Skip to main content
SpringerLink
Log in
Book cover

Obesity and Lipotoxicity pp 327–343Cite as

Adipocyte-Macrophage Cross-Talk in Obesity

  • Chapter
  • First Online:

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 960))

Abstract

Obesity is characterized by the chronic low-grade activation of the innate immune system. In this respect, macrophage-elicited metabolic inflammation and adipocyte-macrophage interaction has a primary importance in obesity. Large amounts of macrophages are accumulated by different mechanisms in obese adipose tissue. Hypertrophic adipocyte-derived chemotactic monocyte chemoattractant protein-1 (MCP-1)/C-C chemokine receptor 2 (CCR2) pathway also promotes more macrophage accumulation into the obese adipose tissue. However, increased local extracellular lipid concentrations is a final mechanism for adipose tissue macrophage accumulation. A paracrine loop involving free fatty acids and tumor necrosis factor-alpha (TNF-alpha) between adipocytes and macrophages establishes a vicious cycle that aggravates inflammatory changes in the adipose tissue. Adipocyte-specific caspase-1 and production of interleukin-1beta (IL-1beta) by macrophages; both adipocyte and macrophage induction by toll like receptor-4 (TLR4) through nuclear factor-kappaB (NF-kappaB) activation; free fatty acid-induced and TLR-mediated activation of c-Jun N-terminal kinase (JNK)-related pro-inflammatory pathways in CD11c+ immune cells; are effective in macrophage accumulation and in the development of adipose tissue inflammation. Old adipocytes are removed by macrophages through trogocytosis or sending an “eat me” signal. The obesity-induced changes in adipose tissue macrophage numbers are mainly due to increases in the triple-positive CD11b+ F4/80+ CD11c+ adipose tissue macrophage subpopulation. The ratio of M1-to-M2 macrophages is increased in obesity. Furthermore, hypoxia along with higher concentrations of free fatty acids exacerbates macrophage-mediated inflammation in obesity. The metabolic status of adipocytes is a major determinant of macrophage inflammatory output. Macrophage/adipocyte fatty-acid-binding proteins act at the interface of metabolic and inflammatory pathways. Both macrophages and adipocytes are the sites for active lipid metabolism and signaling.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   189.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   249.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  • Ahmad, R., P.K. Shihab, R. Thomas, M. Alghanim, A. Hasan, S. Sindhu, and K. Behbehani. 2015. Increased expression of the interleukin-1 receptor-associated kinase (IRAK)-1 is associated with adipose tissue inflammatory state in obesity. Diabetology and Metabolic Syndrome 7: 71. doi:10.1186/s13098-015-0067-7.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Arner, E., N. Mejhert, A. Kulyté, P.J. Balwierz, M. Pachkov, M. Cormont, S. Lorente-Cebrián, A. Ehrlund, J. Laurencikiene, P. Hedén, K. Dahlman-Wright, J.-F. Tanti, Y. Hayashizaki, M. Rydén, I. Dahlman, E. van Nimwegen, C.O. Daub, and P. Arner. 2012. Adipose tissue microRNAs as regulators of CCL2 production in human obesity. Diabetes 61: 1986–1993. doi:10.2337/db11-1508.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bassaganya-Riera, J., S. Misyak, A.J. Guri, and R. Hontecillas. 2009. PPAR gamma is highly expressed in F4/80(hi) adipose tissue macrophages and dampens adipose-tissue inflammation. Cellular Immunology 258: 138–146. doi:10.1016/j.cellimm.2009.04.003.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Benetti, E., F. Chiazza, N.S.A. Patel, and M. Collino. 2013. The NLRP3 Inflammasome as a novel player of the intercellular crosstalk in metabolic disorders. Mediators of Inflammation 2013: 678627. doi:10.1155/2013/678627.

    PubMed  PubMed Central  Google Scholar 

  • Bès-Houtmann, S., R. Roche, L. Hoareau, M.-P. Gonthier, F. Festy, H. Caillens, P. Gasque, C. Lefebvre d’Hellencourt, and M. Cesari. 2007. Presence of functional TLR2 and TLR4 on human adipocytes. Histochemistry and Cell Biology 127: 131–137. doi:10.1007/s00418-006-0230-1.

    Article  PubMed  CAS  Google Scholar 

  • Bing, C. 2015. Is interleukin-1β a culprit in macrophage-adipocyte crosstalk in obesity? Adipocytes 4: 149–152. doi:10.4161/21623945.2014.979661.

    Article  CAS  Google Scholar 

  • Bouhlel, M.A., B. Derudas, E. Rigamonti, R. Dièvart, J. Brozek, S. Haulon, C. Zawadzki, B. Jude, G. Torpier, N. Marx, B. Staels, and G. Chinetti-Gbaguidi. 2007. PPARgamma activation primes human monocytes into alternative M2 macrophages with anti-inflammatory properties. Cell Metabolism 6: 137–143. doi:10.1016/j.cmet.2007.06.010.

    Article  CAS  PubMed  Google Scholar 

  • Castoldi, A., C. Naffah de Souza, N.O.S. Câmara, and P.M. Moraes-Vieira. 2015. The macrophage switch in obesity development. Frontiers in Immunology 6: 637. doi:10.3389/fimmu.2015.00637.

    PubMed  Google Scholar 

  • Chang, H.R., H.J. Kim, X. Xu, and A.W. Ferrante. 2016. Macrophage and adipocyte IGF1 maintain adipose tissue homeostasis during metabolic stresses. Obesity (Silver Spring, Md.) 24: 172–183. doi:10.1002/oby.21354.

    Article  CAS  Google Scholar 

  • Charo, I.F. 2007. Macrophage polarization and insulin resistance: PPARgamma in control. Cell Metabolism 6: 96–98. doi:10.1016/j.cmet.2007.07.006.

