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Published in: Diabetologia 5/2016

Open Access 01-05-2016 | Review

Adipose tissue macrophages: going off track during obesity

Authors: Lily Boutens, Rinke Stienstra

Published in: Diabetologia | Issue 5/2016

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Abstract

Inflammation originating from the adipose tissue is considered to be one of the main driving forces for the development of insulin resistance and type 2 diabetes in obese individuals. Although a plethora of different immune cells shapes adipose tissue inflammation, this review is specifically focused on the contribution of macrophages that reside in adipose tissue in lean and obese conditions. Both conventional and tissue-specific functions of adipose tissue macrophages (ATMs) in lean and obese adipose tissue are discussed and linked with metabolic and inflammatory changes that occur during the development of obesity. Furthermore, we will address various circulating and adipose tissue-derived triggers that may be involved in shaping the ATM phenotype and underlie ATM function in lean and obese conditions. Finally, we will highlight how these changes affect adipose tissue inflammation and may be targeted for therapeutic interventions to improve insulin sensitivity in obese individuals.
Highlights
• Macrophages play a significant role in regulating adipose tissue functioning during health and disease
• In addition to conventional functions such as clearing cellular debris and participating in tissue immune surveillance, lipid buffering is an important function of ATMs
• Obesity-induced inflammation, characterised by an elevated number of proinflammatory macrophages in adipose tissue, has been suggested to contribute to systemic insulin resistance
• Their origin, as well as a combination of peripheral changes and adipose tissue-derived stressors, probably contribute to ATM dysfunction and inflammatory traits during obesity
• Identification of transcriptional differences between ATMs from lean vs obese adipose tissue at several key points during the development of obesity and insulin resistance may reveal upstream triggers, regulatory factors and intracellular pathways that shape ATM function
• Targeting metabolic capacity rather than the inflammatory phenotype of ATMs may hold potential to restore ATM function and adipose tissue homeostasis in obese individuals
Literature
1.
go back to reference Shoelson SE, Herrero L, Naaz A (2007) Obesity, inflammation, and insulin resistance. Gastroenterology 132:2169–2180PubMedCrossRef Shoelson SE, Herrero L, Naaz A (2007) Obesity, inflammation, and insulin resistance. Gastroenterology 132:2169–2180PubMedCrossRef
2.
go back to reference Wild S, Roglic G, Green A, Sicree R, King H (2004) Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care 27:1047–1053PubMedCrossRef Wild S, Roglic G, Green A, Sicree R, King H (2004) Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care 27:1047–1053PubMedCrossRef
3.
go back to reference Trayhurn P, Wood IS (2004) Adipokines: inflammation and the pleiotropic role of white adipose tissue. Br J Nutr 92:347–355PubMedCrossRef Trayhurn P, Wood IS (2004) Adipokines: inflammation and the pleiotropic role of white adipose tissue. Br J Nutr 92:347–355PubMedCrossRef
4.
5.
go back to reference Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW Jr (2003) Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 112:1796–1808PubMedPubMedCentralCrossRef Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW Jr (2003) Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 112:1796–1808PubMedPubMedCentralCrossRef
6.
go back to reference Gericke M, Weyer U, Braune J, Bechmann I, Eilers J (2015) A method for long-term live imaging of tissue macrophages in adipose tissue explants. Am J Physiol Endocrinol Metab 308:E1023–E1033PubMedCrossRef Gericke M, Weyer U, Braune J, Bechmann I, Eilers J (2015) A method for long-term live imaging of tissue macrophages in adipose tissue explants. Am J Physiol Endocrinol Metab 308:E1023–E1033PubMedCrossRef
7.
go back to reference Lumeng CN, Deyoung SM, Bodzin JL, Saltiel AR (2007) Increased inflammatory properties of adipose tissue macrophages recruited during diet-induced obesity. Diabetes 56:16–23PubMedCrossRef Lumeng CN, Deyoung SM, Bodzin JL, Saltiel AR (2007) Increased inflammatory properties of adipose tissue macrophages recruited during diet-induced obesity. Diabetes 56:16–23PubMedCrossRef
8.
go back to reference Lumeng CN, DelProposto JB, Westcott DJ, Saltiel AR (2008) Phenotypic switching of adipose tissue macrophages with obesity is generated by spatiotemporal differences in macrophage subtypes. Diabetes 57:3239–3246PubMedPubMedCentralCrossRef Lumeng CN, DelProposto JB, Westcott DJ, Saltiel AR (2008) Phenotypic switching of adipose tissue macrophages with obesity is generated by spatiotemporal differences in macrophage subtypes. Diabetes 57:3239–3246PubMedPubMedCentralCrossRef
9.
go back to reference Cinti S, Mitchell G, Barbatelli G et al (2005) Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. J Lipid Res 46:2347–2355PubMedCrossRef Cinti S, Mitchell G, Barbatelli G et al (2005) Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. J Lipid Res 46:2347–2355PubMedCrossRef
10.
go back to reference Murano I, Barbatelli G, Parisani V et al (2008) Dead adipocytes, detected as crown-like structures, are prevalent in visceral fat depots of genetically obese mice. J Lipid Res 49:1562–1568PubMedCrossRef Murano I, Barbatelli G, Parisani V et al (2008) Dead adipocytes, detected as crown-like structures, are prevalent in visceral fat depots of genetically obese mice. J Lipid Res 49:1562–1568PubMedCrossRef
11.
go back to reference Lee YS, Li P, Huh JY et al (2011) Inflammation is necessary for long-term but not short-term high-fat diet-induced insulin resistance. Diabetes 60:2474–2483PubMedPubMedCentralCrossRef Lee YS, Li P, Huh JY et al (2011) Inflammation is necessary for long-term but not short-term high-fat diet-induced insulin resistance. Diabetes 60:2474–2483PubMedPubMedCentralCrossRef
12.
