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http://dx.doi.org/10.5483/BMBRep.2019.52.6.140

Metabolic influence on macrophage polarization and pathogenesis  

Thapa, Bikash (Institute of Bioscience and Biotechnology, Hallym University)
Lee, Keunwook (Institute of Bioscience and Biotechnology, Hallym University)
Publication Information
BMB Reports / v.52, no.6, 2019 , pp. 360-372 More about this Journal
Abstract
Macrophages play an essential role not only in mediating the first line of defense but also in maintaining tissue homeostasis. In response to extrinsic factors derived from a given tissue, macrophages activate different functional programs to produce polarized macrophage populations responsible for inducing inflammation against microbes, removing cellular debris, and tissue repair. However, accumulating evidence has revealed that macrophage polarization is pivotal in the pathophysiology of metabolic syndromes and cancer, as well as in infectious and autoimmune diseases. Recent advances in transcriptomic and metabolomic studies have highlighted the link between metabolic rewiring of macrophages and their functional plasticity. These findings imply that metabolic adaption to their surrounding microenvironment instructs activation of macrophages with functionally distinct phenotypes, which in turn probably leads to the pathogenesis of a wide spectrum of diseases. In this review, we have introduced emerging concepts in immunometabolism with focus on the impact on functional activation of macrophages. Furthermore, we have discussed the implication of macrophage plasticity on the pathogenesis of metabolic syndromes and cancer, and how the disease microenvironment manipulates macrophage metabolism with regard to the pathophysiology.
Keywords
Atherosclerosis; Cancer; Macrophage; Macrophage polarization; Metabolism; Obesity;
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1 Folco EJ, Sheikine Y, Rocha VZ et al (2011) Hypoxia but not inflammation augments glucose uptake in human macrophages: Implications for imaging atherosclerosis with 18fluorine-labeled 2-deoxy-D-glucose positron emission tomography. J Am Coll Cardiol 58, 603-614   DOI
2 Benoit M, Desnues B and Mege JL (2008) Macrophage polarization in bacterial infections. J Immunol 181, 3733-3739   DOI
3 Nardin A and Abastado JP (2008) Macrophages and cancer. Front Biosci 13, 3494-3505   DOI
4 Hotamisligil GS, Arner P, Caro JF, Atkinson RL and Spiegelman BM (1995) Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance. J Clin Invest 95, 2409-2415   DOI
5 Sarrazy V, Viaud M, Westerterp M et al (2016) Disruption of Glut1 in Hematopoietic Stem Cells Prevents Myelopoiesis and Enhanced Glucose Flux in Atheromatous Plaques of ApoE(-/-) Mice. Circ Res 118, 1062-1077   DOI
6 Chait A and Bornfeldt KE (2009) Diabetes and atherosclerosis: is there a role for hyperglycemia? J Lipid Res 50 Suppl, S335-339   DOI
7 Nagareddy PR, Murphy AJ, Stirzaker RA et al (2013) Hyperglycemia promotes myelopoiesis and impairs the resolution of atherosclerosis. Cell Metab 17, 695-708   DOI
8 Terasaki M, Hiromura M, Mori Y et al (2015) Amelioration of Hyperglycemia with a Sodium-Glucose Cotransporter 2 Inhibitor Prevents Macrophage-Driven Atherosclerosis through Macrophage Foam Cell Formation Suppression in Type 1 and Type 2 Diabetic Mice. PLoS One 10, e0143396   DOI