    Article  CAS  PubMed  Google Scholar 

  • Charrière, G., B. Cousin, E. Arnaud, M. André, F. Bacou, L. Penicaud, and L. Casteilla. 2003. Preadipocyte conversion to macrophage. Evidence of plasticity. Journal of Biological Chemistry 278: 9850–9855. doi:10.1074/jbc.M210811200.

    Article  PubMed  CAS  Google Scholar 

  • Chawla, A., E.J. Schwarz, D.D. Dimaculangan, and M.A. Lazar. 1994. Peroxisome proliferator-activated receptor (PPAR) gamma: Adipose-predominant expression and induction early in adipocyte differentiation. Endocrinology 135: 798–800. doi:10.1210/endo.135.2.8033830.

    Article  CAS  PubMed  Google Scholar 

  • Chen, H., Y. Liu, D. Li, J. Song, and M. Xia. 2016. PGC-1β suppresses saturated fatty acid-induced macrophage inflammation by inhibiting TAK1 activation. IUBMB Life 68: 145–155. doi:10.1002/iub.1470.

    Article  CAS  PubMed  Google Scholar 

  • Choe, S.S., K.C. Shin, S. Ka, Y.K. Lee, J.-S. Chun, and J.B. Kim. 2014. Macrophage HIF-2α ameliorates adipose tissue inflammation and insulin resistance in obesity. Diabetes 63: 3359–3371. doi:10.2337/db13-1965.

    Article  CAS  PubMed  Google Scholar 

  • Cinti, S., G. Mitchell, G. Barbatelli, I. Murano, E. Ceresi, E. Faloia, S. Wang, M. Fortier, A.S. Greenberg, and M.S. Obin. 2005. Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. Journal of Lipid Research 46: 2347–2355. doi:10.1194/jlr.M500294-JLR200.

    Article  CAS  PubMed  Google Scholar 

  • Cousin, B., O. Munoz, M. Andre, A.M. Fontanilles, C. Dani, J.L. Cousin, P. Laharrague, L. Casteilla, and L. Pénicaud. 1999. A role for preadipocytes as macrophage-like cells. The FASEB Journal 13: 305–312.

    CAS  PubMed  Google Scholar 

  • Cutchins, A., D.B. Harmon, J.L. Kirby, A.C. Doran, S.N. Oldham, M. Skaflen, A.L. Klibanov, N. Meller, S.R. Keller, J. Garmey, and C.A. McNamara. 2012. Inhibitor of differentiation-3 mediates high fat diet-induced visceral fat expansion. Arteriosclerosis, Thrombosis, and Vascular Biology 32: 317–324. doi:10.1161/ATVBAHA.111.234856.

    Article  CAS  PubMed  Google Scholar 

  • Dalmas, E., A. Toubal, F. Alzaid, K. Blazek, H.L. Eames, K. Lebozec, M. Pini, I. Hainault, E. Montastier, R.G.P. Denis, P. Ancel, A. Lacombe, Y. Ling, O. Allatif, C. Cruciani-Guglielmacci, S. André, N. Viguerie, C. Poitou, V. Stich, A. Torcivia, F. Foufelle, S. Luquet, J. Aron-Wisnewsky, D. Langin, K. Clément, I.A. Udalova, and N. Venteclef. 2015. Irf5 deficiency in macrophages promotes beneficial adipose tissue expansion and insulin sensitivity during obesity. Nature Medicine 21: 610–618. doi:10.1038/nm.3829.

    Article  CAS  PubMed  Google Scholar 

  • Duvall, E., A.H. Wyllie, and R.G. Morris. 1985. Macrophage recognition of cells undergoing programmed cell death (apoptosis). Immunology 56: 351–358.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Eguchi, A., A. Mulya, M. Lazic, D. Radhakrishnan, M.P. Berk, D. Povero, A. Gornicka, and A.E. Feldstein. 2015. Microparticles release by adipocytes act as “find-me” signals to promote macrophage migration. PLoS One 10: e0123110. doi:10.1371/journal.pone.0123110.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Fjeldborg, K., S.B. Pedersen, H.J. Møller, T. Christiansen, M. Bennetzen, and B. Richelsen. 2014. Human adipose tissue macrophages are enhanced but changed to an anti-inflammatory profile in obesity. Journal of Immunology Research 2014: 309548. doi:10.1155/2014/309548.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Franckhauser, S., S. Muñoz, A. Pujol, A. Casellas, E. Riu, P. Otaegui, B. Su, and F. Bosch. 2002. Increased fatty acid re-esterification by PEPCK overexpression in adipose tissue leads to obesity without insulin resistance. Diabetes 51: 624–630.

    Article  CAS  PubMed  Google Scholar 

  • Fujisaka, S., I. Usui, A. Bukhari, M. Ikutani, T. Oya, Y. Kanatani, K. Tsuneyama, Y. Nagai, K. Takatsu, M. Urakaze, M. Kobayashi, and K. Tobe. 2009. Regulatory mechanisms for adipose tissue M1 and M2 macrophages in diet-induced obese mice. Diabetes 58: 2574–2582. doi:10.2337/db08-1475.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fujisaka, S., I. Usui, M. Ikutani, A. Aminuddin, A. Takikawa, K. Tsuneyama, A. Mahmood, N. Goda, Y. Nagai, K. Takatsu, and K. Tobe. 2013. Adipose tissue hypoxia induces inflammatory M1 polarity of macrophages in an HIF-1α-dependent and HIF-1α-independent manner in obese mice. Diabetologia 56: 1403–1412. doi:10.1007/s00125-013-2885-1.

