Key Word(s): 1. miR-155; 2. EMT; 3. ERK1

pathway; 4. HSC; Presenting Author: SHIRAN SHETTY Additional Authors: KRISHNAVENI JANARATHANAN, LEELAVENKATAKRISHNAN VENKATAKRISHNAN Corresponding Author: SHIRAN SHETTY Affiliations: PSGIMSR Objective: Bacterial infections are the common cause of morbidity and mortality in chronic liver disease patients. Infections in patients with liver disease have a different clinical presentation and early identification is important for good outcome. Increasing prevalence and antibiotic resistance are on the rise. we aimed Paclitaxel to evaluate the recent changes in microorganisms causing clinical/ sub-clinical infections in cirrhotic patients and their antibiotic resistance pattern. Methods: In this retrospective study, 150 patients of chronic liver disease admitted in department of gastroenterology PSG medical college hospital, Coimbatore india were

included in this study over one year. Institutional Ethics Committee approval was obtained regarding inclusion and exclusion criteria, prior to commencement of study. Results: Of the 150 patients, 58 (38.7%) were found to have culture positive infection. While the most common bacteria isolated from our study was E coli, we also noticed an increasing trend of Gram positive organisms like Staphylococcus. Dabrafenib Our study showed nearly 50% of organism being resistant to 3rd generation Cephalosporins and fluoroquinolones, unlike previous studies. Conclusion: Appropriate usage of antibiotics and strict adherence

of hospital antibiotic policy is required to prevent emergence of resistant organism. Key Word(s): 1. cirrhosis; 2. bacteria infection; 3. resistance; 4. Ecoli; Presenting Author: JUAN ZHAO Additional Authors: NAN TANG, KAIMING WU, WEIPING DAI, CHANGHONG YE, JIAN SHI, BEIFANG NING, XIN ZENG, YONG LIN Corresponding Author: XIN ZENG, YONG LIN Affiliations: Shanghai Changzheng Hospital, Second Military Medical University; Department of Gastroenterology, Shanghai Changzheng Hospital Objective: Activation of extracellular signal-regulated kinase 1 (ERK1) signaling pathway in hepatic stellate cell (HSC) and epithelial-mesenchymal transition (EMT) process in hepatocyte are considered as the important contributors to promoting accumulation of activated fibroblasts and exacerbating hepatic fibrosis. Enhancement of microRNA-21 (miR-21) expression has been 上海皓元医药股份有限公司 confirmed in activated HSC and fibrotic liver. The aim of this study was to explore the mechanism of miR-21 participating in the simultaneous regulation of ERK1 pathway and EMT process in both of HSC and hepatocyte during hepatic fibrogenesis. Methods: miR-21 levels were determined in liver tissues or serum from fibrotic models or serum from patients. Luciferase reporter assay was performed to validate whether miR-21 could directly target sprouty2 (Spry2) and hepatocyte nuclear factor 4α (HNF4α) through 3′-untranslated region (3′-UTR) interactions respectively.

The digit recall task required participants to serially recall lists of digit strings that were set at their own maximum span and read by the examiner at the approximate rate of two per second. Participants performed the tracking and digit recall tasks separately

for a period of 2 min each prior to performing both tasks concurrently for a period of 2 min. A composite selleck inhibitor measure of dual-task performance (μ) was calculated according to the formula: μ = (1 − [(Pm + Pt)/2]) × 100 (Baddeley et al., 1997). Here, μ represents the combined change in dual-task performance relative to performance on the constituent tasks, where Pm is the proportional change in memory performance and Pt is the proportional change in tracking. Pm is calculated according to (ps − pd)/ps, where ps is the proportion of digit strings recalled correctly under single task conditions and pd is the proportion of digit strings recalled under dual task. Pt is calculated according to (ts − td)/ts, where ts is the number of boxes crossed under single-task conditions and td is the number of boxes check details crossed under dual-task conditions. Auditory and visual attentional capacities were measured with digit span and spatial