13.
go back to reference Xu H, Barnes GT, Yang Q et al (2003) Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest 112:1821–1830PubMedPubMedCentralCrossRef Xu H, Barnes GT, Yang Q et al (2003) Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest 112:1821–1830PubMedPubMedCentralCrossRef
14.
go back to reference Stefanovic-Racic M, Yang X, Turner MS et al (2012) Dendritic cells promote macrophage infiltration and comprise a substantial proportion of obesity-associated increases in CD11c+ cells in adipose tissue and liver. Diabetes 61:2330–2339PubMedPubMedCentralCrossRef Stefanovic-Racic M, Yang X, Turner MS et al (2012) Dendritic cells promote macrophage infiltration and comprise a substantial proportion of obesity-associated increases in CD11c+ cells in adipose tissue and liver. Diabetes 61:2330–2339PubMedPubMedCentralCrossRef
15.
go back to reference Liu J, Divoux A, Sun J et al (2009) Genetic deficiency and pharmacological stabilization of mast cells reduce diet-induced obesity and diabetes in mice. Nat Med 15:940–945PubMedPubMedCentralCrossRef Liu J, Divoux A, Sun J et al (2009) Genetic deficiency and pharmacological stabilization of mast cells reduce diet-induced obesity and diabetes in mice. Nat Med 15:940–945PubMedPubMedCentralCrossRef
16.
go back to reference Talukdar S, da Oh Y, Bandyopadhyay G et al (2012) Neutrophils mediate insulin resistance in mice fed a high-fat diet through secreted elastase. Nat Med 18:1407–1412PubMedPubMedCentralCrossRef Talukdar S, da Oh Y, Bandyopadhyay G et al (2012) Neutrophils mediate insulin resistance in mice fed a high-fat diet through secreted elastase. Nat Med 18:1407–1412PubMedPubMedCentralCrossRef
17.
go back to reference Winer DA, Winer S, Shen L et al (2011) B cells promote insulin resistance through modulation of T cells and production of pathogenic IgG antibodies. Nat Med 17:610–617PubMedPubMedCentralCrossRef Winer DA, Winer S, Shen L et al (2011) B cells promote insulin resistance through modulation of T cells and production of pathogenic IgG antibodies. Nat Med 17:610–617PubMedPubMedCentralCrossRef
18.
go back to reference DeFuria J, Belkina AC, Jagannathan-Bogdan M et al (2013) B cells promote inflammation in obesity and type 2 diabetes through regulation of T cell function and an inflammatory cytokine profile. Proc Natl Acad Sci U S A 110:5133–5138PubMedPubMedCentralCrossRef DeFuria J, Belkina AC, Jagannathan-Bogdan M et al (2013) B cells promote inflammation in obesity and type 2 diabetes through regulation of T cell function and an inflammatory cytokine profile. Proc Natl Acad Sci U S A 110:5133–5138PubMedPubMedCentralCrossRef
19.
go back to reference Rausch ME, Weisberg S, Vardhana P, Tortoriello DV (2008) Obesity in C57BL/6J mice is characterized by adipose tissue hypoxia and cytotoxic T cell infiltration. Int J Obes 32:451–463CrossRef Rausch ME, Weisberg S, Vardhana P, Tortoriello DV (2008) Obesity in C57BL/6J mice is characterized by adipose tissue hypoxia and cytotoxic T cell infiltration. Int J Obes 32:451–463CrossRef
21.
go back to reference Lynch L, Nowak M, Varghese B et al (2012) Adipose tissue invariant NKT cells protect against diet-induced obesity and metabolic disorder through regulatory cytokine production. Immunity 37:574–587PubMedCrossRef Lynch L, Nowak M, Varghese B et al (2012) Adipose tissue invariant NKT cells protect against diet-induced obesity and metabolic disorder through regulatory cytokine production. Immunity 37:574–587PubMedCrossRef
22.
go back to reference Kintscher U, Hartge M, Hess K et al (2008) T-lymphocyte infiltration in visceral adipose tissue: a primary event in adipose tissue inflammation and the development of obesity-mediated insulin resistance. Arterioscler Thromb Vasc Biol 28:1304–1310PubMedCrossRef Kintscher U, Hartge M, Hess K et al (2008) T-lymphocyte infiltration in visceral adipose tissue: a primary event in adipose tissue inflammation and the development of obesity-mediated insulin resistance. Arterioscler Thromb Vasc Biol 28:1304–1310PubMedCrossRef
23.
go back to reference Feuerer M, Herrero L, Cipolletta D et al (2009) Lean, but not obese, fat is enriched for a unique population of regulatory T cells that affect metabolic parameters. Nat Med 15:930–939PubMedPubMedCentralCrossRef Feuerer M, Herrero L, Cipolletta D et al (2009) Lean, but not obese, fat is enriched for a unique population of regulatory T cells that affect metabolic parameters. Nat Med 15:930–939PubMedPubMedCentralCrossRef
25.
go back to reference Cildir G, Akincilar SC, Tergaonkar V (2013) Chronic adipose tissue inflammation: all immune cells on the stage. Trends Mol Med 19:487–500PubMedCrossRef Cildir G, Akincilar SC, Tergaonkar V (2013) Chronic adipose tissue inflammation: all immune cells on the stage. Trends Mol Med 19:487–500PubMedCrossRef
27.
28.
go back to reference Kerr JF, Wyllie AH, Currie AR (1972) Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 26:239–257PubMedPubMedCentralCrossRef Kerr JF, Wyllie AH, Currie AR (1972) Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 26:239–257PubMedPubMedCentralCrossRef
29.
