1A), there was a 19% ± 4% increase (P ≤ 0.02) of the adaptor at the membrane in ethanol-treated cells with a reciprocal decrease in diffuse cytosolic staining. Similarly, increased basolateral cortactin-positive puncta were observed in ethanol-treated cells (Fig. 1A). Because of its large,

soluble pool, we permeabilized cells with Triton X-100 before fixation to detect membrane-associated dynamin. In control cells, dynamin was detected at the basolateral membrane (Fig. 1A). However, virtually no dynamin was observed at the basolateral surface in ethanol-treated cells. Coimmunoprecipitations confirmed these results. In control cells, both CHC and cortactin coimmunoprecipitated with dynamin, indicating interactions among these proteins (Fig. 1C). In contrast, click here the coprecipitated levels of CHC and cortactin were decreased after ethanol exposure, reflecting decreased interactions. To further confirm that decreased interactions were not the result of decreased expression levels, we immunoblotted cell lysates for coat components. No changes in levels of dynamin, CHC, AP2, this website cortactin, or actin were observed (Fig. 1D), ruling out this possibility. Together, these results suggest that the clathrin-coated structures are late-stage invaginations unable to bud from the membrane because of impaired dynamin recruitment. To test whether these altered distributions

required ethanol metabolism, we treated cells with the ADH inhibitor, 4-methyl pyrazole. 4-methyl pyrazole prevented CHC and dynamin redistribution, indicating that the defect was likely mediated by acetaldehyde (Supporting Fig. 1). Previously, we determined that ASGP-R internalization is impaired by treatment with TSA, a pan-deacetylase inhibitor.15

To determine whether TSA also induces the redistribution of ASGP-R and the clathrin machinery, we immunostained control and cells treated for MCE公司 30 minutes with 50 nM of TSA at 37°C, conditions that hyperacetylate proteins to the same extent as ethanol.15 As for ethanol-treated cells, TSA addition led to the redistribution of ASGP-R, CHC, AP2 (38% ± 17% increase) and cortactin to the basolateral membrane in discrete puncta (Fig. 1B). Also, as for ethanol-treated cells, virtually no membrane-associated dynamin was observed in TSA-treated cells (Fig. 1B). This suggests that not only are these structures late-stage intermediates, but also that hyperacetylation may explain the internalization defect. If the structures are late-stage intermediates, the prediction is that they are continuous with the plasma membrane. To test this prediction, we used TIRF microscopy to visualize the bottommost 100 nm of the cell, the approximate diameter of a clathrin-coated pit. In control cells, few discrete ASGP-R-positive puncta were observed at the cell surface (Fig. 2A). Additional profiles were also detected, albeit smaller and dimmer, likely representing budding vesicles or receptors not clustered into pits.

Moreover, statin use may potentiate the interferon response in CHC.5 Also, statin therapy may alter 25[OH]D levels in favor of elevation. The inhibition of cholesterol synthesis with statin use causes an excess of 7-dehydrocholesterol, which is the precursor for vitamin D synthesis.6 From this point of view, it is obvious that the authors did not offer

any exclusion criteria regarding the aforementioned parameters. In conclusion, the study reported by Petta et al.1 undoubtedly provides valuable insight Selleckchem Ixazomib into the pathophysiological basis of the low responsiveness to interferon-based therapy in G1 CHC. However, vitamin D metabolism and metabolic syndrome are substantial confounders that make a clear-cut judgment difficult. Tugrul Purnak M.D.*, Cumali Efe M.D.†, Yavuz Beyazit M.D.‡, Ersan Ozaslan M.D.*, * Department of Gastroenterology, AZD9668 Ankara Numune Education and Research Hospital, Ankara, Turkey, † Department of Internal Medicine, Bitlis Government Hospital, Bitlis, Turkey, ‡ Department

of Gastroenterology, Turkiye Yuksek Ihtisas Training and Research Hospital, Ankara, Turkey. “
“We read with interest the article by Roayaie et al. reporting on resection of hepatocellular carcinoma (HCC) ≤2 cm in two Western centers.1 This elegant study shows that excellent results (e.g., up to 80% 5-year survival) can be achieved with adequate surgical resection in selected patients with small HCC. These results are in line with the study from our group published this year in HEPATOLOGY concerning potentially transplantable patients who were resected first in a strategy of salvage transplantation in cases of recurrence.2 In the context of organ shortage, we fully agree with the

