Macrophage fatty acid oxidation and its roles in macrophage polarization and fatty acid-induced inflammation

Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids

Volumn 1861, Issue 11, 2016, Pages 1796-1807

  Namgaladze, Dmitry ^a   Brüne, Bernhard ^a  

^a GOETHE UNIVERSITY   (Germany)

Author keywords

AMP activated protein kinase; Fatty acid oxidation; Fatty acids; Inflammation; Macrophages; Metabolism

Indexed keywords

FATTY ACID; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR; SATURATED FATTY ACID;

ADAPTIVE IMMUNITY; CATABOLISM; DISEASE COURSE; FATTY ACID METABOLISM; FATTY ACID OXIDATION; HUMAN; IMMUNOCOMPETENT CELL; IMMUNOMODULATION; INFLAMMATION; INSULIN RESISTANCE; MACROPHAGE; METABOLIC REGULATION; NON INSULIN DEPENDENT DIABETES MELLITUS; OBESITY; PHENOTYPE; PRIORITY JOURNAL; REVIEW; ANIMAL; BIOLOGICAL MODEL; CELL POLARITY; METABOLISM; OXIDATION REDUCTION REACTION; PATHOLOGY;

ANIMALS; CELL POLARITY; FATTY ACIDS; HUMANS; INFLAMMATION; MACROPHAGES; MODELS, BIOLOGICAL; OXIDATION-REDUCTION;

EID: 84987617421     PISSN: 13881981     EISSN: 18792618     Source Type: Journal    
DOI: 10.1016/j.bbalip.2016.09.002     Document Type: Review

References (161)

1. [1] Samuelsson, B., Role of basic science in the development of new medicines: examples from the eicosanoid field. J. Biol. Chem. 287 (2012), 10070–10080.
2. [2] Newsholme, P., Gordon, S., Newsholme, E.A., Rates of utilization and fates of glucose, glutamine, pyruvate, fatty acids and ketone bodies by mouse macrophages. Biochem. J. 242 (1987), 631–636.
3. [3] O'Neill, L.A.J., Pearce, E.J., Immunometabolism governs dendritic cell and macrophage function. J. Exp. Med. 213 (2016), 15–23.
4. [4] McNelis, J.C., Olefsky, J.M., Macrophages, immunity, and metabolic disease. Immunity 41 (2014), 36–48.
5. [5] Currie, E., Schulze, A., Zechner, R., Walther, T.C., Farese, R.V., Cellular fatty acid metabolism and cancer. Cell Metab. 18 (2013), 153–161.
6. [6] Bartlett, K., Eaton, S., Mitochondrial beta-oxidation. Eur. J. Biochem. 271 (2004), 462–469.
7. [7] Houten, S.M., Violante, S., Ventura, F.V., Wanders, R.J.A., The biochemistry and physiology of mitochondrial fatty acid β-oxidation and its genetic disorders. Annu. Rev. Physiol. 78 (2016), 23–44.
8. [8] Houten, S.M., Wanders, R.J.A., A general introduction to the biochemistry of mitochondrial fatty acid β-oxidation. J. Inherit. Metab. Dis. 33 (2010), 469–477.
9. [9] Samuel, V.T., Shulman, G.I., Mechanisms for insulin resistance: common threads and missing links. Cell 148 (2012), 852–871.
10. [10] Odegaard, J.I., Chawla, A., Pleiotropic actions of insulin resistance and inflammation in metabolic homeostasis. Science 339 (2013), 172–177.
11. [11] Tian, X.Y., Ganeshan, K., Hong, C., Nguyen, K.D., Qiu, Y., Kim, J., Tangirala, R.K., Tontonoz, P., Tonotonoz, P., Chawla, A., Thermoneutral housing accelerates metabolic inflammation to potentiate atherosclerosis but not insulin resistance. Cell Metab. 23 (2016), 165–178.
12. [12] Gregor, M.F., Hotamisligil, G.S., Inflammatory mechanisms in obesity. Annu. Rev. Immunol. 29 (2011), 415–445.
13. [13] Xu, H., Barnes, G.T., Yang, Q., Tan, G., Yang, D., Chou, C.J., Sole, J., Nichols, A., Ross, J.S., Tartaglia, L.A., Chen, H., Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J. Clin. Invest. 112 (2003), 1821–1830.
14. [14] Weisberg, S.P., McCann, D., Desai, M., Rosenbaum, M., Leibel, R.L., Ferrante, A.W., Obesity is associated with macrophage accumulation in adipose tissue. J. Clin. Invest. 112 (2003), 1796–1808.
15. [15] Weisberg, S.P., Hunter, D., Huber, R., Lemieux, J., Slaymaker, S., Vaddi, K., Charo, I., Leibel, R.L., Ferrante, A.W., CCR2 modulates inflammatory and metabolic effects of high-fat feeding. J. Clin. Invest. 116 (2006), 115–124.
16. [16] Keophiphath, M., Rouault, C., Divoux, A., Clément, K., Lacasa, D., CCL5 promotes macrophage recruitment and survival in human adipose tissue. Arterioscler. Thromb. Vasc. Biol. 30 (2010), 39–45.
17. [17] Kitade, H., Sawamoto, K., Nagashimada, M., Inoue, H., Yamamoto, Y., Sai, Y., Takamura, T., Yamamoto, H., Miyamoto, K.-I., Ginsberg, H.N., Mukaida, N., Kaneko, S., Ota, T., CCR5 plays a critical role in obesity-induced adipose tissue inflammation and insulin resistance by regulating both macrophage recruitment and M1/M2 status. Diabetes 61 (2012), 1680–1690.
18. [18] Amano, S.U., Cohen, J.L., Vangala, P., Tencerova, M., Nicoloro, S.M., Yawe, J.C., Shen, Y., Czech, M.P., Aouadi, M., Local proliferation of macrophages contributes to obesity-associated adipose tissue inflammation. Cell Metab. 19 (2014), 162–171.
19. [19] Zheng, C., Yang, Q., Cao, J., Xie, N., Liu, K., Shou, P., Qian, F., Wang, Y., Shi, Y., Local proliferation initiates macrophage accumulation in adipose tissue during obesity. Cell Death Dis., 7, 2016, e2167.
20. [20] Lumeng, C.N., Bodzin, J.L., Saltiel, A.R., Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J. Clin. Invest. 117 (2007), 175–184.
21. [21] Nguyen, M.T.A., Favelyukis, S., Nguyen, A.-K., Reichart, D., Scott, P.A., Jenn, A., Liu-Bryan, R., Glass, C.K., Neels, J.G., Olefsky, J.M., A subpopulation of macrophages infiltrates hypertrophic adipose tissue and is activated by free fatty acids via Toll-like receptors 2 and 4 and JNK-dependent pathways. J. Biol. Chem. 282 (2007), 35279–35292.
