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      Macrophages and lipid metabolism

      research-article
      Author(s): a , b , a , b , c , *
      Publication date PMC-release:
      Journal: Cellular Immunology
      Publisher: Elsevier
      Keywords: Macrophages, Lipid metabolism, NAFLD, PAP, Atherosclerosis, AMD

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          Highlights

          • •

            The transcriptional signature of Kupffer cells & Alveolar macrophages are enriched for lipid metabolism genes.

          • •

            Lipid metabolism may control macrophage phenotype.

          • •

            Dysregulated lipid metabolism in macrophages contributes to disease pathology.

          Abstract

          Distinct macrophage populations throughout the body display highly heterogeneous transcriptional and epigenetic programs. Recent research has highlighted that these profiles enable the different macrophage populations to perform distinct functions as required in their tissue of residence, in addition to the prototypical macrophage functions such as in innate immunity. These ‘extra’ tissue-specific functions have been termed accessory functions. One such putative accessory function is lipid metabolism, with macrophages in the lung and liver in particular being associated with this function. As it is now appreciated that cell metabolism not only provides energy but also greatly influences the phenotype and function of the cell, here we review how lipid metabolism affects macrophage phenotype and function and the specific roles played by macrophages in the pathogenesis of lipid-related diseases. In addition, we highlight the current questions limiting our understanding of the role of macrophages in lipid metabolism.

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          Tissue-Resident Macrophage Ontogeny and Homeostasis.

          Florent Ginhoux, Martin Guilliams (2016)
          Defining the origins and developmental pathways of tissue-resident macrophages should help refine our understanding of the role of these cells in various disease settings and enable the design of novel macrophage-targeted therapies. In recent years the long-held belief that macrophage populations in the adult are continuously replenished by monocytes from the bone marrow (BM) has been overturned with the advent of new techniques to dissect cellular ontogeny. The new paradigm suggests that several tissue-resident macrophage populations are seeded during waves of embryonic hematopoiesis and self-maintain independently of BM contribution during adulthood. However, the exact nature of the embryonic progenitors that give rise to adult tissue-resident macrophages is still debated, and the mechanisms enabling macrophage population maintenance in the adult are undefined. Here, we review the emergence of these concepts and discuss current controversies and future directions in macrophage biology.
          Article 0 comments Cited 713 times – based on 0 reviews     Review now
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            Macrophage-specific PPARgamma controls alternative activation and improves insulin resistance.

            Justin Odegaard, Roberto Ricardo-Gonzalez, Matthew H Goforth … (2007)
            Obesity and insulin resistance, the cardinal features of metabolic syndrome, are closely associated with a state of low-grade inflammation. In adipose tissue chronic overnutrition leads to macrophage infiltration, resulting in local inflammation that potentiates insulin resistance. For instance, transgenic expression of Mcp1 (also known as chemokine ligand 2, Ccl2) in adipose tissue increases macrophage infiltration, inflammation and insulin resistance. Conversely, disruption of Mcp1 or its receptor Ccr2 impairs migration of macrophages into adipose tissue, thereby lowering adipose tissue inflammation and improving insulin sensitivity. These findings together suggest a correlation between macrophage content in adipose tissue and insulin resistance. However, resident macrophages in tissues display tremendous heterogeneity in their activities and functions, primarily reflecting their local metabolic and immune microenvironment. While Mcp1 directs recruitment of pro-inflammatory classically activated macrophages to sites of tissue damage, resident macrophages, such as those present in the adipose tissue of lean mice, display the alternatively activated phenotype. Despite their higher capacity to repair tissue, the precise role of alternatively activated macrophages in obesity-induced insulin resistance remains unknown. Using mice with macrophage-specific deletion of the peroxisome proliferator activated receptor-gamma (PPARgamma), we show here that PPARgamma is required for maturation of alternatively activated macrophages. Disruption of PPARgamma in myeloid cells impairs alternative macrophage activation, and predisposes these animals to development of diet-induced obesity, insulin resistance, and glucose intolerance. Furthermore, gene expression profiling revealed that downregulation of oxidative phosphorylation gene expression in skeletal muscle and liver leads to decreased insulin sensitivity in these tissues. Together, our findings suggest that resident alternatively activated macrophages have a beneficial role in regulating nutrient homeostasis and suggest that macrophage polarization towards the alternative state might be a useful strategy for treating type 2 diabetes.
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              Prevalence of age-related macular degeneration in the United States.

              David Friedman, Benita J O'Colmain, Beatriz Mateos Muñoz … (2004)
              To estimate the prevalence and distribution of age-related macular degeneration (AMD) in the United States by age, race/ethnicity, and gender. Summary prevalence estimates of drusen 125 microm or larger, neovascular AMD, and geographic atrophy were prepared separately for black and white persons in 5-year age intervals starting at 40 years. The estimated rates were based on a meta-analysis of recent population-based studies in the United States, Australia, and Europe. These rates were applied to 2000 US Census data and to projected US population figures for 2020 to estimate the number of the US population with drusen and AMD. The overall prevalence of neovascular AMD and/or geographic atrophy in the US population 40 years and older is estimated to be 1.47% (95% confidence interval, 1.38%-1.55%), with 1.75 million citizens having AMD. The prevalence of AMD increased dramatically with age, with more than 15% of the white women older than 80 years having neovascular AMD and/or geographic atrophy. More than 7 million individuals had drusen measuring 125 microm or larger and were, therefore, at substantial risk of developing AMD. Owing to the rapidly aging population, the number of persons having AMD will increase by 50% to 2.95 million in 2020. Age-related macular degeneration was far more prevalent among white than among black persons. Age-related macular degeneration affects more than 1.75 million individuals in the United States. Owing to the rapid aging of the US population, this number will increase to almost 3 million by 2020.
              Article 0 comments Cited 556 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Charlotte L. Scott
                Journal
                Journal ID (nlm-ta): Cell Immunol
                Journal ID (iso-abbrev): Cell. Immunol
                Title: Cellular Immunology
                Publisher: Elsevier
                ISSN (Print): 0008-8749
                ISSN (Electronic): 1090-2163
                Publication date PMC-release: 1 August 2018
                Publication date (Print): August 2018
                Volume: 330
                Pages: 27-42
                Affiliations
                [a ]Laboratory of Myeloid Cell Ontogeny and Functional Specialization, VIB-UGent Center for Inflammation Research, Technologiepark 927, Ghent, Belgium
                [b ]Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium
                [c ]Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK
                Author notes
                [* ]Corresponding author at: Laboratory of Myeloid Cell Ontogeny and Functional Specialization, VIB-UGent Center for Inflammation Research, Technologiepark 927, Ghent, Belgium. charlotte.scott@ 123456irc.vib-ugent.be
                Article
                Publisher ID: S0008-8749(18)30032-7
                DOI: 10.1016/j.cellimm.2018.01.020
                PMC ID: 6108423
                PubMed ID: 29429624
                SO-VID: 50b75c82-5ca4-46a5-a3a8-6fc4551b279e
                Copyright © © 2018 The Authors
                License:

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 30 October 2017
                Date revision received : 25 January 2018
                Date accepted : 31 January 2018
                Categories
                Subject: Article

                ScienceOpen disciplines: Immunology
                Keywords: macrophages,lipid metabolism,nafld,pap,atherosclerosis,amd
                Data availability:
                ScienceOpen disciplines: Immunology
                Keywords: macrophages, lipid metabolism, nafld, pap, atherosclerosis, amd

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