.

  10. Manifestations of Fasting-Induced Fatty Liver and Rapid Recovery from Steatosis in Voles Fed Lard or Flaxseed Oil Lipids

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    Mustonen, Anne-Mari; Kärjä, Vesa; Kilpiö, Michael; Tammi, Raija; Tammi, Markku; Rouvinen-Watt, Kirsti; Halonen, Toivo; Nieminen, Petteri

    2013-01-01

    Long-chain n-3 polyunsaturated fatty acids (PUFA) can have beneficial effects against fat deposition, cardiovascular diseases, and liver steatosis. We investigated how diets based on lard (predominantly saturated and monounsaturated fatty acids) or flaxseed oil (rich in 18:3n-3) affect liver fat-% and fatty acid profiles of tundra voles (Microtus oeconomus). We also studied potential participation of hyaluronan (HA) in the pathology of fatty liver and whether the development and recovery of fasting-induced steatosis are influenced by n-3 PUFA. The dietary fatty acid composition was manifested in the liver fatty acid signatures. Fasting for 18 h induced macrovesicular steatosis and the liver fat-% increased to 22% independent of the preceding diet. Fasting-induced steatosis did not involve inflammation or connective tissue activation indicated by the absence of both leukocyte accumulation and increased HA. Food deprivation modified the liver fatty acid signatures to resemble more closely the diets. Fasting reduced the proportions of long-chain n-3 PUFA in both dietary regimes and n-3/n-6 PUFA ratios in the lard-fed voles. Decreases in long-chain n-3 PUFA may promote lipid accumulation by modulating the expression of lipid-metabolizing genes. Dietary 18:3n-3 did not prevent the development or attenuate the manifestation of steatosis in the fasted voles or promote the recovery. PMID:24152753

  11. Manifestations of Fasting-Induced Fatty Liver and Rapid Recovery from Steatosis in Voles Fed Lard or Flaxseed Oil Lipids

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    Toivo Halonen

    2013-10-01

    Full Text Available Long-chain n-3 polyunsaturated fatty acids (PUFA can have beneficial effects against fat deposition, cardiovascular diseases, and liver steatosis. We investigated how diets based on lard (predominantly saturated and monounsaturated fatty acids or flaxseed oil (rich in 18:3n-3 affect liver fat-% and fatty acid profiles of tundra voles (Microtus oeconomus. We also studied potential participation of hyaluronan (HA in the pathology of fatty liver and whether the development and recovery of fasting-induced steatosis are influenced by n-3 PUFA. The dietary fatty acid composition was manifested in the liver fatty acid signatures. Fasting for 18 h induced macrovesicular steatosis and the liver fat-% increased to 22% independent of the preceding diet. Fasting-induced steatosis did not involve inflammation or connective tissue activation indicated by the absence of both leukocyte accumulation and increased HA. Food deprivation modified the liver fatty acid signatures to resemble more closely the diets. Fasting reduced the proportions of long-chain n-3 PUFA in both dietary regimes and n-3/n-6 PUFA ratios in the lard-fed voles. Decreases in long-chain n-3 PUFA may promote lipid accumulation by modulating the expression of lipid-metabolizing genes. Dietary 18:3n-3 did not prevent the development or attenuate the manifestation of steatosis in the fasted voles or promote the recovery.

  12. 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.

  13. Glucose amplifies fatty acid-induced endoplasmic reticulum stress in pancreatic beta-cells via activation of mTORC1.

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    Etti Bachar

    Full Text Available BACKGROUND: Palmitate is a potent inducer of endoplasmic reticulum (ER stress in beta-cells. In type 2 diabetes, glucose amplifies fatty-acid toxicity for pancreatic beta-cells, leading to beta-cell dysfunction and death. Why glucose exacerbates beta-cell lipotoxicity is largely unknown. Glucose stimulates mTORC1, an important nutrient sensor involved in the regulation of cellular stress. Our study tested the hypothesis that glucose augments lipotoxicity by stimulating mTORC1 leading to increased beta-cell ER stress. PRINCIPAL FINDINGS: We found that glucose amplifies palmitate-induced ER stress by increasing IRE1alpha protein levels and activating the JNK pathway, leading to increased beta-cell apoptosis. Moreover, glucose increased mTORC1 activity and its inhibition by rapamycin decreased beta-cell apoptosis under conditions of glucolipotoxicity. Inhibition of mTORC1 by rapamycin did not affect proinsulin and total protein synthesis in beta-cells incubated at high glucose with palmitate. However, it decreased IRE1alpha expression and signaling and inhibited JNK pathway activation. In TSC2-deficient mouse embryonic fibroblasts, in which mTORC1 is constitutively active, mTORC1 regulated the stimulation of JNK by ER stressors, but not in response to anisomycin, which activates JNK independent of ER stress. Finally, we found that JNK inhibition decreased beta-cell apoptosis under conditions of glucolipotoxicity. CONCLUSIONS/SIGNIFICANCE: Collectively, our findings suggest that mTORC1 mediates glucose amplification of lipotoxicity, acting through activation of ER stress and JNK. Thus, mTORC1 is an important transducer of ER stress in beta-cell glucolipotoxicity. Moreover, in stressed beta-cells mTORC1 inhibition decreases IRE1alpha protein expression and JNK activity without affecting ER protein load, suggesting that mTORC1 regulates the beta-cell stress response to glucose and fatty acids by modulating the synthesis and activity of specific

  14. Correlation of HIFs/PPAR signaling pathway activation degree and lipid metabolism in liver tissue of alcoholic fatty liver rat model

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    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.

  15. Effect of Vitamin E and Metformin on Fatty Liver Disease in Obese Children- Randomized Clinical Trial.

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    Kobra Shiasi Arani

    2014-10-01

    Full Text Available We evaluated the effect of vitamin E and metformin on fatty liver disease in obese children.This interventional study has been done on 119 children with Non-alcoholic fatty liver disease (based on sonography results. Patients were divided into four treatment groups; they received metformin 1gr daily (age 12 years, vitamin E 800 U daily and vitamin E 400 U daily. Liver sonography was performed for patients for two periods of two months. This trial was registered in Iranian Registry of Clinical Trials (IRCT, No.IRCT2013021012421N1.The study group comprised 119 individuals (62 females, 57 males. The mean age was 10± 3.19 yr. There was no significant difference in terms of sex and BMI between the groups. Overall liver sonography showed normal liver in 66 patients (55.46%, 66.63% after two months and 33.37% after four months. After two months, the most therapeutic response observed in the group which received vitamin E 800 u daily (48.1% and the least therapeutic response was in the group which received vitamin E 400 u daily (14.3%. After four months, the greater response was seen in vitamin E 400 u daily group (45.8% and the least response in the metformin 1 gram daily group (19%.In comparison with metformin, vitamin E is more influential in remission; however both are efficient in treatment of fatty liver. Vitamin E 400 u daily responses better in four-month treatment.

  16. Hepatic Vein Doppler Waveform Changes in Nonalcoholic Fatty Liver Disease with Hepatomegaly

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    Ozum Tuncyurek

    2013-10-01

    Full Text Available Aim: Doppler Ultrasonography (DUS has become an important diagnostic technique in the hepatic vasculature evaluation. Fatty infiltration of the liver can also change the Doppler findings -like cirrhosis- of hepatic veins. Diffuse fatty liver  (DFL is the most common finding in liver with the method of ultrasonography. Most literature reports mention the effect of chronic liver disease with a small-size liver on the waveform alterations. The objective of the study was to evaluate the hepatic vein (HV Doppler waveforms in cases with hepatomegaly and diffuse fatty infiltration of the liver. Material and Method: Steatosis was present in all cases (Grade I: 35 (19.3%; Grade II: 129 (71.3%; and Grade III: 17 (9.4%. Steatosis was accompanied by hepatomegaly in 107 (59.1% cases. However, steatosis was accompanied by nonhepatomegaly in 74 (40.9% cases. Results: Of the cases that were detected to have hepatomegaly, 35 (33% were male and 72 (67% were female. Their ages ranged from 27 to 83 years (mean: 53.5 ± 11.1. Hepatic vein waveforms were examined in all cases. HV waveforms were divided into 3 groups, namely regular triphasic form, biphasic form, and monophasic form. Etiologic factors were diabetes, hypertriglyceridemia, and hypercholesterolemia. An abnormal HV Doppler waveform was present in 119 (65% of 181 cases. A correlation was detected between DFL grade and HV Doppler waveforms (p=0.03, whereas no correlation was detected between DFL grade and hepatomegaly (p=0.5. It is known that there is an association between the grade of steatosis and a change in the hepatic vein waveform. Discussion: Nevertheless, hepatomegaly that is observed with steatosis does not cause any significant change in HV flow, which can be detected with a Doppler apparatus.