22. [22] Xu, X., Grijalva, A., Skowronski, A., van Eijk, M., Serlie, M.J., Ferrante, A.W., Obesity activates a program of lysosomal-dependent lipid metabolism in adipose tissue macrophages independently of classic activation. Cell Metab. 18 (2013), 816–830.
23. [23] Kratz, M., Coats, B.R., Hisert, K.B., Hagman, D., Mutskov, V., Peris, E., Schoenfelt, K.Q., Kuzma, J.N., Larson, I., Billing, P.S., Landerholm, R.W., Crouthamel, M., Gozal, D., Hwang, S., Singh, P.K., Becker, L., Metabolic dysfunction drives a mechanistically distinct proinflammatory phenotype in adipose tissue macrophages. Cell Metab. 20 (2014), 614–625.
24. [24] Prieur, X., Mok, C.Y.L., Velagapudi, V.R., Núñez, V., Fuentes, L., Montaner, D., Ishikawa, K., Camacho, A., Barbarroja, N., O'Rahilly, S., Sethi, J.K., Dopazo, J., Orešič, M., Ricote, M., Vidal-Puig, A., Differential lipid partitioning between adipocytes and tissue macrophages modulates macrophage lipotoxicity and M2/M1 polarization in obese mice. Diabetes 60 (2011), 797–809.
25. [25] Lee, J.Y., Sohn, K.H., Rhee, S.H., Hwang, D., Saturated fatty acids, but not unsaturated fatty acids, induce the expression of cyclooxygenase-2 mediated through Toll-like receptor 4. J. Biol. Chem. 276 (2001), 16683–16689.
26. [26] Shi, H., Kokoeva, M.V., Inouye, K., Tzameli, I., Yin, H., Flier, J.S., TLR4 links innate immunity and fatty acid-induced insulin resistance. J. Clin. Invest. 116 (2006), 3015–3025.
27. [27] Pal, D., Dasgupta, S., Kundu, R., Maitra, S., Das, G., Mukhopadhyay, S., Ray, S., Majumdar, S.S., Bhattacharya, S., Fetuin-A acts as an endogenous ligand of TLR4 to promote lipid-induced insulin resistance. Nat. Med. 18 (2012), 1279–1285.
28. [28] Lee, J.Y., Zhao, L., Youn, H.S., Weatherill, A.R., Tapping, R., Feng, L., Lee, W.H., Fitzgerald, K.A., Hwang, D.H., Saturated fatty acid activates but polyunsaturated fatty acid inhibits Toll-like receptor 2 dimerized with Toll-like receptor 6 or 1. J. Biol. Chem. 279 (2004), 16971–16979.
29. [29] Erridge, C., Samani, N.J., Saturated fatty acids do not directly stimulate Toll-like receptor signaling. Arterioscler. Thromb. Vasc. Biol. 29 (2009), 1944–1949.
30. [30] Huang, S., Rutkowsky, J.M., Snodgrass, R.G., Ono-Moore, K.D., Schneider, D.A., Newman, J.W., Adams, S.H., Hwang, D.H., Saturated fatty acids activate TLR-mediated proinflammatory signaling pathways. J. Lipid Res. 53 (2012), 2002–2013.
31. [31] Håversen, L., Danielsson, K.N., Fogelstrand, L., Wiklund, O., Induction of proinflammatory cytokines by long-chain saturated fatty acids in human macrophages. Atherosclerosis 202 (2009), 382–393.
32. [32] Holland, W.L., Bikman, B.T., Wang, L.-P., Yuguang, G., Sargent, K.M., Bulchand, S., Knotts, T.A., Shui, G., Clegg, D.J., Wenk, M.R., Pagliassotti, M.J., Scherer, P.E., Summers, S.A., Lipid-induced insulin resistance mediated by the proinflammatory receptor TLR4 requires saturated fatty acid-induced ceramide biosynthesis in mice. J. Clin. Invest. 121 (2011), 1858–1870.
33. [33] Vandanmagsar, B., Youm, Y.-H., Ravussin, A., Galgani, J.E., Stadler, K., Mynatt, R.L., Ravussin, E., Stephens, J.M., Dixit, V.D., The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance. Nat. Med. 17 (2011), 179–188.
34. [34] Hotamisligil, G.S., Endoplasmic reticulum stress and the inflammatory basis of metabolic disease. Cell 140 (2010), 900–917.
35. [35] Lee, J., Ozcan, U., Unfolded protein response signaling and metabolic diseases. J. Biol. Chem. 289 (2014), 1203–1211.
36. [36] Urano, F., Wang, X., Bertolotti, A., Zhang, Y., Chung, P., Harding, H.P., Ron, D., Coupling of stress in the ER to activation of JNK protein kinases by transmembrane protein kinase IRE1. Science 287 (2000), 664–666.
37. [37] Hu, P., Han, Z., Couvillon, A.D., Kaufman, R.J., Exton, J.H., Autocrine tumor necrosis factor alpha links endoplasmic reticulum stress to the membrane death receptor pathway through IRE1alpha-mediated NF-kappaB activation and down-regulation of TRAF2 expression. Mol. Cell. Biol. 26 (2006), 3071–3084.
38. [38] Deng, J., Lu, P.D., Zhang, Y., Scheuner, D., Kaufman, R.J., Sonenberg, N., Harding, H.P., Ron, D., Translational repression mediates activation of nuclear factor kappa B by phosphorylated translation initiation factor 2. Mol. Cell. Biol. 24 (2004), 10161–10168.
39. [39] Nakamura, T., Furuhashi, M., Li, P., Cao, H., Tuncman, G., Sonenberg, N., Gorgun, C.Z., Hotamisligil, G.S., Double-stranded RNA-dependent protein kinase links pathogen sensing with stress and metabolic homeostasis. Cell 140 (2010), 338–348.
40. [40] Borradaile, N.M., Han, X., Harp, J.D., Gale, S.E., Ory, D.S., Schaffer, J.E., Disruption of endoplasmic reticulum structure and integrity in lipotoxic cell death. J. Lipid Res. 47 (2006), 2726–2737.
41. [41] Wei, Y., Wang, D., Topczewski, F., Pagliassotti, M.J., Saturated fatty acids induce endoplasmic reticulum stress and apoptosis independently of ceramide in liver cells. Am. J. Physiol. Endocrinol. Metab. 291 (2006), E275–E281.
42. [42] Erbay, E., Babaev, V.R., Mayers, J.R., Makowski, L., Charles, K.N., Snitow, M.E., Fazio, S., Wiest, M.M., Watkins, S.M., Linton, M.F., Hotamisligil, G.S., Reducing endoplasmic reticulum stress through a macrophage lipid chaperone alleviates atherosclerosis. Nat. Med. 15 (2009), 1383–1391.