    Article  CAS  PubMed  Google Scholar 

  • Furuhashi, M., and G.S. Hotamisligil. 2008. Fatty acid-binding proteins: Role in metabolic diseases and potential as drug targets. Nature Reviews Drug Discovery 7: 489–503. doi:10.1038/nrd2589.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Furuhashi, M., R. Fucho, C.Z. Görgün, G. Tuncman, H. Cao, and G.S. Hotamisligil. 2008. Adipocyte/macrophage fatty acid-binding proteins contribute to metabolic deterioration through actions in both macrophages and adipocytes in mice. The Journal of Clinical Investigation 118: 2640–2650. doi:10.1172/JCI34750.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Furukawa, S., T. Fujita, M. Shimabukuro, M. Iwaki, Y. Yamada, Y. Nakajima, O. Nakayama, M. Makishima, M. Matsuda, and I. Shimomura. 2004. Increased oxidative stress in obesity and its impact on metabolic syndrome. The Journal of Clinical Investigation 114: 1752–1761. doi:10.1172/JCI21625.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Furuoka, M., K.-I. Ozaki, D. Sadatomi, S. Mamiya, T. Yonezawa, S. Tanimura, and K. Takeda. 2016. TNF-α induces caspase-1 activation independently of simultaneously induced NLRP3 in 3T3-L1 cells. Journal of Cellular Physiology 231: 2761–2767. doi:10.1002/jcp.25385.

    Article  CAS  PubMed  Google Scholar 

  • Galván-Peña, S., and L.A.J. O’Neill. 2014. Metabolic reprograming in macrophage polarization. Frontiers in Immunology 5: 420. doi:10.3389/fimmu.2014.00420.

    PubMed  PubMed Central  Google Scholar 

  • Gao, D., M. Madi, C. Ding, M. Fok, T. Steele, C. Ford, L. Hunter, and C. Bing. 2014. Interleukin-1β mediates macrophage-induced impairment of insulin signaling in human primary adipocytes. American Journal of Physiology: Endocrinology and Metabolism 307: E289–E304. doi:10.1152/ajpendo.00430.2013.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Gordon, S., and P.R. Taylor. 2005. Monocyte and macrophage heterogeneity. Nature Reviews Immunology 5: 953–964. doi:10.1038/nri1733.

    Article  CAS  PubMed  Google Scholar 

  • Gurung, P., J.R. Lukens, and T.-D. Kanneganti. 2015. Mitochondria: Diversity in the regulation of the NLRP3 inflammasome. Trends in Molecular Medicine 21: 193–201. doi:10.1016/j.molmed.2014.11.008.

    Article  CAS  PubMed  Google Scholar 

  • Halberg, N., T. Khan, M.E. Trujillo, I. Wernstedt-Asterholm, A.D. Attie, S. Sherwani, Z.V. Wang, S. Landskroner-Eiger, S. Dineen, U.J. Magalang, R.A. Brekken, and P.E. Scherer. 2009. Hypoxia-inducible factor 1alpha induces fibrosis and insulin resistance in white adipose tissue. Molecular and Cellular Biology 29: 4467–4483. doi:10.1128/MCB.00192-09.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hanayama, R., M. Tanaka, K. Miwa, A. Shinohara, A. Iwamatsu, and S. Nagata. 2002. Identification of a factor that links apoptotic cells to phagocytes. Nature 417: 182–187. doi:10.1038/417182a.

    Article  CAS  PubMed  Google Scholar 

  • Hashimoto, D., J. Miller, and M. Merad. 2011. Dendritic cell and macrophage heterogeneity in vivo. Immunity 35: 323–335. doi:10.1016/j.immuni.2011.09.007.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Henegar, C., J. Tordjman, V. Achard, D. Lacasa, I. Cremer, M. Guerre-Millo, C. Poitou, A. Basdevant, V. Stich, N. Viguerie, D. Langin, P. Bedossa, J.-D. Zucker, and K. Clement. 2008. Adipose tissue transcriptomic signature highlights the pathological relevance of extracellular matrix in human obesity. Genome Biology 9: R14. doi:10.1186/gb-2008-9-1-r14.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Hsu, D.K., and F.-T. Liu. 2004. Regulation of cellular homeostasis by galectins. Glycoconjugate Journal 19: 507–515. doi:10.1023/B:GLYC.0000014080.95829.52.

    Article  PubMed  Google Scholar 

  • Huh, J.Y., Y.J. Park, M. Ham, and J.B. Kim. 2014. Crosstalk between adipocytes and immune cells in adipose tissue inflammation and metabolic dysregulation in obesity. Molecules and Cells 37: 365–371. doi:10.14348/molcells.2014.0074.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ichioka, M., T. Suganami, N. Tsuda, I. Shirakawa, Y. Hirata, N. Satoh-Asahara, Y. Shimoda, M. Tanaka, M. Kim-Saijo, Y. Miyamoto, Y. Kamei, M. Sata, and Y. Ogawa. 2011. Increased expression of macrophage-inducible C-type lectin in adipose tissue of obese mice and humans. Diabetes 60: 819–826. doi:10.2337/db10-0864.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ito, A., T. Suganami, A. Yamauchi, M. Degawa-Yamauchi, M. Tanaka, R. Kouyama, Y. Kobayashi, N. Nitta, K. Yasuda, Y. Hirata, W.A. Kuziel, M. Takeya, S. Kanegasaki, Y. Kamei, and Y. Ogawa. 2008. Role of CC chemokine receptor 2 in bone marrow cells in the recruitment of macrophages into obese adipose tissue. The Journal of Biological Chemistry 283: 35715–35723. doi:10.1074/jbc.M804220200.

    Article  CAS  PubMed  Google Scholar 

  • Juhas, U., M. Ryba-Stanisławowska, P. Szargiej, and J. Myśliwska. 2015. Different pathways of macrophage activation and polarization. Postepy Higieny i Medycyny Doswiadczalnej (Online) 69: 496–502. doi:10.5604/17322693.1150133.