30.
go back to reference Spalding KL, Arner E, Westermark PO et al (2008) Dynamics of fat cell turnover in humans. Nature 453:783–787PubMedCrossRef Spalding KL, Arner E, Westermark PO et al (2008) Dynamics of fat cell turnover in humans. Nature 453:783–787PubMedCrossRef
31.
go back to reference Strawford A, Antelo F, Christiansen M, Hellerstein MK (2004) Adipose tissue triglyceride turnover, de novo lipogenesis, and cell proliferation in humans measured with 2H2O. Am J Physiol Endocrinol Metab 286:E577–E588PubMedCrossRef Strawford A, Antelo F, Christiansen M, Hellerstein MK (2004) Adipose tissue triglyceride turnover, de novo lipogenesis, and cell proliferation in humans measured with 2H2O. Am J Physiol Endocrinol Metab 286:E577–E588PubMedCrossRef
32.
go back to reference Hirsch J, Batchelor B (1976) Adipose tissue cellularity in human obesity. Clin Endocrinol Metab 5:299–311PubMedCrossRef Hirsch J, Batchelor B (1976) Adipose tissue cellularity in human obesity. Clin Endocrinol Metab 5:299–311PubMedCrossRef
33.
go back to reference Fischer-Posovszky P, Wang QA, Asterholm IW, Rutkowski JM, Scherer PE (2011) Targeted deletion of adipocytes by apoptosis leads to adipose tissue recruitment of alternatively activated M2 macrophages. Endocrinology 152:3074–3081PubMedPubMedCentralCrossRef Fischer-Posovszky P, Wang QA, Asterholm IW, Rutkowski JM, Scherer PE (2011) Targeted deletion of adipocytes by apoptosis leads to adipose tissue recruitment of alternatively activated M2 macrophages. Endocrinology 152:3074–3081PubMedPubMedCentralCrossRef
34.
35.
go back to reference Kosteli A, Sugaru E, Haemmerle G et al (2010) Weight loss and lipolysis promote a dynamic immune response in murine adipose tissue. J Clin Invest 120:3466–3479PubMedPubMedCentralCrossRef Kosteli A, Sugaru E, Haemmerle G et al (2010) Weight loss and lipolysis promote a dynamic immune response in murine adipose tissue. J Clin Invest 120:3466–3479PubMedPubMedCentralCrossRef
36.
go back to reference Nguyen KD, Qiu Y, Cui X et al (2011) Alternatively activated macrophages produce catecholamines to sustain adaptive thermogenesis. Nature 480:104–108PubMedPubMedCentralCrossRef Nguyen KD, Qiu Y, Cui X et al (2011) Alternatively activated macrophages produce catecholamines to sustain adaptive thermogenesis. Nature 480:104–108PubMedPubMedCentralCrossRef
37.
go back to reference Rao RR, Long JZ, White JP et al (2014) Meteorin-like is a hormone that regulates immune-adipose interactions to increase beige fat thermogenesis. Cell 157:1279–1291PubMedPubMedCentralCrossRef Rao RR, Long JZ, White JP et al (2014) Meteorin-like is a hormone that regulates immune-adipose interactions to increase beige fat thermogenesis. Cell 157:1279–1291PubMedPubMedCentralCrossRef
38.
go back to reference Qiu Y, Nguyen KD, Odegaard JI et al (2014) Eosinophils and type 2 cytokine signaling in macrophages orchestrate development of functional beige fat. Cell 157:1292–1308PubMedPubMedCentralCrossRef Qiu Y, Nguyen KD, Odegaard JI et al (2014) Eosinophils and type 2 cytokine signaling in macrophages orchestrate development of functional beige fat. Cell 157:1292–1308PubMedPubMedCentralCrossRef
39.
go back to reference Liu PS, Lin YW, Lee B, McCrady-Spitzer SK, Levine JA, Wei LN (2014) Reducing RIP140 expression in macrophage alters ATM infiltration, facilitates white adipose tissue browning, and prevents high-fat diet-induced insulin resistance. Diabetes 63:4021–4031PubMedPubMedCentralCrossRef Liu PS, Lin YW, Lee B, McCrady-Spitzer SK, Levine JA, Wei LN (2014) Reducing RIP140 expression in macrophage alters ATM infiltration, facilitates white adipose tissue browning, and prevents high-fat diet-induced insulin resistance. Diabetes 63:4021–4031PubMedPubMedCentralCrossRef
40.
go back to reference Hui X, Gu P, Zhang J et al (2015) Adiponectin enhances cold-induced browning of subcutaneous adipose tissue via promoting M2 macrophage proliferation. Cell Metab 22:279–290PubMedCrossRef Hui X, Gu P, Zhang J et al (2015) Adiponectin enhances cold-induced browning of subcutaneous adipose tissue via promoting M2 macrophage proliferation. Cell Metab 22:279–290PubMedCrossRef
41.
go back to reference Xu X, Grijalva A, Skowronski A, van Eijk M, Serlie MJ, Ferrante AW Jr (2013) Obesity activates a program of lysosomal-dependent lipid metabolism in adipose tissue macrophages independently of classic activation. Cell Metab 18:816–830PubMedPubMedCentralCrossRef Xu X, Grijalva A, Skowronski A, van Eijk M, Serlie MJ, Ferrante AW Jr (2013) Obesity activates a program of lysosomal-dependent lipid metabolism in adipose tissue macrophages independently of classic activation. Cell Metab 18:816–830PubMedPubMedCentralCrossRef
42.
go back to reference Shapiro H, Pecht T, Shaco-Levy R et al (2013) Adipose tissue foam cells are present in human obesity. J Clin Endocrinol Metab 98:1173–1181PubMedCrossRef Shapiro H, Pecht T, Shaco-Levy R et al (2013) Adipose tissue foam cells are present in human obesity. J Clin Endocrinol Metab 98:1173–1181PubMedCrossRef
43.