43. [43] Volmer, R., van der Ploeg, K., Ron, D., Membrane lipid saturation activates endoplasmic reticulum unfolded protein response transducers through their transmembrane domains. Proc. Natl. Acad. Sci. U. S. A. 110 (2013), 4628–4633.
44. [44] Masuda, M., Miyazaki-Anzai, S., Keenan, A.L., Okamura, K., Kendrick, J., Chonchol, M., Offermanns, S., Ntambi, J.M., Kuro-O, M., Miyazaki, M., Saturated phosphatidic acids mediate saturated fatty acid-induced vascular calcification and lipotoxicity. J. Clin. Invest., 2015, 2015.
45. [45] Holzer, R.G., Park, E.-J., Li, N., Tran, H., Chen, M., Choi, C., Solinas, G., Karin, M., Saturated fatty acids induce c-Src clustering within membrane subdomains, leading to JNK activation. Cell 147 (2011), 173–184.
46. [46] Nakamura, S., Takamura, T., Matsuzawa-Nagata, N., Takayama, H., Misu, H., Noda, H., Nabemoto, S., Kurita, S., Ota, T., Ando, H., Miyamoto, K.-I., Kaneko, S., Palmitate induces insulin resistance in H4IIEC3 hepatocytes through reactive oxygen species produced by mitochondria. J. Biol. Chem. 284 (2009), 14809–14818.
47. [47] Barazzoni, R., Zanetti, M., Cappellari, G.G., Semolic, A., Boschelle, M., Codarin, E., Pirulli, A., Cattin, L., Guarnieri, G., Fatty acids acutely enhance insulin-induced oxidative stress and cause insulin resistance by increasing mitochondrial reactive oxygen species (ROS) generation and nuclear factor-κB inhibitor (IκB)–nuclear factor-κB (NFκB) activation in rat muscle, in the absence of mitochondrial dysfunction. Diabetologia 55 (2012), 773–782.
48. [48] Zhou, R., Yazdi, A.S., Menu, P., Tschopp, J., A role for mitochondria in NLRP3 inflammasome activation. Nature 469 (2010), 221–225.
49. [49] Wen, H., Gris, D., Lei, Y., Jha, S., Zhang, L., Huang, M.T.-H., Brickey, W.J., Ting, J.P.-Y., Fatty acid-induced NLRP3-ASC inflammasome activation interferes with insulin signaling. Nat. Immunol. 12 (2011), 408–415.
50. [50] Schilling, J.D., Machkovech, H.M., He, L., Diwan, A., Schaffer, J.E., TLR4 activation under lipotoxic conditions leads to synergistic macrophage cell death through a TRIF-dependent pathway. J. Immunol. 190 (2013), 1285–1296.
51. [51] Weber, K., Schilling, J.D., Lysosomes integrate metabolic-inflammatory cross-talk in primary macrophage inflammasome activation. J. Biol. Chem. 289 (2014), 9158–9171.
52. [52] Robblee, M.M., Kim, C.C., Porter Abate, J., Valdearcos, M., Sandlund, K.L.M., Shenoy, M.K., Volmer, R., Iwawaki, T., Koliwad, S.K., Saturated fatty acids engage an IRE1α-dependent pathway to activate the NLRP3 inflammasome in myeloid cells. Cell Rep. 14 (2016), 2611–2623.
53. [53] Virtue, S., Vidal-Puig, A., Adipose tissue expandability, lipotoxicity and the metabolic syndrome–an allostatic perspective. Biochim. Biophys. Acta 1801 (2010), 338–349.
54. [54] Listenberger, L.L., Han, X., Lewis, S.E., Cases, S., Farese, R.V., Ory, D.S., Schaffer, J.E., Triglyceride accumulation protects against fatty acid-induced lipotoxicity. Proc. Natl. Acad. Sci. U. S. A. 100 (2003), 3077–3082.
55. [55] Koliwad, S.K., Streeper, R.S., Monetti, M., Cornelissen, I., Chan, L., Terayama, K., Naylor, S., Rao, M., Hubbard, B., Farese, R.V., DGAT1-dependent triacylglycerol storage by macrophages protects mice from diet-induced insulin resistance and inflammation. J. Clin. Invest. 120 (2010), 756–767.
56. [56] L'homme, L., Esser, N., Riva, L., Scheen, A., Paquot, N., Piette, J., Legrand-Poels, S., Unsaturated fatty acids prevent activation of NLRP3 inflammasome in human monocytes/macrophages. J. Lipid Res. 54 (2013), 2998–3008.
57. [57] Snodgrass, R.G., Huang, S., Choi, I.-W., Rutledge, J.C., Hwang, D.H., Inflammasome-mediated secretion of IL-1β in human monocytes through TLR2 activation; modulation by dietary fatty acids. J. Immunol. 191 (2013), 4337–4347.
58. [58] Oh, D.Y., Talukdar, S., Bae, E.J., Imamura, T., Morinaga, H., Fan, W., Li, P., Lu, W.J., Watkins, S.M., Olefsky, J.M., GPR120 is an omega-3 fatty acid receptor mediating potent anti-inflammatory and insulin-sensitizing effects. Cell 142 (2010), 687–698.
59. [59] Coll, T., Eyre, E., Rodríguez-Calvo, R., Palomer, X., Sánchez, R.M., Merlos, M., Laguna, J.C., Vázquez-Carrera, M., Oleate reverses palmitate-induced insulin resistance and inflammation in skeletal muscle cells. J. Biol. Chem. 283 (2008), 11107–11116.
60. [60] Mantzaris, M.D., Tsianos, E.V., Galaris, D., Interruption of triacylglycerol synthesis in the endoplasmic reticulum is the initiating event for saturated fatty acid-induced lipotoxicity in liver cells. FEBS J. 278 (2011), 519–530.
61. [61] Leamy, A.K., Egnatchik, R.A., Shiota, M., Ivanova, P.T., Myers, D.S., Brown, H.A., Young, J.D., Enhanced synthesis of saturated phospholipids is associated with ER stress and lipotoxicity in palmitate treated hepatic cells. J. Lipid Res. 55 (2014), 1478–1488.
62. [62] Namgaladze, D., Lips, S., Leiker, T.J., Murphy, R.C., Ekroos, K., Ferreiros, N., Geisslinger, G., Brüne, B., Inhibition of macrophage fatty acid β-oxidation exacerbates palmitate-induced inflammatory and endoplasmic reticulum stress responses. Diabetologia 57 (2014), 1067–1077.
63. [63] Malandrino, M.I., Fucho, R., Weber, M., Calderon-Dominguez, M., Mir, J.F., Valcarcel, L., Escoté, X., Gómez-Serrano, M., Peral, B., Salvadó, L., Fernández-Veledo, S., Casals, N., Vázquez-Carrera, M., Villarroya, F., Vendrell, J.J., Serra, D., Herrero, L., Enhanced fatty acid oxidation in adipocytes and macrophages reduces lipid-induced triglyceride accumulation and inflammation. Am. J. Physiol. Endocrinol. Metab., 308, 2015, E756.