    Article  Google Scholar 

  • Kanda, H., S. Tateya, Y. Tamori, K. Kotani, K. Hiasa, R. Kitazawa, S. Kitazawa, H. Miyachi, S. Maeda, K. Egashira, and M. Kasuga. 2006. MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity. The Journal of Clinical Investigation 116: 1494–1505. doi:10.1172/JCI26498.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kang, K., S.M. Reilly, V. Karabacak, M.R. Gangl, K. Fitzgerald, B. Hatano, and C.-H. Lee. 2008. Adipocyte-derived Th2 cytokines and myeloid PPARdelta regulate macrophage polarization and insulin sensitivity. Cell Metabolism 7: 485–495. doi:10.1016/j.cmet.2008.04.002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kaplan, J.L., M.A. Marshall, C.C. McSkimming, D.B. Harmon, J.C. Garmey, S.N. Oldham, P. Hallowell, and C.A. McNamara. 2015. Adipocyte progenitor cells initiate monocyte chemoattractant protein-1-mediated macrophage accumulation in visceral adipose tissue. Molecular Metabolism 4: 779–794. doi:10.1016/j.molmet.2015.07.010.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kawai, T., and S. Akira. 2007. TLR signaling. Seminars in Immunology 19: 24–32. doi:10.1016/j.smim.2006.12.004.

    Article  CAS  PubMed  Google Scholar 

  • Keuper, M., M. Blüher, M.R. Schön, P. Möller, A. Dzyakanchuk, K. Amrein, K.-M. Debatin, M. Wabitsch, and P. Fischer-Posovszky. 2011. An inflammatory micro-environment promotes human adipocyte apoptosis. Molecular and Cellular Endocrinology 339: 105–113. doi:10.1016/j.mce.2011.04.004.

    Article  CAS  PubMed  Google Scholar 

  • Kim, S.Y., E. Jeong, S.M. Joung, and J.Y. Lee. 2012. PI3K/Akt contributes to increased expression of Toll-like receptor 4 in macrophages exposed to hypoxic stress. Biochemical and Biophysical Research Communications 419: 466–471. doi:10.1016/j.bbrc.2012.02.015.

    Article  CAS  PubMed  Google Scholar 

  • Kosteli, A., E. Sugaru, G. Haemmerle, J.F. Martin, J. Lei, R. Zechner, and A.W. Ferrante. 2010. Weight loss and lipolysis promote a dynamic immune response in murine adipose tissue. The Journal of Clinical Investigation 120: 3466–3479. doi:10.1172/JCI42845.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Krahling, S., M.K. Callahan, P. Williamson, and R.A. Schlegel. 1999. Exposure of phosphatidylserine is a general feature in the phagocytosis of apoptotic lymphocytes by macrophages. Cell Death and Differentiation 6: 183–189. doi:10.1038/sj.cdd.4400473.

    Article  CAS  PubMed  Google Scholar 

  • Krausgruber, T., K. Blazek, T. Smallie, S. Alzabin, H. Lockstone, N. Sahgal, T. Hussell, M. Feldmann, and I.A. Udalova. 2011. IRF5 promotes inflammatory macrophage polarization and TH1-TH17 responses. Nature Immunology 12: 231–238. doi:10.1038/ni.1990.

    Article  CAS  PubMed  Google Scholar 

  • Kulyté, A., Y. Belarbi, S. Lorente-Cebrián, C. Bambace, E. Arner, C.O. Daub, P. Hedén, M. Rydén, N. Mejhert, and P. Arner. 2014. Additive effects of microRNAs and transcription factors on CCL2 production in human white adipose tissue. Diabetes 63: 1248–1258. doi:10.2337/db13-0702.

    Article  PubMed  CAS  Google Scholar 

  • Lee, B.-C., and J. Lee. 2014. Cellular and molecular players in adipose tissue inflammation in the development of obesity-induced insulin resistance. Biochimica et Biophysica Acta 1842: 446–462. doi:10.1016/j.bbadis.2013.05.017.

    Article  CAS  PubMed  Google Scholar 

  • Li, H.-B., C. Jin, Y. Chen, and R.A. Flavell. 2014. Inflammasome activation and metabolic disease progression. Cytokine & Growth Factor Reviews 25: 699–706. doi:10.1016/j.cytogfr.2014.07.020.

    Article  CAS  Google Scholar 

  • Lin, Y., H. Lee, A.H. Berg, M.P. Lisanti, L. Shapiro, and P.E. Scherer. 2000. The lipopolysaccharide-activated toll-like receptor (TLR)-4 induces synthesis of the closely related receptor TLR-2 in adipocytes. The Journal of Biological Chemistry 275: 24255–24263. doi:10.1074/jbc.M002137200.

    Article  CAS  PubMed  Google Scholar 

  • Lumeng, C.N., J.L. Bodzin, and A.R. Saltiel. 2007a. Obesity induces a phenotypic switch in adipose tissue macrophage polarization. The Journal of Clinical Investigation 117: 175–184. doi:10.1172/JCI29881.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lumeng, C.N., S.M. Deyoung, J.L. Bodzin, and A.R. Saltiel. 2007b. Increased inflammatory properties of adipose tissue macrophages recruited during diet-induced obesity. Diabetes 56: 16–23. doi:10.2337/db06-1076.

    Article  CAS  PubMed  Google Scholar 

  • Lumeng, C.N., S.M. Deyoung, and A.R. Saltiel. 2007c. Macrophages block insulin action in adipocytes by altering expression of signaling and glucose transport proteins. American Journal of Physiology: Endocrinology and Metabolism 292: E166–E174. doi:10.1152/ajpendo.00284.2006.