span respectively (see Lezak, Howieson, Bigler, & Tranel, 2012). The TMT (see Lezak et al., 2012) was used to measure divided attention; the elevator counting task from the Test of Everyday Attention (TEA-2; Robertson, Ward, Ridgeway, & Nimmo-Smith, 1994) measured sustained attention; the elevator task with distraction (TEA-3) was deployed to measure selective attention. The ability to maintain and shift mental set was assessed with the Odd-Man-Out test (OMO; Flowers & Roberston, 1985). The mean MCE scores and standard deviations for the digit recall and tracking tasks achieved under single- and dual-task conditions

are displayed in Table 2. To ensure that any differences found between the groups reflect dual-task deficits per se and not inflated single-task differences, we followed Baddeley and colleagues (e.g., Cocchini, Logie, Della Sala, MacPherson, & Baddeley, 2002) and excluded data from participants who scored below 70% accuracy under single-digit recall conditions. Accordingly, data from four TLE patients (three left-sided and one right-sided) was excluded from further analyses. A 2 × 2 ANOVA of digit recall for the remaining participants, treating Group (TLE or control) as a between-subjects factor and condition (single or dual task) as a within-subjects factor did not reveal a main effect of group [F(1, 34) = 3.556, p > .068]. A main effect of condition was found [F(1, 34) = 5.880, p < .021] indicating that a higher proportion of digits were correctly recalled under single-task conditions. The interaction between group and condition did not approach significance [F(1, 34) = 0.501, p > .484].

However, the occurrence of severe manifestations remained variant-independent; (4) patients without macroscopic gallstones associated with intrahepatic bile duct dilatations became asymptomatic under UDCA treatment; (5) The occurrence of biliary cirrhosis and intrahepatic cholangiocarcinoma was observed but was rare. Despite very similar clinical features, half of the patients did not harbor ABCB4 alteration. The screening method used in ABCB4 analysis did not include the promoter or other potential regulatory regions of the gene and did not allow for the detection of DNA rearrangements.

Synonymous single nucleotide polymorphisms (SNPs) located in coding regions, Belnacasan chemical structure although seemingly translationally silent, could also have a profound influence on alternative splicing and could lead to exon skipping or aberrant splicing. Alternatively, defects in other regions of the genes or in other genes leading to biliary phospholipid secretion disruption or underlying susceptibility to cholelithiasis might be involved. In this context, high-resolution

gene dosage methodologies were used recently in 43 negative LPAC patients for heterozygous point or selleck screening library short insertion/deletion mutations. A partial or complete heterozygous deletion was detected in 7% of them.[23] The present results highlight the strong association of LPAC with or without ABCB4 gene sequence variation with ICP. It is assumed that the prevalence of ICP in Europe is around 2% and ∼15% of ICP are associated with ABCB4 deficiency.[11] In our cohort, half of the patients who were pregnant developed the symptoms of both syndromes. Several explanations may be proposed for the association of these two phenotypic traits. During pregnancy biliary sludge develops

in approximately one-third of the women. By the time of delivery 10% of women exhibit gallstones on ultrasonography examination MCE and approximately one-third of those having gallstones are symptomatic.[24, 25] The prevalence of cholelithiasis is higher in ICP patients than in the normal population. Symptoms of cholelithiasis are found in up to 22% of the patients presenting with severe forms of ICP.[26] Evidence has been provided to indicate that ICP might result from either ABCB11 defect or FXR dysfunction resulting from gene mutation or inhibition induced by high levels of progesterone sulfate metabolites.[27, 28] ABCB4 as ABCB11 expression being under the control of FXR, it may be expected that FXR-reduced activity would promote defective bile acids and phospholipid secretion that could lead to ICP or LPAC or both.