go back to reference Nishimura S, Manabe I, Nagasaki M et al (2007) Adipogenesis in obesity requires close interplay between differentiating adipocytes, stromal cells, and blood vessels. Diabetes 56:1517–1526PubMedCrossRef Nishimura S, Manabe I, Nagasaki M et al (2007) Adipogenesis in obesity requires close interplay between differentiating adipocytes, stromal cells, and blood vessels. Diabetes 56:1517–1526PubMedCrossRef
44.
go back to reference Cho CH, Koh YJ, Han J et al (2007) Angiogenic role of LYVE-1-positive macrophages in adipose tissue. Circ Res 100:e47–e57PubMedCrossRef Cho CH, Koh YJ, Han J et al (2007) Angiogenic role of LYVE-1-positive macrophages in adipose tissue. Circ Res 100:e47–e57PubMedCrossRef
45.
go back to reference Wernstedt Asterholm I, Tao C, Morley TS et al (2014) Adipocyte inflammation is essential for healthy adipose tissue expansion and remodeling. Cell Metab 20:103–118PubMedCrossRef Wernstedt Asterholm I, Tao C, Morley TS et al (2014) Adipocyte inflammation is essential for healthy adipose tissue expansion and remodeling. Cell Metab 20:103–118PubMedCrossRef
46.
go back to reference Lacasa D, Taleb S, Keophiphath M, Miranville A, Clement K (2007) Macrophage-secreted factors impair human adipogenesis: involvement of proinflammatory state in preadipocytes. Endocrinology 148:868–877PubMedCrossRef Lacasa D, Taleb S, Keophiphath M, Miranville A, Clement K (2007) Macrophage-secreted factors impair human adipogenesis: involvement of proinflammatory state in preadipocytes. Endocrinology 148:868–877PubMedCrossRef
47.
go back to reference Constant VA, Gagnon A, Yarmo M, Sorisky A (2008) The antiadipogenic effect of macrophage-conditioned medium depends on ERK1/2 activation. Metab Clin Exp 57:465–472PubMedCrossRef Constant VA, Gagnon A, Yarmo M, Sorisky A (2008) The antiadipogenic effect of macrophage-conditioned medium depends on ERK1/2 activation. Metab Clin Exp 57:465–472PubMedCrossRef
48.
go back to reference Maumus M, Sengenes C, Decaunes P et al (2008) Evidence of in situ proliferation of adult adipose tissue-derived progenitor cells: influence of fat mass microenvironment and growth. J Clin Endocrinol Metab 93:4098–4106PubMedCrossRef Maumus M, Sengenes C, Decaunes P et al (2008) Evidence of in situ proliferation of adult adipose tissue-derived progenitor cells: influence of fat mass microenvironment and growth. J Clin Endocrinol Metab 93:4098–4106PubMedCrossRef
49.
go back to reference Zaragosi LE, Wdziekonski B, Villageois P et al (2010) Activin a plays a critical role in proliferation and differentiation of human adipose progenitors. Diabetes 59:2513–2521PubMedPubMedCentralCrossRef Zaragosi LE, Wdziekonski B, Villageois P et al (2010) Activin a plays a critical role in proliferation and differentiation of human adipose progenitors. Diabetes 59:2513–2521PubMedPubMedCentralCrossRef
50.
go back to reference Bilkovski R, Schulte DM, Oberhauser F et al (2011) Adipose tissue macrophages inhibit adipogenesis of mesenchymal precursor cells via wnt-5a in humans. Int J Obes 35:1450–1454CrossRef Bilkovski R, Schulte DM, Oberhauser F et al (2011) Adipose tissue macrophages inhibit adipogenesis of mesenchymal precursor cells via wnt-5a in humans. Int J Obes 35:1450–1454CrossRef
51.
go back to reference Hossain P, Kawar B, El Nahas M (2007) Obesity and diabetes in the developing world—a growing challenge. N Engl J Med 356:213–215PubMedCrossRef Hossain P, Kawar B, El Nahas M (2007) Obesity and diabetes in the developing world—a growing challenge. N Engl J Med 356:213–215PubMedCrossRef
52.
go back to reference MacDougald OA, Mandrup S (2002) Adipogenesis: forces that tip the scales. Trends Endocrinol Metab 13:5–11PubMedCrossRef MacDougald OA, Mandrup S (2002) Adipogenesis: forces that tip the scales. Trends Endocrinol Metab 13:5–11PubMedCrossRef
53.
go back to reference Osborn O, Olefsky JM (2012) The cellular and signaling networks linking the immune system and metabolism in disease. Nat Med 18:363–374PubMedCrossRef Osborn O, Olefsky JM (2012) The cellular and signaling networks linking the immune system and metabolism in disease. Nat Med 18:363–374PubMedCrossRef
54.
go back to reference Heilbronn LK, Campbell LV (2008) Adipose tissue macrophages, low grade inflammation and insulin resistance in human obesity. Curr Pharm Des 14:1225–1230PubMedCrossRef Heilbronn LK, Campbell LV (2008) Adipose tissue macrophages, low grade inflammation and insulin resistance in human obesity. Curr Pharm Des 14:1225–1230PubMedCrossRef
55.
go back to reference Zeyda M, Gollinger K, Kriehuber E, Kiefer FW, Neuhofer A, Stulnig TM (2010) Newly identified adipose tissue macrophage populations in obesity with distinct chemokine and chemokine receptor expression. Int J Obes 34:1684–1694CrossRef Zeyda M, Gollinger K, Kriehuber E, Kiefer FW, Neuhofer A, Stulnig TM (2010) Newly identified adipose tissue macrophage populations in obesity with distinct chemokine and chemokine receptor expression. Int J Obes 34:1684–1694CrossRef
56.
go back to reference Li P, Lu M, Nguyen MT et al (2010) Functional heterogeneity of CD11c-positive adipose tissue macrophages in diet-induced obese mice. J Biol Chem 285:15333–15345PubMedPubMedCentralCrossRef Li P, Lu M, Nguyen MT et al (2010) Functional heterogeneity of CD11c-positive adipose tissue macrophages in diet-induced obese mice. J Biol Chem 285:15333–15345PubMedPubMedCentralCrossRef
57.