    CAS  PubMed  Google Scholar 

  • Lumeng, C.N., J.B. DelProposto, D.J. Westcott, and A.R. Saltiel. 2008. Phenotypic switching of adipose tissue macrophages with obesity is generated by spatiotemporal differences in macrophage subtypes. Diabetes 57: 3239–3246. doi:10.2337/db08-0872.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Makowski, L., and G.S. Hotamisligil. 2005. The role of fatty acid binding proteins in metabolic syndrome and atherosclerosis. Current Opinion in Lipidology 16: 543–548.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Makowski, L., J.B. Boord, K. Maeda, V.R. Babaev, K.T. Uysal, M.A. Morgan, R.A. Parker, J. Suttles, S. Fazio, G.S. Hotamisligil, and M.F. Linton. 2001. Lack of macrophage fatty-acid-binding protein aP2 protects mice deficient in apolipoprotein E against atherosclerosis. Nature Medicine 7: 699–705. doi:10.1038/89076.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Makowski, L., K.C. Brittingham, J.M. Reynolds, J. Suttles, and G.S. Hotamisligil. 2005. The fatty acid-binding protein, aP2, coordinates macrophage cholesterol trafficking and inflammatory activity. Macrophage expression of aP2 impacts peroxisome proliferator-activated receptor gamma and IkappaB kinase activities. The Journal of Biological Chemistry 280: 12888–12895. doi:10.1074/jbc.M413788200.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Malandrino, M.I., R. Fucho, M. Weber, M. Calderon-Dominguez, J.F. Mir, L. Valcarcel, X. Escoté, M. Gómez-Serrano, B. Peral, L. Salvadó, S. Fernández-Veledo, N. Casals, M. Vázquez-Carrera, F. Villarroya, J.J. Vendrell, D. Serra, and L. Herrero. 2015. Enhanced fatty acid oxidation in adipocytes and macrophages reduces lipid-induced triglyceride accumulation and inflammation. American Journal of Physiology: Endocrinology and Metabolism 308: E756–E769. doi:10.1152/ajpendo.00362.2014.

    PubMed  Google Scholar 

  • Martin, S.J., D.M. Finucane, G.P. Amarante-Mendes, G.A. O’Brien, and D.R. Green. 1996. Phosphatidylserine externalization during CD95-induced apoptosis of cells and cytoplasts requires ICE/CED-3 protease activity. The Journal of Biological Chemistry 271: 28753–28756.

    Article  CAS  PubMed  Google Scholar 

  • Masoodi, M., O. Kuda, M. Rossmeisl, P. Flachs, and J. Kopecky. 2015. Lipid signaling in adipose tissue: Connecting inflammation & metabolism. Biochimica et Biophysica Acta 1851: 503–518. doi:10.1016/j.bbalip.2014.09.023.

    Article  CAS  PubMed  Google Scholar 

  • McNelis, J.C., and J.M. Olefsky. 2014. Macrophages, immunity, and metabolic disease. Immunity 41: 36–48. doi:10.1016/j.immuni.2014.05.010.

    Article  CAS  PubMed  Google Scholar 

  • Miyanishi, M., K. Tada, M. Koike, Y. Uchiyama, T. Kitamura, and S. Nagata. 2007. Identification of Tim4 as a phosphatidylserine receptor. Nature 450: 435–439. doi:10.1038/nature06307.

    Article  CAS  PubMed  Google Scholar 

  • Murdoch, C., A. Giannoudis, and C.E. Lewis. 2004. Mechanisms regulating the recruitment of macrophages into hypoxic areas of tumors and other ischemic tissues. Blood 104: 2224–2234. doi:10.1182/blood-2004-03-1109.

    Article  CAS  PubMed  Google Scholar 

  • Neacsu, O., K. Cleveland, H. Xu, T.T. Tchkonia, J.L. Kirkland, and C.M. Boney. 2013. IGF-I attenuates FFA-induced activation of JNK1 phosphorylation and TNFα expression in human subcutaneous preadipocytes. Obesity (Silver Spring, Md.) 21: 1843–1849. doi:10.1002/oby.20329.

    CAS  Google Scholar 

  • Nguyen, M.T.A., S. Favelyukis, A.-K. Nguyen, D. Reichart, P.A. Scott, A. Jenn, R. Liu-Bryan, C.K. Glass, J.G. Neels, and J.M. Olefsky. 2007. 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. The Journal of Biological Chemistry 282: 35279–35292. doi:10.1074/jbc.M706762200.

    Article  CAS  PubMed  Google Scholar 

  • Nishimura, S., I. Manabe, M. Nagasaki, Y. Hosoya, H. Yamashita, H. Fujita, M. Ohsugi, K. Tobe, T. Kadowaki, R. Nagai, and S. Sugiura. 2007. Adipogenesis in obesity requires close interplay between differentiating adipocytes, stromal cells, and blood vessels. Diabetes 56: 1517–1526. doi:10.2337/db06-1749.

    Article  CAS  PubMed  Google Scholar 

  • Norton, J.D. 2000. ID helix-loop-helix proteins in cell growth, differentiation and tumorigenesis. Journal of Cell Science 113(Pt 22): 3897–3905.

    CAS  PubMed  Google Scholar 

  • O’Rourke, R.W., M.D. Metcalf, A.E. White, A. Madala, B.R. Winters, I.I. Maizlin, B.A. Jobe, C.T. Roberts, M.K. Slifka, and D.L. Marks. 2009. Depot-specific differences in inflammatory mediators and a role for NK cells and IFN-gamma in inflammation in human adipose tissue. International Journal of Obesity 2005(33): 978–990. doi:10.1038/ijo.2009.133.