9 Nishizawa T, Kanter JE, Kramer F et al (2014) Testing the role of myeloid cell glucose flux in inflammation and atherosclerosis. Cell Rep 7, 356-365   DOI
10 Yang X, Li Y, Ren X et al (2017) Oxidative Stress-Mediated Atherosclerosis: Mechanisms and Therapies. Front Physiol 8, 600   DOI
11 Wang Y, Wang GZ, Rabinovitch PS and Tabas I (2014) Macrophage mitochondrial oxidative stress promotes atherosclerosis and nuclear factor-kappaB-mediated inflammation in macrophages. Circ Res 114, 421-433   DOI
12 Cardilo-Reis L, Gruber S, Schreier SM et al (2012) Interleukin-13 protects from atherosclerosis and modulates plaque composition by skewing the macrophage phenotype. EMBO Mol Med 4, 1072-1086   DOI
13 Pirzgalska RM and Domingos AI (2018) Macrophages in obesity. Cell Immunol 330, 183-187   DOI
14 Schreyer SA, Chua SC, Jr. and LeBoeuf RC (1998) Obesity and diabetes in TNF-alpha receptor- deficient mice. J Clin Invest 102, 402-411   DOI
15 Gonzalez-Gay MA, Gonzalez-Juanatey C, Vazquez-Rodriguez TR, Miranda-Filloy JA and Llorca J (2010) Insulin resistance in rheumatoid arthritis: the impact of the anti-TNF-alpha therapy. Ann N Y Acad Sci 1193, 153-159   DOI
16 Lumeng CN, Bodzin JL and Saltiel AR (2007) Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J Clin Invest 117, 175-184   DOI
17 Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL and Ferrante AW Jr (2003) Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 112, 1796-1808   DOI
18 Frikke-Schmidt H, Zamarron BF, O'Rourke RW, Sandoval DA, Lumeng CN and Seeley RJ (2017) Weight loss independent changes in adipose tissue macrophage and T cell populations after sleeve gastrectomy in mice. Mol Metab 6, 317-326   DOI
19 Vandanmagsar B, Youm YH, Ravussin A et al (2011) The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance. Nat Med 17, 179-188   DOI
20 Matute-Bello G, Lee JS, Frevert CW et al (2004) Optimal timing to repopulation of resident alveolar macrophages with donor cells following total body irradiation and bone marrow transplantation in mice. J Immunol Methods 292, 25-34   DOI
21 Clambey ET, McNamee EN, Westrich JA et al (2012) Hypoxia-inducible factor-1 alpha-dependent induction of FoxP3 drives regulatory T-cell abundance and function during inflammatory hypoxia of the mucosa. Proc Natl Acad Sci U S A 109, E2784-2793   DOI
22 Scott CL, Zheng F, De Baetselier P et al (2016) Bone marrow-derived monocytes give rise to self-renewing and fully differentiated Kupffer cells. Nat Commun 7, 10321   DOI
23 Chang CH, Qiu J, O'Sullivan D et al (2015) Metabolic Competition in the Tumor Microenvironment Is a Driver of Cancer Progression. Cell 162, 1229-1241   DOI
24 Westendorf AM, Skibbe K, Adamczyk A et al (2017) Hypoxia Enhances Immunosuppression by Inhibiting CD4+ Effector T Cell Function and Promoting Treg Activity. Cell Physiol Biochem 41, 1271-1284   DOI
25 Bantug GR, Galluzzi L, Kroemer G and Hess C (2018) The spectrum of T cell metabolism in health and disease. Nat Rev Immunol 18, 19-34   DOI
26 Mackaness GB (1962) Cellular resistance to infection. J Exp Med 116, 381-406   DOI
27 Mosser DM and Edwards JP (2008) Exploring the full spectrum of macrophage activation. Nat Rev Immunol 8, 958-969   DOI
28 Sica A and Mantovani A (2012) Macrophage plasticity and polarization: in vivo veritas. J Clin Invest 122, 787-795   DOI
