Blog
About

  • Record: found
  • Abstract: found
  • Article: found
Is Open Access

The Role of Tissue Macrophage-Mediated Inflammation on NAFLD Pathogenesis and Its Clinical Implications

Read this article at

Bookmark
      There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

      Abstract

      The obese phenotype is characterized by a state of chronic low-grade systemic inflammation that contributes to the development of comorbidities, including nonalcoholic fatty liver disease (NAFLD). In fact, NAFLD is often associated with adipocyte enlargement and consequent macrophage recruitment and inflammation. Macrophage polarization is often associated with the proinflammatory state in adipose tissue. In particular, an increase of M1 macrophages number or of M1/M2 ratio triggers the production and secretion of various proinflammatory signals (i.e., adipocytokines). Next, these inflammatory factors may reach the liver leading to local M1/M2 macrophage polarization and consequent onset of the histological damage characteristic of NAFLD. Thus, the role of macrophage polarization and inflammatory signals appears to be central for pathogenesis and progression of NAFLD, even if the heterogeneity of macrophages and molecular mechanisms that govern their phenotype switch remain incompletely understood. In this review, we discuss the role of adipose and liver tissue macrophage-mediated inflammation in experimental and human NAFLD. This focus is relevant because it may help researchers that approach clinical and experimental studies on this disease advancing the knowledge of mechanisms that could be targeted in order to revert NAFLD-related fibrosis.

      Related collections

      Most cited references 159

      • Record: found
      • Abstract: found
      • Article: not found

      Macrophage plasticity and polarization: in vivo veritas.

      Diversity and plasticity are hallmarks of cells of the monocyte-macrophage lineage. In response to IFNs, Toll-like receptor engagement, or IL-4/IL-13 signaling, macrophages undergo M1 (classical) or M2 (alternative) activation, which represent extremes of a continuum in a universe of activation states. Progress has now been made in defining the signaling pathways, transcriptional networks, and epigenetic mechanisms underlying M1-M2 or M2-like polarized activation. Functional skewing of mononuclear phagocytes occurs in vivo under physiological conditions (e.g., ontogenesis and pregnancy) and in pathology (allergic and chronic inflammation, tissue repair, infection, and cancer). However, in selected preclinical and clinical conditions, coexistence of cells in different activation states and unique or mixed phenotypes have been observed, a reflection of dynamic changes and complex tissue-derived signals. The identification of mechanisms and molecules associated with macrophage plasticity and polarized activation provides a basis for macrophage-centered diagnostic and therapeutic strategies.
        Bookmark
        • Record: found
        • Abstract: found
        • Article: not found

        Obesity induces a phenotypic switch in adipose tissue macrophage polarization.

        Adipose tissue macrophages (ATMs) infiltrate adipose tissue during obesity and contribute to insulin resistance. We hypothesized that macrophages migrating to adipose tissue upon high-fat feeding may differ from those that reside there under normal diet conditions. To this end, we found a novel F4/80(+)CD11c(+) population of ATMs in adipose tissue of obese mice that was not seen in lean mice. ATMs from lean mice expressed many genes characteristic of M2 or "alternatively activated" macrophages, including Ym1, arginase 1, and Il10. Diet-induced obesity decreased expression of these genes in ATMs while increasing expression of genes such as those encoding TNF-alpha and iNOS that are characteristic of M1 or "classically activated" macrophages. Interestingly, ATMs from obese C-C motif chemokine receptor 2-KO (Ccr2-KO) mice express M2 markers at levels similar to those from lean mice. The antiinflammatory cytokine IL-10, which was overexpressed in ATMs from lean mice, protected adipocytes from TNF-alpha-induced insulin resistance. Thus, diet-induced obesity leads to a shift in the activation state of ATMs from an M2-polarized state in lean animals that may protect adipocytes from inflammation to an M1 proinflammatory state that contributes to insulin resistance.
          Bookmark
          • Record: found
          • Abstract: found
          • Article: not found

          Macrophage activation and polarization: nomenclature and experimental guidelines.

          Description of macrophage activation is currently contentious and confusing. Like the biblical Tower of Babel, macrophage activation encompasses a panoply of descriptors used in different ways. The lack of consensus on how to define macrophage activation in experiments in vitro and in vivo impedes progress in multiple ways, including the fact that many researchers still consider there to be only two types of activated macrophages, often termed M1 and M2. Here, we describe a set of standards encompassing three principles-the source of macrophages, definition of the activators, and a consensus collection of markers to describe macrophage activation-with the goal of unifying experimental standards for diverse experimental scenarios. Collectively, we propose a common framework for macrophage-activation nomenclature. Copyright © 2014 Elsevier Inc. All rights reserved.
            Bookmark

            Author and article information

            Affiliations
            1Liver Research Unit of Bambino Gesù Children's Hospital and IRCCS, Rome, Italy
            2Department of Movement, Human and Health Sciences, Division of Health Sciences, University of Rome “Foro Italico”, Rome, Italy
            3Federal University of Rio de Janeiro, Institute of Biomedical Sciences, Rio de Janeiro, Brazil
            4Hepato-Metabolic Disease Unit of Bambino Gesù Children's Hospital and IRCCS, Rome, Italy
            5Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University of Rome, Rome, Italy
            Author notes

            Academic Editor: Dah-Yuu Lu

            Journal
            Mediators Inflamm
            Mediators Inflamm
            MI
            Mediators of Inflammation
            Hindawi Publishing Corporation
            0962-9351
            1466-1861
            2017
            1 January 2017
            : 2017
            5237469 10.1155/2017/8162421
            Copyright © 2017 Anna Alisi et al.

            This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

            Funding
            Funded by: Italian Ministry of Health Funds
            Funded by: Science without Borders,” a Brazilian Federal Programme by CAPES
            Categories
            Review Article

            Immunology

            Comments

            Comment on this article