conclusion that resection should continue to be a first-line option in patients with preserved liver function.1 In addition to classical tumor factors, these two studies confirm that nonanatomic resection and presence of cirrhosis were associated with a higher risk of recurrence. In our series, 上海皓元 for instance, 64% of the patients who did not experience recurrence after resection had stage 3 fibrosis. The feasibility of anatomic resection, which was independently associated with less recurrence, as well as postoperative morbidity, obviously depends upon the extent of underlying fibrosis. Although Roayaie et al. have shown that advances in the management of HCC could come from the underlying liver parenchyma, they do not mention the usefulness of preoperative biopsy of nontumorous liver parenchyma, to better select the optimal candidates for resection. The importance of nontumorous parenchyma is illustrated by the finding by the same group that gene expression signatures in the adjacent liver parenchyma, but not in the tumor, were highly correlated to recurrence and survival after resection.

The model estimated the costs related to the treatment with SOF/RBV, the costs associated to each health state, the life-years find more (LYSs), the quality-adjusted life-years (QALYs), and the incremental cost-effectiveness ratio (ICER) expressed as € per QALY gained. The analysis was performed from the Italian National Health System perspective with a lifetime time horizon and one-month Markov cycles. Future costs and clinical benefits, expressed as QALYs, were discounted at 3% per year. Results: in the base-case analysis the ICER for 24 weeks of SOF/RBVR was €30,518 per QALY

gained in HCV-cirrhosis patients and €41,610 in HCV-HCC patients. The reliability of our results was confirmed by the one way sensitivity-analysis and by the cost-effectiveness acceptability curve that reported 97.5% probability of SOF/RBV to be cost-effective at a willingness to pay threshold of €60,000 in the HCV-cirrhosis scenario, and 88.1% in the

HCV-HCC scenario. Further, SOF/RBV cost-effectiveness was clearly sensitive to the duration of treatment; assuming 12 weeks SOF/RBV treatment duration, the ICER decreased to €19,317 in HCV-Cirrhosis and €29,540 in HCV-HCC. In conclusion, Fostamatinib molecular weight our study shows that treating patients with HCV-cirrhosis or HCV-HCC in the transplant waiting list with SOF/RBV is cost-effective and may become the new standard of care for these patients. However a well-defined prospective study is needed to confirm the value of the parameters assumed in the model and the results. Furthermore, associations of direct acting antivirals will soon appear

into the horizon also in the transplant setting and bring new challenges and opportunities. Disclosures: Lorenzo G. Mantovani – Advisory Committees or Review Panels: Bayer; Grant/ Research Support: Jansen, Merck and Co; Speaking and Teaching: Bayer The following people have nothing to disclose: Paolo A. Cortesi, Antonio Ciaccio, Matteo Rota, Giancarlo Cesana, Mario Strazzabosco, Luca S Belli MCE公司 Background: In studies predominantly from Europe, chronic HEV infection has been shown to be an important cause of chronic and progressive hepatitis among solid organ transplant recipients. Limited data indicate that HEV is endemic in the United States, but the prevalence, incidence and significance of HEV infection among US transplant patients is largely unknown. Methods: This A2ALL-approved ancillary study, evaluated liver transplant (LT) recipients with deceased and living donors in 9 LT programs from geographically diverse regions of the US between 1998 and 2009.

In summary, the crosstalk between metabolic signaling pathways that receive input from a high-fat and high-cholesterol diet may result in inappropriate suppression of β-oxidation that promotes NASH and diminished circulating bile acids, resulting in inappropriately improved energy efficiency leading to weight gain. These are testable hypotheses with major implications for human health that could be exploited pharmacologically to prevent NASH and improve energy disposal and weight management. “
“Division of Liver Diseases, Mount Sinai School of Medicine, New York, New York, USA Okuno Gastroenterology Clinic,

Akashi, Hyogo, Japan Hepatocellular carcinoma (HCC) is one of the common sequelae of hepatitis C virus Trametinib in vitro (HCV) infection. It remains controversial, however, SB203580 whether HCV itself plays a direct role in the development of HCC. Although HCV core, NS3, and NS5A proteins were reported to display tumorigenic activities in cell culture and experimental animal systems, their clinical impact on HCC development in humans is still unclear. In this study we investigated sequence polymorphisms in the core

protein, NS3, and NS5A of HCV genotype 1b (HCV-1b) in 49 patients who later developed HCC during a follow-up of an average of 6.5 years and in 100 patients who did not develop HCC after a 15-year follow-up. Sequence analysis revealed that Gln at position 70 of the core protein (core-Gln70),