29 Stein M, Keshav S, Harris N and Gordon S (1992) Interleukin 4 potently enhances murine macrophage mannose receptor activity: a marker of alternative immunologic macrophage activation. J Exp Med 176, 287-292   DOI
30 Meier CA, Bobbioni E, Gabay C, Assimacopoulos-Jeannet F, Golay A and Dayer JM (2002) IL-1 receptor antagonist serum levels are increased in human obesity: a possible link to the resistance to leptin? J Clin Endocrinol Metab 87, 1184-1188   DOI
31 Spranger J, Kroke A, Mohlig M et al (2003) Inflammatory cytokines and the risk to develop type 2 diabetes: results of the prospective population-based European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study. Diabetes 52, 812-817   DOI
32 Sauter NS, Schulthess FT, Galasso R, Castellani LW and Maedler K (2008) The antiinflammatory cytokine interleukin-1 receptor antagonist protects from high-fat diet-induced hyperglycemia. Endocrinology 149, 2208-2218   DOI
33 Thomas D and Apovian C (2017) Macrophage functions in lean and obese adipose tissue. Metabolism 72, 120-143   DOI
34 Ricardo-Gonzalez RR, Red Eagle A, Odegaard JI et al (2010) IL-4/STAT6 immune axis regulates peripheral nutrient metabolism and insulin sensitivity. Proc Natl Acad Sci U S A 107, 22617-22622   DOI
35 Lesna IK, Cejkova S, Kralova A et al (2017) Human adipose tissue accumulation is associated with pro-inflammatory changes in subcutaneous rather than visceral adipose tissue. Nutr Diabetes 7, e264   DOI
36 Boutens L, Hooiveld GJ, Dhingra S, Cramer RA, Netea MG and Stienstra R (2018) Unique metabolic activation of adipose tissue macrophages in obesity promotes inflammatory responses. Diabetologia 61, 942-953   DOI
37 Wynn TA and Vannella KM (2016) Macrophages in Tissue Repair, Regeneration, and Fibrosis. Immunity 44, 450-462   DOI
38 Johnson AR, Qin Y, Cozzo AJ et al (2016) Metabolic reprogramming through fatty acid transport protein 1 (FATP1) regulates macrophage inflammatory potential and adipose inflammation. Mol Metab 5, 506-526   DOI
39 Shapiro H, Pecht T, Shaco-Levy R et al (2013) Adipose tissue foam cells are present in human obesity. J Clin Endocrinol Metab 98, 1173-1181   DOI
40 Gordon S and Martinez FO (2010) Alternative activation of macrophages: mechanism and functions. Immunity 32, 593-604   DOI
41 Rath M, Muller I, Kropf P, Closs EI and Munder M (2014) Metabolism via Arginase or Nitric Oxide Synthase: Two Competing Arginine Pathways in Macrophages. Front Immunol 5, 532
42 Mills CD, Kincaid K, Alt JM, Heilman MJ and Hill AM (2000) M-1/M-2 macrophages and the Th1/Th2 paradigm. J Immunol 164, 6166-6173   DOI
43 Murray PJ, Allen JE, Biswas SK et al (2014) Macrophage activation and polarization: nomenclature and experimental guidelines. Immunity 41, 14-20   DOI
44 Qian BZ and Pollard JW (2010) Macrophage diversity enhances tumor progression and metastasis. Cell 141, 39-51   DOI
45 Mantovani A, Sica A, Sozzani S, Allavena P, Vecchi A and Locati M (2004) The chemokine system in diverse forms of macrophage activation and polarization. Trends Immunol 25, 677-686   DOI
46 Roszer T (2015) Understanding the Mysterious M2 Macrophage through Activation Markers and Effector Mechanisms. Mediators Inflamm 2015, 816460   DOI
47 Pearce EL (2010) Metabolism in T cell activation and differentiation. Curr Opin Immunol 22, 314-320   DOI