go back to reference Kratz M, Coats BR, Hisert KB et al (2014) Metabolic dysfunction drives a mechanistically distinct proinflammatory phenotype in adipose tissue macrophages. Cell Metab 20:614–625PubMedPubMedCentralCrossRef Kratz M, Coats BR, Hisert KB et al (2014) Metabolic dysfunction drives a mechanistically distinct proinflammatory phenotype in adipose tissue macrophages. Cell Metab 20:614–625PubMedPubMedCentralCrossRef
58.
go back to reference Zeyda M, Farmer D, Todoric J et al (2007) Human adipose tissue macrophages are of an anti-inflammatory phenotype but capable of excessive pro-inflammatory mediator production. Int J Obes 31:1420–1428CrossRef Zeyda M, Farmer D, Todoric J et al (2007) Human adipose tissue macrophages are of an anti-inflammatory phenotype but capable of excessive pro-inflammatory mediator production. Int J Obes 31:1420–1428CrossRef
59.
go back to reference Bourlier V, Zakaroff-Girard A, Miranville A et al (2008) Remodeling phenotype of human subcutaneous adipose tissue macrophages. Circulation 117:806–815PubMedCrossRef Bourlier V, Zakaroff-Girard A, Miranville A et al (2008) Remodeling phenotype of human subcutaneous adipose tissue macrophages. Circulation 117:806–815PubMedCrossRef
60.
go back to reference Wentworth JM, Naselli G, Brown WA et al (2010) Pro-inflammatory CD11c+CD206+ adipose tissue macrophages are associated with insulin resistance in human obesity. Diabetes 59:1648–1656PubMedPubMedCentralCrossRef Wentworth JM, Naselli G, Brown WA et al (2010) Pro-inflammatory CD11c+CD206+ adipose tissue macrophages are associated with insulin resistance in human obesity. Diabetes 59:1648–1656PubMedPubMedCentralCrossRef
61.
go back to reference Fjeldborg K, Pedersen SB, Moller HJ, Christiansen T, Bennetzen M, Richelsen B (2014) Human adipose tissue macrophages are enhanced but changed to an anti-inflammatory profile in obesity. J Immunol Res 2014:309548PubMedPubMedCentralCrossRef Fjeldborg K, Pedersen SB, Moller HJ, Christiansen T, Bennetzen M, Richelsen B (2014) Human adipose tissue macrophages are enhanced but changed to an anti-inflammatory profile in obesity. J Immunol Res 2014:309548PubMedPubMedCentralCrossRef
62.
go back to reference Cancello R, Tordjman J, Poitou C et al (2006) Increased infiltration of macrophages in omental adipose tissue is associated with marked hepatic lesions in morbid human obesity. Diabetes 55:1554–1561PubMedCrossRef Cancello R, Tordjman J, Poitou C et al (2006) Increased infiltration of macrophages in omental adipose tissue is associated with marked hepatic lesions in morbid human obesity. Diabetes 55:1554–1561PubMedCrossRef
63.
go back to reference Makkonen J, Westerbacka J, Kolak M et al (2007) Increased expression of the macrophage markers and of 11β-HSD-1 in subcutaneous adipose tissue, but not in cultured monocyte-derived macrophages, is associated with liver fat in human obesity. Int J Obes 31:1617–1625CrossRef Makkonen J, Westerbacka J, Kolak M et al (2007) Increased expression of the macrophage markers and of 11β-HSD-1 in subcutaneous adipose tissue, but not in cultured monocyte-derived macrophages, is associated with liver fat in human obesity. Int J Obes 31:1617–1625CrossRef
64.
go back to reference Harman-Boehm I, Bluher M, Redel H et al (2007) Macrophage infiltration into omental versus subcutaneous fat across different populations: effect of regional adiposity and the comorbidities of obesity. J Clin Endocrinol Metab 92:2240–2247PubMedCrossRef Harman-Boehm I, Bluher M, Redel H et al (2007) Macrophage infiltration into omental versus subcutaneous fat across different populations: effect of regional adiposity and the comorbidities of obesity. J Clin Endocrinol Metab 92:2240–2247PubMedCrossRef
65.
go back to reference Fox CS, Massaro JM, Hoffmann U et al (2007) Abdominal visceral and subcutaneous adipose tissue compartments: association with metabolic risk factors in the Framingham Heart Study. Circulation 116:39–48PubMedCrossRef Fox CS, Massaro JM, Hoffmann U et al (2007) Abdominal visceral and subcutaneous adipose tissue compartments: association with metabolic risk factors in the Framingham Heart Study. Circulation 116:39–48PubMedCrossRef
66.
go back to reference Koenen TB, Stienstra R, van Tits LJ et al (2011) The inflammasome and caspase-1 activation: a new mechanism underlying increased inflammatory activity in human visceral adipose tissue. Endocrinology 152:3769–3778PubMedCrossRef Koenen TB, Stienstra R, van Tits LJ et al (2011) The inflammasome and caspase-1 activation: a new mechanism underlying increased inflammatory activity in human visceral adipose tissue. Endocrinology 152:3769–3778PubMedCrossRef
67.
go back to reference O’Rourke RW, Metcalf MD, White AE et al (2009) Depot-specific differences in inflammatory mediators and a role for NK cells and IFN-γ in inflammation in human adipose tissue. Int J Obes 33:978–990CrossRef O’Rourke RW, Metcalf MD, White AE et al (2009) Depot-specific differences in inflammatory mediators and a role for NK cells and IFN-γ in inflammation in human adipose tissue. Int J Obes 33:978–990CrossRef
69.