64. [64] Sebastián, D., Herrero, L., Serra, D., Asins, G., Hegardt, F.G., CPT I overexpression protects L6E9 muscle cells from fatty acid-induced insulin resistance. Am. J. Physiol. Endocrinol. Metab. 292 (2007), E677–E686.
65. [65] Bruce, C.R., Hoy, A.J., Turner, N., Watt, M.J., Allen, T.L., Carpenter, K., Cooney, G.J., Febbraio, M.A., Kraegen, E.W., Overexpression of carnitine palmitoyltransferase-1 in skeletal muscle is sufficient to enhance fatty acid oxidation and improve high-fat diet-induced insulin resistance. Diabetes 58 (2009), 550–558.
66. [66] Orellana-Gavaldà, J.M., Herrero, L., Malandrino, M.I., Pañeda, A., Sol Rodríguez-Peña, M., Petry, H., Asins, G., van Deventer, S., Hegardt, F.G., Serra, D., Molecular therapy for obesity and diabetes based on a long-term increase in hepatic fatty-acid oxidation. Hepatology 53 (2011), 821–832.
67. [67] Barnett, M., Collier, G.R., O'Dea, K., The longitudinal effect of inhibiting fatty acid oxidation in diabetic rats fed a high fat diet. Horm. Metab. Res. 24 (1992), 360–362.
68. [68] Hübinger, A., Weikert, G., Wolf, H.P., Gries, F.A., The effect of etomoxir on insulin sensitivity in type 2 diabetic patients. Horm. Metab. Res. 24 (1992), 115–118.
69. [69] Timmers, S., Nabben, M., Bosma, M., van Bree, B., Lenaers, E., van Beurden, D., Schaart, G., Westerterp-Plantenga, M.S., Langhans, W., Hesselink, M.K.C., Schrauwen-Hinderling, V.B., Schrauwen, P., Augmenting muscle diacylglycerol and triacylglycerol content by blocking fatty acid oxidation does not impede insulin sensitivity. Proc. Natl. Acad. Sci. U. S. A. 109 (2012), 11711–11716.
70. [70] Keung, W., Ussher, J.R., Jaswal, J.S., Raubenheimer, M., Lam, V.H.M., Wagg, C.S., Lopaschuk, G.D., Inhibition of carnitine palmitoyltransferase-1 activity alleviates insulin resistance in diet-induced obese mice. Diabetes 62 (2013), 711–720.
71. [71] Gillingham, M.B., Harding, C.O., Schoeller, D.A., Matern, D., Purnell, J.Q., Altered body composition and energy expenditure but normal glucose tolerance among humans with a long-chain fatty acid oxidation disorder. Am. J. Physiol. Endocrinol. Metab. 305 (2013), E1299–E1308.
72. [72] Muoio, D.M., Neufer, P.D., Lipid-induced mitochondrial stress and insulin action in muscle. Cell Metab. 15 (2012), 595–605.
73. [73] Randle, P.J., Garland, P.B., Hales, C.N., Newsholme, E.A., The glucose fatty-acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet 1 (1963), 785–789.
74. [74] Koves, T.R., Ussher, J.R., Noland, R.C., Slentz, D., Mosedale, M., Ilkayeva, O., Bain, J., Stevens, R., Dyck, J.R.B., Newgard, C.B., Lopaschuk, G.D., Muoio, D.M., Mitochondrial overload and incomplete fatty acid oxidation contribute to skeletal muscle insulin resistance. Cell Metab. 7 (2008), 45–56.
75. [75] Aguer, C., McCoin, C.S., Knotts, T.A., Thrush, A.B., Ono-Moore, K., McPherson, R., Dent, R., Hwang, D.H., Adams, S.H., Harper, M.-E., Acylcarnitines: potential implications for skeletal muscle insulin resistance. FASEB J. 29 (2015), 336–345.
76. [76] Rutkowsky, J.M., Knotts, T.A., Ono-Moore, K.D., McCoin, C.S., Huang, S., Schneider, D., Singh, S., Adams, S.H., Hwang, D.H., Acylcarnitines activate proinflammatory signaling pathways. Am. J. Physiol. Endocrinol. Metab. 306 (2014), E1378–E1387.
77. 2 emission during long-chain fatty acid oxidation. J. Biol. Chem. 285 (2010), 5748–5758.
78. 2 emission and cellular redox state link excess fat intake to insulin resistance in both rodents and humans. J. Clin. Invest. 119 (2009), 573–581.
79. [79] Yuzefovych, L.V., Solodushko, V.A., Wilson, G.L., Rachek, L.I., Protection from palmitate-induced mitochondrial DNA damage prevents from mitochondrial oxidative stress, mitochondrial dysfunction, apoptosis, and impaired insulin signaling in rat L6 skeletal muscle cells. Endocrinology 153 (2012), 92–100.
80. [80] Ma, C., Kesarwala, A.H., Eggert, T., Medina-Echeverz, J., Kleiner, D.E., Jin, P., Stroncek, D.F., Terabe, M., Kapoor, V., ElGindi, M., Han, M., Thornton, A.M., Zhang, H., Egger, M., Luo, J., Felsher, D.W., McVicar, D.W., Weber, A., Heikenwalder, M., Greten, T.F., NAFLD causes selective CD4(+) T lymphocyte loss and promotes hepatocarcinogenesis. Nature, 2016.
81. [81] Snodgrass, R.G., Boß, M., Zezina, E., Weigert, A., Dehne, N., Fleming, I., Brüne, B., Namgaladze, D., Hypoxia potentiates palmitate-induced pro-inflammatory activation of primary human macrophages. J. Biol. Chem. 291 (2016), 413–424.
82. [82] Ginhoux, F., Schultze, J.L., Murray, P.J., Ochando, J., Biswas, S.K., New insights into the multidimensional concept of macrophage ontogeny, activation and function. Nat. Immunol. 17 (2015), 34–40.
83. [83] Murray, P.J., Allen, J.E., Biswas, S.K., Fisher, E.A., Gilroy, D.W., Goerdt, S., Gordon, S., Hamilton, J.A., Ivashkiv, L.B., Lawrence, T., Locati, M., Mantovani, A., Martinez, F.O., Mege, J.-L., Mosser, D.M., Natoli, G., Saeij, J.P., Schultze, J.L., Shirey, K.A., Sica, A., Suttles, J., Udalova, I., van Ginderachter, J.A., Vogel, S.N., Wynn, T.A., Macrophage activation and polarization: nomenclature and experimental guidelines. Immunity 41 (2014), 14–20.
84. [84] Stein, M., Keshav, S., Harris, N., Gordon, S., Interleukin 4 potently enhances murine macrophage mannose receptor activity: a marker of alternative immunologic macrophage activation. J. Exp. Med. 176 (1992), 287–292.