48 Buck MD, O'Sullivan D and Pearce EL (2015) T cell metabolism drives immunity. J Exp Med 212, 1345-1360   DOI
49 O'Sullivan D, van der Windt GJ, Huang SC et al (2014) Memory CD8(+) T cells use cell-intrinsic lipolysis to support the metabolic programming necessary for development. Immunity 41, 75-88   DOI
50 Wang T, Liu H, Lian G, Zhang SY, Wang X and Jiang C (2017) HIF1alpha-Induced Glycolysis Metabolism Is Essential to the Activation of Inflammatory Macrophages. Mediators Inflamm 2017, 9029327   DOI
51 Freemerman AJ, Johnson AR, Sacks GN et al (2014) Metabolic reprogramming of macrophages: glucose transporter 1 (GLUT1)-mediated glucose metabolism drives a proinflammatory phenotype. J Biol Chem 289, 7884-7896   DOI
52 Shirai T, Nazarewicz RR, Wallis BB et al (2016) The glycolytic enzyme PKM2 bridges metabolic and inflammatory dysfunction in coronary artery disease. J Exp Med 213, 337-354   DOI
53 Semba H, Takeda N, Isagawa T et al (2016) HIF-1alpha-PDK1 axis-induced active glycolysis plays an essential role in macrophage migratory capacity. Nat Commun 7, 11635   DOI
54 Geeraerts X, Bolli E, Fendt SM and Van Ginderachter JA (2017) Macrophage Metabolism As Therapeutic Target for Cancer, Atherosclerosis, and Obesity. Front Immunol 8, 289
55 Ryan DG and O'Neill LAJ (2017) Krebs cycle rewired for macrophage and dendritic cell effector functions. FEBS Lett 591, 2992-3006   DOI
56 Van den Bossche J, Baardman J, Otto NA et al (2016) Mitochondrial Dysfunction Prevents Repolarization of Inflammatory Macrophages. Cell Rep 17, 684-696   DOI
57 Slack M, Wang T and Wang R (2015) T cell metabolic reprogramming and plasticity. Mol Immunol 68, 507-512   DOI
58 Williams NC and O'Neill LAJ (2018) A Role for the Krebs Cycle Intermediate Citrate in Metabolic Reprogramming in Innate Immunity and Inflammation. Front Immunol 9, 141   DOI
59 Infantino V, Convertini P, Cucci L et al (2011) The mitochondrial citrate carrier: a new player in inflammation. Biochem J 438, 433-436   DOI
60 Everts B, Amiel E, van der Windt GJ et al (2012) Commitment to glycolysis sustains survival of NO-producing inflammatory dendritic cells. Blood 120, 1422-1431   DOI
61 Witting A, Muller P, Herrmann A, Kettenmann H and Nolte C (2000) Phagocytic clearance of apoptotic neurons by Microglia/Brain macrophages in vitro: involvement of lectin-, integrin-, and phosphatidylserinemediated recognition. J Neurochem 75, 1060-1070   DOI
62 Cohn ZA and Benson B (1965) The Differentiation of Mononuclear Phagocytes. Morphology, Cytochemistry, and Biochemistry. J Exp Med 121, 153-170   DOI
63 Rouzer CA, Scott WA, Hamill AL, Liu FT, Katz DH and Cohn ZA (1982) Secretion of leukotriene C and other arachidonic acid metabolites by macrophages challenged with immunoglobulin E immune complexes. J Exp Med 156, 1077-1086   DOI
64 Poltorak A, He X, Smirnova I et al (1998) Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science 282, 2085-2088   DOI
65 Takeda K, Kaisho T and Akira S (2003) Toll-like receptors. Annu Rev Immunol 21, 335-376   DOI
66 Medzhitov R, Preston-Hurlburt P and Janeway CA, Jr. (1997) A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature 388, 394-397   DOI
67 Teitelbaum SL (2000) Bone resorption by osteoclasts. Science 289, 1504-1508   DOI
68 Huang SC, Smith AM, Everts B et al (2016) Metabolic Reprogramming Mediated by the mTORC2-IRF4 Signaling Axis Is Essential for Macrophage Alternative Activation. Immunity 45, 817-830   DOI
