11 In this study we found an increase of serum BAs in NASH as compared to less severe stages of NAFLD, which is inversely correlated with serum adiponectin levels in obese Erlotinib purchase patients who underwent bariatric surgery. In NASH, serum adiponectin levels are decreased and hepatic expression of the adiponectin receptor 2 (ApoR2) is compensatory up-regulated. Repression of Cyp7A1 and NTCP by SHP appears impaired in this cohort and free fatty acid (FFA) treatment of hepatoma cells mimics these effects in

vitro. ABCB11/BSEP: ATP-binding cassette, subfamily B member 11, bile salt export pump; BMI: body mass index; CD95/Fas: apoptosis-inducing cell surface receptor (advanced nomenclature: TNF superfamily receptor 6); CYP7A1: cholesterol 7 alpha-hydroxylase; FFA: free (nonesterified) fatty acids; FXR: farnesoid X receptor; HSC: hepatic stellate cell; M30: cytokeratin-18 fragment epitope exposed upon cleavage by caspases; NAFL: nonalcoholic fatty liver; NAFLD: nonalcoholic fatty liver disease; NAS, NAFLD activity score; NASH: nonalcoholic steatohepatitis; NTCP: high-affinity Na+/taurocholate cotransporter; qRT-PCR: quantitative real-time polymerase chain reaction;

SHP: small heterodimer partner; TGF-β: transforming growth factor β. In all, 113 patients suffering from morbid obesity (body mass index [BMI] > 40kg/m2) undergoing bariatric surgery were enrolled in the study (Table 1). Individuals aged <18 or >65 or with liver injuries MK0683 order and pathologies (infectious disease with hepatitis B virus [HBV], hepatitis C virus [HCV], or human immunodeficiency virus [HIV]), history of organ transplantation, history of malignancy within the past 5 years, excessive alcohol consumption indicating alcoholic liver disease (>20 g/day in males or >10 g/day in females) or drug abuse, autoimmunity, genetic disorders, and therapy with immunosuppressive or cytotoxic

agents were excluded. Indication for performance of bariatric surgery was made by the surgeon, a dietician, and the primary physician according to National Institutes of Health (NIH) guidelines (BMI >40 kg/m2 or ≥35 kg/m2, plus comorbidities) and patients had to prove unsuccessful attempts to lose weight by lifestyle modification, diet, and exercise. Wedge liver biopsies were taken medchemexpress at the time of bariatric surgery. The control group consisting of 10 healthy volunteers whose blood samples were taken had an average BMI of 22.4 ± 2.46 kg/m2 (Table 1). Control samples of liver specimens were obtained from liver transplantation donors (n = 7). We furthermore assessed serum markers of NAFLD and adiponectin levels from a cohort of 39 moderately obese (BMI of 29.6 ± 1.15 kg/m2) patients with the established diagnosis of NAFLD. The study protocol conformed to the ethical guidelines of the 1975 Declaration of Helsinki and was approved by the Ethics Committee (Institutional Review Board) of the University Hospital Essen.