Search results for "FATTY LIVER"

Serial combination of noninvasive tools improves the diagnostic accuracy of severe liver fibrosis in patients with nonalcoholic fatty liver disease

2017

Gliptins Suppress Inflammatory Macrophage Activation to Mitigate Inflammation, Fibrosis, Oxidative Stress, and Vascular Dysfunction in Models of Nona…

2017

Abstract Aims: Nonalcoholic steatohepatitis (NASH) is characterized by steatosis, panlobular inflammation, liver fibrosis, and increased cardiovascular mortality. Dipeptidyl peptidase-4 inhibitors (gliptins) are indirect glucagon-like peptide 1 agonists with antidiabetic and anti-inflammatory activity, used for the treatment of type 2 diabetes. Their potential and underlying mechanisms to treat metabolic liver inflammation and fibrosis as well as the associated vascular dysfunction remain to be explored. Results: In the methionine/choline-deficient (MCD) diet and Mdr2−/− models of NASH and liver fibrosis, treatment with sitagliptin and linagliptin significantly decreased parameters of steat…

NUPR1 protects liver from lipotoxic injury by improving the endoplasmic reticulum stress response

2021

AbstractBackground and AimsNon-alcoholic fatty liver disease and related hepatic syndromes affect up to one third of the adult population. The molecular mechanisms underlying NAFL etiology remain elusive. Nuclear Protein 1 (NUPR1) expression increases upon cell injury in all organs and recently we report its active participation in the activation of the Unfolded Protein Response (UPR). The UPR typically maintains protein homeostasis, but downstream mediators of the pathway regulate metabolic functions, including lipid metabolism. NUPR1 and UPR increase have been reported in obesity and liver pathologies and the goal of this study was to investigate the roles of NUPR1 in this context.Methods…

Protein phosphatase 1 regulatory subunit 3B gene variation protects against hepatic fat accumulation and fibrosis in individuals at high risk of nona…

2018

Nonalcoholic fatty liver disease (NAFLD) is a major cause of liver damage and has a strong genetic component. The rs4841132 G>A variant, modulating the expression of protein phosphatase 1 regulatory subunit 3B (PPP1R3B), which is involved in glycogen synthesis, has been reported to reduce the risk of NAFLD but at the same time may favor liver disease by facilitating glycogen accumulation. The aim of this study was to assess the impact of rs4841132 on development of histologic steatosis and fibrosis in 1,388 European individuals in a liver biopsy cohort, on NAFLD hepatocellular carcinoma in a cross-sectional Italian cohort (n = 132 cases), and on liver disease at the population level in the …

Transient elastography for screening of liver fibrosis: cost-effectiveness analysis from six prospective cohorts in Europe and Asia

2019

Background & Aims: Non-alcoholic fatty liver disease and alcohol-related liver disease pose an important challenge to current clinical healthcare pathways because of the large number of at-risk patients. Therefore, we aimed to explore the cost-effectiveness of transient elastography (TE) as a screening method to detect liver fibrosis in a primary care pathway. Methods: Cost-effectiveness analysis was performed using real-life individual patient data from 6 independent prospective cohorts (5 from Europe and 1 from Asia). A diagnostic algorithm with conditional inference trees was developed to explore the relationships between liver stiffness, socio-demographics, comorbidities, and hepati…

Beyond the Paradigm of Weight Loss in Non-Alcoholic Fatty Liver Disease: From Pathophysiology to Novel Dietary Approaches

2021

Current treatment recommendations for non-alcoholic fatty liver disease (NAFLD) rely heavily on lifestyle interventions. The Mediterranean diet and physical activity, aiming at weight loss, have shown good results in achieving an improvement of this liver disease. However, concerns related to compliance and food accessibility limit the feasibility of this approach, and data on the long-term effects on liver-related outcomes are lacking. Insulin resistance is a central aspect in the pathophysiology of NAFLD; therefore, interventions aiming at the improvement of insulin sensitivity may be preferable. In this literature review, we provide a comprehensive summary of the available evidence on nu…

2020

Understanding the importance of the gut microbiota (GM) in non-alcoholic fatty liver disease (NAFLD) has raised the hope for therapeutic microbes. We have shown that high hepatic fat content associated with low abundance of Faecalibacterium prausnitzii in humans and, further, the administration of F. prausnitzii prevented NAFLD in mice. Here, we aimed at targeting F. prausnitzii by prebiotic xylo-oligosaccharides (XOS) to treat NAFLD. First, the effect of XOS on F. prausnitzii growth was assessed in vitro. Then, XOS was supplemented or not with high (HFD, 60% of energy from fat) or low (LFD) fat diet for 12 weeks in Wistar rats (n = 10/group). XOS increased F. prausnitzii growth, having onl…

Steatohepatitis Impairs T-cell-Directed Immunotherapies Against Liver Tumors in Mice.

2019

Background & Aims Nonalcoholic steatohepatitis causes loss of hepatic CD4+ T cells and promotes tumor growth. The liver is the most common site of distant metastases from a variety of malignancies, many of which respond to immunotherapy. We investigated the effects of steatohepatitis on the efficacy of immunotherapeutic agents against liver tumors in mice. Methods Steatohepatitis was induced by feeding C57BL/6NCrl or BALB/c AnNCr mice a methionine and choline–deficient diet or a choline-deficient l-amino acid–defined diet. Mice were given intrahepatic or subcutaneous injections of B16 melanoma and CT26 colon cancer cells, followed by intravenous injections of M30-RNA vaccine (M30) or intrap…

PCSK7 gene variation bridges atherogenic dyslipidemia with hepatic inflammation in NAFLD patients

2019

Dyslipidemia and altered iron metabolism are typical features of nonalcoholic fatty liver disease (NAFLD). Proprotein convertase subtilisin/kexin type 7 (PCSK7) gene variation has been associated with circulating lipids and liver damage during iron overload. The aim of this study was to examine the impact of the PCSK7 rs236918 variant on NAFLDrelated traits in 1,801 individuals from the Liver Biopsy Cohort (LBC), 500,000 from the UK Biobank Cohort (UKBBC), and 4,580 from the Dallas Heart Study (DHS). The minor PCSK7 rs236918 C allele was associated with higher triglycerides, aminotransferases, and hepatic inflammation in the LBC (P < 0.05) and with hypercholesterolemia and liver disease …

Xanthohumol ameliorates Diet-Induced Liver Dysfunction via Farnesoid X Receptor-Dependent and Independent Signaling

2020

The farnesoid X receptor (FXR) plays a critical role in the regulation of lipid and bile acid (BA) homeostasis. Hepatic FXR loss results in lipid and BA accumulation, and progression from hepatic steatosis to nonalcoholic steatohepatitis (NASH). This study aimed to evaluate the effects of xanthohumol (XN), a hop-derived compound mitigating metabolic syndrome, on liver damage induced by diet and FXR deficiency in mice. Wild-type (WT) and liver-specific FXR-null mice (FXRLiver−/−) were fed a high-fat diet (HFD) containing XN or the vehicle formation followed by histological characterization, lipid, BA and gene profiling. HFD supplemented with XN resulted in amelioration of hepatic steatosis a…