69 Nomura M, Liu J, Rovira II et al (2016) Fatty acid oxidation in macrophage polarization. Nat Immunol 17, 216-217   DOI
70 Namgaladze D and Brune B (2014) Fatty acid oxidation is dispensable for human macrophage IL-4-induced polarization. Biochim Biophys Acta 1841, 1329-1335   DOI
71 Covarrubias AJ, Aksoylar HI, Yu J et al (2016) Akt-mTORC1 signaling regulates Acly to integrate metabolic input to control of macrophage activation. Elife 5, e11612   DOI
72 Wang F, Zhang S, Vuckovic I et al (2018) Glycolytic Stimulation Is Not a Requirement for M2 Macrophage Differentiation. Cell Metab 28, 463-475 e464   DOI
73 Yang C, Ko B, Hensley CT et al (2014) Glutamine oxidation maintains the TCA cycle and cell survival during impaired mitochondrial pyruvate transport. Mol Cell 56, 414-424   DOI
74 Wise DR and Thompson CB (2010) Glutamine addiction: a new therapeutic target in cancer. Trends Biochem Sci 35, 427-433   DOI
75 Ligthart-Melis GC, van de Poll MC, Boelens PG, Dejong CH, Deutz NE and van Leeuwen PA (2008) Glutamine is an important precursor for de novo synthesis of arginine in humans. Am J Clin Nutr 87, 1282-1289   DOI
76 Tannahill GM, Curtis AM, Adamik J et al (2013) Succinate is an inflammatory signal that induces IL-1beta through HIF-1alpha. Nature 496, 238-242   DOI
77 Michelucci A, Cordes T, Ghelfi J et al (2013) Immune-responsive gene 1 protein links metabolism to immunity by catalyzing itaconic acid production. Proc Natl Acad Sci U S A 110, 7820-7825   DOI
78 Cordes T, Wallace M, Michelucci A et al (2016) Immunoresponsive Gene 1 and Itaconate Inhibit Succinate Dehydrogenase to Modulate Intracellular Succinate Levels. J Biol Chem 291, 14274-14284   DOI
79 Lampropoulou V, Sergushichev A, Bambouskova M et al (2016) Itaconate Links Inhibition of Succinate Dehydrogenase with Macrophage Metabolic Remodeling and Regulation of Inflammation. Cell Metab 24, 158-166   DOI
80 van Iwaarden JF, Claassen E, Jeurissen SH, Haagsman HP and Kraal G (2001) Alveolar macrophages, surfactant lipids, and surfactant protein B regulate the induction of immune responses via the airways. Am J Respir Cell Mol Biol 24, 452-458   DOI
81 Willekens FL, Werre JM, Kruijt JK et al (2005) Liver Kupffer cells rapidly remove red blood cell-derived vesicles from the circulation by scavenger receptors. Blood 105, 2141-2145   DOI
82 Leibovich SJ and Ross R (1975) The role of the macrophage in wound repair. A study with hydrocortisone and antimacrophage serum. Am J Pathol 78, 71-100
83 Haschemi A, Kosma P, Gille L et al (2012) The sedoheptulose kinase CARKL directs macrophage polarization through control of glucose metabolism. Cell Metab 15, 813-826   DOI
84 Palmieri EM, Menga A, Martin-Perez R et al (2017) Pharmacologic or Genetic Targeting of Glutamine Synthetase Skews Macrophages toward an M1-like Phenotype and Inhibits Tumor Metastasis. Cell Rep 20, 1654-1666   DOI
85 Mori M and Gotoh T (2004) Arginine metabolic enzymes, nitric oxide and infection. J Nutr 134, 2820S-2825S; discussion 2853S   DOI
86 Eggleston LV and Krebs HA (1974) Regulation of the pentose phosphate cycle. Biochem J 138, 425-435   DOI
87 Everts B, Amiel E, Huang SC et al (2014) TLR-driven early glycolytic reprogramming via the kinases TBK1-IKKvarepsilon supports the anabolic demands of dendritic cell activation. Nat Immunol 15, 323-332   DOI