85. [85] Martinez, F.O., Gordon, S., The M1 and M2 paradigm of macrophage activation: time for reassessment. F1000Prime Rep., 6, 2014, 13.
86. [86] Gordon, S., Martinez, F.O., Alternative activation of macrophages: mechanism and functions. Immunity 32 (2010), 593–604.
87. [87] Mantovani, A., Sica, A., Sozzani, S., Allavena, P., Vecchi, A., Locati, M., The chemokine system in diverse forms of macrophage activation and polarization. Trends Immunol. 25 (2004), 677–686.
88. [88] Xue, J., Schmidt, S.V., Sander, J., Draffehn, A., Krebs, W., Quester, I., de Nardo, D., Gohel, T.D., Emde, M., Schmidleithner, L., Ganesan, H., Nino-Castro, A., Mallmann, M.R., Labzin, L., Theis, H., Kraut, M., Beyer, M., Latz, E., Freeman, T.C., Ulas, T., Schultze, J.L., Transcriptome-based network analysis reveals a spectrum model of human macrophage activation. Immunity 40 (2014), 274–288.
89. [89] Lavin, Y., Winter, D., Blecher-Gonen, R., David, E., Keren-Shaul, H., Merad, M., Jung, S., Amit, I., Tissue-resident macrophage enhancer landscapes are shaped by the local microenvironment. Cell 159 (2014), 1312–1326.
90. [90] Gosselin, D., Link, V.M., Romanoski, C.E., Fonseca, G.J., Eichenfield, D.Z., Spann, N.J., Stender, J.D., Chun, H.B., Garner, H., Geissmann, F., Glass, C.K., Environment drives selection and function of enhancers controlling tissue-specific macrophage identities. Cell 159 (2014), 1327–1340.
91. [91] Hard, G.C., Some biochemical aspects of the immune macrophage. Br. J. Exp. Pathol. 51 (1970), 97–105.
92. [92] Newsholme, P., Newsholme, E.A., Rates of utilization of glucose, glutamine and oleate and formation of end-products by mouse peritoneal macrophages in culture. Biochem. J. 261 (1989), 211–218.
93. [93] Rodríguez-Prados, J.-C., Través, P.G., Cuenca, J., Rico, D., Aragonés, J., Martín-Sanz, P., Cascante, M., Boscá, L., Substrate fate in activated macrophages: a comparison between innate, classic, and alternative activation. J. Immunol. 185 (2010), 605–614.
94. [94] Haschemi, A., Kosma, P., Gille, L., Evans, C.R., Burant, C.F., Starkl, P., Knapp, B., Haas, R., Schmid, J.A., Jandl, C., Amir, S., Lubec, G., Park, J., Esterbauer, H., Bilban, M., Brizuela, L., Pospisilik, J.A., Otterbein, L.E., Wagner, O., The sedoheptulose kinase CARKL directs macrophage polarization through control of glucose metabolism. Cell Metab. 15 (2012), 813–826.
95. [95] Jha, A.K., Huang, S.C.-C., Sergushichev, A., Lampropoulou, V., Ivanova, Y., Loginicheva, E., Chmielewski, K., Stewart, K.M., Ashall, J., Everts, B., Pearce, E.J., Driggers, E.M., Artyomov, M.N., Network integration of parallel metabolic and transcriptional data reveals metabolic modules that regulate macrophage polarization. Immunity 42 (2015), 419–430.
96. [96] Krawczyk, C.M., Holowka, T., Sun, J., Blagih, J., Amiel, E., DeBerardinis, R.J., Cross, J.R., Jung, E., Thompson, C.B., Jones, R.G., Pearce, E.J., Toll-like receptor-induced changes in glycolytic metabolism regulate dendritic cell activation. Blood 115 (2010), 4742–4749.
97. [97] Everts, B., Amiel, E., van der Windt, G.J.W., Freitas, T.C., Chott, R., Yarasheski, K.E., Pearce, E.L., Pearce, E.J., Commitment to glycolysis sustains survival of NO-producing inflammatory dendritic cells. Blood 120 (2012), 1422–1431.
98. [98] Tannahill, G.M., Curtis, A.M., Adamik, J., Palsson-McDermott, E.M., McGettrick, A.F., Goel, G., Frezza, C., Bernard, N.J., Kelly, B., Foley, N.H., Zheng, L., Gardet, A., Tong, Z., Jany, S.S., Corr, S.C., Haneklaus, M., Caffrey, B.E., Pierce, K., Walmsley, S., Beasley, F.C., Cummins, E., Nizet, V., Whyte, M., Taylor, C.T., Lin, H., Masters, S.L., Gottlieb, E., Kelly, V.P., Clish, C., Auron, P.E., Xavier, R.J., O'Neill, L.A.J., Succinate is an inflammatory signal that induces IL-1β through HIF-1α. Nature 496 (2013), 238–242.
99. [99] Meiser, J., Krämer, L., Sapcariu, S.C., Battello, N., Ghelfi, J., D'Herouel, A.F., Skupin, A., Hiller, K., Pro-inflammatory macrophages sustain pyruvate oxidation through pyruvate dehydrogenase for the synthesis of Itaconate and to enable cytokine expression. J. Biol. Chem. 291 (2016), 3932–3946.
100. [100] Hossain, F., Al-Khami, A.A., Wyczechowska, D., Hernandez, C., Zheng, L., Reiss, K., Valle, L.D., Trillo-Tinoco, J., Maj, T., Zou, W., Rodriguez, P.C., Ochoa, A.C., Inhibition of fatty acid oxidation modulates immunosuppressive functions of myeloid-derived suppressor cells and enhances cancer therapies. Cancer Immunol. Res. 3 (2015), 1236–1247.
101. [101] Chang, C.-H., Qiu, J., O'Sullivan, D., Buck, M.D., Noguchi, T., Curtis, J.D., Chen, Q., Gindin, M., Gubin, M.M., van der Windt, G.J.W., Tonc, E., Schreiber, R.D., Pearce, E.J., Pearce, E.L., Metabolic competition in the tumor microenvironment is a driver of cancer progression. Cell 162 (2015), 1229–1241.
102. [102] Ho, P.-C., Bihuniak, J.D., Macintyre, A.N., Staron, M., Liu, X., Amezquita, R., Tsui, Y.-C., Cui, G., Micevic, G., Perales, J.C., Kleinstein, S.H., Abel, E.D., Insogna, K.L., Feske, S., Locasale, J.W., Bosenberg, M.W., Rathmell, J.C., Kaech, S.M., Phosphoenolpyruvate is a metabolic checkpoint of anti-tumor T cell responses. Cell 162 (2015), 1217–1228.
103. [103] Colegio, O.R., Chu, N.-Q., Szabo, A.L., Chu, T., Rhebergen, A.M., Jairam, V., Cyrus, N., Brokowski, C.E., Eisenbarth, S.C., Phillips, G.M., Cline, G.W., Phillips, A.J., Medzhitov, R., Functional polarization of tumour-associated macrophages by tumour-derived lactic acid. Nature 513 (2014), 559–563.