    Article  CAS  Google Scholar 

  • Odegaard, J.I., R.R. Ricardo-Gonzalez, M.H. Goforth, C.R. Morel, V. Subramanian, L. Mukundan, A. Red Eagle, D. Vats, F. Brombacher, A.W. Ferrante, and A. Chawla. 2007. Macrophage-specific PPARgamma controls alternative activation and improves insulin resistance. Nature 447: 1116–1120. doi:10.1038/nature05894.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Olefsky, J.M., and C.K. Glass. 2010. Macrophages, inflammation, and insulin resistance. Annual Review of Physiology 72: 219–246. doi:10.1146/annurev-physiol-021909-135846.

    Article  CAS  PubMed  Google Scholar 

  • Ortega, F.J., M. Moreno, J.M. Mercader, J.M. Moreno-Navarrete, N. Fuentes-Batllevell, M. Sabater, W. Ricart, and J.M. Fernández-Real. 2015. Inflammation triggers specific microRNA profiles in human adipocytes and macrophages and in their supernatants. Clinical Epigenetics 7: 49. doi:10.1186/s13148-015-0083-3.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Pasarica, M., O.R. Sereda, L.M. Redman, D.C. Albarado, D.T. Hymel, L.E. Roan, J.C. Rood, D.H. Burk, and S.R. Smith. 2009. Reduced adipose tissue oxygenation in human obesity: Evidence for rarefaction, macrophage chemotaxis, and inflammation without an angiogenic response. Diabetes 58: 718–725. doi:10.2337/db08-1098.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Patsouris, D., P.-P. Li, D. Thapar, J. Chapman, J.M. Olefsky, and J.G. Neels. 2008. Ablation of CD11c-positive cells normalizes insulin sensitivity in obese insulin resistant animals. Cell Metabolism 8: 301–309. doi:10.1016/j.cmet.2008.08.015.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pelton, P.D., L. Zhou, K.T. Demarest, and T.P. Burris. 1999. PPARgamma activation induces the expression of the adipocyte fatty acid binding protein gene in human monocytes. Biochemical and Biophysical Research Communications 261: 456–458. doi:10.1006/bbrc.1999.1071.

    Article  CAS  PubMed  Google Scholar 

  • Poursharifi, P., M. Lapointe, D. Pétrin, D. Devost, D. Gauvreau, T.E. Hébert, and K. Cianflone. 2013. C5L2 and C5aR interaction in adipocytes and macrophages: Insights into adipoimmunology. Cellular Signalling 25: 910–918. doi:10.1016/j.cellsig.2012.12.010.

    Article  CAS  PubMed  Google Scholar 

  • Prieur, X., C.Y.L. Mok, V.R. Velagapudi, V. Núñez, L. Fuentes, D. Montaner, K. Ishikawa, A. Camacho, N. Barbarroja, S. O’Rahilly, J.K. Sethi, J. Dopazo, M. Orešič, M. Ricote, and A. Vidal-Puig. 2011. Differential lipid partitioning between adipocytes and tissue macrophages modulates macrophage lipotoxicity and M2/M1 polarization in obese mice. Diabetes 60: 797–809. doi:10.2337/db10-0705.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rocha, V.Z., E.J. Folco, G. Sukhova, K. Shimizu, I. Gotsman, A.H. Vernon, and P. Libby. 2008. Interferon-gamma, a Th1 cytokine, regulates fat inflammation: A role for adaptive immunity in obesity. Circulation Research 103: 467–476. doi:10.1161/CIRCRESAHA.108.177105.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sano, H., D.K. Hsu, L. Yu, J.R. Apgar, I. Kuwabara, T. Yamanaka, M. Hirashima, and F.T. Liu. 2000. Human galectin-3 is a novel chemoattractant for monocytes and macrophages. Journal of Immunology (Baltimore, Md.) 1950(165): 2156–2164.

    Google Scholar 

  • Sartipy, P., and D.J. Loskutoff. 2003. Monocyte chemoattractant protein 1 in obesity and insulin resistance. Proceedings of the National Academy of Sciences of the United States of America 100: 7265–7270. doi:10.1073/pnas.1133870100.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sárvári, A.K., Q.-M. Doan-Xuan, Z. Bacsó, I. Csomós, Z. Balajthy, and L. Fésüs. 2015. Interaction of differentiated human adipocytes with macrophages leads to trogocytosis and selective IL-6 secretion. Cell Death & Disease 6: e1613. doi:10.1038/cddis.2014.579.

    Article  CAS  Google Scholar 

  • Satoh, T., O. Takeuchi, A. Vandenbon, K. Yasuda, Y. Tanaka, Y. Kumagai, T. Miyake, K. Matsushita, T. Okazaki, T. Saitoh, K. Honma, T. Matsuyama, K. Yui, T. Tsujimura, D.M. Standley, K. Nakanishi, K. Nakai, and S. Akira. 2010. The Jmjd3-Irf4 axis regulates M2 macrophage polarization and host responses against helminth infection. Nature Immunology 11: 936–944. doi:10.1038/ni.1920.

    Article  CAS  PubMed  Google Scholar 

  • Skinner, A.C., M.J. Steiner, F.W. Henderson, and E.M. Perrin. 2010. Multiple markers of inflammation and weight status: Cross-sectional analyses throughout childhood. Pediatrics 125: e801–e809. doi:10.1542/peds.2009-2182.

    Article  PubMed  PubMed Central  Google Scholar 

  • Snodgrass, R.G., M. Boß, E. Zezina, A. Weigert, N. Dehne, I. Fleming, B. Brüne, and D. Namgaladze. 2016. Hypoxia potentiates palmitate-induced pro-inflammatory activation of primary human macrophages. The Journal of Biological Chemistry 291: 413–424. doi:10.1074/jbc.M115.686709.

    Article  CAS  PubMed  Google Scholar 

  • Solinas, G., and M. Karin. 2010. JNK1 and IKKbeta: Molecular links between obesity and metabolic dysfunction. The FASEB Journal 24: 2596–2611. doi:10.1096/fj.09-151340.