Tyr at position 1082 plus Gln at 1112 of NS3 (NS3-Tyr1082/Gln1112), and six or more mutations in the interferon/ribavirin resistance-determining region of NS5A (NS5A-IRRDR≥6) were significantly associated with development of HCC. Multivariate analysis identified core-Gln70, NS3-Tyr1082/Gln1112, and α-fetoprotein (AFP) levels (>20 ng/L) as independent factors associated 上海皓元医药股份有限公司 with HCC. Kaplan-Meier analysis revealed a higher cumulative incidence of HCC for patients infected with HCV isolates with core-Gln70, NS3-Tyr1082/Gln1112 or both than for those with non-(Gln70 plus NS3-Tyr1082/Gln1112). In most cases, neither the residues at position 70 of the core protein nor positions 1082 and 1112 of the NS3 protein changed during the observation period. Conclusion: HCV isolates with core-Gln70 and/or NS3-Tyr1082/Gln1112 are more closely associated with HCC development compared to those with non-(Gln70 plus NS3-Tyr1082/Gln1112). (HEPATOLOGY 2013;58:555-563) Hepatitis C virus (HCV) is a major etiologic agent of chronic hepatitis worldwide, with the estimated number of infected individuals being more than 180 million. Approximately 15% to 20% of chronically infected individuals undergo liver cirrhosis in a decade or so after infection, with hepatocellular carcinoma (HCC) arising from cirrhosis at an estimated rate of 1% to 4% per year.

Therefore, the highly significant reduction in head pain referral during the cervical intervention could be a clinical correlate of lessening central sensitization of the TCN. In particular, it is conceivable that palpation and stretch of dysfunctional cervical paraspinal tissues elicits tenderness that lessens

as remodeling occurs.[35, see more 36, 39] This could explain why tenderness ratings decreased during the cervical intervention and not the arm for, presumably, participants’ arm tissues were not dysfunctional and subject to remodeling. However, the perception of pain is not only determined by the intensity of the afferent pain signal (nociception).[45] Nociceptive inputs to the dorsal horn of the spinal cord are also influenced by potent endogenous

descending inhibitory and facilitatory processes from supraspinal regions. This bidirectional, central control incorporates a frontal, limbic, brainstem, and spinal cord neuronexus46-49 that is driven primarily by noxious inputs and associated emotional responses. Importantly, this includes spinal cord activity because the spinally mediated nociceptive flexion reflex is influenced by central pain modulation processes.[50] While the exact mechanisms responsible for emotional modulation of pain are not fully understood, heightened anxiety appears to increase sensitivity to pain (hyperalgesia),51-68 while moderate fear inhibits pain (hypoalgesia).51,69-77 Pexidartinib in vitro This suggests that anticipation of an unpredictable, threatening intervention could result in enhanced pain, while hypoalgesia results from exposure to a predictable, threatening MCE公司 event

(fear).[51] As we did not assess the participants’ psychological state, we are unsure whether this changed over the course of the experiment. Nevertheless, it seems unlikely that psychological factors had a major influence on our findings for the following reasons. First, participants were included only if usual head pain could be produced when stressing either the AO or C2-3 segments – the “inclusion/exclusion” session. In the case of head pain referral, both segments were examined (prior to the experimental sessions) to ascertain which segment reproduced usual head pain most clearly. Thus, participants experienced reproduction of their usual head pain, which ceased immediately on cessation of the technique (ie, essentially, participants were “cued” to believe that the procedures were not threatening). Second, participants, armed with the knowledge that they could terminate the experimental session at any time, were in control, further lessening the role of psychological factors.78-83 Third, pain ratings to the supraorbital stimuli were comparable for the cervical and arm interventions, and remained unchanged across the trials.

A control population of mixed ethnicities showed that 9% of the subjects possessing the variant allele had detectable hepatic steatosis versus 0% of those possessing the wild-type genotype. The implications of these findings are 2-fold. First, APOC3 and plasma triglyceride concentrations appear

