Hepatocyte expressed chemerin-156 does not protect from experimental non-alcoholic steatohepatitis.

Non-alcoholic steatohepatitis (NASH) is a rapidly growing liver disease. The chemoattractant chemerin is abundant in hepatocytes, and hepatocyte expressed prochemerin protected from NASH. Prochemerin is inactive and different active isoforms have been described.

Chemerin Overexpression in the Liver Protects against Inflammation in Experimental Non-Alcoholic Steatohepatitis.

Non-alcoholic steatohepatitis (NASH) is marked by macrophage infiltration and inflammation. Chemerin is a chemoattractant protein and is abundant in hepatocytes. The aim of this study was to gain insight into the role of hepatocyte-produced prochemerin in NASH.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) levels are not associated with severity of liver disease and are inversely related to cholesterol in a cohort of thirty eight patients with liver cirrhosis.

Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is of particular importance in cholesterol metabolism with high levels contributing to hypercholesterolemia. Cholesterol and sphingolipids are low in patients with liver cirrhosis. Purpose of this study was to find associations of plasma PCSK9 with circulating cholesterol and sphingolipid species and measures of liver disease severity in patients with liver cirrhosis.

Chemerin Is Induced in Non-Alcoholic Fatty Liver Disease and Hepatitis B-Related Hepatocellular Carcinoma.

Chemerin is protective in experimental models of hepatocellular carcinoma (HCC). Noteworthy, chemerin mRNA and protein were reduced in HCC tissues of Asian patients with mostly hepatitis B disease etiology. The current study nevertheless showed that chemerin protein was induced in tumor tissues of European HCC patients with non-alcoholic fatty liver disease (NAFLD) and patients with unclear disease etiology.

Chemerin Isoform-Specific Effects on Hepatocyte Migration and Immune Cell Inflammation.

Murine chemerin is C-terminally processed to the bioactive isoforms, muChem-156 and muChem-155, among which the longer variant protects from hepatocellular carcinoma (HCC). However, the role of muChem-155 is mostly unknown. Here, we aimed to compare the effects of these isoforms on the proliferation, migration and the secretome of the human hepatocyte cell lines HepG2 and Huh7 and the murine Hepa1-6 cell line.

Pentraxin-3 is not related to disease severity in cirrhosis and hepatocellular carcinoma patients.

The acute-phase protein pentraxin-3 (PTX3) is a component of the innate immune system. Inflammation and tissue injury increased PTX3 in the injured liver, and accordingly, circulating PTX3 was induced in patients with chronic liver diseases. In the present study, PTX3 protein was determined in systemic, hepatic, and portal vein plasma of patients with liver cirrhosis to assess a possible association between hepatic PTX3 release and extent of liver injury.

Overexpression of Hepatocyte Chemerin-156 Lowers Tumor Burden in a Murine Model of Diethylnitrosamine-Induced Hepatocellular Carcinoma.

The tumor inhibitory potential of the highly active chemerin-156 isoform was described in orthotopic models of hepatocellular carcinoma (HCC). The majority of HCC arises in the fibrotic liver, which was not reproduced in these studies. Here, a potential therapeutic activity of chemerin-156 was evaluated in diethylnitrosamine (DEN)-induced liver cancer, which mimics fibrosis-associated HCC.

Serum Adiponectin Levels Do Not Distinguish Primary from Metastatic Liver Tumors.

Background/aim: Adiponectin protects from metabolic disease and cancer. Accordingly, serum adiponectin was reduced in patients with colorectal cancer (CRC). This hepatoprotective factor was definitely increased in hepatocellular carcinoma (HCC).

Alpha-syntrophin deficiency protects against non-alcoholic steatohepatitis associated increase of macrophages, CD8 T-cells and galectin-3 in the liver.