    Article  CAS  PubMed  Google Scholar 

  • Spalding, K.L., E. Arner, P.O. Westermark, S. Bernard, B.A. Buchholz, O. Bergmann, L. Blomqvist, J. Hoffstedt, E. Näslund, T. Britton, H. Concha, M. Hassan, M. Rydén, J. Frisén, and P. Arner. 2008. Dynamics of fat cell turnover in humans. Nature 453: 783–787. doi:10.1038/nature06902.

    Article  CAS  PubMed  Google Scholar 

  • Spencer, M., A. Yao-Borengasser, R. Unal, N. Rasouli, C.M. Gurley, B. Zhu, C.A. Peterson, and P.A. Kern. 2010. Adipose tissue macrophages in insulin-resistant subjects are associated with collagen VI and fibrosis and demonstrate alternative activation. American Journal of Physiology: Endocrinology and Metabolism 299: E1016–E1027. doi:10.1152/ajpendo.00329.2010.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Stienstra, R., L.A.B. Joosten, T. Koenen, B. van Tits, J.A. van Diepen, S.A.A. van den Berg, P.C.N. Rensen, P.J. Voshol, G. Fantuzzi, A. Hijmans, S. Kersten, M. Müller, W.B. van den Berg, N. van Rooijen, M. Wabitsch, B.-J. Kullberg, J.W.M. van der Meer, T. Kanneganti, C.J. Tack, and M.G. Netea. 2010. The inflammasome-mediated caspase-1 activation controls adipocyte differentiation and insulin sensitivity. Cell Metabolism 12: 593–605. doi:10.1016/j.cmet.2010.11.011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stienstra, R., J.A. van Diepen, C.J. Tack, M.H. Zaki, F.L. van de Veerdonk, D. Perera, G.A. Neale, G.J. Hooiveld, A. Hijmans, I. Vroegrijk, S. van den Berg, J. Romijn, P.C.N. Rensen, L.A.B. Joosten, M.G. Netea, and T.-D. Kanneganti. 2011. Inflammasome is a central player in the induction of obesity and insulin resistance. Proceedings of the National Academy of Sciences of the United States of America 108: 15324–15329. doi:10.1073/pnas.1100255108.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • St-Pierre, J., J. Lin, S. Krauss, P.T. Tarr, R. Yang, C.B. Newgard, and B.M. Spiegelman. 2003. Bioenergetic analysis of peroxisome proliferator-activated receptor gamma coactivators 1alpha and 1beta (PGC-1alpha and PGC-1beta) in muscle cells. The Journal of Biological Chemistry 278: 26597–26603. doi:10.1074/jbc.M301850200.

    Article  CAS  PubMed  Google Scholar 

  • Strissel, K.J., Z. Stancheva, H. Miyoshi, J.W. Perfield, J. DeFuria, Z. Jick, A.S. Greenberg, and M.S. Obin. 2007. Adipocyte death, adipose tissue remodeling, and obesity complications. Diabetes 56: 2910–2918. doi:10.2337/db07-0767.

    Article  CAS  PubMed  Google Scholar 

  • Suganami, T., J. Nishida, and Y. Ogawa. 2005. A paracrine loop between adipocytes and macrophages aggravates inflammatory changes: Role of free fatty acids and tumor necrosis factor alpha. Arteriosclerosis, Thrombosis, and Vascular Biology 25: 2062–2068. doi:10.1161/01.ATV.0000183883.72263.13.

    Article  CAS  PubMed  Google Scholar 

  • Suganami, T., K. Tanimoto-Koyama, J. Nishida, M. Itoh, X. Yuan, S. Mizuarai, H. Kotani, S. Yamaoka, K. Miyake, S. Aoe, Y. Kamei, and Y. Ogawa. 2007. Role of the Toll-like receptor 4/NF-kappaB pathway in saturated fatty acid-induced inflammatory changes in the interaction between adipocytes and macrophages. Arteriosclerosis, Thrombosis, and Vascular Biology 27: 84–91. doi:10.1161/01.ATV.0000251608.09329.9a.

    Article  CAS  PubMed  Google Scholar 

  • Sun, K., C.M. Kusminski, and P.E. Scherer. 2011. Adipose tissue remodeling and obesity. The Journal of Clinical Investigation 121: 2094–2101. doi:10.1172/JCI45887.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Takahashi, K., S. Mizuarai, H. Araki, S. Mashiko, A. Ishihara, A. Kanatani, H. Itadani, and H. Kotani. 2003. Adiposity elevates plasma MCP-1 levels leading to the increased CD11b-positive monocytes in mice. The Journal of Biological Chemistry 278: 46654–46660. doi:10.1074/jbc.M309895200.

    Article  CAS  PubMed  Google Scholar 

  • Tateya, S., F. Kim, and Y. Tamori. 2013. Recent advances in obesity-induced inflammation and insulin resistance. Frontiers in Endocrinology 4: 93. doi:10.3389/fendo.2013.00093.

    Article  PubMed  PubMed Central  Google Scholar 

  • Thompson, B.R., S. Lobo, and D.A. Bernlohr. 2010. Fatty acid flux in adipocytes: The in’s and out’s of fat cell lipid trafficking. Molecular and Cellular Endocrinology 318: 24–33. doi:10.1016/j.mce.2009.08.015.

    Article  CAS  PubMed  Google Scholar 

  • Toda, S., R. Hanayama, and S. Nagata. 2012. Two-step engulfment of apoptotic cells. Molecular and Cellular Biology 32: 118–125. doi:10.1128/MCB.05993-11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tom, F.-Q., D. Gauvreau, M. Lapointe, H. Lu, P. Poursharifi, X.-P. Luo, and K. Cianflone. 2013. Differential chemoattractant response in adipocytes and macrophages to the action of acylation stimulating protein. European Journal of Cell Biology 92: 61–69. doi:10.1016/j.ejcb.2012.10.005.