88 Koo SJ, Szczesny B, Wan X, Putluri N and Garg NJ (2018) Pentose Phosphate Shunt Modulates Reactive Oxygen Species and Nitric Oxide Production Controlling Trypanosoma cruzi in Macrophages. Front Immunol 9, 202   DOI
89 Baardman J, Verberk SGS, Prange KHM et al (2018) A Defective Pentose Phosphate Pathway Reduces Inflammatory Macrophage Responses during Hypercholesterolemia. Cell Rep 25, 2044-2052 e2045   DOI
90 Galvan-Pena S and O'Neill LA (2014) Metabolic reprograming in macrophage polarization. Front Immunol 5, 420
91 Alliot F, Godin I and Pessac B (1999) Microglia derive from progenitors, originating from the yolk sac, and which proliferate in the brain. Brain Res Dev Brain Res 117, 145-152   DOI
92 Polverini PJ, Cotran PS, Gimbrone MA Jr and Unanue ER (1977) Activated macrophages induce vascular proliferation. Nature 269, 804-806   DOI
93 Hunt TK, Knighton DR, Thakral KK, Goodson WH 3rd and Andrews WS (1984) Studies on inflammation and wound healing: angiogenesis and collagen synthesis stimulated in vivo by resident and activated wound macrophages. Surgery 96, 48-54
94 Koh TJ and DiPietro LA (2011) Inflammation and wound healing: the role of the macrophage. Expert Rev Mol Med 13, e23   DOI
95 Naito M, Hasegawa G and Takahashi K (1997) Development, differentiation, and maturation of Kupffer cells. Microsc Res Tech 39, 350-364   DOI
96 Guilliams M, De Kleer I, Henri S et al (2013) Alveolar macrophages develop from fetal monocytes that differentiate into long-lived cells in the first week of life via GM-CSF. J Exp Med 210, 1977-1992   DOI
97 Ginhoux F and Guilliams M (2016) Tissue-Resident Macrophage Ontogeny and Homeostasis. Immunity 44, 439-449   DOI
98 Hick RW, Gruver AL, Ventevogel MS, Haynes BF and Sempowski GD (2006) Leptin selectively augments thymopoiesis in leptin deficiency and lipopolysaccharideinduced thymic atrophy. J Immunol 177, 169-176   DOI
99 Wang Y, Wang W, Wang N, Tall AR and Tabas I (2017) Mitochondrial Oxidative Stress Promotes Atherosclerosis and Neutrophil Extracellular Traps in Aged Mice. Arterioscler Thromb Vasc Biol 37, e99-e107   DOI
100 Xu X, Grijalva A, Skowronski A, van Eijk M, Serlie MJ and Ferrante AW Jr (2013) Obesity activates a program of lysosomal-dependent lipid metabolism in adipose tissue macrophages independently of classic activation. Cell Metab 18, 816-830   DOI
101 Fernandez-Riejos P, Najib S, Santos-Alvarez J et al (2010) Role of leptin in the activation of immune cells. Mediators Inflamm 2010, 568343
102 Sheng T and Yang K (2008) Adiponectin and its association with insulin resistance and type 2 diabetes. J Genet Genomics 35, 321-326   DOI
103 Ajuwon KM and Spurlock ME (2005) Adiponectin inhibits LPS-induced NF-kappaB activation and IL-6 production and increases PPARgamma2 expression in adipocytes. Am J Physiol Regul Integr Comp Physiol 288, R1220-1225   DOI
104 Argyle D and Kitamura T (2018) Targeting Macrophage-Recruiting Chemokines as a Novel Therapeutic Strategy to Prevent the Progression of Solid Tumors. Front Immunol 9, 2629   DOI
105 Clementi E, Brown GC, Feelisch M and Moncada S (1998) Persistent inhibition of cell respiration by nitric oxide: crucial role of S-nitrosylation of mitochondrial complex I and protective action of glutathione. Proc Natl Acad Sci U S A 95, 7631-7636   DOI