  17. 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.

  18. 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.

  19. The effect of magnesium supplementation and weight loss on liver enzymes in patients with nonalcoholic fatty liver disease

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    Majid Karandish

    2013-01-01

    Full Text Available Background: There have been few studies to examine the effect of magnesium (Mg supplementation on liver enzymes. The aim of this study was to evaluate the effect of Mg supplementation and weight loss on liver enzymes, lipid profile, and fasting blood sugar in patients with nonalcoholic fatty liver disease (NAFLD. Materials and 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 ≥ 40 U/L and without other hepatic diseases. A total of 68 participants (18-59 years with NAFLD were randomly divided into two groups to receive either Mg supplement (350 mg elemental Mg per day or placebo for 90 days. At baseline and at the end of the intervention serum ALT, aspartate aminotransferase (AST, alkaline phosphatase (ALP, total cholesterol (TCHO, high-density lipoprotein cholesterol (HDL-C, triglyceride (TG, blood sugar and serum insulin, and Mg levels were measured in fasting state. Low-density lipoprotein cholesterol (LDL-C and insulin resistance (IR were calculated using Friedewald formula and homeostasis model assessment of insulin resistance (HOMA-IR, respectively. All participants received lifestyle recommendations including low calorie diet and physical activity. Results: Significant decreases within the intervention and placebo groups were observed in ALT (57.00 (25 to 41.82 ± 19.40 U/L, P = 0.000; 68.50 ± 26.96 to 40.17 ± 19.40 U/L, P = 0.000 in Mg and placebo groups, respectively. Similar significant decreases were observed in AST and fasting serum insulin within the study groups. The decrease in weight was also significant in both groups (91.05 ± 13.77 to 87.60 ± 14.37 kg and 94.59 ± 16.85 to 91.45 ± 16.39 kg in Mg and placebo groups, respectively. LDL-C and TCHO were decreased significantly in placebo group but not in the intervention group. Serum Mg was increased significantly in the intervention group. No

  20. Protective Effects of Korean Red Ginseng against Alcohol-Induced Fatty Liver in Rats

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    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.

  1. The Detrimental Role Played by Lipocalin-2 in Alcoholic Fatty Liver in Mice.

    Science.gov (United States)

    Cai, Yan; Jogasuria, Alvin; Yin, Huquan; Xu, Ming-Jiang; Hu, Xudong; Wang, Jiayou; Kim, Chunki; Wu, Jiashin; Lee, Kwangwon; Gao, Bin; You, Min

    2016-09-01

    We have previously shown that the ethanol-mediated elevation of lipocaline-2 (LCN2) is closely associated with the development of alcoholic fatty liver disease (AFLD) in mice. Herein, we aimed to understand the functional significance of LCN2 induction by ethanol and to explore its underlying mechanisms. We evaluated the effects of LCN2 in an in vitro cellular alcoholic steatosis model and in an animal study using wild-type and LCN2 knockout mice fed for 4 weeks with an ethanol-supplemented Lieber-DeCarli diet. In the cellular model of alcoholic steatosis, recombinant LCN2 or overexpression of LCN2 exacerbated ethanol-induced fat accumulation, whereas knocking down LCN2 prevented steatosis in hepatocytes exposed to ethanol. Consistently, removal of LCN2 partially but significantly alleviated alcoholic fatty liver injury in mice. Mechanistically, LCN2 mediates detrimental effects of ethanol in the liver via disrupted multiple signaling pathways, including aberrant nicotinamide phosphoribosyltransferase-sirtuin 1 axis, perturbed endocrine metabolic regulatory fibroblast growth factor 15/19 signaling, and impaired chaperone-mediated autophagy. Finally, compared with healthy human livers, liver samples from patients with AFLD had lower gene expression of several LCN2-regualted molecules. Our study demonstrated a pivotal and causal role of LCN2 in the development of AFLD and suggested that targeting the LCN2 could be of great value for the treatment of human AFLD. PMID:27427417

  2. 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.

  3. Exercise and diet in the management of nonalcoholic fatty liver disease.

    Science.gov (United States)

    Mahady, Suzanne E; George, Jacob

    2016-08-01

    Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver condition worldwide, and is projected to become the leading cause for liver transplantation in the United States as early as 2020. The mainstay of treatment remains lifestyle modification with diet and exercise recommendations, as although some pharmacological treatments such as glitazones and Vitamin E have shown benefit, there are concerns regarding long term safety. The evidence base for dietary interventions in NAFLD such as the Mediterranean diet, omega-3 polyunsaturated fatty acids and coffee is mainly derived from observational data with questionable validity. Where trials exist, they have shown benefit for surrogate outcomes such as hepatic steatosis and insulin resistance, but no trials have been conducted with salient clinical outcomes such as reduction in progression to chronic liver disease. Benefit in surrogate outcomes has also been seen for aerobic, anaerobic and combined modality exercise but it remains unclear if one type is superior. Furthermore, a reduction in sedentary time appears equally important. To provide a sound evidence base for lifestyle recommendations to people with NAFLD, longer duration trials of standardized dietary or exercise interventions, and testing various doses, types and with liver related outcomes, are essential. PMID:26805014

  4. 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

  5. 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.

  6. 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.

  7. 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...

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. 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

  16. 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 .

  17. Enterocyte Fatty Acid Binding Proteins (FABPs): Different Functions of Liver- and Intestinal- FABPs in the Intestine

    Science.gov (United States)

    Gajda, Angela M.; Storch, Judith

    2014-01-01

    SUMMARY Fatty acid binding proteins (FABP) are highly abundant cytosolic proteins that are expressed in most mammalian tissues. In the intestinal enterocyte, both Liver- (LFABP; FABP1) and Intestinal-fatty acid binding proteins (IFABP; FABP2) are expressed. These proteins display high affinity binding for long chain fatty acids (FA) and other hydrophobic ligands, thus they are believed to be involved with uptake and trafficking of lipids in the intestine. In vitro studies have identified differences in ligand binding stoichiometry and specificity, and in mechanisms of FA transfer to membranes, and it has been hypothesized that LFABP and IFABP have difference functions in the enterocyte. Studies directly comparing LFABP- and IFABP-null mice have revealed markedly different phenotypes, indicating that these proteins indeed have different functions in intestinal lipid metabolism and whole body energy homeostasis. In this review, we discuss the evolving knowledge of the functions of LFABP and IFABP in the intestinal enterocyte. PMID:25458898

  18. 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.

  19. The serum vitamin D level is inversely correlated with nonalcoholic fatty liver disease

    OpenAIRE

    Chung, Goh Eun; Kim, Donghee; Kwak, Min-Sun; Yang, Jong In; Yim, Jeong Yoon; Lim, Seon Hee; Itani, Mustafa

    2016-01-01

    Background/Aims: A low vitamin D level has been associated with metabolic syndrome and diabetes. However, an association between a low vitamin D level and nonalcoholic fatty liver disease (NAFLD) has not yet been definitively established. This study aimed to characterize the relationship between a vitamin D level and NAFLD in Korea. Methods: A cross-sectional study involving 6,055 health check-up subjects was conducted. NAFLD was diagnosed on the basis of typical ultrasonographic findings and...

  20. Non-alcoholic fatty liver disease and mortality among US adults: prospective cohort study

    OpenAIRE

    Lazo, Mariana; Hernaez, Ruben; Bonekamp, Susanne; Kamel, Ihab R.; Frederick L Brancati; Guallar, Eliseo; Clark, Jeanne M.

    2011-01-01

    Objective To evaluate the association between non-alcoholic fatty liver disease and all cause and cause specific mortality in a representative sample of the US general population. Design Prospective cohort study. Setting US Third National Health and Nutrition Examination Survey (NHANES III: 1988-94) with follow-up of mortality to 2006. Participants 11 371 adults aged 20-74 participating in the Third National Health and Nutrition Examination Survey, with assessment of hepatic steatosis. Main o...

