Rebelos E, Iozzo P, Guzzardi MA, Brunetto MR, Bonino F. Brain-gut-liver interactions across the spectrum of insulin resistance in metabolic fatty liver disease. World J Gastroenterol 2021; 27(30): 4999-5018 [PMID: 34497431 DOI: 10.3748/wjg.v27.i30.4999]
Corresponding Author of This Article
Ferruccio Bonino, MD, PhD, Professor, Senior Scientist, Institute of Biostructure and Bioimaging, National Research Council, Via Tommaso De Amicis, 95, Napoli 80145, Italy. ferruccio.bonino@unipi.it
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Review
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Eleni Rebelos, Turku PET Centre, University of Turku, Turku 20500, Finland
Patricia Iozzo, Maria Angela Guzzardi, Institute of Clinical Physiology, National Research Council, Pisa 56124, Italy
Maurizia Rossana Brunetto, Hepatology Unit and Laboratory of Molecular Genetics and Pathology of Hepatitis, Pisa University Hospital, Pisa 56121, Italy
Maurizia Rossana Brunetto, Department of Clinical and Experimental Medicine, University of Pisa, Pisa 56121, Italy
Maurizia Rossana Brunetto, Ferruccio Bonino, Institute of Biostructure and Bioimaging, National Research Council, Napoli 80145, Italy
Author contributions: Rebelos E and Iozzo P drafted the manuscript; Bonino F conceived the study idea; Guzzardi MA, Brunetto MR and Bonino F critically revised the manuscript; all authors approved the final version of the text; Rebelos E and Iozzo P contributed equally.
Conflict-of-interest statement: Authors declare that they have no conflicting interests.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Ferruccio Bonino, MD, PhD, Professor, Senior Scientist, Institute of Biostructure and Bioimaging, National Research Council, Via Tommaso De Amicis, 95, Napoli 80145, Italy. ferruccio.bonino@unipi.it
Received: February 10, 2021 Peer-review started: February 10, 2021 First decision: April 18, 2021 Revised: April 29, 2021 Accepted: July 13, 2021 Article in press: July 13, 2021 Published online: August 14, 2021
Abstract
Metabolic associated fatty liver disease (MAFLD), formerly named “nonalcoholic fatty liver disease” occurs in about one-third of the general population of developed countries worldwide and behaves as a major morbidity and mortality risk factor for major causes of death, such as cardiovascular, digestive, metabolic, neoplastic and neuro-degenerative diseases. However, progression of MAFLD and its associated systemic complications occur almost invariably in patients who experience the additional burden of intrahepatic and/or systemic inflammation, which acts as disease accelerator. Our review is focused on the new knowledge about the brain-gut-liver axis in the context of metabolic dysregulations associated with fatty liver, where insulin resistance has been assumed to play an important role. Special emphasis has been given to digital imaging studies and in particular to positron emission tomography, as it represents a unique opportunity for the noninvasive in vivo study of tissue metabolism. An exhaustive revision of targeted animal models is also provided in order to clarify what the available preclinical evidence suggests for the causal interactions between fatty liver, dysregulated endogenous glucose production and insulin resistance.
Core Tip: From studies using tissue-targeted animal models, it emerges that neither insulin resistance per se induces hepatic steatosis, nor steatosis induces whole-body insulin resistance. However, it is evident that reducing inflammation has several beneficial effects both at the hepatic and whole-body level. In fact, either hepatic or systemic inflammation act as major throttle of progressive liver and systemic diseases.