Results: Four pairs of liver tissues were selected for RNA extraction. miRNA microarray and FDR calculation were performed and four genes were selected due to the previous report on their correlation with HCC. The results of luciferase assay and transfection of HepG2 cells indicated that miRNA-128 indeed binds to the 3′ UTR of Axin1. In Western blotting study miR-128 indeed decreased Axin1 protein levels, demonstrating that Axin1 is indeed a target of miR-128 in HepG2 cells. Conclusion: In this study we report that miR-128 is up-regualted in clinical HCC tissues and that miR-128 binds to 3′ UTR of Axin1. The identification of miR-128 as oncomir and determination of its target gene Axin 1

will shed light on the pathogenesis of HCC. Key Word(s): 1. hepatocellular carcinoma; 2. microRNA; MI-503 3. tumorigenesis Presenting Author: EUNAE CHO Additional Authors: MOON JONG HAN, CHAN YOUNG OAK, DONG IK KIM, MI YOUNG KIM, DU HYEON selleck screening library LEE, SHI HYUN YOO Corresponding Author: EUNAE CHO Affiliations: Chonnam National University Hospital, Chonnam National University Hospital, Chonnam National University Hospital, Chonnam National University Hospital, Chonnam National University Hospital, Chonnam National University Hospital Objective: 18F-fluorodeoxyglucose PET computed tomography (18F-FDG PET CT)

has been used widely in oncology part as a part of staging workup, prediction of treatment response and clinical outcomes in various malignancies. However, its use in hepatocellular carcinoma (HCC) has been limited to evaluation of extrahepatic metastasis. The aim of this study was to investigate the role of 18F-FDG PET CT as an independent prognostic factor in hepatocellular carcinoma. 上海皓元 Methods: A total of 77 patients with newly diagnosed HCC who underwent 18F-FDG PET CT before treatment from January 2009 to December 2013 were reviewed retrospectively. Maximal standardized uptake values (SUVmax)

of the tumors were obtained. Results: Sixty-four patients were male (83.1%) and 13 patients were female (16.9%). Mean age of the enrolled patients was 61.73 years and mean duration of follow-up was 8.6 months. High SUVmax (≥5.0) was significantly associated with the tumor burden such as α-fetoprotein (P = 0.003), amino transaminase (AST) (P = 0.001), tumor size (P = 0.01), and TNM staging (P = 0.04). The overall survival rates in patients with high SUVmax (≥5.0) were 24.3% while those in patients with low SUVmax (<5.0) were 64.5% (P < 0.001). In subgroup analysis, among the 42 patients who received transarterial chemoembolization (TACE), patients with high SUVmax (≥5.0) were more likely to have earlier recurrence (P = 0.019). Conclusion: SUVmax of 18F-FDG PET CT can not only serve as an indicator of tumor burden and an independent prognostic factor in HCC but also predict recurrence after TACE. Key Word(s): 1. hepatocellular carcinoma; 2.

CA fed hearts had a significant attenuation (∼ 50%) in pMYHC/ aMYHC ratio (marker for hypertrophy) and BNP (marker for heart failure) at RNA level post-TAC compared with chow fed TAC mice. Post TAC hearts of CA fed mice had a significant 2 fold increase in Thr32 and Ser256 phosphorylation (inhibition) of FOXO-1, along with 70% downregulation of PDK4, known to regulate glucose oxidation in the heart. Separately, TGR5del mice had higher mortality (70% vs 30%; p=0.03, Mantel-Cox) and significantly decreased %FS (10±5 vs 20±7) 8 wks post TAC compared to littermates. CONCLUSION: CA feeding functionally activates TGR5 in the heart. CA attenuates contractile failure

and pathologic hypertrophy in mouse model of HF. CA fed hearts show molecular evidence of enhanced glucose oxidation, a crucial step in cardiac adaptation to stress. Separately, TGR5 deletion in