go back to reference Wajchenberg BL (2000) Subcutaneous and visceral adipose tissue: their relation to the metabolic syndrome. Endocr Rev 21:697–738PubMedCrossRef Wajchenberg BL (2000) Subcutaneous and visceral adipose tissue: their relation to the metabolic syndrome. Endocr Rev 21:697–738PubMedCrossRef
70.
go back to reference O’Rourke RW, White AE, Metcalf MD et al (2011) Hypoxia-induced inflammatory cytokine secretion in human adipose tissue stromovascular cells. Diabetologia 54:1480–1490PubMedPubMedCentralCrossRef O’Rourke RW, White AE, Metcalf MD et al (2011) Hypoxia-induced inflammatory cytokine secretion in human adipose tissue stromovascular cells. Diabetologia 54:1480–1490PubMedPubMedCentralCrossRef
71.
go back to reference Spoto B, Di Betta E, Mattace-Raso F et al (2014) Pro- and anti-inflammatory cytokine gene expression in subcutaneous and visceral fat in severe obesity. Nutr Metab Cardiovasc Dis 24:1137–1143PubMedCrossRef Spoto B, Di Betta E, Mattace-Raso F et al (2014) Pro- and anti-inflammatory cytokine gene expression in subcutaneous and visceral fat in severe obesity. Nutr Metab Cardiovasc Dis 24:1137–1143PubMedCrossRef
72.
go back to reference Gautier EL, Yvan-Charvet L (2014) Understanding macrophage diversity at the ontogenic and transcriptomic levels. Immunol Rev 262:85–95PubMedCrossRef Gautier EL, Yvan-Charvet L (2014) Understanding macrophage diversity at the ontogenic and transcriptomic levels. Immunol Rev 262:85–95PubMedCrossRef
74.
go back to reference Epelman S, Lavine KJ, Beaudin AE et al (2014) Embryonic and adult-derived resident cardiac macrophages are maintained through distinct mechanisms at steady state and during inflammation. Immunity 40:91–104PubMedPubMedCentralCrossRef Epelman S, Lavine KJ, Beaudin AE et al (2014) Embryonic and adult-derived resident cardiac macrophages are maintained through distinct mechanisms at steady state and during inflammation. Immunity 40:91–104PubMedPubMedCentralCrossRef
75.
76.
go back to reference Kamei N, Tobe K, Suzuki R et al (2006) Overexpression of monocyte chemoattractant protein-1 in adipose tissues causes macrophage recruitment and insulin resistance. J Biol Chem 281:26602–26614PubMedCrossRef Kamei N, Tobe K, Suzuki R et al (2006) Overexpression of monocyte chemoattractant protein-1 in adipose tissues causes macrophage recruitment and insulin resistance. J Biol Chem 281:26602–26614PubMedCrossRef
77.
go back to reference Krinninger P, Ensenauer R, Ehlers K et al (2014) Peripheral monocytes of obese women display increased chemokine receptor expression and migration capacity. J Clin Endocrinol Metab 99:2500–2509PubMedCrossRef Krinninger P, Ensenauer R, Ehlers K et al (2014) Peripheral monocytes of obese women display increased chemokine receptor expression and migration capacity. J Clin Endocrinol Metab 99:2500–2509PubMedCrossRef
78.
go back to reference Nguyen MT, Favelyukis S, Nguyen AK et al (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. J Biol Chem 282:35279–35292PubMedCrossRef Nguyen MT, Favelyukis S, Nguyen AK et al (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. J Biol Chem 282:35279–35292PubMedCrossRef
79.
go back to reference Vandanmagsar B, Youm YH, Ravussin A et al (2011) The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance. Nat Med 17:179–188PubMedPubMedCentralCrossRef Vandanmagsar B, Youm YH, Ravussin A et al (2011) The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance. Nat Med 17:179–188PubMedPubMedCentralCrossRef
80.
go back to reference Gao D, Madi M, Ding C et al (2014) Interleukin-1β mediates macrophage-induced impairment of insulin signaling in human primary adipocytes. Am J Physiol Endocrinol Metab 307:E289–E304PubMedPubMedCentralCrossRef Gao D, Madi M, Ding C et al (2014) Interleukin-1β mediates macrophage-induced impairment of insulin signaling in human primary adipocytes. Am J Physiol Endocrinol Metab 307:E289–E304PubMedPubMedCentralCrossRef
81.
go back to reference Kanda H, Tateya S, Tamori Y et al (2006) MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity. J Clin Invest 116:1494–1505PubMedPubMedCentralCrossRef Kanda H, Tateya S, Tamori Y et al (2006) MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity. J Clin Invest 116:1494–1505PubMedPubMedCentralCrossRef
82.
go back to reference Kitade H, Sawamoto K, Nagashimada M et al (2012) CCR5 plays a critical role in obesity-induced adipose tissue inflammation and insulin resistance by regulating both macrophage recruitment and M1/M2 status. Diabetes 61:1680–1690PubMedPubMedCentralCrossRef Kitade H, Sawamoto K, Nagashimada M et al (2012) CCR5 plays a critical role in obesity-induced adipose tissue inflammation and insulin resistance by regulating both macrophage recruitment and M1/M2 status. Diabetes 61:1680–1690PubMedPubMedCentralCrossRef
83.
go back to reference Koh YJ, Kang S, Lee HJ et al (2007) Bone marrow-derived circulating progenitor cells fail to transdifferentiate into adipocytes in adult adipose tissues in mice. J Clin Invest 117:3684–3695PubMedPubMedCentralCrossRef Koh YJ, Kang S, Lee HJ et al (2007) Bone marrow-derived circulating progenitor cells fail to transdifferentiate into adipocytes in adult adipose tissues in mice. J Clin Invest 117:3684–3695PubMedPubMedCentralCrossRef
84.