to be important in the development of hepatic steatosis, even in the absence of obesity. All patients possessing variant alleles for the APOC3 gene had markedly higher average hepatic triglyceride contents (7.5% ± 10.3% versus 1.5% ± 1.3%). In fat-tolerance Selleckchem Epigenetics Compound Library testing of a subgroup of variant-allele and wild-type individuals, variant-allele subjects were also found to have significantly higher levels of plasma triglyceride. Similarly, plasma triglyceride clearance was decreased in a subgroup of patients with the variant allele versus their wild-type counterparts. In all, this provides compelling evidence that APOC3 can contribute to triglyceride excess both intrahepatically and systemically. The Erastin chemical structure second and more novel finding of these authors is the genetic association between Asian Indian men and this polymorphism. This population has a high prevalence of NAFLD, and this is the first study to associate a specific genetic variation with hepatic steatosis in healthy men of Asian Indian descent. This finding was substantiated

in an independent group of non-Asian men, and the authors noted that no wild-type homozygotes at this allele were found to have hepatic steatosis by magnetic resonance spectroscopy. It is important to understand that the frequency of variant alleles was no greater in the Asian Indian study population versus the control group composed of multiple ethnicities, and this suggests that this APOC3 variant allele does not explain the high rates of hepatic steatosis among Asian Indians. Other genetic variations, such as that encoding the patatin-like phospholipase domain-containing

3 protein (PNPLA3), have also been independently associated with NAFLD,5 with recent research linking specific polymorphisms MCE to disease severity.6-8 In the study by Petersen etal.,3 PNPLA3 variants were also shown to be associated with NAFLD, and the relative risk appeared additive in those individuals having both PNPLA3 and APOC3 variants. However, only 13.1% of the variance in risk for NAFLD could be explained by the combination of these two different SNPs, and this suggests that additional factors may be involved in the development of NAFLD. The authors also selected seven subjects with hepatic steatosis and insulin resistance (IR) for enrollment in a 6-month weight-loss program; during this time, they experienced a mean weight loss of approximately 6 kg along with a significant reduction in their hepatic triglyceride content from 14.0% to 3.8% (P = 0.05) and an improvement in the insulin sensitivity index from 1.8 to 3.7 (P < 0.01).

A control population of mixed ethnicities showed that 9% of the subjects possessing the variant allele had detectable hepatic steatosis versus 0% of those possessing the wild-type genotype. The implications of these findings are 2-fold. First, APOC3 and plasma triglyceride concentrations appear

to be important in the development of hepatic steatosis, even in the absence of obesity. All patients possessing variant alleles for the APOC3 gene had markedly higher average hepatic triglyceride contents (7.5% ± 10.3% versus 1.5% ± 1.3%). In fat-tolerance selleck chemicals testing of a subgroup of variant-allele and wild-type individuals, variant-allele subjects were also found to have significantly higher levels of plasma triglyceride. Similarly, plasma triglyceride clearance was decreased in a subgroup of patients with the variant allele versus their wild-type counterparts. In all, this provides compelling evidence that APOC3 can contribute to triglyceride excess both intrahepatically and systemically. The Dactolisib cost second and more novel finding of these authors is the genetic association between Asian Indian men and this polymorphism. This population has a high prevalence of NAFLD, and this is the first study to associate a specific genetic variation with hepatic steatosis in healthy men of Asian Indian descent. This finding was substantiated

in an independent group of non-Asian men, and the authors noted that no wild-type homozygotes at this allele were found to have hepatic steatosis by magnetic resonance spectroscopy. It is important to understand that the frequency of variant alleles was no greater in the Asian Indian study population versus the control group composed of multiple ethnicities, and this suggests that this APOC3 variant allele does not explain the high rates of hepatic steatosis among Asian Indians. Other genetic variations, such as that encoding the patatin-like phospholipase domain-containing

3 protein (PNPLA3), have also been independently associated with NAFLD,5 with recent research linking specific polymorphisms 上海皓元 to disease severity.6-8 In the study by Petersen etal.,3 PNPLA3 variants were also shown to be associated with NAFLD, and the relative risk appeared additive in those individuals having both PNPLA3 and APOC3 variants. However, only 13.1% of the variance in risk for NAFLD could be explained by the combination of these two different SNPs, and this suggests that additional factors may be involved in the development of NAFLD. The authors also selected seven subjects with hepatic steatosis and insulin resistance (IR) for enrollment in a 6-month weight-loss program; during this time, they experienced a mean weight loss of approximately 6 kg along with a significant reduction in their hepatic triglyceride content from 14.0% to 3.8% (P = 0.05) and an improvement in the insulin sensitivity index from 1.8 to 3.7 (P < 0.01).