    Article  CAS  PubMed  Google Scholar 

  • Tontonoz, P., E. Hu, R.A. Graves, A.I. Budavari, and B.M. Spiegelman. 1994. mPPAR gamma 2: Tissue-specific regulator of an adipocyte enhancer. Genes & Development 8: 1224–1234.

    Article  CAS  Google Scholar 

  • Vandanmagsar, B., Y.-H. Youm, A. Ravussin, J.E. Galgani, K. Stadler, R.L. Mynatt, E. Ravussin, J.M. Stephens, and V.D. Dixit. 2011. The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance. Nature Medicine 17: 179–188. doi:10.1038/nm.2279.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vats, D., L. Mukundan, J.I. Odegaard, L. Zhang, K.L. Smith, C.R. Morel, R.A. Wagner, D.R. Greaves, P.J. Murray, and A. Chawla. 2006. Oxidative metabolism and PGC-1beta attenuate macrophage-mediated inflammation. Cell Metabolism 4: 13–24. doi:10.1016/j.cmet.2006.05.011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vlaicu, S.I., A. Tatomir, D. Boodhoo, S. Vesa, P.A. Mircea, and H. Rus. 2016. The role of complement system in adipose tissue-related inflammation. Immunologic Research 64: 653–664. doi:10.1007/s12026-015-8783-5.

    Article  CAS  PubMed  Google Scholar 

  • Wang, P.-X., X.-J. Zhang, P. Luo, X. Jiang, P. Zhang, J. Guo, G.-N. Zhao, X. Zhu, Y. Zhang, S. Yang, and H. Li. 2016. Hepatocyte TRAF3 promotes liver steatosis and systemic insulin resistance through targeting TAK1-dependent signalling. Nature Communications 7: 10592. doi:10.1038/ncomms10592.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Weisberg, S.P., D. McCann, M. Desai, M. Rosenbaum, R.L. Leibel, and A.W. Ferrante. 2003. Obesity is associated with macrophage accumulation in adipose tissue. The Journal of Clinical Investigation 112: 1796–1808. doi:10.1172/JCI19246.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Weisberg, S.P., D. Hunter, R. Huber, J. Lemieux, S. Slaymaker, K. Vaddi, I. Charo, R.L. Leibel, and A.W. Ferrante. 2006. CCR2 modulates inflammatory and metabolic effects of high-fat feeding. The Journal of Clinical Investigation 116: 115–124. doi:10.1172/JCI24335.

    Article  CAS  PubMed  Google Scholar 

  • Wellen, K.E., and G.S. Hotamisligil. 2003. Obesity-induced inflammatory changes in adipose tissue. The Journal of Clinical Investigation 112: 1785–1788. doi:10.1172/JCI20514.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wensveen, F.M., S. Valentić, M. Šestan, T. Turk Wensveen, and B. Polić. 2015. The “Big Bang” in obese fat: Events initiating obesity-induced adipose tissue inflammation. European Journal of Immunology 45: 2446–2456. doi:10.1002/eji.201545502.

    Article  CAS  PubMed  Google Scholar 

  • Wentworth, J.M., G. Naselli, W.A. Brown, L. Doyle, B. Phipson, G.K. Smyth, M. Wabitsch, P.E. O’Brien, and L.C. Harrison. 2010. Pro-inflammatory CD11c+CD206+ adipose tissue macrophages are associated with insulin resistance in human obesity. Diabetes 59: 1648–1656. doi:10.2337/db09-0287.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wolowczuk, I., C. Verwaerde, O. Viltart, A. Delanoye, M. Delacre, B. Pot, and C. Grangette. 2008. Feeding our immune system: Impact on metabolism. Clinical & Developmental Immunology 2008: 639803. doi:10.1155/2008/639803.

    Article  Google Scholar 

  • Yin, R., L. Fang, Y. Li, P. Xue, Y. Li, Y. Guan, Y. Chang, C. Chen, and N. Wang. 2015. Pro-inflammatory Macrophages suppress PPARγ activity in Adipocytes via S-nitrosylation. Free Radical Biology & Medicine 89: 895–905. doi:10.1016/j.freeradbiomed.2015.10.406.

    Article  CAS  Google Scholar 

  • Zheng, C., Q. Yang, J. Cao, N. Xie, K. Liu, P. Shou, F. Qian, Y. Wang, and Y. Shi. 2016. Local proliferation initiates macrophage accumulation in adipose tissue during obesity. Cell Death & Disease 7: e2167. doi:10.1038/cddis.2016.54.

    Article  CAS  Google Scholar 

  • Zhou, R., A.S. Yazdi, P. Menu, and J. Tschopp. 2011. A role for mitochondria in NLRP3 inflammasome activation. Nature 469: 221–225. doi:10.1038/nature09663.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Faculty of Pharmacy, Department of Toxicology, Gazi University, Hipodrom, Ankara, Turkey

    Ayse Basak Engin Ph.D., Ph.D.

Authors
  1. Ayse Basak Engin Ph.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ayse Basak Engin Ph.D., Ph.D. .

Editor information

Editors and Affiliations

  1. Faculty of Pharmacy, Department of Toxicology, Gazi University, Hipodrom, Ankara, Turkey

    Ayse Basak Engin

  2. Faculty of Medicine, Department of General Surgery, Gazi University, Besevler, Ankara, Turkey

    Atilla Engin

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing AG

About this chapter

Cite this chapter

Engin, A.B. (2017). Adipocyte-Macrophage Cross-Talk in Obesity. In: Engin, A., Engin, A. (eds) Obesity and Lipotoxicity. Advances in Experimental Medicine and Biology, vol 960. Springer, Cham. https://doi.org/10.1007/978-3-319-48382-5_14

Download citation

Publish with us

Policies and ethics

Search

Navigation