85.
go back to reference Laharrague P, Larrouy D, Fontanilles AM et al (1998) High expression of leptin by human bone marrow adipocytes in primary culture. FASEB J 12:747–752PubMed Laharrague P, Larrouy D, Fontanilles AM et al (1998) High expression of leptin by human bone marrow adipocytes in primary culture. FASEB J 12:747–752PubMed
86.
go back to reference Krings A, Rahman S, Huang S, Lu Y, Czernik PJ, Lecka-Czernik B (2012) Bone marrow fat has brown adipose tissue characteristics, which are attenuated with aging and diabetes. Bone 50:546–552PubMedPubMedCentralCrossRef Krings A, Rahman S, Huang S, Lu Y, Czernik PJ, Lecka-Czernik B (2012) Bone marrow fat has brown adipose tissue characteristics, which are attenuated with aging and diabetes. Bone 50:546–552PubMedPubMedCentralCrossRef
87.
88.
go back to reference Chan KL, Pillon NJ, Sivaloganathan DM et al (2015) Palmitoleate reverses high fat-induced proinflammatory macrophage polarization via AMP-activated protein kinase (AMPK). J Biol Chem 290:16979–16988PubMedCrossRef Chan KL, Pillon NJ, Sivaloganathan DM et al (2015) Palmitoleate reverses high fat-induced proinflammatory macrophage polarization via AMP-activated protein kinase (AMPK). J Biol Chem 290:16979–16988PubMedCrossRef
89.
90.
go back to reference Okabe Y, Medzhitov R (2014) Tissue-specific signals control reversible program of localization and functional polarization of macrophages. Cell 157:832–844PubMedPubMedCentralCrossRef Okabe Y, Medzhitov R (2014) Tissue-specific signals control reversible program of localization and functional polarization of macrophages. Cell 157:832–844PubMedPubMedCentralCrossRef
91.
go back to reference Pinho Mde F, Hurtado SP, El-Cheikh MC, Rossi MI, Dutra HS, Borojevic R (2002) Myelopoiesis in the omentum of normal mice and during abdominal inflammatory processes. Cell Tissue Res 308:87–96PubMedCrossRef Pinho Mde F, Hurtado SP, El-Cheikh MC, Rossi MI, Dutra HS, Borojevic R (2002) Myelopoiesis in the omentum of normal mice and during abdominal inflammatory processes. Cell Tissue Res 308:87–96PubMedCrossRef
92.
go back to reference Poglio S, De Toni F, Lewandowski D et al (2012) In situ production of innate immune cells in murine white adipose tissue. Blood 120:4952–4962PubMedCrossRef Poglio S, De Toni F, Lewandowski D et al (2012) In situ production of innate immune cells in murine white adipose tissue. Blood 120:4952–4962PubMedCrossRef
93.
go back to reference Cousin B, Munoz O, Andre M et al (1999) A role for preadipocytes as macrophage-like cells. FASEB J 13:305–312PubMed Cousin B, Munoz O, Andre M et al (1999) A role for preadipocytes as macrophage-like cells. FASEB J 13:305–312PubMed
94.
go back to reference Charriere G, Cousin B, Arnaud E et al (2003) Preadipocyte conversion to macrophage. Evidence of plasticity. J Biol Chem 278:9850–9855PubMedCrossRef Charriere G, Cousin B, Arnaud E et al (2003) Preadipocyte conversion to macrophage. Evidence of plasticity. J Biol Chem 278:9850–9855PubMedCrossRef
95.
go back to reference Amano SU, Cohen JL, Vangala P et al (2014) Local proliferation of macrophages contributes to obesity-associated adipose tissue inflammation. Cell Metab 19:162–171PubMedPubMedCentralCrossRef Amano SU, Cohen JL, Vangala P et al (2014) Local proliferation of macrophages contributes to obesity-associated adipose tissue inflammation. Cell Metab 19:162–171PubMedPubMedCentralCrossRef
96.
go back to reference Ramkhelawon B, Hennessy EJ, Menager M et al (2014) Netrin-1 promotes adipose tissue macrophage retention and insulin resistance in obesity. Nat Med 20:377–384PubMedPubMedCentralCrossRef Ramkhelawon B, Hennessy EJ, Menager M et al (2014) Netrin-1 promotes adipose tissue macrophage retention and insulin resistance in obesity. Nat Med 20:377–384PubMedPubMedCentralCrossRef
97.
go back to reference Hill AA, Anderson-Baucum EK, Kennedy AJ, Webb CD, Yull FE, Hasty AH (2015) Activation of NF-κB drives the enhanced survival of adipose tissue macrophages in an obesogenic environment. Mol Metab 4:665–677PubMedPubMedCentralCrossRef Hill AA, Anderson-Baucum EK, Kennedy AJ, Webb CD, Yull FE, Hasty AH (2015) Activation of NF-κB drives the enhanced survival of adipose tissue macrophages in an obesogenic environment. Mol Metab 4:665–677PubMedPubMedCentralCrossRef
98.
go back to reference Barnes MA, Carson MJ, Nair MG (2015) Non-traditional cytokines: how catecholamines and adipokines influence macrophages in immunity, metabolism and the central nervous system. Cytokine 72:210–219PubMedPubMedCentralCrossRef Barnes MA, Carson MJ, Nair MG (2015) Non-traditional cytokines: how catecholamines and adipokines influence macrophages in immunity, metabolism and the central nervous system. Cytokine 72:210–219PubMedPubMedCentralCrossRef
100.
go back to reference Trayhurn P (2013) Hypoxia and adipose tissue function and dysfunction in obesity. Physiol Rev 93:1–21PubMedCrossRef Trayhurn P (2013) Hypoxia and adipose tissue function and dysfunction in obesity. Physiol Rev 93:1–21PubMedCrossRef
101.