[17] These heavy-chain antibodies also lack the CH1

region, and their variable region is referred to as VHH or nanobody. Recombinant nanobodies (∼14 kD) are intact antigen-binding domains and exhibit a broad antigen-binding repertoire. They have unique characteristics, including an extended complementarity determining region 3 (CDR3) loop that can adopt a protruding conformation allowing interaction with concave epitopes that are occluded for conventional antibodies.[18] To stabilize the enlarged CDRs, nanobodies often possess an additional disulfide bond between CDR1 and CDR3 in dromedaries, buy Tanespimycin and CDR2 and CDR3 in llamas.[19] Nanobodies have been raised to numerous viruses (reviewed by Vanlandschoot et al.[20]) and despite being

monovalent, they frequently exhibit biological activities comparable to conventional bivalent antibody molecules.[21] Selleck p38 MAPK inhibitor As such, nanobodies are a promising tool for the targeted immunotherapy of viral infections. Here, we report the isolation and characterization of four anti-HCV alpaca nanobodies raised by immunizing an alpaca with recombinant hepatitis C virus E2 glycoprotein. One of these nanobodies neutralized HCV pseudoparticles (HCVpp) representing diverse genotypes, authentic HCV cell culture–grown infectious particles (HCVcc) virions, and uniquely inhibited HCV cell-to-cell transmission. This provides the first evidence of nanobodies as potential candidates for immunotherapeutic administration in chronic hepatitis C. HCVpp and 100 focus-forming units of Japanese fulminant hepatitis isolate 1 (JFH-1), respectively, were mixed with serum, nanobody, or monoclonal antibody for 1 hour before being added to Huh7.5 cells. Further experimental details are provided in the 上海皓元医药股份有限公司 Supporting Information. Crystals of the nanobody D03 were grown at 293 K using the sitting-drop vapor-diffusion method in drops containing 1.2 μL protein (∼20 mg/mL in 10 mM Tris [pH 8.0], 150 mM NaCl) mixed with 1.2 μL reservoir solution containing

2,005 mM LiSO4. Diffraction quality rod-like crystals belonging to spacegroup P65 appeared after 4 weeks. Data collection, processing, and structure solution are described in detail in the Supporting Information. The atomic coordinates and structure factors have been deposited in the Protein Data Bank, www.pdb.org, under the accession number 4JVP. Cell-to cell transmission was analyzed as described.[22] HCV-infected producer Huh-7.5 cells were labeled with 5-chloromethylfluorescein diacetate (CMFDA) and cocultured with naïve cells in a 1:1 ratio for 2 hours. Antibodies, antibody fragments, or nanobodies were added, extracellular media was collected after 24 hours, and infectious virus was quantified by infecting naïve Huh-7.5 cells. Cell cocultures were fixed, permeabilized, stained for HCV NS5A expression, and analyzed by flow cytometry to quantify the number of newly infected target cells (NS5A+/CMFDA−).

Factors associated with clustering were assessed using logistic regression. Among 655 eligible participants, HCV genotype prevalence was: G1a: 48% (n = 313), G1b: 6% (n = 41), G2a: 3% (n = 20),

G2b: 7% (n = 46), G3a: 33% (n = 213), G4a: <1% (n = 4), G6a: 1% (n = 8), G6e: <1% (n = 1), and unclassifiable: 1% (n = 9). The mean age was 36 years, 162 (25%) were female, and 164 (25%) were HIV+. Among 501 participants with HCV G1a and G3a, 31% (n = 156) were in a pair/cluster. Factors independently associated with phylogenetic clustering included: age <40 (versus age ≥40, adjusted odds ratio [AOR] = 1.64; 95% confidence interval [CI] 1.03, 2.63), human immunodeficiency virus (HIV) infection (AOR = 1.82; 95% CI 1.18, 2.81), HCV seroconversion (AOR = 3.05; 95% CI 1.40, 6.66), and recent syringe borrowing (AOR 1.59; 95% CI 1.07, 2.36). Conclusion: In this sample of PWID, one-third demonstrated phylogenetic clustering. Factors

click here independently associated with phylogenetic clustering included younger age, recent HCV seroconversion, prevalent HIV infection, and recent syringe borrowing. Strategies to enhance the delivery of prevention and/or Selleck Idasanutlin treatment strategies to those with HIV and recent HCV seroconversion should be explored, given an increased likelihood of HCV transmission in these subpopulations. (Hepatology 2014;60:1571–1580) “
“The purpose of this study is to assess whether the decrease in CD8 cells has any role in the development of non-alcoholic fatty liver disease (NAFLD). In this study, we therefore used antigen peptide transporter 1 (TAP1−/−) mice that cannot transport major histocompatibility complex class I antigens onto the cell surface resulting in failure of the generation of CD8 cells. Wild-type C57Bl/6J and TAP1−/− mice were fed with 30% fructose solution for 8 weeks. The percentage of CD4, CD8 cells in peripheral