Non-alcoholic steatohepatitis (NASH) is characterized by immune cell infiltration. Loss of the scaffold protein alpha-syntrophin (SNTA) protected mice from hepatic inflammation in the methionine-choline-deficient (MCD) diet model. Here, we determined increased numbers of macrophages and CD8 T-cells in MCD diet induced NASH liver of wild type mice.

Variations in hepatic lipid species of age-matched male mice fed a methionine-choline-deficient diet and housed in different animal facilities.

Background: Non-alcoholic steatohepatitis (NASH) is a common disease and feeding mice a methionine-choline-deficient (MCD) diet is a frequently used model to study its pathophysiology. Genetic and environmental factors influence NASH development and liver lipid content, which was studied herein using C57BL/6 J mice bred in two different animal facilities.

Methods: Age-matched male C57BL/6 J mice bred in two different animal facilities (later on referred to as WT1 and WT2) at the University Hospital of Regensburg were fed identical MCD or control chows for 2 weeks.

Serum Chemerin Does Not Differentiate Colorectal Liver Metastases from Hepatocellular Carcinoma.

The chemoattractant adipokine chemerin is related to the metabolic syndrome, which is a risk factor for different cancers. Recent studies provide evidence that chemerin is an important molecule in colorectal cancer (CRC) and hepatocellular carcinoma (HCC). Serum chemerin is high in CRC patients and low in HCC patients and may serve as a differential diagnostic marker for HCC and liver metastases from CRC.

Chemerin Isoforms and Activity in Obesity.

Overweight and adiposity are risk factors for several diseases, like type 2 diabetes and cancer. White adipose tissue is a major source for adipokines, comprising a diverse group of proteins exerting various functions. Chemerin is one of these proteins whose systemic levels are increased in obesity.

Alpha-syntrophin dependent expression of tubulin alpha 8 protein in hepatocytes.

The scaffold protein alpha-syntrophin (SNTA) is a component of the dystrophin glycoprotein complex and has been comprehensively studied in skeletal muscle and adipocytes. SNTA is further expressed in the liver where its biological role remains unclear. Unpublished data from our group suggested that SNTA deficiency is associated with altered tubulin alpha 8 (TUBA8) levels in fat.

The utrophin-beta 2 syntrophin complex regulates adipocyte lipid droplet size independent of adipogenesis.

Utrophin is a widely expressed cytoskeleton protein and is associated with lipid droplets (LDs) in adipocytes. The scaffold protein beta 2 syntrophin (SNTB2) controls signaling events by recruiting distinct membrane and cytoskeletal proteins, and binds to utrophin. Here we show that SNTB2 forms a complex with utrophin in adipocytes.

Chemerin in a Mouse Model of Non-alcoholic Steatohepatitis and Hepatocarcinogenesis.

Background/aim: Non-alcoholic steatohepatitis (NASH) is a risk factor for hepatocellular carcinoma (HCC). The adipokine chemerin protects from HCC and is reduced in human HCC. In this study, chemerin expression was analyzed in a murine model of NASH-HCC.

Alpha-syntrophin null mice are protected from non-alcoholic steatohepatitis in the methionine-choline-deficient diet model but not the atherogenic diet model.

Adipose tissue dysfunction contributes to the pathogenesis of non-alcoholic steatohepatitis (NASH). The adapter protein alpha-syntrophin (SNTA) is expressed in adipocytes. Knock-down of SNTA increases preadipocyte proliferation and formation of small lipid droplets, which are both characteristics of healthy adipose tissue.

Ex vivo analysis of serum chemerin activity in murine models of obesity.

Objectives: Chemerin is an adipokine with established roles in inflammation, adipogenesis and the regulation of glucose and lipid homeostasis. Extracellular proteolytic processing of chemerin generates a spectrum of isoforms that differ significantly with respect to the ability to activate the cognate receptors chemokine-like receptor 1 (CMKLR1) and G-protein-coupled receptor 1 (GPR1). Increased total serum chemerin has been widely reported in obese humans as well as in preclinical rodent models of adiposity.