CCI-779 heart accelerates TAC induced car-diomyopathy. Results suggest that TGR5 regulates myocardial adaptive response to stress. Disclosures: The following people have nothing to disclose: Moreshwar S. Desai, Zainuer Shabier, Jorge Coss-Bu, Sundararajah Thevananther, David D. Moore, Saul J. Karpen, Daniel J. Penny Background & Aim: SLC25A13 (Citrin) is a liver-type aspar-tate-glutamate carrier located on the mitochondrial membrane and its genetic deficiency leads to adult-onset type II citrul-linemia (CTLN2). CTLN2 is frequently accompanied with hepatic steatosis even in the absence of obesity, insulin resistance and ethanol consumption. The aim of this study is to clarify Inhibitor Library cell line the precise mechanism of steatogenesis in patients with CTLN2. Methods: The expression of genes associated medchemexpress with fatty acid (FA) and triglyceride (TG) metabolism was examined using liver samples obtained from sixteen CTLN2 patients and compared with seven healthy individuals. Results: Although expression of hepatic

genes associated with lipogenesis and TG hydrolysis were not changed, the mRNAs encoding enzymes involved in FA oxidation (carnitine palmitoyltransfer-ase 1 alpha, medium- and very-long-chain acyl-coenzyme A dehydrogenases, and acyl-coenzyme A oxidase 1), very-low-density lipoprotein secretion (microsomal TG transfer protein), and FA transport (CD36 and FA-binding protein 1) were markedly suppressed in CTLN2 patients. Serum concentrations of ketone bodies were also decreased in these patients, suggesting reduced mitochondrial beta-oxidation activity. Consistent with these findings, expression of peroxisome proliferator-acti-vated receptor alpha (PPAR alpha), a master nuclear receptor regulating FA oxidation activity, was significantly down-regulated. Hepatic PPAR alpha expression was in inverse proportion to severity of steatosis and circulating ammonia and citrulline levels. In CTLN2 livers, phosphorylation of c-Jun-N-ter-minal kinase was enhanced, which was likely associated with lower hepatic PPAR alpha. Conclusions: Down-regulation of PPAR alpha is associated with steatogenesis in the patients having CTLN2.

PTN and PTPRZ1 were

Dasatinib also assessed in the clonally derived mouse cholangiocyte cell line 603B. Cells were activated in culture for up to seven days. Three injury models were used in wild type mice: CCl4, high fat diet with and without CCl4, and bile duct ligation. To assess PTN expression when Hh was blocked, cultured HSC cells were treated with DMSO (control) or 0.4μM-2.0μM of the hedgehog inhibitor GDC-0449. Adult a-smaCreERT2/floxed Smoothened double transgenic mice underwent BDL (n=8 mice/group) or partial hepatectomy to evaluate PTN response after liver injury in animals with abolished HSC Hh signaling. Results: In healthy livers, PTN expression was highest in LSEC and HSC and PTPRZ1 expression was highest in HSC. Healthy adult PTN-GFP mice expressed GFP in stromal cells in periportal areas, a putative progenitor niche. Serial sections suggest co-expression of PTN with desmin, supporting HSC expression of PTN. After activation in culture PTN

expression fell in LSEC but increased in activated myofibroblastic (MF)-HSC suggesting MF-HSC are the major PīN source in liver Fluorouracil injury. PTN expression also increased in in vivo mouse models of acute and chronic liver injury. Treating MF-HSC cultures with Hh inhibitor decreased PTN expression. Treating a-smaCreERT2/floxed Smoothened mice with tamoxifen to block MF-HSC Hh signaling was associated with decreased PTN expression after bile duct ligation and partial hepatectomy. Conclusion: HSC express PīN and increase expression