104. [104] Brüne, B., Dehne, N., Grossmann, N., Jung, M., Namgaladze, D., Schmid, T., von Knethen, A., Weigert, A., Redox control of inflammation in macrophages. Antioxid. Redox Signal. 19 (2013), 595–637.
105. [105] Fuhrmann, D.C., Wittig, I., Heide, H., Dehne, N., Brüne, B., Chronic hypoxia alters mitochondrial composition in human macrophages. Biochim. Biophys. Acta 1834 (2013), 2750–2760.
106. [106] Boström, P., Magnusson, B., Svensson, P.-A., Wiklund, O., Borén, J., Carlsson, L.M.S., Ståhlman, M., Olofsson, S.-O., Hultén, L.M., Hypoxia converts human macrophages into triglyceride-loaded foam cells. Arterioscler. Thromb. Vasc. Biol. 26 (2006), 1871–1876.
107. [107] Huang, D., Li, T., Li, X., Zhang, L., Sun, L., He, X., Zhong, X., Jia, D., Song, L., Semenza, G.L., Gao, P., Zhang, H., HIF-1-mediated suppression of acyl-CoA dehydrogenases and fatty acid oxidation is critical for cancer progression. Cell Rep. 8 (2014), 1930–1942.
108. [108] Tan, Z., Xie, N., Cui, H., Moellering, D.R., Abraham, E., Thannickal, V.J., Liu, G., Pyruvate dehydrogenase kinase 1 participates in macrophage polarization via regulating glucose metabolism. J. Immunol. 194 (2015), 6082–6089.
109. [109] Freemerman, A.J., Johnson, A.R., Sacks, G.N., Milner, J.J., Kirk, E.L., Troester, M.A., Macintyre, A.N., Goraksha-Hicks, P., Rathmell, J.C., Makowski, L., Metabolic reprogramming of macrophages: glucose transporter 1 (GLUT1)-mediated glucose metabolism drives a proinflammatory phenotype. J. Biol. Chem. 289 (2014), 7884–7896.
110. [110] Nishizawa, T., Kanter, J.E., Kramer, F., Barnhart, S., Shen, X., Vivekanandan-Giri, A., Wall, V.Z., Kowitz, J., Devaraj, S., O'Brien, K.D., Pennathur, S., Tang, J., Miyaoka, R.S., Raines, E.W., Bornfeldt, K.E., Testing the role of myeloid cell glucose flux in inflammation and atherosclerosis. Cell Rep. 7 (2014), 356–365.
111. [111] Jantsch, J., Chakravortty, D., Turza, N., Prechtel, A.T., Buchholz, B., Gerlach, R.G., Volke, M., Glasner, J., Warnecke, C., Wiesener, M.S., Eckardt, K.-U., Steinkasserer, A., Hensel, M., Willam, C., Hypoxia and hypoxia-inducible factor-1 modulate lipopolysaccharide-induced dendritic cell activation and function. J. Immunol. 180 (2008), 4697–4705.
112. [112] Vats, D., Mukundan, L., Odegaard, J.I., Zhang, L., Smith, K.L., Morel, C.R., Wagner, R.A., Greaves, D.R., Murray, P.J., Chawla, A., Oxidative metabolism and PGC-1beta attenuate macrophage-mediated inflammation. Cell Metab. 4 (2006), 13–24.
113. [113] Huang, S.C.-C., Everts, B., Ivanova, Y., O'Sullivan, D., Nascimento, M., Smith, A.M., Beatty, W., Love-Gregory, L., Lam, W.Y., O'Neill, C.M., Yan, C., Du, H., Abumrad, N.A., Urban, J.F., Artyomov, M.N., Pearce, E.L., Pearce, E.J., Cell-intrinsic lysosomal lipolysis is essential for alternative activation of macrophages. Nat. Immunol. 15 (2014), 846–855.
114. [114] Namgaladze, D., Brüne, B., Fatty acid oxidation is dispensable for human macrophage IL-4-induced polarization. Biochim. Biophys. Acta 1841 (2014), 1329–1335.
115. [115] Martinez, F.O., Helming, L., Milde, R., Varin, A., Melgert, B.N., Draijer, C., Thomas, B., Fabbri, M., Crawshaw, A., Ho, L.P., Ten Hacken, N.H., Cobos Jiménez, V., Kootstra, N.A., Hamann, J., Greaves, D.R., Locati, M., Mantovani, A., Gordon, S., Genetic programs expressed in resting and IL-4 alternatively activated mouse and human macrophages: similarities and differences. Blood 121 (2013), e57–e69.
116. [116] Pike, L.S., Smift, A.L., Croteau, N.J., Ferrick, D.A., Wu, M., Inhibition of fatty acid oxidation by etomoxir impairs NADPH production and increases reactive oxygen species resulting in ATP depletion and cell death in human glioblastoma cells. Biochim. Biophys. Acta Bioenerg. 1807 (2011), 726–734.
117. [117] Nomura, M., Liu, J., Rovira, I.I., Gonzalez-Hurtado, E., Lee, J., Wolfgang, M.J., Finkel, T., Fatty acid oxidation in macrophage polarization. Nat. Immunol. 17 (2016), 216–217.
118. [118] Muoio, D.M., Metabolic inflexibility: when mitochondrial indecision leads to metabolic gridlock. Cell 159 (2014), 1253–1262.
119. [119] Walker, C., Bauer, W., Braun, R.K., Menz, G., Braun, P., Schwarz, F., Hansel, T.T., Villiger, B., Activated T cells and cytokines in bronchoalveolar lavages from patients with various lung diseases associated with eosinophilia. Am. J. Respir. Crit. Care Med. 150 (1994), 1038–1048.
120. [120] Boss, M., Kemmerer, M., Brüne, B., Namgaladze, D., FABP4 inhibition suppresses PPARγ activity and VLDL-induced foam cell formation in IL-4-polarized human macrophages. Atherosclerosis 240 (2015), 424–430.
121. [121] Chandak, P.G., Radovic, B., Aflaki, E., Kolb, D., Buchebner, M., Fröhlich, E., Magnes, C., Sinner, F., Haemmerle, G., Zechner, R., Tabas, I., Levak-Frank, S., Kratky, D., Efficient phagocytosis requires triacylglycerol hydrolysis by adipose triglyceride lipase. J. Biol. Chem. 285 (2010), 20192–20201.
122. [122] Aflaki, E., Balenga, N.A.B., Luschnig-Schratl, P., Wolinski, H., Povoden, S., Chandak, P.G., Bogner-Strauss, J.G., Eder, S., Konya, V., Kohlwein, S.-D., Heinemann, A., Kratky, D., Impaired Rho GTPase activation abrogates cell polarization and migration in macrophages with defective lipolysis. Cell. Mol. Life Sci. 68 (2011), 3933–3947.