  1. Deterioration of Heart Rate Recovery Index in Patients with Non-Alcoholic Fatty Liver Disease (NAFLD)

    OpenAIRE

    Ozveren, Olcay; Dogdu, Orhan; SENGUL, Cihan; Cinar, Veysel; Eroglu, Elif; Kucukdurmaz, Zekeriya; Degertekin, Muzaffer

    2014-01-01

    Background Non-alcoholic fatty liver disease (NAFLD) has been considered as a benign disease often associated with central obesity and insulin resistance and, in general, with factors of the metabolic syndrome. Heart rate recovery after exercise is a function of vagal reactivation, and its impairment is an independent prognostic indicator for cardiovascular and all-cause mortality. The aim of our study was to evaluate the heart rate recovery index in patients with NAFLD. Material/Methods The ...

  2. Correlation between leptin level with lipid profile and free fatty acid in liver cirrhosis patients

    OpenAIRE

    Siti Maryani; Neneng Ratnasari; Siti Nurdjanah

    2015-01-01

    Malnutrition is a common condition in liver cirrhotic patients. Leptin regulates body weightphysiologically by suppressing appetite and increasing energy expenditure. Leptin is higher in femalethan male. Studies have shown correlation between leptin with metabolic factors like body massindex (BMI) and lipid profile in cirrhotic patients. This study was conducted to investigate thecorrelation between serum leptin levels with lipid profile and free fatty acid in male patients with livercirrhosi...

  3. Urinary liver-type fatty acid-binding protein predicts adverse outcomes in acute kidney injury

    OpenAIRE

    Ferguson, Michael A.; Vaidya, Vishal S.; Waikar, Sushrut S.; Collings, Fitz B.; Sunderland, Kelsey E.; Gioules, Costas J.; Bonventre, Joseph V.

    2009-01-01

    Acute kidney injury (AKI) is a common condition with significant associated morbidity and mortality. The insensitivity and non-specificity of traditional markers of renal dysfunction prevent timely diagnosis, estimation of the severity of renal injury, and the administration of possible therapeutic agents. Here, we determine the prognostic ability of urinary liver-type fatty acid-binding protein (L-FABP), and further characterize its sensitivity and specificity as a biomarker of AKI. Initial ...

  4. The Role of Urinary Liver-Type Fatty Acid-Binding Protein in Critically Ill Patients

    OpenAIRE

    Cho, Eunjung; Yang, Ha Na; Jo, Sang-Kyung; Cho, Won-Yong; Kim, Hyoung-Kyu

    2013-01-01

    Although several urinary biomarkers have been validated as early diagnostic markers of acute kidney injury (AKI), their usefulness as outcome predictors is not well established. This study aimed to determine the diagnostic and prognostic abilities of urinary liver-type fatty acid-binding protein (L-FABP) in heterogeneous critically ill patients. We prospectively collected data on patients admitted to medical and surgical intensive care units (ICUs) from July 2010 to June 2011. Urine neutrophi...

  5. Buffer Interference with Protein Dynamics: A Case Study on Human Liver Fatty Acid Binding Protein

    OpenAIRE

    Long, Dong; Yang, Daiwen

    2009-01-01

    Selection of suitable buffer types is often a crucial step for generating appropriate protein samples for NMR and x-ray crystallographic studies. Although the possible interaction between MES buffer (2-(N-morpholino)ethanesulfonic acid) and proteins has been discussed previously, the interaction is usually thought to have no significant effects on the structures of proteins. In this study, we demonstrate the direct, albeit weak, interaction between MES and human liver fatty acid binding prote...

  6. New insights into body condition score and its association with fatty liver in holstein dairy cows

    OpenAIRE

    Šamanc H.; Kirovski Danijela; Jovanović M.; Vujanac I.; Bojković-Kovačević Slavica; Jakić-Dimić Dobrila; Prodanović R.; Stajković Silvana

    2010-01-01

    The aim of this study was to estimate the association between body condition and fatty liver in high-yielding dairy cows. One hundred dry Holstein cows were selected. Cows were scored once for body condition during the dry period, puerperium and month 2 of lactation, according to the system provided by Elanco Animal Health Buletin Al 8478. Body condition loss was determined as marked if loss was over 0.7 points between two consecutive phases of cycles and o...

  7. The Global Nonalcoholic Fatty Liver Disease Epidemic: What a Radiologist Needs to Know

    OpenAIRE

    Keith Pereira; Jason Salsamendi; Javier Casillas

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of disorders from a benign steatosis to hepatocellular carcinoma (HCC). Metabolic syndrome, mainly obesity, plays an important role, both as an independent risk factor and in the pathogenesis of NAFLD. With the progressive epidemics of obesity and diabetes mellitus, the prevalence of NAFLD and its associated complications is expected to increase dramatically. Therapeutic strategies for treating NAFLD and metabolic syndrome, partic...

  8. 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...

  9. Gut Microbiota and Clinical Disease: Obesity and Nonalcoholic Fatty Liver Disease

    OpenAIRE

    Park, Ji Sook; Seo, Ji Hyun; Youn, Hee-Shang

    2013-01-01

    The prevalence of obesity is increasing worldwide. Obesity can cause hyperlipidemia, hypertension, cardiovascular diseases, metabolic syndrome and non-alcoholic fatty liver disease (NAFLD). Many environmental or genetic factors have been suggested to contribute to the development of obesity, but there is no satisfactory explanation for its increased prevalence. This review discusses the latest updates on the role of the gut microbiota in obesity and NAFLD.

  10. 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...

  11. 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...

  12. [Genomic, proteomic and metabolomic predictors of nonalcoholic fatty liver disease development in obese patients. Part I].

    Science.gov (United States)

    Chernyak, O O; Sentsova, T B; Vorozhko, I V; Tutelyan, V A; Gapparova, K M; Isakov, V A

    2015-01-01

    The prevention, diagnosis and treatment of diseases associated to obesity require a qualitative increase of efficiency. There are still disputable questions about diagnostic significance of some molecules, including genomic, proteomic and metabolomic biomarkers. We observed 72 obese patients (20 men and 52 women, mean age--41.3 +/- 2.5) and performed ultrasound elastography and ultrasound of liver. We have identified two groups of patients: Group 1 consisted of 50 obese patients without complications (BMI 43.2 +/- 0.6), group 2 consisted of 22 patients with obesity complicated with nonalcoholic fatty liver disease (BMI 45.8 +/- 2.3). Determination of the adipokines (adiponectin, ghrelin, resistin, visfatin, and apelin), cytokine (interleukin--6, TNFalpha) oxidized lipoproteins (oxLDL), adhesion molecule sICAM (soluble intercellular cell adhesion molecule), fatty acid transporter L-FABP in serum was performed by ELISA. The study of the lipid metabolism involved determination of the concentration of total cholesterols, triglycerides, low and high density lipoproteins (LDL and HDL) by turbidimetry and spectrophotometry by analyzer. In addition, we conducted analysis of polymorphic alleles epsilon2, epsilon3, episolon4 of ApoE gene using polymerase chain reaction. Our data indicate that reducing the concentration of adiponectin (0.46-1.71 mcg/ml), increasing the level of glucose (5.57-6.25 mmol/l), triglycerides (2.06-3.94 mmol/l), TNFalpha (5.07-16.68 pg/ml) and L-FABP (11.62-23.76 pg/ml) are predictors of nonalcoholic fatty liver disease in obese patients, and the presence of genotype epsilon3/epsilon4 of ApoE gene is a poor prognostic marker of severity of nonalcoholic fatty liver disease. PMID:26852528

  13. 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. PMID:26254248

  14. 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...

  15. 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.

  16. Association Between Pulmonary Function and Nonalcoholic Fatty Liver Disease in the NHANES III Study

    OpenAIRE

    Peng, Tao-Chun; Kao, Tung-Wei; Wu, Li-Wei; Chen, Ying-Jen; Chang, Yaw-Wen; Wang, Chung-Ching; Tsao, Yu-Tzu; Chen, Wei-liang

    2015-01-01

    Abstract Emerging evidence indicates that nonalcoholic fatty liver disease (NAFLD) is associated with a wide variety of extrahepatic complications. However, the potential association between impaired pulmonary function and NAFLD has been less investigated. This study examined the relationship between pulmonary function and hepatic steatosis in 9976 adults participating in a cross-sectional analysis of the Third National Health and Nutrition Examination Survey (NHANES III). NAFLD was defined a...