during activation. PTN expression increases in liver injury. Since PTN expression is decreased when Hh signaling is blocked, Hh signaling 上海皓元医药股份有限公司 modulates PTN expression during HSC activation and liver injury in vivo. Our results suggest a novel liver repair mechanism involving Hhdependent HSC PTN production. PTN may show promise for staging or treatment of human liver disease. Disclosures: Anna Mae Diehl – Consulting: Bristol Myers Sguibb, Synergy, GlaxoSmithKline, Norgine; Grant/Research Support: GlaxoSmithKline The following people have nothing to disclose: Anikia Tucker, Gregory A. Michelotti, Steve S. Choi, Guanhua Xie, Gamze Karaca, Marzena Swiderska-Syn, Leandi Kruger, Mariana V. Machado, Katherine S. Garman Developing new strategies for mimicking early organogenesis and deriving functional hepatocytes from human pluripotent stem cells (hPSCs) has a high scientific relevance and therapeutic potential. The role of oxygen tension as a key regulatory mechanism in hepatic differentiation has not yet been well described. Aims: a) to recapitulate early in vitro organogenesis in physiological conditions and efficiently derive mature hepatic cells from hPSCs under a stable oxygen gradient. b) to integrate the specific lineages into a microfluidic platform to obtain a functional liver tissue on a chip.

Nonetheless, in certain cases, prolonged statin therapy has been associated with hepatotoxicity, rhabdomyolysis, and compromised cardiac function.34 The side effects of statins, as well as the substantial numbers of people who either do not tolerate them or whose LDL levels are still significant, have prompted the search for new drugs that target other cholesterol-biosynthesis enzymes.22, 35 Because the toxicity resulting from AhR activation is mediated through DRE binding, the discovery that the AhR can coordinately attenuate the expression of cholesterol-biosynthetic genes and, subsequently, cholesterol biosynthesis in a DRE-independent manner is a very important observation. We

have recently described that the AhR can be activated this website by selective AhR modulators to repress cytokine-mediated acute-phase gene expression in the liver; it will be important to test whether these compounds can also

attenuate cholesterol biosynthesis.36 Thus, whether the AhR can be used as a therapeutic target to repress the expression of cholesterol-synthesis genes in vivo and thereby RG7420 mw lower cholesterol synthesis rate to induce LDL receptors will require further investigation. The authors thank Dr. Stephen C. Strom and Dr. Curtis J. Omiecinski for the primary human hepatocytes. Additional Supporting Information may be found in the online version of this article. “
“Eph/Ephrin family, one of the largest receptor tyrosine kinase families, has been extensively studied in morphogenesis and neural development. Recently, growing attention has been paid to its role in the initiation and progression of various cancers. However, the role of Eph/Ephrins in hepatocellular carcinoma (HCC) has been rarely investigated. In this study, we found that the expression of EphrinA2 was significantly up-regulated in both established cell lines and clinical tissue samples of HCC, and the most significant increase was observed in the tumors invading the portal veins. Forced expression of EphrinA2 in HCC cells significantly

promoted in vivo tumorigenicity, whereas knockdown of this gene inhibited this oncogenic effect. We further medchemexpress found that suppression of apoptosis, rather than accelerating proliferation, was responsible for EphrinA2-enhanced tumorigenicity. In addition, EphrinA2 endowed cancer cells with resistance to tumor necrosis factor alpha (TNF-α)–induced apoptosis, thus facilitating their survival. Furthermore, we disclosed a novel EphrinA2/ras-related c3 botulinum toxin substrate 1 (Rac1)/V-akt murine thymoma viral oncogene homolog (Akt)/nuclear factor-kappa B (NF-κB) pathway contributing to the inhibitory effect on apoptosis in HCC cells. Conclusion: This study revealed that EphrinA2 played an important role in the development and progression of HCC by promoting the survival of cancer cells, indicating its role as a potential therapeutic target in HCC. (HEPATOLOGY 2010.