123. [123] Goeritzer, M., Schlager, S., Radovic, B., Madreiter, C.T., Rainer, S., Thomas, G., Lord, C.C., Sacks, J., Brown, A.L., Vujic, N., Obrowsky, S., Sachdev, V., Kolb, D., Chandak, P.G., Graier, W.F., Sattler, W., Brown, J.M., Kratky, D., Deletion of CGI-58 or adipose triglyceride lipase differently affects macrophage function and atherosclerosis. J. Lipid Res. 55 (2014), 2562–2575.
124. [124] O'Neill, L.A.J., Hardie, D.G., Metabolism of inflammation limited by AMPK and pseudo-starvation. Nature 493 (2013), 346–355.
125. [125] Hardie, D.G., AMP-activated protein kinase: maintaining energy homeostasis at the cellular and whole-body levels. Annu. Rev. Nutr. 34 (2014), 31–55.
126. [126] Carling, D., Zammit, V.A., Hardie, D.G., A common bicyclic protein kinase cascade inactivates the regulatory enzymes of fatty acid and cholesterol biosynthesis. FEBS Lett. 223 (1987), 217–222.
127. [127] Luiken, J.J.F.P., Coort, S.L.M., Willems, J., Coumans, W.A., Bonen, A., van der Vusse, G.J., Glatz, J.F.C., Contraction-induced fatty acid translocase/CD36 translocation in rat cardiac myocytes is mediated through AMP-activated protein kinase signaling. Diabetes 52 (2003), 1627–1634.
128. [128] Jäger, S., Handschin, C., St-Pierre, J., Spiegelman, B.M., AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1alpha. Proc. Natl. Acad. Sci. U. S. A. 104 (2007), 12017–12022.
129. [129] Galic, S., Fullerton, M.D., Schertzer, J.D., Sikkema, S., Marcinko, K., Walkley, C.R., Izon, D., Honeyman, J., Chen, Z.-P., van Denderen, B.J., Kemp, B.E., Steinberg, G.R., Hematopoietic AMPK β1 reduces mouse adipose tissue macrophage inflammation and insulin resistance in obesity. J. Clin. Invest. 121 (2011), 4903–4915.
130. [130] Ouimet, M., Ediriweera, H.N., Gundra, U.M., Sheedy, F.J., Ramkhelawon, B., Hutchison, S.B., Rinehold, K., van Solingen, C., Fullerton, M.D., Cecchini, K., Rayner, K.J., Steinberg, G.R., Zamore, P.D., Fisher, E.A., Loke, P., Moore, K.J., MicroRNA-33-dependent regulation of macrophage metabolism directs immune cell polarization in atherosclerosis. J. Clin. Invest., 2015, 2015.
131. [131] Chan, K.L., Pillon, N.J., Sivaloganathan, D.M., Costford, S.R., Liu, Z., Théret, M., Chazaud, B., Klip, A., Palmitoleate reverses high fat-induced proinflammatory macrophage polarization via AMP-activated protein kinase (AMPK). J. Biol. Chem. 290 (2015), 16979–16988.
132. [132] Lee, H.-M., Kim, J.-J., Kim, H.J., Shong, M., Ku, B.J., Jo, E.-K., Upregulated NLRP3 inflammasome activation in patients with type 2 diabetes. Diabetes 62 (2013), 194–204.
133. [133] Cantó, C., Gerhart-Hines, Z., Feige, J.N., Lagouge, M., Noriega, L., Milne, J.C., Elliott, P.J., Puigserver, P., Auwerx, J., AMPK regulates energy expenditure by modulating NAD + metabolism and SIRT1 activity. Nature 458 (2009), 1056–1060.
134. [134] Yang, Z., Kahn, B.B., Shi, H., Xue, B.-Z., Macrophage alpha1 AMP-activated protein kinase (alpha1AMPK) antagonizes fatty acid-induced inflammation through SIRT1. J. Biol. Chem. 285 (2010), 19051–19059.
135. [135] Lee, C.-W., Wong, L.L.-Y., Tse, E.Y.-T., Liu, H.-F., Leong, V.Y.-L., Lee, J.M.-F., Hardie, D.G., Ng, I.O.-L., Ching, Y.-P., AMPK promotes p53 acetylation via phosphorylation and inactivation of SIRT1 in liver cancer cells. Cancer Res. 72 (2012), 4394–4404.
136. [136] Sag, D., Carling, D., Stout, R.D., Suttles, J., Adenosine 5′-monophosphate-activated protein kinase promotes macrophage polarization to an anti-inflammatory functional phenotype. J. Immunol. 181 (2008), 8633–8641.
137. [137] Mounier, R., Théret, M., Arnold, L., Cuvellier, S., Bultot, L., Göransson, O., Sanz, N., Ferry, A., Sakamoto, K., Foretz, M., Viollet, B., Chazaud, B., AMPKα1 regulates macrophage skewing at the time of resolution of inflammation during skeletal muscle regeneration. Cell Metab. 18 (2013), 251–264.
138. [138] Carroll, K.C., Viollet, B., Suttles, J., AMPKα1 deficiency amplifies proinflammatory myeloid APC activity and CD40 signaling. J. Leukoc. Biol. 94 (2013), 1113–1121.
139. [139] Zhu, Y.P., Brown, J.R., Sag, D., Zhang, L., Suttles, J., Adenosine 5′-monophosphate-activated protein kinase regulates IL-10-mediated anti-inflammatory signaling pathways in macrophages. J. Immunol. 194 (2015), 584–594.
140. [140] Namgaladze, D., Snodgrass, R.G., Angioni, C., Grossmann, N., Dehne, N., Geisslinger, G., Brüne, B., AMP-activated protein kinase suppresses arachidonate 15-lipoxygenase expression in interleukin 4-polarized human macrophages. J. Biol. Chem. 290 (2015), 24484–24494.
141. [141] Kelly, B., Tannahill, G.M., Murphy, M.P., O'Neill, L.A.J., Metformin inhibits the production of reactive oxygen species from NADH:ubiquinone oxidoreductase to limit induction of interleukin-1β (IL-1β) and boosts interleukin-10 (IL-10) in lipopolysaccharide (LPS)-activated macrophages. J. Biol. Chem. 290 (2015), 20348–20359.
142. [142] Kuo, C.-L., Ho, F.-M., Chang, M.Y., Prakash, E., Lin, W.-W., Inhibition of lipopolysaccharide-induced inducible nitric oxide synthase and cyclooxygenase-2 gene expression by 5-aminoimidazole-4-carboxamide riboside is independent of AMP-activated protein kinase. J. Cell. Biochem. 103 (2008), 931–940.
143. [143] Chawla, A., Control of macrophage activation and function by PPARs. Circ. Res. 106 (2010), 1559–1569.