106 Heming M, Gran S, Jauch SL et al (2018) Peroxisome Proliferator-Activated Receptor-gamma Modulates the Response of Macrophages to Lipopolysaccharide and Glucocorticoids. Front Immunol 9, 893   DOI
107 Vink A, Schoneveld AH, Lamers D et al (2007) HIF-1 alpha expression is associated with an atheromatous inflammatory plaque phenotype and upregulated in activated macrophages. Atherosclerosis 195, e69-75   DOI
108 Aarup A, Pedersen TX, Junker N et al (2016) Hypoxia-Inducible Factor-1alpha Expression in Macrophages Promotes Development of Atherosclerosis. Arterioscler Thromb Vasc Biol 36, 1782-1790   DOI
109 Zhang QW, Liu L, Gong CY et al (2012) Prognostic significance of tumor-associated macrophages in solid tumor: a meta-analysis of the literature. PLoS One 7, e50946   DOI
110 Chanmee T, Ontong P, Konno K and Itano N (2014) Tumor-associated macrophages as major players in the tumor microenvironment. Cancers (Basel) 6, 1670-1690   DOI
111 Lin EY, Nguyen AV, Russell RG and Pollard JW (2001) Colony-stimulating factor 1 promotes progression of mammary tumors to malignancy. J Exp Med 193, 727-740   DOI
112 Quatromoni JG and Eruslanov E (2012) Tumor-associated macrophages: function, phenotype, and link to prognosis in human lung cancer. Am J Transl Res 4, 376-389
113 Liberti MV and Locasale JW (2016) The Warburg Effect: How Does it Benefit Cancer Cells? Trends Biochem Sci 41, 211-218   DOI
114 Romero-Garcia S, Moreno-Altamirano MM, Prado-Garcia H and Sanchez-Garcia FJ (2016) Lactate Contribution to the Tumor Microenvironment: Mechanisms, Effects on Immune Cells and Therapeutic Relevance. Front Immunol 7, 52
115 Rogero MM and Calder PC (2018) Obesity, Inflammation, Toll-Like Receptor 4 and Fatty Acids. Nutrients 10, 432   DOI
116 Ohashi K, Parker JL, Ouchi N et al (2010) Adiponectin promotes macrophage polarization toward an antiinflammatory phenotype. J Biol Chem 285, 6153-6160   DOI
117 Tsatsanis C, Zacharioudaki V, Androulidaki A et al (2005) Adiponectin induces TNF-alpha and IL-6 in macrophages and promotes tolerance to itself and other pro-inflammatory stimuli. Biochem Biophys Res Commun 335, 1254-1263   DOI
118 Moore KJ, Sheedy FJ and Fisher EA (2013) Macrophages in atherosclerosis: a dynamic balance. Nat Rev Immunol 13, 709-721   DOI
119 Chen W, Bural GG, Torigian DA, Rader DJ and Alavi A (2009) Emerging role of FDG-PET/CT in assessing atherosclerosis in large arteries. Eur J Nucl Med Mol Imaging 36, 144-151   DOI
120 Lee JH, Phelan P, Shin M et al (2018) SREBP-1astimulated lipid synthesis is required for macrophage phagocytosis downstream of TLR4-directed mTORC1. Proc Natl Acad Sci U S A 115, E12228-E12234   DOI
121 Horton JD, Goldstein JL and Brown MS (2002) SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver. J Clin Invest 109, 1125-1131   DOI
122 Im SS, Yousef L, Blaschitz C et al (2011) Linking lipid metabolism to the innate immune response in macrophages through sterol regulatory element binding protein-1a. Cell Metab 13, 540-549   DOI
123 Schneider JG, Yang Z, Chakravarthy MV et al (2010) Macrophage fatty-acid synthase deficiency decreases diet-induced atherosclerosis. J Biol Chem 285, 23398-23409   DOI
124 Vats D, Mukundan L, Odegaard JI et al (2006) Oxidative metabolism and PGC-1beta attenuate macrophagemediated inflammation. Cell Metab 4, 13-24   DOI