40, 41 Extracellular Cl− then stimulates Cl−/HCO exchange over the membrane.42 Extracellular ATP has also been shown to up-regulate the inflammatory

cytokine interleukin-6 in bile duct epithelium in a cAMP- and Ca++-dependent way through the activation of purinergic receptors43 and to recruit macrophages, possibly through induction of intercellular cell adhesion of molecules on the epithelium.44 P2Y receptors on the basolateral membrane are probably involved in recognition of extracellular ATP due to destruction of neighboring cells. The activation of receptors on the apical membrane leads to a net alkalinization of bile through Ca++- and/or cAMP-mediated stimulation of Cl− secretion.33 Forskolin-induced BKM120 cell line HCO secretion was shown to be dependent on luminal ATP. In isolated bile

ductules, ATP hydrolyzing apyrase reduced forskolin- and thus cAMP-induced HCO secretion by ≈80%, and P2Y blockade with suramin abolished intracellular Ca++ increase and HCO secretion.33 Hepatocytes and cholangiocytes release ATP in a paracrine/autocrine Cisplatin supplier fashion by yet unresolved molecular mechanisms.35, 45 Release through undefined ATP channels and CFTR-mediated ATP release35, 46 but also ATP release through exocytosis of ATP-enriched vesicles47 or even maxi-anion channels described in macula densa cells of the rabbit kidney, rat cardiomyocytes, and mouse astrocytes48 have been discussed. Whatever the molecular

mechanisms of hepatobiliary ATP release are, it is attractive to speculate that cholestatic injury per se may hamper biliary 上海皓元医药股份有限公司 ATP release and thereby ductular HCO secretion as targeting of vesicles, vesicular exocytosis, and membrane insertion of transport proteins into their target membrane are impaired in cholestatic liver.49, 50 Thus, cholestatic injury might even be a primary culprit for a defective biliary HCO umbrella. In this regard, the recent finding of bile flow–induced mechanosensitive Ca++- and PKCζ-dependent ATP release and associated ATP-dependent Cl− secretion from human biliary cells as well as rat cholangiocytes deserves particular attention.51 It is attractive to link mechano-sensitive ATP and Cl− secretion to the stabilization of the biliary HCO umbrella through stimulation of Cl−/HCO exchange when higher amounts of bile salts as a major driving force of stimulated hepatocellular bile flow reach the cilia of cholangiocytes. Given their putative role in stabilization of the biliary HCO umbrella, but also their potential proinflammatory effects, ATP levels in bile have to be tightly controlled. Alkaline phosphatase catalyzes the dephosphorylation of ATP to ADP, AMP, and eventually adenosine in various tissues.

A similar

pattern of AEs were seen in the sub-study compared to the main study population. Most frequent AEs reported (≥25% pts) during TVR treatment were pruritus SSC (53% [vs 43% in TVR treatment phase of main study]), influenza-like illness (41% [vs 25%]), anorectal SSC (41% [vs 30%]), insomnia (35% [vs 17%]), rash SSC (35% vs [34%]), and nausea and headache (29% each [vs 19% and 16%]). Anemia SSC was reported in 6% of pts. One pt had a serious AE. Although total and unbound darunavir GS-1101 price and total TVR exposures were reduced after co-administration of darunavir-based HAART and TVR + PR, historical data suggest TVR concentrations are similar to the lowest quartiles observed in prior studies. Conclusions: In this substudy, similar response rates were seen as in the overall INSIGHT study. Safety and tolerability CHIR-99021 ic50 of TVR/PR in this group was broadly comparable with that reported for the main study population. Disclosures: Marisa L. Montes – Consulting: Janssen, BMS, Viiv; Speaking and Teaching: Janssen, BMS, Viiv Enrique Ortega – Board Membership: Gilead, Jannsen, VIIV Mark Nelson – Advisory Committees or Review Panels: Boehringer Ingelheim, Janssen, MSD, BMS, Abbott, Viiv, Gilead; Consulting: Boehringer Ingelheim, Janssen, MSD,

