Loss of macrophage fatty acid oxidation does not potentiate systemic metabolic dysfunction

American Journal of Physiology - Endocrinology and Metabolism

Volumn 312, Issue 5, 2017, Pages E381-E393

  Gonzalez Hurtado, Elsie ^a   Lee, Jieun ^a   Choi, Joseph ^a   Selen Alpergin, Ebru S ^a   Collins, Samuel L ^a   Horton, Maureen R ^a   Wolfgang, Michael J ^a  

^a JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Adipose tissue; Fatty acid; Inflammation; Macrophage; Obesity

Indexed keywords

CARNITINE PALMITOYLTRANSFERASE; CARNITINE PALMITOYLTRANSFERASE II; CYCLOOXYGENASE 2; INTERLEUKIN 4; INTERLEUKIN 6; LONG CHAIN FATTY ACID; MESSENGER RNA; MITOCHONDRIAL DNA; UNCLASSIFIED DRUG; FATTY ACID;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BODY COMPOSITION; BONE MARROW DERIVED MACROPHAGE; CELL LINEAGE; CELL LOSS; CONTROLLED STUDY; DIET INDUCED OBESITY; FATTY ACID OXIDATION; FLOW CYTOMETRY; GENE EXPRESSION; GLUCOSE INTOLERANCE; GLUCOSE OXIDATION; IN VIVO STUDY; MACROPHAGE; MALE; METABOLIC DISORDER; MOUSE; NONHUMAN; OXIDATIVE STRESS; POLARIZATION; PRIORITY JOURNAL; PROTON NUCLEAR MAGNETIC RESONANCE; ANIMAL; CELL CULTURE; IMMUNOLOGY; KNOCKOUT MOUSE; LIPID DIET; MACROPHAGE ACTIVATION; OBESITY; OXIDATION REDUCTION REACTION; PATHOLOGY; TRANSGENIC MOUSE;

ANIMALS; CELLS, CULTURED; DIET, HIGH-FAT; FATTY ACIDS; INTERLEUKIN-4; MACROPHAGE ACTIVATION; MACROPHAGES; MALE; METABOLIC DISEASES; MICE; MICE, KNOCKOUT; MICE, TRANSGENIC; OBESITY; OXIDATION-REDUCTION;

EID: 85018724259     PISSN: 01931849     EISSN: 15221555     Source Type: Journal    
DOI: 10.1152/ajpendo.00408.2016     Document Type: Article

References (46)