125 Huang SC, Everts B, Ivanova Y et al (2014) Cell-intrinsic lysosomal lipolysis is essential for alternative activation of macrophages. Nat Immunol 15, 846-855   DOI
126 Malandrino MI, Fucho R, Weber M et al (2015) Enhanced fatty acid oxidation in adipocytes and macrophages reduces lipid-induced triglyceride accumulation and inflammation. Am J Physiol Endocrinol Metab 308, E756-769   DOI
127 Park JE, Dutta B, Tse SW et al (2019) Hypoxia-induced tumor exosomes promote M2-like macrophage polarization of infiltrating myeloid cells and microRNAmediated metabolic shift. Oncogene [Epub ahead of print]
128 Penny HL, Sieow JL, Adriani G et al (2016) Warburg metabolism in tumor-conditioned macrophages promotes metastasis in human pancreatic ductal adenocarcinoma. Oncoimmunology 5, e1191731   DOI
129 Wenes M, Shang M, Di Matteo M et al (2016) Macrophage Metabolism Controls Tumor Blood Vessel Morphogenesis and Metastasis. Cell Metab 24, 701-715   DOI
130 Movahedi K, Laoui D, Gysemans C et al (2010) Different tumor microenvironments contain functionally distinct subsets of macrophages derived from Ly6C(high) monocytes. Cancer Res 70, 5728-5739   DOI
131 Pyonteck SM, Akkari L, Schuhmacher AJ et al (2013) CSF-1R inhibition alters macrophage polarization and blocks glioma progression. Nat Med 19, 1264-1272   DOI
132 Casazza A, Laoui D, Wenes M et al (2013) Impeding macrophage entry into hypoxic tumor areas by Sema3A/Nrp1 signaling blockade inhibits angiogenesis and restores antitumor immunity. Cancer Cell 24, 695-709   DOI
133 Ouimet M, Ediriweera HN, Gundra UM et al (2015) MicroRNA-33-dependent regulation of macrophage metabolism directs immune cell polarization in atherosclerosis. J Clin Invest 125, 4334-4348   DOI
134 Liu M, O'Connor RS, Trefely S, Graham K, Snyder NW and Beatty GL (2019) Metabolic rewiring of macrophages by CpG potentiates clearance of cancer cells and overcomes tumor-expressed CD47-mediated 'don't-eat-me' signal. Nat Immunol 20, 265-275   DOI
135 Miller AM, Asquith DL, Hueber AJ et al (2010) Interleukin-33 induces protective effects in adipose tissue inflammation during obesity in mice. Circ Res 107, 650-658   DOI
136 Jung MJ, Lee J, Shin NR et al (2016) Chronic Repression of mTOR Complex 2 Induces Changes in the Gut Microbiota of Diet-induced Obese Mice. Sci Rep 6, 30887   DOI
137 Rombaldova M, Janovska P, Kopecky J and Kuda O (2017) Omega-3 fatty acids promote fatty acid utilization and production of pro-resolving lipid mediators in alternatively activated adipose tissue macrophages. Biochem Biophys Res Commun 490, 1080-1085   DOI
138 Furukawa S, Fujita T, Shimabukuro M et al (2004) Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Invest 114, 1752-1761   DOI
139 Xu J, Chi F, Guo T et al (2015) NOTCH reprograms mitochondrial metabolism for proinflammatory macrophage activation. J Clin Invest 125, 1579-1590   DOI
140 Spann NJ, Garmire LX, McDonald JG et al (2012) Regulated accumulation of desmosterol integrates macrophage lipid metabolism and inflammatory responses. Cell 151, 138-152   DOI
141 Deng J, Lu S, Liu H et al (2017) Homocysteine Activates B Cells via Regulating PKM2-Dependent Metabolic Reprogramming. J Immunol 198, 170-183   DOI
142 Liao X, Sluimer JC, Wang Y et al (2012) Macrophage autophagy plays a protective role in advanced atherosclerosis. Cell Metab 15, 545-553   DOI