  17. 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.

  18. 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.

  19. Ameliorative Effects of Pomegranate Peel Extract against Dietary-Induced Nonalcoholic Fatty Liver in Rats.

    Science.gov (United States)

    Al-Shaaibi, Siham N K; Waly, Mostafa I; Al-Subhi, Lyutha; Tageldin, Mohamed H; Al-Balushi, Nada M; Rahman, Mohammad S

    2016-03-01

    Non-alcoholic fatty liver disease (NAFLD) is caused by fat accumulation and is associated with oxidative stress. In this study, we investigated the potential protective effect of pomegranate (Punica granatum L.) peel extract (PPE) against oxidative stress in the liver of rats with NAFLD. Sprague-Dawley rats were fed a high fat diet (HFD), 20% corn oil, or palm oil for 8 weeks in the presence or absence of PPE. The control group was fed a basal diet. The progression of NAFLD was evaluated histologically and by measuring liver enzymes (alanine transaminase and aspartate transaminase), serum lipids (triglycerides and total cholesterol), and oxidative stress markers. The HFD feeding increased the body weight and caused NAFLD, liver steatosis, hyperlipidemia, oxidative stress, and elevated liver enzymes. Administration of PPE ameliorated the hepatic morphology, reduced body weight, improved liver enzymes, and inhibited lipogenesis. Furthermore, PPE enhanced the cellular redox status in the liver tissue of rats with NAFLD. Our findings suggest that PPE could improve HFD-induced NAFLD via abolishment of hepatic oxidative damage and hyperlipidemia. PPE might be considered as a potential lead material in the treatment of NAFLD and obesity through the modulation of lipid metabolism. PMID:27069901

  20. Paraoxonase Activity and Expression Is Modulated by Therapeutics in Experimental Rat Nonalcoholic Fatty Liver Disease

    Science.gov (United States)

    Hussein, O.; Zidan, J.; Abu Jabal, K.; Shams, I.; Szvalb, S.; Grozovski, M.; Bersudsky, I.; Karry, R.; Aviram, M.

    2012-01-01

    Objective. The objective of the present study is to investigate the effect of rosiglitazone, metformin, ezetimibe, and valsartan (alone or in combinations) on paraoxonase (PON) activity and PON-mRNA expression in nonalcoholic fatty liver disease (NAFLD). Methods. 54 Male Sprague–Dawley rats were divided to 9 groups: chow diet group (15 weeks); methionine-choline-deficient diet (MCDD) group (15 weeks); MCDD-treated groups for the last 6 weeks with either metformin (M), rosiglitazone (R), metformin plus rosiglitazone (M+R), ezetimibe (E), valsartan (V), or a combination of R+M+V or of R+M+V+E for a total period of 15 weeks. Results. PON activities in serum and liver were decreased in MCDD rats. PON activity in serum increased significantly in all treatment groups. PON activity in liver was also increased significantly, except only in groups R, E, V, R+M+V, and R+M+V+E. Liver PON3 mRNA expression increased significantly in groups R+M, E, V, R+M+V, and R+M+V+E whereas liver PON2 mRNA expression increased significantly in MCDD, R+M, E, V, R+M+V, and R+M+V+E. Conclusions. PON activities in serum and liver were decreased in NAFLD. Treatment with insulin sensitizers, ezetimibe, and valsartan increased PON activity and reduced oxidative stress both in serum and liver. PMID:22536512

  1. Paraoxonase Activity and Expression Is Modulated by Therapeutics in Experimental Rat Nonalcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    O. Hussein

    2012-01-01

    Full Text Available Objective. The objective of the present study is to investigate the effect of rosiglitazone, metformin, ezetimibe, and valsartan (alone or in combinations on paraoxonase (PON activity and PON-mRNA expression in nonalcoholic fatty liver disease (NAFLD. Methods. 54 Male Sprague–Dawley rats were divided to 9 groups: chow diet group (15 weeks; methionine-choline-deficient diet (MCDD group (15 weeks; MCDD-treated groups for the last 6 weeks with either metformin (M, rosiglitazone (R, metformin plus rosiglitazone (M+R, ezetimibe (E, valsartan (V, or a combination of R+M+V or of R+M+V+E for a total period of 15 weeks. Results. PON activities in serum and liver were decreased in MCDD rats. PON activity in serum increased significantly in all treatment groups. PON activity in liver was also increased significantly, except only in groups R, E, V, R+M+V, and R+M+V+E. Liver PON3 mRNA expression increased significantly in groups R+M, E, V, R+M+V, and R+M+V+E whereas liver PON2 mRNA expression increased significantly in MCDD, R+M, E, V, R+M+V, and R+M+V+E. Conclusions. PON activities in serum and liver were decreased in NAFLD. Treatment with insulin sensitizers, ezetimibe, and valsartan increased PON activity and reduced oxidative stress both in serum and liver.

  2. 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.

  3. 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

  4. 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...

  5. Comparison of Serum Ferritin and Vitamin D in Association with the Severity of Nonalcoholic Fatty Liver Disease in Korean Adults

    OpenAIRE

    Jeong, Dong Wook; Lee, Hye Won; Cho, Young Hye; Yi, Dong Won; Lee, Sang Yeoup; Son, Seok Man; Kang, Yang Ho

    2014-01-01

    Background Increased serum ferritin and decreased vitamin D levels associated with nonalcoholic fatty liver disease (NAFLD). However, their association with the severity of NAFLD has not been fully evaluated. The aim of this study was to compare the association of serum ferritin and 25(OH)D3 levels with the severity of ultrasonographically detected NAFLD (US-NAFLD) and hepatic steatosis defined by fatty liver index (FLI) in Korean adults. Methods A cross-sectional analysis of clinical and ant...

  6. Lung metastasis of fatty hepatocellular carcinoma after liver transplant: a case report.

    Science.gov (United States)

    Tepeoğlu, Merih; Özdemir, B Handan; Ok Atılgan, Alev; Akdur, Aydıncan; Haberal, Mehmet

    2014-03-01

    Hepatocellular carcinoma with prominent fatty change is rare, and to date only a few cases have been reported. In this article, we present a 57-yearold woman who underwent a liver transplant for hepatocellular carcinoma. Ten months after liver transplant, she presented with a persistent cough. Computed tomography of the chest was performed, revealing a solid lung mass that measured 1 × 0.9 cm in the right inferior lobe. Right inferior lobectomy was performed, and the final diagnosis was noted as hepatocellular carcinoma with prominent fatty change. Fatty change was extensive in the tumor; therefore, lipoid pneumonia was the first condition that was considered in the differential diagnosis during examination of the lobectomy material. For the differential diagnosis, the immunohistochemistry panel was studied to show the hepatocellular nature of the tumor. Although metastasis of hepatocellular carcinoma to the lungs is expected, hepatocellular carcinoma with prominent fatty change can cause diagnostic difficulties, such as lipoid pneumonia, especially in small lung biopsies. PMID:24635803

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. Doppler waveforms of the hepatic veins in children with diffuse fatty infiltration of the liver

    International Nuclear Information System (INIS)

    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.