1. Biswas SK, Mantovani A. Orchestration of metabolism by macrophages. Cell Metab 15: 432–437, 2012. doi:10.1016/j.cmet.2011.11.013.
2. Chandak PG, 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: 20192–20201, 2010. doi:10. 1074/jbc.M110.107854.
3. Clausen BE, Burkhardt C, Reith W, Renkawitz R, Förster I. Conditional gene targeting in macrophages and granulocytes using LysMcre mice. Transgenic Res 8: 265–277, 1999. doi:10.1023/A:1008942828960.
4. Covarrubias AJ, Aksoylar HI, Yu J, Snyder NW, Worth AJ, Iyer SS, Wang J, Ben-Sahra I, Byles V, Polynne-Stapornkul T, Espinosa EC, Lamming D, Manning BD, Zhang Y, Blair IA, Horng T. Akt-mTORC1 signaling regulates Acly to integrate metabolic input to control of macrophage activation. eLife 5: e11612, 2016. doi:10.7554/eLife.11612.
5. Ellis JM, Wong GW, Wolfgang MJ. Acyl coenzyme A thioesterase 7 regulates neuronal fatty acid metabolism to prevent neurotoxicity. Mol Cell Biol 33: 1869–1882, 2013. doi:10.1128/MCB.01548-12.
6. + efflux. J Immunol 193: 4214–4222, 2014. doi:10.4049/jimmunol.1400582.
7. Furuhashi M, Tuncman G, Görgün CZ, Makowski L, Atsumi G, Vaillancourt E, Kono K, Babaev VR, Fazio S, Linton MF, Sulsky R, Robl JA, Parker RA, Hotamisligil GS. Treatment of diabetes and atherosclerosis by inhibiting fatty-acid-binding protein aP2. Nature 447: 959–965, 2007. doi:10.1038/nature05844.
8. Furukawa S, Fujita T, Shimabukuro M, Iwaki M, Yamada Y, Nakajima Y, Nakayama O, Makishima M, Matsuda M, Shimomura I. Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Invest 114: 1752–1761, 2004. doi:10.1172/JCI21625.
9. 1 reduces mouse adipose tissue macrophage inflammation and insulin resistance in obesity. J Clin Invest 121: 4903–4915, 2011. doi:10.1172/JCI58577.
10. Glass CK, Olefsky JM. Inflammation and lipid signaling in the etiology of insulin resistance. Cell Metab 15: 635–645, 2012. doi:10.1016/j.cmet.2012.04.001.
11. Gordon S. Alternative activation of macrophages. Nat Rev Immunol 3: 23–35, 2003. doi:10.1038/nri978.
12. Guo H, Callaway JB, Ting JP. Inflammasomes: mechanism of action, role in disease, and therapeutics. Nat Med 21: 677–687, 2015. doi:10. 1038/nm.3893.
13. Hevener AL, Olefsky JM, Reichart D, Nguyen MT, Bandyopadyhay G, Leung HY, Watt MJ, Benner C, Febbraio MA, Nguyen AK, Folian B, Subramaniam S, Gonzalez FJ, Glass CK, Ricote M. Macrophage PPARγ is required for normal skeletal muscle and hepatic insulin sensitivity and full antidiabetic effects of thiazolidinediones. J Clin Invest 117: 1658–1669, 2007. doi:10.1172/JCI31561.
14. Hotamisligil GS. Inflammation and metabolic disorders. Nature 444: 860–867, 2006. doi:10.1038/nature05485.
15. Hotamisligil GS, Arner P, Caro JF, Atkinson RL, Spiegelman BM. Increased adipose tissue expression of tumor necrosis factor-α in human obesity and insulin resistance. J Clin Invest 95: 2409–2415, 1995. doi:10.1172/JCI117936.
16. Houstis N, Rosen ED, Lander ES. Reactive oxygen species have a causal role in multiple forms of insulin resistance. Nature 440: 944–948, 2006. doi:10.1038/nature04634.
17. Hua KF, Chou JC, Ka SM, Tasi YL, Chen A, Wu SH, Chiu HW, Wong WT, Wang YF, Tsai CL, Ho CL, Lin CH. Cyclooxygenase-2 regulates NLRP3 inflammasome-derived IL-1β production. J Cell Physiol 230: 863–874, 2015. doi:10.1002/jcp.24815.
18. Huang JT, Welch JS, Ricote M, Binder CJ, Wilson TM, Kelly C, Witztum JL, Funk CD, Conrad D, Glass CK. Interleukin-4-dependent production of PPARδ ligands in macrophages by 12/15-lipoxygenase. Nature 400: 378–382, 1999. doi:10.1038/22572.
19. Huang SC, Everts B, Ivanova Y, O’Sullivan D, Nascimento M, Smith AM, Beatty W, Love-Gregory L, Lam WY, O’Neill CM, Yan C, Du H, Abumrad NA, Urban JF Jr, Artyomov MN, Pearce EL, Pearce EJ. Cell-intrinsic lysosomal lipolysis is essential for alternative activation of macrophages. Nat Immunol 15: 846–855, 2014. doi:10.1038/ni.2956.
20. Kang K, Reilly SM, Karabacak V, Gangl MR, Fitzgerald K, Hatano B, Lee CH. Adipocyte-derived Th2 cytokines and myeloid PPARδ regulate macrophage polarization and insulin sensitivity. Cell Metab 7: 485–495, 2008. doi:10.1016/j.cmet.2008.04.002.
21. Koliwad SK, Streeper RS, Monetti M, Cornelissen I, Chan L, Terayama K, Naylor S, Rao M, Hubbard B, Farese RV Jr. DGAT1dependent triacylglycerol storage by macrophages protects mice from diet-induced insulin resistance and inflammation. J Clin Invest 120: 756–767, 2010. doi:10.1172/JCI36066.
22. Kratz M, Coats BR, Hisert KB, Hagman D, Mutskov V, Peris E, Schoenfelt KQ, Kuzma JN, Larson I, Billing PS, Landerholm RW, Crouthamel M, Gozal D, Hwang S, Singh PK, Becker L. Metabolic dysfunction drives a mechanistically distinct proinflammatory phenotype in adipose tissue macrophages. Cell Metab 20: 614–625, 2014. doi:10.1016/j.cmet.2014.08.010.
