Hepatic Expression of ACBP Is a Prognostic Marker for Weight Loss After Bariatric Surgery.

The incidence and prevalence of obesity and related cardio-metabolic diseases are on the rise, posing a critical health care challenge to systems across the globe. Bariatric surgery is a therapeutic cornerstone for morbidly obese patients, besides novel medical treatments, partly by ameliorating metabolic inflammation, a hallmark of metabolic diseases. Acyl-CoA Binding Protein (ACBP), also known as diazepam-binding inhibitor (DBI), is a regulator of autophagy and metabolism, and has recently been shown to increase in individuals undergoing voluntary fasting and in patients with cancer cachexia-induced malnutrition.

Apelin and the gut microbiome: Potential interaction in human MASLD.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading cause of chronic liver disease with increasing numbers worldwide. Adipokines like apelin (APLN) can act as key players in the complex pathophysiology of MASLD.

Aims: Investigating the role of APLN in MASLD.

A gut bacterial signature in blood and liver tissue characterizes cirrhosis and hepatocellular carcinoma.

Background: HCC is the leading cause of cancer in chronic liver disease. A growing body of experimental mouse models supports the notion that gut-resident and liver-resident microbes control hepatic immune responses and, thereby, crucially contribute to liver tumorigenesis. However, a comprehensive characterization of the intestinal microbiome in fueling the transition from chronic liver disease to HCC in humans is currently missing.

Recovery of ameliorates hepatic steatosis in experimental alcohol-related liver disease.

Alcohol-related liver disease (ALD) is a major cause of liver disease and represents a global burden, as treatment options are scarce. Whereas 90% of ethanol abusers develop alcoholic fatty liver disease (AFLD), only a minority evolves to steatohepatitis and cirrhosis. Alcohol increases lipogenesis and suppresses lipid-oxidation implying steatosis, although the key role of intestinal barrier integrity and microbiota in ALD has recently emerged.

Interleukin-11 drives human and mouse alcohol-related liver disease.

Objective: Alcoholic hepatitis (AH) reflects acute exacerbation of alcoholic liver disease (ALD) and is a growing healthcare burden worldwide. Interleukin-11 (IL-11) is a profibrotic, proinflammatory cytokine with increasingly recognised toxicities in parenchymal and epithelial cells. We explored IL-11 serum levels and their prognostic value in patients suffering from AH and cirrhosis of various aetiology and experimental ALD.

Adipocyte GPX4 protects against inflammation, hepatic insulin resistance and metabolic dysregulation.

Objectives: Metabolic inflammation is a hallmark of obesity and related disorders, afflicting substantial morbidity and mortality to individuals worldwide. White visceral and subcutaneous adipose tissue not only serves as energy storage but also controls metabolism. Adipose tissue inflammation, commonly observed in human obesity, is considered a critical driver of metabolic perturbation while molecular hubs are poorly explored.

PUFA-Induced Metabolic Enteritis as a Fuel for Crohn's Disease.

Background & Aims: Crohn's disease (CD) globally emerges with Westernization of lifestyle and nutritional habits. However, a specific dietary constituent that comprehensively evokes gut inflammation in human inflammatory bowel diseases remains elusive. We aimed to delineate how increased intake of polyunsaturated fatty acids (PUFAs) in a Western diet, known to impart risk for developing CD, affects gut inflammation and disease course.

Hepatic Meteorin-like and Krüppel-like Factor 3 are Associated with Weight Loss and Liver Injury.

Objective: Laparoscopic adjustable gastric banding (LAGB) was found to be effective in reducing body weight and improving insulin resistance in patients with obesity and non-alcoholic fatty liver disease (NAFLD). The adipokine/myokine meteorin-like (METNRL) is an important regulator of whole-body energy expenditure. Krüppel-like factor 3 (KLF3), a regulator of METRNL expression in eosinophils, inhibits the beiging of adipose tissue in mice and therefore regulates adipose tissue development.

Increased Fecal Neopterin Parallels Gastrointestinal Symptoms in COVID-19.

Introduction: Coronavirus disease (COVID-19) has spread from Wuhan, China, and become a worldwide pandemic. Most patients display respiratory symptoms but up to 50% report gastrointestinal symptoms. Neopterin is a surrogate marker for viral inflammation, and its production by macrophages is driven by interferon-γ.

The role of gut vascular barrier in experimental alcoholic liver disease and A. muciniphila supplementation.

The translocation of bacterial components from the intestinal lumen into the portal circulation is crucial in the pathogenesis of alcoholic liver disease (ALD). Recently the important role of the gut vascular barrier (GVB) was elucidated in alcoholic liver disease. Here we report about the influence of supplementation in experimental ALD on the GVB.

Alpha-1 antitrypsin governs alcohol-related liver disease in mice and humans.

Objective: Alcohol-related liver disease (ALD) is a global healthcare problem with limited treatment options. Alpha-1 antitrypsin (AAT, encoded by ) shows potent anti-inflammatory activities in many preclinical and clinical trials. In our study, we aimed to explore the role of AAT in ALD.

Gastric banding-associated weight loss diminishes hepatic Tsukushi expression.

Obesity has emerged as a substantial global healthcare issue that is frequently associated with insulin resistance and non-alcoholic fatty liver disease (NAFLD). Tsukushi (TSK), a liver-derived molecule, was recently identified as a major driver of NAFLD. Laparoscopic adjustable gastric banding (LAGB) has proven effective in reducing body weight and improving NAFLD.

Dietary lipids fuel GPX4-restricted enteritis resembling Crohn's disease.

The increased incidence of inflammatory bowel disease (IBD) has become a global phenomenon that could be related to adoption of a Western life-style. Westernization of dietary habits is partly characterized by enrichment with the ω-6 polyunsaturated fatty acid (PUFA) arachidonic acid (AA), which entails risk for developing IBD. Glutathione peroxidase 4 (GPX4) protects against lipid peroxidation (LPO) and cell death termed ferroptosis.