  13. 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

  14. Spontaneous nonalcoholic fatty liver disease and ER stress in Sidt2 deficiency mice.

    Science.gov (United States)

    Gao, Jialin; Zhang, Yao; Yu, Cui; Tan, Fengbiao; Wang, Lizhuo

    2016-08-01

    Sidt2 is a newly discovered lysosomal membrane protein that is closely related to glucose metabolism. In the present study, we found that Sidt2 is also closely related to lipid metabolism. Gradual increases in serum triglyceride (TG) and free fatty acid, as well as elevated aspartate transaminase and alanine transaminase levels were observed in Sidt2(-/-) mice fed a normal diet from the age of 3 months, suggesting the presence of lipid metabolism disorders and impaired liver function in these mice. In the liver slices of 6-month-old Sidt2(-/-) mice, there were obvious fat degeneration and inflammatory changes. Almost all of the liver cells demonstrated different levels of lipid droplet accumulation and cell swelling, and some of the cells demonstrated balloon-like changes. Infiltration of inflammatory cells was observed in the portal area and hepatic lobule. Electron microscopy showed that macrophages tended to be attached to the endothelial cells, and a large number of lipid droplets were present in the liver cells. Oil red O staining showed that there were significantly increased number of deep straining particles in the liver cells of Sidt2(-/-) mice, and the TG content in liver tissue was also significantly increased. Detection of key genes and proteins related to fat synthesis showed that mRNA and protein levels of the SREBP1c in the liver of Sidt2(-/-) mice were significantly elevated, and the downstream genes acetyl-CoA carboxylase, fatty acid synthase, and mitochondrial glycerol 3-phosphate acyltransferase were significantly upregulated. In addition, there was severe endoplasmic reticulum stress (ERS) in the liver of Sidt2(-/-) mice, which had significantly increased levels of markers specific for unfolded protein response activation, Grp78 and CHOP, as well as significant elevation of downstream p-PERK, p-eIF2a, p-IRE1a, along with ER damage. These results suggest that Sidt2(-/-) mice had spontaneous nonalcoholic fatty liver disease (NAFLD) accompanied by

  15. Acetylation of Mitochondrial Trifunctional Protein α-Subunit Enhances Its Stability To Promote Fatty Acid Oxidation and Is Decreased in Nonalcoholic Fatty Liver Disease.

    Science.gov (United States)

    Guo, Liang; Zhou, Shui-Rong; Wei, Xiang-Bo; Liu, Yuan; Chang, Xin-Xia; Liu, Yang; Ge, Xin; Dou, Xin; Huang, Hai-Yan; Qian, Shu-Wen; Li, Xi; Lei, Qun-Ying; Gao, Xin; Tang, Qi-Qun

    2016-10-15

    Nonalcoholic fatty liver disease (NAFLD) has become the most common liver disease, and decreased fatty acid oxidation is one of the important contributors to NAFLD. Mitochondrial trifunctional protein α-subunit (MTPα) functions as a critical enzyme for fatty acid β-oxidation, but whether dysregulation of MTPα is pathogenically connected to NAFLD is poorly understood. We show that MTPα is acetylated at lysine residues 350, 383, and 406 (MTPα-3K), which promotes its protein stability by antagonizing its ubiquitylation on the same three lysines (MTPα-3K) and blocking its subsequent degradation. Sirtuin 4 (SIRT4) has been identified as the deacetylase, deacetylating and destabilizing MTPα. Replacement of MTPα-3K with either MTPα-3KR or MTPα-3KQ inhibits cellular lipid accumulation both in free fatty acid (FFA)-treated alpha mouse liver 12 (AML12) cells and primary hepatocytes and in the livers of high-fat/high-sucrose (HF/HS) diet-fed mice. Moreover, knockdown of SIRT4 could phenocopy the effects of MTPα-3K mutant expression in mouse livers, and MTPα-3K mutants more efficiently attenuate SIRT4-mediated hepatic steatosis in HF/HS diet-fed mice. Importantly, acetylation of both MTPα and MTPα-3K is decreased while SIRT4 is increased in the livers of mice and humans with NAFLD. Our study reveals a novel mechanism of MTPα regulation by acetylation and ubiquitylation and a direct functional link of this regulation to NAFLD. PMID:27457618

  16. 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.

  17. Effects of sodium arsenate exposure on liver fatty acid profiles and oxidative stress in rats.

    Science.gov (United States)

    Kharroubi, Wafa; Dhibi, Madiha; Haouas, Zohra; Chreif, Imed; Neffati, Fadoua; Hammami, Mohamed; Sakly, Rachid

    2014-02-01

    The present study aimed to evaluate the effect of arsenic on liver fatty acids (FA) composition, hepatotoxicity and oxidative status markers in rats. Male rats were randomly devised to six groups (n=10 per group) and exposed to sodium arsenate at a dose of 1 and 10 mg/l for 45 and 90 days. Arsenate exposure is associated with significant changes in the FA composition in liver. A significant increase of saturated fatty acids (SFA) in all treated groups (p<0.01) and trans unsaturated fatty acids (trans UFA) in rats exposed both for short term for 10 mg/l (p<0.05) and long term for 1 and 10 mg/l (p<0.001) was observed. However, the cis UFA were significantly decreased in these groups (p<0.05). A markedly increase of indicator in cell membrane viscosity expressed as SFA/UFA was reported in the treated groups (p<0.001). A significant increase in the level of malondialdehyde by 38.3 % after 90 days of exposure at 10 mg/l was observed. Compared to control rats, significant liver damage was observed at 10 mg/l of arsenate by increasing plasma marker enzymes after 90 days. It is through the histological investigations in hepatic tissues of exposed rats that these damage effects of arsenate were confirmed. The antioxidant perturbations were observed to be more important at groups treated by the high dose (p<0.05). An increase in the level of protein carbonyls was observed in all treated groups (p<0.05). The present study provides evidence for a direct effect of arsenite on FA composition disturbance causing an increase of SFA and TFAs isomers, liver dysfunction and oxidative stress. Therefore, arsenate can lead to hepatic damage and propensity towards liver cancer. PMID:23949113

  18. 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.

  19. Nonalcoholic fatty liver disease progression in rats is accelerated by splenic regulation of liver PTEN/AKT

    Directory of Open Access Journals (Sweden)

    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.

  20. 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...

  1. Effect of physical training on liver expression of activin A and follistatin in a nonalcoholic fatty liver disease model in rats

    OpenAIRE

    de Silva, R N; Bueno, P.G.; L.R.S. Avó; Nonaka, K.O.; H.S. Selistre-Araújo; A.M.O. Leal

    2014-01-01

    Nonalcoholic fatty liver disease (NAFLD) is characterized by fat accumulation in the liver and is associated with obesity and insulin resistance. Activin A is a member of the transforming growth factor beta (TGF)-β superfamily and inhibits hepatocyte growth. Follistatin antagonizes the biological actions of activin. Exercise is an important therapeutic strategy to reduce the metabolic effects of obesity. We evaluated the pattern of activin A and follistatin liver expression in obese rats subj...

  2. Metformin protects rat hepatocytes against bile acid-induced apoptosis.

    Directory of Open Access Journals (Sweden)

    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.

  3. 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

  4. 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

  5. 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.

  6. 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.

  7. 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. PMID:27289203

  8. 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.

  9. EFFECTS OF HIGH DIETARY FAT ON SERUM CHOLESTEROL AND FATTY LIVER SYNDROME IN BROILERS

    Directory of Open Access Journals (Sweden)

    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.

  10. 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.

  11. 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.

  12. 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.

  13. 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......,414 type 2 diabetes mellitus (T2DM) cases and 4,567 controls were genotyped. Liver expression of the associated gene was measured and the effect of its potential role was studied by silencing the gene in vitro. Whole genome expression, oxidative stress (OS), and the consequences of oleic acid (OA...... association with NAFLD, but not with T2DM, being the haplotype containing the minor allele of SLC2A1 sequence related to the susceptibility to develop NAFLD. Gene-expression analysis demonstrated a significant down-regulation of SLC2A1 in NAFLD livers. Enrichment functional analyses of transcriptome profiles...

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

    DEFF Research Database (Denmark)

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

    2013-01-01

    after the exercise program and the increase was positively correlated with the increase in liver PUI (r = 0.52, P = .05). Body weight remained stable during the program (P > .05). Conclusion: Short-term exercise can target hepatic lipid composition, which may reduce the risk of NAFLD progression......Hepatic steatosis, insulin resistance, inflammation, low levels of polyunsaturated lipids, and adiponectin are implicated in the development and progression of nonalcoholic fatty liver disease (NAFLD). Objective: We examined the effects of short-term aerobic exercise on these metabolic risk factors...... measures included hepatic triglyceride content, and a lipid saturation index and polyunsaturated lipid index (PUI) of the liver, obtained by 1H magnetic resonance spectroscopy (N = 14). Insulin sensitivity was estimated from an oral glucose tolerance test (OGTT), and mononuclear cells were isolated...