23. Lee J, Choi J, Aja S, Scafidi S, Wolfgang MJ. Loss of adipose fatty acid oxidation does not potentiate obesity at thermoneutrality. Cell Reports 14: 1308–1316, 2016. doi:10.1016/j.celrep.2016.01.029.
24. Lee J, Choi J, Scafidi S, Wolfgang MJ. Hepatic fatty acid oxidation restrains systemic catabolism during starvation. Cell Reports 16: 201–212, 2016. doi:10.1016/j.celrep.2016.05.062.
25. Lee J, Ellis JM, Wolfgang MJ. Adipose fatty acid oxidation is required for thermogenesis and potentiates oxidative stress-induced inflammation. Cell Reports 10: 266–279, 2015. doi:10.1016/j.celrep.2014.12.023.
26. Lee JY, Sohn KH, Rhee SH, 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: 16683–16689, 2001. doi:10.1074/jbc.M011695200.
27. Lin Y, Berg AH, Iyengar P, Lam TK, Giacca A, Combs TP, Rajala MW, Du X, Rollman B, Li W, Hawkins M, Barzilai N, Rhodes CJ, Fantus IG, Brownlee M, Scherer PE. The hyperglycemia-induced inflammatory response in adipocytes: the role of reactive oxygen species. J Biol Chem 280: 4617–4626, 2005. doi:10.1074/jbc.M411863200.
28. Lumeng CN, Bodzin JL, Saltiel AR. Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J Clin Invest 117: 175–184, 2007. doi:10.1172/JCI29881.
29. Moon JS, Nakahira K, Chung KP, DeNicola GM, Koo MJ, Pabón MA, Rooney KT, Yoon JH, Ryter SW, Stout-Delgado H, Choi AM. NOX4-dependent fatty acid oxidation promotes NLRP3 inflammasome activation in macrophages. Nat Med 22: 1002–1012, 2016. doi:10.1038/nm.4153.
30. Nguyen KD, Qiu Y, Cui X, Goh YP, Mwangi J, David T, Mukundan L, Brombacher F, Locksley RM, Chawla A. Alternatively activated macrophages produce catecholamines to sustain adaptive thermogenesis. Nature 480: 104–108, 2011. doi:10.1038/nature10653.
31. Nomura M, Liu J, Rovira II, Gonzalez-Hurtado E, Lee J, Wolfgang MJ, Finkel T. Fatty acid oxidation in macrophage polarization. Nat Immunol 17: 216–217, 2016. doi:10.1038/ni.3366.
32. O’Neill LA, Pearce EJ. Immunometabolism governs dendritic cell and macrophage function. J Exp Med 213: 15–23, 2016. doi:10.1084/jem.20151570.
33. Odegaard JI, Ricardo-Gonzalez RR, Goforth MH, Morel CR, Subramanian V, Mukundan L, Red Eagle A, Vats D, Brombacher F, Ferrante AW, Chawla A. Macrophage-specific PPARγ controls alternative activation and improves insulin resistance. Nature 447: 1116–1120, 2007. doi:10.1038/nature05894.
34. Odegaard JI, Ricardo-Gonzalez RR, Red Eagle A, Vats D, Morel CR, Goforth MH, Subramanian V, Mukundan L, Ferrante AW, Chawla A. Alternative M2 activation of Kupffer cells by PPARδ ameliorates obesity-induced insulin resistance. Cell Metab 7: 496–507, 2008. doi:10.1016/j.cmet.2008.04.003.
35. Olefsky JM, Glass CK. Macrophages, inflammation, and insulin resistance. Annu Rev Physiol 72: 219–246, 2010. doi:10.1146/annurev-physiol-021909-135846.
36. Rajan JV, Warren SE, Miao EA, Aderem A. Activation of the NLRP3 inflammasome by intracellular poly I:C. FEBS Lett 584: 4627–4632, 2010. doi:10.1016/j.febslet.2010.10.036.
37. Sag D, Carling D, Stout RD, Suttles J. Adenosine 5=-monophosphate-activated protein kinase promotes macrophage polarization to an antiinflammatory functional phenotype. J Immunol 181: 8633–8641, 2008. doi:10.4049/jimmunol.181.12.8633.
38. Schoggins JW, Rice CM. Interferon-stimulated genes and their antiviral effector functions. Curr Opin Virol 1: 519–525, 2011. doi:10.1016/j.coviro.2011.10.008.
39. Shi H, Kokoeva MV, Inouye K, Tzameli I, Yin H, Flier JS. TLR4 links innate immunity and fatty acid-induced insulin resistance. J Clin Invest 116: 3015–3025, 2006. doi:10.1172/JCI28898.
40. Shoelson SE, Herrero L, Naaz A. Obesity, inflammation, and insulin resistance. Gastroenterology 132: 2169–2180, 2007. doi:10.1053/j.gastro.2007.03.059.
41. Sica A, Mantovani A. Macrophage plasticity and polarization: in vivo veritas. J Clin Invest 122: 787–795, 2012. doi:10.1172/JCI59643.
42. Uysal KT, Wiesbrock SM, Marino MW, Hotamisligil GS. Protection from obesity-induced insulin resistance in mice lacking TNF-α function. Nature 389: 610–614, 1997. doi:10.1038/39335.
43. Vats D, Mukundan L, Odegaard JI, Zhang L, Smith KL, Morel CR, Wagner RA, Greaves DR, Murray PJ, Chawla A. Oxidative metabo lism and PGC-1β attenuate macrophage-mediated inflammation. Cell Metab 4: 13–24, 2006. doi:10.1016/j.cmet.2006.05.011.
44. Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW Jr. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 112: 1796–1808, 2003. doi:10.1172/JCI200319246.
45. West AP, Khoury-Hanold W, Staron M, Tal MC, Pineda CM, Lang SM, Bestwick M, Duguay BA, Raimundo N, MacDuff DA, Kaech SM, Smiley JR, Means RE, Iwasaki A, Shadel GS. Mitochondrial DNA stress primes the antiviral innate immune response. Nature 520: 553–557, 2015. doi:10.1038/nature14156.
46. Xu H, Barnes GT, Yang Q, Tan G, Yang D, Chou CJ, Sole J, Nichols A, Ross JS, Tartaglia LA, Chen H. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest 112: 1821–1830, 2003. doi:10.1172/JCI200319451.