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      Changes in Nutritional Status Impact Immune Cell Metabolism and Function

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          Abstract

          Immune cell function and metabolism are closely linked. Many studies have now clearly demonstrated that alterations in cellular metabolism influence immune cell function and that, conversely, immune cell function determines the cellular metabolic state. Less well understood, however, are the effects of systemic metabolism or whole organism nutritional status on immune cell function and metabolism. Several studies have demonstrated that undernutrition is associated with immunosuppression, which leads to both increased susceptibility to infection and protection against several types of autoimmune disease, whereas overnutrition is associated with low-grade, chronic inflammation that increases the risk of metabolic and cardiovascular disease, promotes autoreactivity, and disrupts protective immunity. Here, we review the effects of nutritional status on immunity and highlight the effects of nutrition on circulating cytokines and immune cell populations in both human studies and mouse models. As T cells are critical members of the immune system, which direct overall immune response, we will focus this review on the influence of systemic nutritional status on T cell metabolism and function. Several cytokines and hormones have been identified which mediate the effects of nutrition on T cell metabolism and function through the expression and action of key regulatory signaling proteins. Understanding how T cells are sensitive to both inadequate and overabundant nutrients may enhance our ability to target immune cell metabolism and alter immunity in both malnutrition and obesity.

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              The Warburg Effect: How Does it Benefit Cancer Cells?

              Cancer cells rewire their metabolism to promote growth, survival, proliferation, and long-term maintenance. The common feature of this altered metabolism is the increased glucose uptake and fermentation of glucose to lactate. This phenomenon is observed even in the presence of completely functioning mitochondria and, together, is known as the 'Warburg Effect'. The Warburg Effect has been documented for over 90 years and extensively studied over the past 10 years, with thousands of papers reporting to have established either its causes or its functions. Despite this intense interest, the function of the Warburg Effect remains unclear. Here, we analyze several proposed explanations for the function of Warburg Effect, emphasize their rationale, and discuss their controversies.
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                Author and article information

                Contributors
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                16 May 2018
                2018
                : 9
                : 1055
                Affiliations
                [1] 1Department of Pediatrics, Duke University Medical Center , Durham, NC, United States
                [2] 2Department of Immunology, Duke University Medical Center , Durham, NC, United States
                [3] 3Department of Pharmacology and Cancer Biology, Duke University Medical Center , Durham, NC, United States
                Author notes

                Edited by: Claudio Mauro, Queen Mary University of London, United Kingdom

                Reviewed by: Jeffrey Louis Curtis, University of Michigan, United States; Hans-Dieter Volk, Charité Universitätsmedizin, Germany

                *Correspondence: Nancie J. MacIver, nancie.maciver@ 123456duke.edu

                Specialty section: This article was submitted to Immunological Tolerance and Regulation, a section of the journal Frontiers in Immunology

                Article
                10.3389/fimmu.2018.01055
                5968375
                29868016
                1a13b5da-4516-4123-b2ba-b01f84dc175f
                Copyright © 2018 Alwarawrah, Kiernan and MacIver.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 01 December 2017
                : 27 April 2018
                Page count
                Figures: 1, Tables: 1, Equations: 0, References: 182, Pages: 14, Words: 12565
                Funding
                Funded by: National Institutes of Health 10.13039/100000002
                Award ID: R01-DK106090, T32-AI052077
                Funded by: National Multiple Sclerosis Society 10.13039/100000890
                Award ID: RG-5333-A-1
                Categories
                Immunology
                Review

                Immunology
                malnutrition,obesity,t cells,cellular metabolism,inflammation,leptin
                Immunology
                malnutrition, obesity, t cells, cellular metabolism, inflammation, leptin

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