  15. Fluorescent n-3 and n-6 Very Long Chain Polyunsaturated Fatty Acids: THREE-PHOTON IMAGING IN LIVING CELLS EXPRESSING LIVER FATTY ACID-BINDING PROTEIN*

    OpenAIRE

    McIntosh, Avery L.; Huang, Huan; Atshaves, Barbara P.; Wellberg, Elizabeth; Kuklev, Dmitry V.; Smith, William L.; Kier, Ann B.; Schroeder, Friedhelm

    2010-01-01

    Despite the considerable beneficial effects of n-3 and n-6 very long chain polyunsaturated fatty acids (VLC-PUFAs), very little is known about the factors that regulate their uptake and intracellular distribution in living cells. This issue was addressed in cells expressing liver-type fatty acid-binding protein (L-FABP) by real time multiphoton laser scanning microscopy of novel fluorescent VLC-PUFAs containing a conjugated tetraene fluorophore near the carboxyl group and natural methylene-in...

  16. 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...

  17. 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

  18. Fructose as a key player in the development of fatty liver disease.

    Science.gov (United States)

    Basaranoglu, Metin; Basaranoglu, Gokcen; Sabuncu, Tevfik; Sentürk, Hakan

    2013-02-28

    We aimed to investigate whether increased consumption of fructose is linked to the increased prevalence of fatty liver. The prevalence of nonalcoholic steatohepatitis (NASH) is 3% and 20% in nonobese and obese subjects, respectively. Obesity is a low-grade chronic inflammatory condition and obesity-related cytokines such as interleukin-6, adiponectin, leptin, and tumor necrosis factor-α may play important roles in the development of nonalcoholic fatty liver disease (NAFLD). Additionally, the prevalence of NASH associated with both cirrhosis and hepatocellular carcinoma was reported to be high among patients with type 2 diabetes with or without obesity. Our research group previously showed that consumption of fructose is associated with adverse alterations of plasma lipid profiles and metabolic changes in mice, the American Lifestyle-Induced Obesity Syndrome model, which included consumption of a high-fructose corn syrup in amounts relevant to that consumed by some Americans. The observation reinforces the concerns about the role of fructose in the obesity epidemic. Increased availability of fructose (e.g., high-fructose corn syrup) increases not only abnormal glucose flux but also fructose metabolism in the hepatocyte. Thus, the anatomic position of the liver places it in a strategic buffering position for absorbed carbohydrates and amino acids. Fructose was previously accepted as a beneficial dietary component because it does not stimulate insulin secretion. However, since insulin signaling plays an important role in central mechanisms of NAFLD, this property of fructose may be undesirable. Fructose has a selective hepatic metabolism, and provokes a hepatic stress response involving activation of c-Jun N-terminal kinases and subsequent reduced hepatic insulin signaling. As high fat diet alone produces obesity, insulin resistance, and some degree of fatty liver with minimal inflammation and no fibrosis, the fast food diet which includes fructose and fats produces

  19. Effective treatment of steatosis and steatohepatitis by fibroblast growth factor 1 in mouse models of nonalcoholic fatty liver disease

    NARCIS (Netherlands)

    Liu, Weilin; Struik, Dicky; Nies, Vera J M; Jurdzinski, Angelika; Harkema, Liesbeth; de Bruin, Alain; Verkade, Henkjan J; Downes, Michael; Evans, Ronald M; van Zutphen, Tim; Jonker, Johan W

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder and is strongly associated with obesity and type 2 diabetes. Currently, there is no approved pharmacological treatment for this disease, but improvement of insulin resistance using peroxisome proliferator-activated re

  20. 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

  1. Non-Alcoholic Fatty Liver Disease and Metabolic Syndrome after Liver Transplant

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    Stefano Gitto

    2016-04-01

    Full Text Available 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, onset of insulin resistance and drug-induced alterations of metabolism are reported in liver transplant recipients. In this context, post-transplant diabetes mellitus, hyperlipidemia, and arterial hypertension can be often diagnosed. Multifactorial illnesses occurring in the post-transplant period represent significant causes of morbidity and mortality. This is especially true for metabolic syndrome. Non-alcoholic steatosis and steatohepatitis are hepatic manifestations of metabolic syndrome and after liver transplant both recurrent and de novo steatosis can be found. Usually, post-transplant steatosis shows an indolent outcome with few cases of fibrosis progression. However, in the post-transplant setting, both metabolic syndrome and steatosis might play a key role in the stratification of morbidity and mortality risk, being commonly associated with cardiovascular disease. The single components of metabolic syndrome can be treated with targeted drugs while lifestyle intervention is the only reasonable therapeutic approach for transplant patients with non-alcoholic steatosis or steatohepatitis.

  2. Fatty Liver Index Associates with Relative Sarcopenia and GH/ IGF- 1 Status in Obese Subjects.

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    Eleonora Poggiogalle

    Full Text Available Recently the association between hepatic steatosis and sarcopenia has been described. GH/IGF-1 axis has been postulated to play a role in linking fatty liver and low muscle mass. The aim of our study was to explore the association between fatty liver index, sarcopenic obesity, insulin sensitivity, and GH/IGF-1 status.427 subjects [age: 45.65±13.94 years, BMI: 36.92±6.43 kg/m2] were enrolled. Participants were divided into three groups: fatty liver index (FLI <20, 20≥FLI<60, and FLI≥60. Body composition was assessed by DXA. The truncal fat mass (TrFM to appendicular skeletal muscle (ASM ratio was used as an indicator of sarcopenic obesity. ISI-Matsuda index was used.BMI, fat mass, and the TrFM/ASM ratio were higher in subjects with FLI≥60. GH, IGF-1 and ISI-Matsuda were lower in the high FLI group (all p<0.05. A significantly positive correlation between FLI and TrFM/ ASM ratio (r = 0.221, p<0.001 was found, whereas FLI levels were negatively correlated with ISI- Matsuda (r = -0.335, p<0.001, GH (r = -0.200, p = 0.006, and IGF- 1 levels (r = -0.157, p = 0.028. Stepwise linear regression analysis showed that GH levels were significantly negatively correlated with FLI, while the TrFM/ ASM ratio was positively associated with FLI, after adjustment for age, BMI, total fat mass, truncal fat mass, fat- free mass, and ISI- Matsuda.Impairment of GH/IGF-1 axis seems to be associated to the risk of the development of sarcopenic obesity and ectopic fat deposition in the liver. Metabolic and hormonal derangements as determinants of ectopic fat deposition and body composition deserve to be evaluated in obese subjects.

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

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    Mônica Rodrigues de Araújo Souza

    2012-03-01

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

  4. Correlation between leptin level with lipid profile and free fatty acid in liver cirrhosis patients

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    Siti Maryani

    2015-09-01

    Full Text Available Malnutrition is a common condition in liver cirrhotic patients. Leptin regulates body weightphysiologically by suppressing appetite and increasing energy expenditure. Leptin is higher in femalethan male. Studies have shown correlation between leptin with metabolic factors like body massindex (BMI and lipid profile in cirrhotic patients. This study was conducted to investigate thecorrelation between serum leptin levels with lipid profile and free fatty acid in male patients with livercirrhosis. This was a cross sectional study that conducted at Gastroentero-Hepatology Clinic andInternal Ward at Dr. Sardjito General Hospital, Yogyakarta. The inclusion criteria were patients withliver cirrhosis > 18 years old, male, with Child-Pugh classification B and C, and provided informedconsent. The exclusion criteria were liver cirrhotic patients with comorbidity chronic kidney disease,chronic heart failure, diabetic, cancer, infection/septic, pregnancy, breast feeding, and steroid use.Data collecting was performed by anamnesis, physical examination, abdominal ultrasonographyexamination, and blood chemistry test. Pearson test was used to evaluate the correlation betweenthe serum leptin level with the lipid profile and free fatty acid. The results showed that no significantnegative correlation was observed between the serum leptin level with the total cholesterol (r= -0.052; p=0.766, high-density lipoprotein/HDL (r= -0.078; p=0.658 and triglyceride (r= -0.170; p=0.328 in male patients with liver cirrhosis. Furthermore, no significant positive correlationwas observed between the serum leptin levels with the low-density lipoprotein/LDL (r= -0.013; p=0.942 and free fatty acid/FFA (r= 0.007; p=0.968. In conclusion, there was no correlationbetween serum leptin levels with lipid profile and FFA in male patients with liver cirrhosis.

