Pro‐inflammatory signalling and gut‐liver axis in non‐alcoholic and alcoholic steatohepatitis: Differences and similarities along the path
Open Access
- 21 April 2020
- journal article
- review article
- Published by Wiley in Journal of Cellular and Molecular Medicine
- Vol. 24 (11), 5955-5965
- https://doi.org/10.1111/jcmm.15182
Abstract
Non‐alcoholic fatty liver disease (NAFLD) and alcohol‐associated liver disease (ALD) represent a spectrum of injury, ranging from simple steatosis to steatohepatitis and cirrhosis. In humans, in fact, fatty changes in the liver, possibly leading to end‐stage disease, were observed after chronic alcohol intake or in conditions of metabolic impairment. In this article, we examined the features and the pro‐inflammatory pathways leading to non‐alcoholic and alcoholic steatohepatitis. The involvement of several events (hits) and multiple inter‐related pathways in the pathogenesis of these diseases suggest that a single therapeutic agent is unlikely to be an effective treatment strategy. Hence, a combination treatment towards multiple pro‐inflammatory targets would eventually be required. Gut‐liver crosstalk is involved not only in the impairment of lipid and glucose homoeostasis leading to steatogenesis, but also in the initiation of inflammation and fibrogenesis in both NAFLD and ALD. Modulation of the gut‐liver axis has been suggested as a possible therapeutic approach since gut‐derived components are likely to be involved in both the onset and the progression of liver damage. This review summarizes the translational mechanisms underlying pro‐inflammatory signalling and gut‐liver axis in non‐alcoholic and alcoholic steatohepatitis. With a multitude of people being affected by liver diseases, identification of possible treatments and the elucidation of pathogenic mechanisms are elements of paramount importance.Keywords
Funding Information
- PSC Partners Seeking a Cure
This publication has 101 references indexed in Scilit:
- Leptin Deficiency Contributes to the Pathogenesis of Alcoholic Fatty Liver Disease in MiceThe American Journal of Pathology, 2012
- Excessive Hepatic Mitochondrial TCA Cycle and Gluconeogenesis in Humans with Nonalcoholic Fatty Liver DiseaseCell Metabolism, 2011
- Adipokines in inflammation and metabolic diseaseNature Reviews Immunology, 2011
- The role of lipopolysaccharide/toll-like receptor 4 signaling in chronic liver diseasesHepatology International, 2010
- Taurine supplementation prevents ethanol-induced decrease in serum adiponectin and reduces hepatic steatosis in ratsHepatology, 2008
- The critical role of toll-like receptor (TLR) 4 in alcoholic liver disease is independent of the common TLR adapter MyD88Hepatology, 2008
- Nonalcoholic steatohepatitis is associated with altered hepatic MicroRNA expressionHepatology, 2008
- Toll-like receptor-4 signaling and Kupffer cells play pivotal roles in the pathogenesis of non-alcoholic steatohepatitisJournal of Hepatology, 2007
- Embryonic stem cell-derived microvesicles reprogram hematopoietic progenitors: evidence for horizontal transfer of mRNA and protein deliveryLeukemia, 2006
- The functions of animal microRNAsNature, 2004