BMS, Abbott, Viiv, Gilead; Grant/Research Support: Boehringer Ingelheim, Janssen, MSD, BMS, Abbott, Viiv, Gilead, Roche; Speaking and Teaching: Boehringer Ingelheim, Janssen, MSD, BMS, Abbott, Viiv, Gilead Katrien Janssen – Employment: Janssen Pharmaceutica NV Sivi Ouwerkerk-Mahadevan 上海皓元 – Employment: Janssen The following people have nothing to disclose: Andrzej Horban, Jacques Durant, Katrien de Backer “
“Acute liver failure is a challenging and complex condition that demands input from a broad range of services, with hepatologists, intensivists and transplant surgeons at the core, but supported by many other speciality services. A rapid cascade from accurate diagnosis to prognostication

and formulation of a management is required for each individual patient. The outcomes in acute liver failure have improved dramatically due to a combination of emergency liver transplantation and advances in intensive care protocols and now 60% of patients with acute liver failure should survive. The contribution of liver support devices to further improvement remains under evaluation. “
“The vertical transmission of hepatitis C virus (HCV-VT) is a major route of HCV infection in children, but the risk factors remain incompletely understood. This study analyzed the role of interleukin 28B (IL28B) in HCV-VT and in the spontaneous clearance of HCV among infected infants. Between 1991 and 2009, 145 mothers were recruited for this study: 100 were HCV-RNA+ve / human immunodeficiency virus negative (HIV−ve), with 128 children, and 33 were HCV-RNA−ve/HCV antibody+ve, with 43 children.

Hepatic gene

expression revealed strong reduction in inflammation markers and an activation of genes involved in mitochondrial BVD-523 fatty acid oxidation, mechanisms that are compatible with the mode of action of GFT505. Conclusions: Our study has demonstrated that GFT505 has a curative action in a widely recognized preclinical model of NASH. Disclosures: Isabelle A. Leclercq – Independent Contractor: Genfit Benoit Noel – Employment: Genfit SA Rémy Hanf – Management Position: GENFIT Dean W. Hum – Management Position: Genfit Robert Walczak – Management Position: Genfit SA The following people have nothing to disclose: Vanessa Legry Background and aim: Branched-chain amino acids (BCAA) have been used as oral supplementation therapy for patients with decompensated cirrhosis. These also decreased the cumulative incidence of complications. Moreover, it has been reported that BCAA had the anti-carcinogenic effect and decreased hepatic steatosis in male patients with BMI 25 or more. Choline-deficient and high fat diet (CDHF) has been reported to be one of the diets inducing NASH in mice. In order to elucidate mechanisms responsible for the BCAA effects on decreased hepatic steatosis and inhibition of fibrosis progression, we investigated the mechanism of suppression of hepatic

steatosis by BCAA in CDHF-induced NASH mouse model. Methods: Male C57BL/6J mice were allocated into four experimental groups receiving either (1) choline-deficient and high fat (CDHF) diet (CDHF-control group),

(2) choline-sufficient and high fat (CSHF) diet (CSHF-control group), (3) CDHF-BCAA selleckchem (2% in the drinking water) group, and (4) CSHF-BCAA group for 8 weeks. We determined liver injury, hepatic steatosis and lipid metabolism genes. Fat accumulation was measured in the liver. Area of lipid droplets medchemexpress in the liver was quantified by image analysis software. Results: Serum alanine aminotransfer-ase (ALT) levels and hepatic triglyceride (TG) were significantly increased in the CDHF-control group than that in CSHF-control group. Liver histopathology indicated severe steatosis, hepatic inflammation and pericellular fibrosis, confirming NASH findings in CDHF-control group. Serum ALT levels, hepatic TG and area of lipid droplets were significantly decreased in the CDHF-BCAA group than in CDHF-control group. Gene expression of fatty acid synthase (FAS), which is last step in fatty acid biosynthesis, was significantly increased in CDHF-control compared to CSHF-control, and significantly suppressed in CDHF-BCAA group. Activity of citrate synthase, which is mitochondrial marker enzyme, was significantly decreased in CDHF-con-trol group than in CSHF-control, and significantly increased in CDHF-BCAA group. Gene expression of sterol regulatory element-binding protein 2 (Srebf2), which is upstream of cholesterol synthesis, was significantly decreased in CDHF-BCAA group compared to CDHF-control group.