  5. Efficacy of oral nicotinic acid and choline in the treatment and prevention of fatty liver in dairy cow

    Institute of Scientific and Technical Information of China (English)

    TianWenru; YangDianjun; 等

    1994-01-01

    Nicotinic acid (N.C.)and choline were given orally to the periparturient cows to treat and prevent fatty liver.Blood parameters of glucose,β-hydroxybutyrate,albumin,total protein,magnesium,aspartate aminotransferase(AST) and non-esterified fatty acid(NEFA) were measured.There were no significant differences between the reated and untreated groups in the plasma concentrations of albumin,total,protein and magnsium.Significant decrease in plasma concentrations of β-hydroxybutyrate,NEFA and AST were observed in the treated cows following administration of N.C.and choline.All the fatty liver cows(100%) treated with N.C.and choline recovered within 5 weeks after calving compared with 71.4%(5/7) of untreated cows recovered.The incident ate of fatty liver postpartum in the cows with N.C.and choline given 2 weeks before calving was 30%(3/10),and the affected cows had a range of mild to moderate fatty liver whilst the incident rate was 50%(5/10)in the untreated cows.which had a range of mild to of severe fatty liver,Meanwhile,the treated cows had a significant higher prodection of milk and shorter intervals from calving to uterine involution,to the first postpartum ovulation and to conception.

  6. Ultrasound imaging in an experimental model of fatty liver disease and cirrhosis in rats

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    Campos de Carvalho Antonio

    2010-01-01

    Full Text Available Abstract Background Domestic dogs and cats are very well known to develop chronic hepatic diseases, including hepatic lipidosis and cirrhosis. Ultrasonographic examination is extensively used to detect them. However, there are still few reports on the use of the ultrasound B-mode scan in correlation with histological findings to evaluate diffuse hepatic changes in rodents, which represent the most important animal group used in experimental models of liver diseases. The purpose of this study was to determine the reliability of ultrasound findings in the assessment of fatty liver disease and cirrhosis when compared to histological results in Wistar rats by following up a murine model of chronic hepatic disease. Results Forty Wistar rats (30 treated, 10 controls were included. Liver injury was induced by dual exposure to CCl4 and ethanol for 4, 8 and 15 weeks. Liver echogenicity, its correlation to the right renal cortex echogenicity, measurement of portal vein diameter (PVD and the presence of ascites were evaluated and compared to histological findings of hepatic steatosis and cirrhosis. Liver echogenicity correlated to hepatic steatosis when it was greater or equal to the right renal cortex echogenicity, with a sensitivity of 90%, specificity of 100%, positive and negative predictive values of 100% and 76.9% respectively, and accuracy of 92.5%. Findings of heterogeneous liver echogenicity and irregular surface correlated to liver cirrhosis with a sensitivity of 70.6%, specificity of 100%, positive and negative predictive values of 100% and 82.1% respectively, and accuracy of 87.5%. PVD was significantly increased in both steatotic and cirrhotic rats; however, the later had greater diameters. PVD cut-off point separating steatosis from cirrhosis was 2.1 mm (sensitivity of 100% and specificity of 90.5%. One third of cirrhotic rats presented with ascites. Conclusion The use of ultrasound imaging in the follow-up of murine diffuse liver disease

  7. Non-alcoholic fatty liver disease and metabolic syndrome in obese children

    Institute of Scientific and Technical Information of China (English)

    Mehmet Emre Atabek

    2011-01-01

    I read with great interest the article of Fu et al who investigated whether non-alcoholic fatty liver disease (NAFLD) is an early mediator for prediction of metabolic syndrome, and whether liver B-ultrasound could be used for its diagnosis, in a study involving 861 obese children (6-16 years old). In this study, it was reported that NAFLD is not only a liver disease, but also an early mediator that reflects metabolic disorder, and that liver B-ultrasound can be a useful tool for metabolic syndrome (MS) screening.Theauthorsreportedthat The authorsreportedthat reported that NAFLD and MS were present in 68.18% and 25.67% of obese children, respectively. Moreover, they observed that the prevalence of MS in NAFLD children was 37.64%, which was much higher than that in the non-NAFLD group. Criteria analogous to those of the Adult Treatment Panel Ⅲ definition for MS were used for children in this study. The reported prevalence data on MS in the young has varied markedly, in large part because of disagreement among the variously proposed definitions of MS. Therefore, in my opinion, a study aiming to assess the association between MS components and NAFLD in obese children has to take into account a simple, easy-to-apply clinical definition proposed by the international diabetes federation for MS. Interpretation of the results of the Fu et al study are limited by another major caveat: that the diagnosis or exclusion of NAFLD was based on liver enzymes and ultrasound imaging, but was not confirmed by liver biopsy. Indeed, it is known that liver enzymes may be within the reference interval in up to 70% of patients with diagnosed NAFLD and that the full histopathological spectrum of NAFLD may be present in patients with normal liver enzymes, which therefore cannot be reliably used to exclude the presence of NAFLD.

  8. Effect of dietary fatty acids on serum parameters, fatty acid compositions, and liver histology in Shaoxing laying ducks

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    Wei-meng LIU; Guo-qin LI; De-qian WANG; Jin-jun LI; Yong TIAN; Shu-jing LAI; Li-zhi LU; Fang-xiong SHI; Jing ZHANG; Yu LIU; Bo YU; Zheng-rong TAO; Jun-da SHEN

    2011-01-01

    The effects of different fatty acid (FA) contents in diet on serum parameters,FA compositions of eggs and meat,and liver morphological changes were studied in Shaoxing laying ducks.A total of 264 ducks at 17 weeks were fed a control diet or a diet containing 30 g/kg fish oil (FO),25 g/kg sunflower oil (SO),or 30 g/kg palm oil with 20 g/kg beef tallow (PBO).Malondialdehyde (MDA) content in the liver and the serum of ducks fed the PBO diet was significantly (P<0.05) higher than that of ducks fed the other diets.Triglyceride (TG) and total cholesterol (TC) levels were significantly lower (P<0.05) in ducks fed the FO diet.Serum TC also was lower in ducks fed the SO diet.Superoxide dismutase (SOD) activity was also affected by diets.The contents of polyunsaturated FAs (PUFAs) in eggs and meat were significantly higher (P<0.001) in ducks fed the FO and SO diets than in ducks fed the control diet.The level of C22:6 (n-3) FA in ducks fed the FO diet was significantly higher than that in ducks fed the other diets.However,the conversion efficiency of the longer-chain C20:5 (n-3) FA was higher than that of C22:6 (n-3).Ducks fed the PBO diet exhibited lipid droplet accumulation in the liver.These results demonstrate that a diet enriched with different FAs has strong effects on serum lipid levels and the deposition of PUFAs into tissue lipids.

  9. Association of homocysteine level with biopsy-proven non-alcoholic fatty liver disease: a meta-analysis

    Science.gov (United States)

    Dai, Yining; Zhu, Jinzhou; Meng, Di; Yu, Chaohui; Li, Youming

    2016-01-01

    Previous studies have reported inconsistent findings regarding the association between plasmatic higher of homocysteine level and non-alcoholic fatty liver disease. We aimed to investigate this association by conducting a meta-analysis. Literature was searched on PubMed from inception to January 2015. Eight studies evaluating plasma level of homocysteine in biopsy-proven non-alcoholic fatty liver disease subjects compared to healthy controls were included. Compared with the controls, non-alcoholic fatty liver disease patients witnessed a higher level of homocysteine [standard mean difference (SMD): 0.66 µmol/L, 95% CI: 0.41, 0.92 µmol/L], and were associated with a significant increased risk for hyperhomocysteinemia [odds ratio (OR) 5.09, 95% CI: 1.69, 15.32]. In addition, patients with non-alcoholic fatty liver presented 0.45 µmol/L higher levels of homocysteine compared to healthy controls (95% CI: 0.09, 0.82 µmol/L), whereas non-alcoholic steatohepatitis patients had 1.02 µmol/L higher levels of homocysteine (95% CI: 0.28, 1.76 µmol/L). There was neither difference of folate level nor vitamin B12 level between non-alcoholic fatty liver disease subjects and healthy controls. This study revealed that non-alcoholic fatty liver disease patients presented an increased serum concentration of homocysteine, and were associated with an increased risk of hyperhomocysteinemia. Further studies are needed to demonstrate a causal role of hyperhomocysteinemia in non-alcoholic fatty liver disease. PMID:26798201