blood mononuclear cells, and liver medchemexpress were sorted by fluorescence-activated cell sorting in both control and fructose-treated mice. Bodyweight, histopathological changes, oil red O staining, glucose tolerance test, intraperitoneal insulin tolerance test, serum levels of triglycerides, cholesterol, aspartate aminotransferase, and alanine aminotransferase were also evaluated. Quantitative real-time polymerase chain reaction was performed to determine the expression of specific genes involved in development of fatty changes in the liver. Chronic consumption of fructose in TAP1−/− mice did not develop NAFLD, insulin resistance, or change in level of CD8 cells. Moreover, there was delay in relative expression levels of genes involved in development of NAFLD in fructose-treated TAP1−/− mice. Taken together, the data suggest that TAP1−/−-deficient mice displayed reduced levels of CD8 cells that have a vital role in the initiation and propagation of liver inflammation and is a casual role in the beginning of fructose-induced liver damage as well as insulin resistance in mice. “
“Do, or do not.

Approximately 40∼50% of East Asians carry an inactive ALDH2 gene and exhibit acetaldehyde accumulation after alcohol consumption. However, the role of ALDH2 deficiency in the pathogene-sis of alcoholic liver injury remains obscure. METHODS: Wild-type (WT) and ALDH2-/- mice were subjected to ethanol feeding and/or carbon tetrachloride (CCl4) treatment, and liver injury was assessed. RESULTS: Compared with WT mice, ethanol-fed ALDH2-/- mice had higher levels of malondialde-hyde and acetaldehyde (MAA) adduct and greater hepatic inflammation, with higher hepatic interleukin-6 (IL-6) expression but surprisingly lower levels

of steatosis and serum alanine transaminase (ALT). Higher IL-6 levels were also detected in ethanol-treated, precision-cut liver slices from ALDH2-/- mice and in Kupffer cells isolated from ethanol-fed ALDH2-/- mice than those levels in WT mice. In vitro incubation with MAA enhanced the LPS-mediated Lapatinib stimulation of IL-6 production in Kupffer cells. In agreement with these findings, hepatic activation of the major IL-6 downstream signaling molecule signal transducer and activator of transcription 3 (STAT3) was higher in ethanol-fed ALDH2-/- mice than in WT mice. An additional deletion of hepatic STAT3 resulted in teatosis and hepatocellu-lar damage in ALDH2-/- mice. Finally,

ethanol-fed ALDH2-/-mice were more prone to CCl4-induced liver inflammation and fibrosis than ethanol-fed WT mice. CONCLUSIONS: ALDH2-/-mice are resistant to ethanol-induced steatosis medchemexpress but prone to inflammation and fibrosis via MAA-mediated paracrine activation of IL-6 in Kupffer cells. These findings suggest that individuals who have ALDH2 deficiency may be resistant Sunitinib manufacturer to steatosis, but are more prone to liver inflammation and fibrosis following alcohol consumption. Disclosures: The following people have nothing to disclose: Hyo-Jung Kwon, Young-Suk Won, Ogyi Park, Michael J. Duryee, Geoffrey Thiele, Akiko Matsumoto, Surendra Singh, Toshihiro

Kawamoto, Mohamed A. Abdelmegeed, Byoung-Joon Song, Vasilis Vasiliou, Geoffrey M. Thiele, Bin Gao Background: Under physiological state, free fatty acids (FFA) enter adipocytes and stored in the adipose tissues in the form of triglycerides (TG). Patients with alcoholic liver disease have been shown to have significantly lower percentage of body fat (%BF). This results in reducing TG storage as reflected by increasing serum FFA. In adipose tissue, Pref-1 is specifically expressed in preadipocytes but not in adipocytes. Increasing Pref-1 leads to inhibition of adipogenesis and reduced adipose tissue mass. Our aim is to investigate the association between alcohol consumption, serum Pref-1, and %BF in heavy drinkers compared to controls. Methods: 97 chronic heavy drinkers (mean age 41.3 years/69% men/81% Caucasian) were enrolled from Fairbanks Alcohol Treatment Center. 51 non-heavy drinkers (mean age 31.8 years/88% men/84% Caucasian) were recruited from Roudebush VAMC.