144. [144] Chinetti-Gbaguidi, G., Staels, B., Lipid ligand-activated transcription factors regulating lipid storage and release in human macrophages. Biochim. Biophys. Acta 1791 (2009), 486–493.
145. [145] Lee, C.-H., Kang, K., Mehl, I.R., Nofsinger, R., Alaynick, W.A., Chong, L.-W., Rosenfeld, J.M., Evans, R.M., Peroxisome proliferator-activated receptor delta promotes very low-density lipoprotein-derived fatty acid catabolism in the macrophage. Proc. Natl. Acad. Sci. U. S. A. 103 (2006), 2434–2439.
146. [146] Chinetti, G., Lestavel, S., Fruchart, J.-C., Clavey, V., Staels, B., Peroxisome proliferator-activated receptor alpha reduces cholesterol esterification in macrophages. Circ. Res. 92 (2003), 212–217.
147. [147] Bojic, L.A., Sawyez, C.G., Telford, D.E., Edwards, J.Y., Hegele, R.A., Huff, M.W., Activation of peroxisome proliferator-activated receptor δ inhibits human macrophage foam cell formation and the inflammatory response induced by very low-density lipoprotein. Arterioscler. Thromb. Vasc. Biol. 32 (2012), 2919–2928.
148. [148] Odegaard, J.I., Ricardo-Gonzalez, R.R., Red Eagle, A., Vats, D., Morel, C.R., Goforth, M.H., Subramanian, V., Mukundan, L., Ferrante, A.W., Chawla, A., Alternative M2 activation of Kupffer cells by PPARdelta ameliorates obesity-induced insulin resistance. Cell Metab. 7 (2008), 496–507.
149. [149] Kang, K., Reilly, S.M., Karabacak, V., Gangl, M.R., Fitzgerald, K., Hatano, B., Lee, C.-H., Adipocyte-derived Th2 cytokines and myeloid PPARdelta regulate macrophage polarization and insulin sensitivity. Cell Metab. 7 (2008), 485–495.
150. [150] Wan, J., Jiang, L., Lü, Q., Ke, L., Li, X., Tong, N., Activation of PPARdelta up-regulates fatty acid oxidation and energy uncoupling genes of mitochondria and reduces palmitate-induced apoptosis in pancreatic beta-cells. Biochem. Biophys. Res. Commun. 391 (2010), 1567–1572.
151. [151] Coll, T., Alvarez-Guardia, D., Barroso, E., Gómez-Foix, A.M., Palomer, X., Laguna, J.C., Vázquez-Carrera, M., Activation of peroxisome proliferator-activated receptor-{delta} by GW501516 prevents fatty acid-induced nuclear factor-{kappa}B activation and insulin resistance in skeletal muscle cells. Endocrinology 151 (2010), 1560–1569.
152. [152] Toral, M., Romero, M., Jiménez, R., Mahmoud, A.M., Barroso, E., Gómez-Guzmán, M., Sánchez, M., Cogolludo, Á., García-Redondo, A.B., Briones, A.M., Vázquez-Carrera, M., Pérez-Vizcaíno, F., Duarte, J., Carnitine palmitoyltransferase-1 up-regulation by PPAR-β/δ prevents lipid-induced endothelial dysfunction. Clin. Sci. 129 (2015), 823–837.
153. [153] Odegaard, J.I., Ricardo-Gonzalez, R.R., Goforth, M.H., Morel, C.R., Subramanian, V., Mukundan, L., Red Eagle, A., Vats, D., Brombacher, F., Ferrante, A.W., Chawla, A., Macrophage-specific PPARgamma controls alternative activation and improves insulin resistance. Nature 447 (2007), 1116–1120.
154. [154] Bouhlel, M.A., Derudas, B., Rigamonti, E., Dièvart, R., Brozek, J., Haulon, S., Zawadzki, C., Jude, B., Torpier, G., Marx, N., Staels, B., Chinetti-Gbaguidi, G., PPARgamma activation primes human monocytes into alternative M2 macrophages with anti-inflammatory properties. Cell Metab. 6 (2007), 137–143.
155. [155] Bouhlel, M.A., Brozek, J., Derudas, B., Zawadzki, C., Jude, B., Staels, B., Chinetti-Gbaguidi, G., Unlike PPARgamma, PPARalpha or PPARbeta/delta activation does not promote human monocyte differentiation toward alternative macrophages. Biochem. Biophys. Res. Commun. 386 (2009), 459–462.
156. [156] Szanto, A., Balint, B.L., Nagy, Z.S., Barta, E., Dezso, B., Pap, A., Szeles, L., Poliska, S., Oros, M., Evans, R.M., Barak, Y., Schwabe, J., Nagy, L., STAT6 transcription factor is a facilitator of the nuclear receptor PPARγ-regulated gene expression in macrophages and dendritic cells. Immunity 33 (2010), 699–712.
157. [157] Furuhashi, M., Hotamisligil, G.S., Fatty acid-binding proteins: role in metabolic diseases and potential as drug targets. Nat. Rev. Drug Discov. 7 (2008), 489–503.
158. [158] Hofer, P., Boeszoermenyi, A., Jaeger, D., Feiler, U., Arthanari, H., Mayer, N., Zehender, F., Rechberger, G., Oberer, M., Zimmermann, R., Lass, A., Haemmerle, G., Breinbauer, R., Zechner, R., Preiss-Landl, K., Fatty acid-binding proteins interact with comparative gene identification-58 linking lipolysis with lipid ligand shuttling. J. Biol. Chem. 290 (2015), 18438–18453.
159. [159] Narkar, V.A., Downes, M., Yu, R.T., Embler, E., Wang, Y.-X., Banayo, E., Mihaylova, M.M., Nelson, M.C., Zou, Y., Juguilon, H., Kang, H., Shaw, R.J., Evans, R.M., AMPK and PPARdelta agonists are exercise mimetics. Cell 134 (2008), 405–415.
160. [160] Kemmerer, M., Finkernagel, F., Cavalcante, M.F., Abdalla, D.S.P., Müller, R., Brüne, B., Namgaladze, D., AMP-activated protein kinase interacts with the peroxisome proliferator-activated receptor delta to induce genes affecting fatty acid oxidation in human macrophages. PLoS ONE, 10, 2015, e0130893.
161. [161] Zhang, H., Xue, C., Shah, R., Bermingham, K., Hinkle, C.C., Li, W., Rodrigues, A., Tabita-Martinez, J., Millar, J.S., Cuchel, M., Pashos, E.E., Liu, Y., Yan, R., Yang, W., Gosai, S.J., VanDorn, D., Chou, S.T., Gregory, B.D., Morrisey, E.E., Li, M., Rader, D.J., Reilly, M.P., Functional analysis and transcriptomic profiling of iPSC-derived macrophages and their application in modeling Mendelian disease. Circ. Res. 117 (2015), 17–28.