  10. Effect of baicalin on toll-like receptor 4-mediated ischemia/reperfusion inflammatory responses in alcoholic fatty liver condition

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    Kim, Seok-Joo; Lee, Sun-Mee, E-mail: sunmee@skku.edu

    2012-01-01

    Alcoholic fatty liver is susceptible to secondary stresses such as ischemia/reperfusion (I/R). Baicalin is an active component extracted from Scutellaria baicalensis, which is widely used in herbal preparations for treatment of hepatic diseases and inflammatory disorders. This study evaluated the potential beneficial effect of baicalin on I/R injury in alcoholic fatty liver. Rats were fed an alcohol liquid diet or a control isocaloric diet for 5 weeks, and then subjected to 60 min of hepatic ischemia and 5 h of reperfusion. Baicalin (200 mg/kg) was intraperitoneally administered 24 and 1 h before ischemia. After reperfusion, baicalin attenuated the increases in serum alanine aminotransferase activity, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) levels in alcoholic fatty liver. The increased levels of TNF-α and IL-6 mRNA expression and inducible nitric oxide synthase and cyclooxygenase-2 protein and mRNA expressions increased after reperfusion, which were higher in ethanol-fed animals, were attenuated by baicalin. In ethanol-fed animals, baicalin attenuated the increases in toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 protein expressions and the nuclear translocation of NF-κB after reperfusion. In conclusion, our findings suggest that baicalin ameliorates I/R-induced hepatocellular damage by suppressing TLR4-mediated inflammatory responses in alcoholic fatty liver. -- Highlights: ► Baicalin attenuates hepatic I/R-induced inflammation in alcoholic fatty liver. ► Baicalin downregulates TLR4, MyD88 expression during I/R in alcoholic fatty liver. ► Baicalin attenuates NF-κB nuclear translocation during I/R in alcoholic fatty liver.

  11. NONALCOHOLIC FATTY LIVER DISEASE IN SEVERE OBESE PATIENTS, SUBJECTED TO BARIATRIC SURGERY

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    Alexandre LOSEKANN

    2013-12-01

    Full Text Available Context Nonalcoholic fatty liver disease encompasses a spectrum of histopathological changes that range from simple steatosis to nonalcoholic steatohepatitis. Works suggest that iron (Fe deposits in the liver are involved in the physiopathology of nonalcoholic steatohepatitis. Objective The aim of this study was to determine the prevalence of simple steatosis and nonalcoholic steatohepatitis in patients with morbid obesity, subjected to bariatric surgery and to establish a correlation of the anatomopathological findings with the presence of liver fibrosis. Methods A total of 250 liver biopsies were conducted in the transoperation of the surgeries. Results Steatosis was present in 226 (90.4% of the samples, 76 (30.4% being classified as mild; 71 (28.4% as moderate and 79 (31.6% as intense. Nonalcoholic steatohepatitis was diagnosed in 176 (70.4% cases, where 120 (48.4% were mild; 50 (20% were moderate, and 6 (2.4% cases were intense. Fibrosis was referred to in 108 (43.2% biopsies, 95 of which (38% were mild; 2 (0.8% were moderate; 7 (2.8% were intense, and cirrhosis was diagnosed in 4 (1.6% cases. There was a correlation between the degree of steatosis and the level of inflammatory activity (rs = 0.460; P<0.001 and between the degree of this activity and the degree of fibrosis (rs = 0.583; P<0.001. Only 13 (5.2% samples showed Fe deposits. Conclusion There is a high prevalence of nonalcoholic steatohepatitis in these patients and a positive correlation of the degrees of nonalcoholic steatohepatitis with the intensity of fibrosis. The low prevalence of Fe deposits found makes it questionable that the presence of this ion has any participation in the physiopathogeny of nonalcoholic fatty liver disease.

  12. Understanding the pathophysiological mechanisms inthe pediatric non-alcoholic fatty liver disease: The role ofgenetics

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Classically, the non-alcoholic fatty liver disease (NAFLD)physiopathology and progression has been summarizedin the two hits hypothesis. The first hit is represented by the action of hyperinsulinemia and insulin resistance,accompanying obesity, that leads to liver steatosisincreasing the absolute non esterified fatty acids uptakein the liver and the esterification to form triacylglycerol.The oxidative stress is involved in the second hit leadingto the progression to nonalcoholic steatohepatitis(NASH) because of its harmful action on steatosichepatocytes. However, at the present time, the two hitshypothesis needs to be updated because of the discoverof genetic polymorphisms involved both in the liver fataccumulation and progression to NASH that make moreintriguing understanding the NAFLD pathophysiologicalmechanisms. In this editorial, we want to underline therole of PNPLA3 I148M, GPR120 R270H and TM6SF2E167K in the pediatric NAFLD development becausethey add new pieces to the comprehension of theNAFLD pathophysiological puzzle. The PNPLA3 I148Mpolymorphism encodes for an abnormal protein whichpredisposes to intrahepatic triglycerides accumulationboth for a loss-of-function of its triglyceride hydrolaseactivity and for a gain-of-function of its lipogenic activity.Therefore, it is involved in the first hit, such as TM6SF2E167K polymorphisms that lead to intrahepatic fat accumulationthrough a reduced very low density lipoproteinsecretion. On the other hand, the GPR120 R270H variant,reducing the anti-inflammatory action of the GPR120receptor expressed by Kuppfer cells, is involved in thesecond hit leading to the liver injury.

  13. Protective effects of Ginkgo biloba leaf polysaccharide on nonalcoholic fatty liver disease and its mechanisms.

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    Yan, Zhengui; Fan, Ruifeng; Yin, Shaojie; Zhao, Xiaona; Liu, Jianzhu; Li, Liuhui; Zhang, Wenqi; Ge, Lijiang

    2015-09-01

    A water-soluble polysaccharide fraction extracted from the leaf of Ginkgo biloba was named GBLP. The protective effect of GBLP on nonalcoholic fatty liver disease (NAFLD) was observed and underlying mechanism was explored. Wistar male rats were randomly divided into five groups, namely, normal control group, model control group and GBLP groups (100, 200 and 400 mg/kg/d). A rat model of NAFLD was established in male Wistar rats by feeding with high-fat diet (HFD) for 8 weeks. On day 57, the intragastric administration of GBLP started once daily for 4 weeks. The results showed that GBLP supplementation significantly and dose-dependently lowered the weight gain of body, liver index and serum lipid parameters in HFD-fed rat. Meanwhile, GBLP attenuated HFD-induced liver injury through reducing hepatic steatosis, TG accumulation, serum ALT, AST and ALP levels. GBLP had a positive effect on obesity-associated insulin resistance (IR) via reducing serum glucose and insulin levels. Furthermore, GBLP enhanced the activities of antioxidant enzymes and reduced MDA levels in serum and liver. These results indicate that GBLP can play a certain protective role against HFD-induced NAFLD, and the protective effects may be associated with attenuating IR, preserving liver function, enhancing antioxidant defense system, and reducing lipid peroxidation.

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

    Science.gov (United States)

    Temple, Jonathan L; Cordero, Paul; Li, Jiawei; Nguyen, Vi; Oben, Jude A

    2016-01-01

    Non-Alcoholic Fatty Liver Disease (NAFLD) is now the most prevalent form of chronic liver disease, affecting 10%-20% of the general paediatric population. Within the next 10 years it is expected to become the leading cause of liver pathology, liver failure and indication for liver transplantation in childhood and adolescence in the Western world. While our understanding of the pathophysiological mechanisms underlying this disease remains limited, it is thought to be the hepatic manifestation of more widespread metabolic dysfunction and is strongly associated with a number of metabolic risk factors, including insulin resistance, dyslipidaemia, cardiovascular disease and, most significantly, obesity. Despite this, "paediatric" NAFLD remains under-studied, under-recognised and, potentially, undermanaged. This article will explore and evaluate our current understanding of NAFLD in childhood and adolescence and how it differs from adult NAFLD, in terms of its epidemiology, pathophysiology, natural history, diagnosis and clinical management. Given the current absence of definitive radiological and histopathological diagnostic tests, maintenance of a high clinical suspicion by all members of the multidisciplinary team in primary and specialist care settings remains the most potent of diagnostic t