Weight Loss Induced by Bariatric Surgery Restricts Hepatic Expression.

Introduction: Obesity and related nonalcoholic fatty liver disease (NAFLD) are an emerging health care issue that imposes substantial morbidity to individuals. Growth and differentiation factor 15 () limits food uptake, body weight, and energy balance by modulation of GDNF-family receptor -like (GFRAL) signalling in the hindbrain. However, the regulation of expression in obesity and NAFLD is incompletely understood.

Ethanol-mediated suppression of IL-37 licenses alcoholic liver disease.

Background & Aims: Chronic alcohol consumption and alcoholic liver disease (ALD) afflicts individuals with substantial morbidity and mortality with limited treatment options available. Hepatic inflammation, triggered by activated Kupffer cells, is a driving force in alcoholic liver disease. Interleukin 37 (IL-37) exerts anti-inflammatory effects in hepatic diseases, however, the impact of Interleukin 37 on alcoholic liver disease is unknown.

Dynamics of Bile Acid Profiles, GLP-1, and FGF19 After Laparoscopic Gastric Banding.

Context: An increase of bile acids (BAs), fibroblast growth factor 19 (FGF19), and glucagon-like peptide 1 (GLP-1) has been implicated in metabolic improvements after Roux-en-Y gastric bypass and vertical sleeve gastrectomy. However, data are still conflicting regarding their role after laparoscopic adjustable gastric banding (LAGB).

Objective: To assess the fasting BA, FGF19, and GLP-1 concentrations in plasma before and after LAGB and to test for correlations with immunometabolic parameters.

Adipose type I interferon signalling protects against metabolic dysfunction.

Objective: Low-grade chronic inflammation emerges as a potent driver of insulin resistance and glucose dysregulation in obesity and associated non-alcoholic fatty liver disease (NAFLD). The liver, subcutaneous fat and the immune system participate in disturbances of metabolism. Type I interferon (IFN) signalling initiated by innate and adaptive immunity modulates inflammatory responses consequent to infection.

Weight loss induced by bariatric surgery restores adipose tissue PNPLA3 expression.

Background & Aims: Obesity and its related co-morbidities such as non-alcoholic fatty liver disease (NAFLD) are increasing dramatically worldwide. The genetic variation in Patatin-like phospholipase domain-containing protein 3 (PNPLA3), which is also called adiponutrin (ADPN), in residue 148 (I148M, rs738409) has been associated with NAFLD. However, the regulation and function of PNPLA3 in metabolic diseases remains unclear.

Reversal of murine alcoholic steatohepatitis by pepducin-based functional blockade of interleukin-8 receptors.

Objective: Alcoholic steatohepatitis is a life-threatening condition with short-term mortality up to 40%. It features hepatic neutrophil infiltration and blood neutrophilia, and may evolve from ethanol-induced breakdown of the enteric barrier and consequent bacteraemia. Signalling through CXCR1/2 G-protein-coupled-receptors (GPCRs), the interleukin (IL)-8 receptors, is critical for the recruitment and activation of neutrophils.

Lipocalin 2 drives neutrophilic inflammation in alcoholic liver disease.

Background & Aims: Alcoholic steatohepatitis (ASH) is characterised by neutrophil infiltration that contributes to hepatic injury and disease. Lipocalin-2 (LCN2) was originally identified as siderophore binding peptide in neutrophils, which exerted tissue protective effects in several disease models. Here we investigate the role of LCN2 in the pathogenesis of alcohol-induced liver injury.

Adipose tissue and liver expression of SIRT1, 3, and 6 increase after extensive weight loss in morbid obesity.

Background & Aims: Severe obesity is associated with a state of chronic inflammation. Sirtuins (SIRT) are a family of conserved enzymes which are able to affect many metabolic and inflammatory pathways thereby potentially improving health and increasing lifespan.

Methods: We investigated the effect of weight loss on subcutaneous adipose tissue and liver mRNA and immunohistochemical expression of SIRT1, SIRT3, and SIRT6.

Adipose and liver expression of interleukin (IL)-1 family members in morbid obesity and effects of weight loss.

Morbid obesity is associated with a state of chronic inflammation. Interleukin-1 family (IL-1F) cytokine members are produced by human adipose tissue in obesity. Whereas certain IL-1F members such as IL-1β or IL-18 are potently proinflammatory, others such as IL-1 receptor antagonist (IL-1Ra) or IL-37 (formerly IL-1F7) are antiinflammatory.

Role for hedgehog pathway in regulating growth and function of invariant NKT cells.

Lymphocyte accumulation is characteristic of chronic hepatitis, but the mechanisms regulating lymphocyte numbers and their roles in liver disease progression are poorly understood. The Hedgehog (Hh) pathway regulates thymic development and lymphopoeisis during embryogenesis, and is activated in fibrosing liver disease in adults. Our objective was to determine if Hh ligands regulate the viability and phenotype of NKT cells, which comprise a substantial sub-population of resident lymphocytes in healthy adult livers and often accumulate during liver fibrosis.

Impaired counter-regulation of interleukin-1 by the soluble IL-1 receptor type II in patients with chronic liver disease.

Objective: To assess the production of the endogenous IL-1 modulators IL-1 receptor antagonist (IL-1Ra), type I and II soluble IL-1 receptors (IL-1sRI and II) in patients with chronic liver disease (CLD).

Material And Methods: Plasma levels of IL-1beta (IL-1beta) and IL-1 modulators were assessed in 126 CLD patients and 39 healthy controls. IL-1sRII was also measured in the supernatants of primary hepatocyte cultures.