go back to reference Fujisaka S, Usui I, Ikutani M et al (2013) Adipose tissue hypoxia induces inflammatory M1 polarity of macrophages in an HIF-1α-dependent and HIF-1α-independent manner in obese mice. Diabetologia 56:1403–1412PubMedCrossRef Fujisaka S, Usui I, Ikutani M et al (2013) Adipose tissue hypoxia induces inflammatory M1 polarity of macrophages in an HIF-1α-dependent and HIF-1α-independent manner in obese mice. Diabetologia 56:1403–1412PubMedCrossRef
102.
go back to reference Hosogai N, Fukuhara A, Oshima K et al (2007) Adipose tissue hypoxia in obesity and its impact on adipocytokine dysregulation. Diabetes 56:901–911PubMedCrossRef Hosogai N, Fukuhara A, Oshima K et al (2007) Adipose tissue hypoxia in obesity and its impact on adipocytokine dysregulation. Diabetes 56:901–911PubMedCrossRef
103.
go back to reference Ye J, Gao Z, Yin J, He Q (2007) Hypoxia is a potential risk factor for chronic inflammation and adiponectin reduction in adipose tissue of ob/ob and dietary obese mice. Am J Physiol Endocrinol Metab 293:E1118–E1128PubMedCrossRef Ye J, Gao Z, Yin J, He Q (2007) Hypoxia is a potential risk factor for chronic inflammation and adiponectin reduction in adipose tissue of ob/ob and dietary obese mice. Am J Physiol Endocrinol Metab 293:E1118–E1128PubMedCrossRef
104.
go back to reference Pasarica M, Sereda OR, Redman LM et al (2009) Reduced adipose tissue oxygenation in human obesity: evidence for rarefaction, macrophage chemotaxis, and inflammation without an angiogenic response. Diabetes 58:718–725PubMedPubMedCentralCrossRef Pasarica M, Sereda OR, Redman LM et al (2009) Reduced adipose tissue oxygenation in human obesity: evidence for rarefaction, macrophage chemotaxis, and inflammation without an angiogenic response. Diabetes 58:718–725PubMedPubMedCentralCrossRef
106.
go back to reference Goossens GH, Bizzarri A, Venteclef N et al (2011) Increased adipose tissue oxygen tension in obese compared with lean men is accompanied by insulin resistance, impaired adipose tissue capillarization, and inflammation. Circulation 124:67–76PubMedCrossRef Goossens GH, Bizzarri A, Venteclef N et al (2011) Increased adipose tissue oxygen tension in obese compared with lean men is accompanied by insulin resistance, impaired adipose tissue capillarization, and inflammation. Circulation 124:67–76PubMedCrossRef
107.
go back to reference Halberg N, Khan T, Trujillo ME et al (2009) Hypoxia-inducible factor 1α induces fibrosis and insulin resistance in white adipose tissue. Mol Cell Biol 29:4467–4483PubMedPubMedCentralCrossRef Halberg N, Khan T, Trujillo ME et al (2009) Hypoxia-inducible factor 1α induces fibrosis and insulin resistance in white adipose tissue. Mol Cell Biol 29:4467–4483PubMedPubMedCentralCrossRef
108.
go back to reference Choe SS, Shin KC, Ka S, Lee YK, Chun JS, Kim JB (2014) Macrophage HIF-2α ameliorates adipose tissue inflammation and insulin resistance in obesity. Diabetes 63:3359–3371PubMedCrossRef Choe SS, Shin KC, Ka S, Lee YK, Chun JS, Kim JB (2014) Macrophage HIF-2α ameliorates adipose tissue inflammation and insulin resistance in obesity. Diabetes 63:3359–3371PubMedCrossRef
109.
go back to reference Snodgrass RG, Boss M, Zezina E et al (2016) Hypoxia potentiates palmitate-induced proinflammatory activation of primary human macrophages. J Biol Chem 291:413–424PubMedCrossRef Snodgrass RG, Boss M, Zezina E et al (2016) Hypoxia potentiates palmitate-induced proinflammatory activation of primary human macrophages. J Biol Chem 291:413–424PubMedCrossRef
110.
111.
go back to reference Haddad JJ, Harb HL (2005) Cytokines and the regulation of hypoxia-inducible factor (HIF)-1α. Int Immunopharmacol 5:461–483PubMedCrossRef Haddad JJ, Harb HL (2005) Cytokines and the regulation of hypoxia-inducible factor (HIF)-1α. Int Immunopharmacol 5:461–483PubMedCrossRef
112.
go back to reference Fang HY, Hughes R, Murdoch C et al (2009) Hypoxia-inducible factors 1 and 2 are important transcriptional effectors in primary macrophages experiencing hypoxia. Blood 114:844–859PubMedPubMedCentralCrossRef Fang HY, Hughes R, Murdoch C et al (2009) Hypoxia-inducible factors 1 and 2 are important transcriptional effectors in primary macrophages experiencing hypoxia. Blood 114:844–859PubMedPubMedCentralCrossRef
113.
go back to reference Takeda N, O’Dea EL, Doedens A et al (2010) Differential activation and antagonistic function of HIF-α isoforms in macrophages are essential for NO homeostasis. Genes Dev 24:491–501PubMedPubMedCentralCrossRef Takeda N, O’Dea EL, Doedens A et al (2010) Differential activation and antagonistic function of HIF-α isoforms in macrophages are essential for NO homeostasis. Genes Dev 24:491–501PubMedPubMedCentralCrossRef
114.
go back to reference Lee YS, Kim JW, Osborne O et al (2014) Increased adipocyte O2 consumption triggers HIF-1α, causing inflammation and insulin resistance in obesity. Cell 157:1339–1352PubMedPubMedCentralCrossRef Lee YS, Kim JW, Osborne O et al (2014) Increased adipocyte O2 consumption triggers HIF-1α, causing inflammation and insulin resistance in obesity. Cell 157:1339–1352PubMedPubMedCentralCrossRef
115.
go back to reference Divoux A, Tordjman J, Lacasa D et al (2010) Fibrosis in human adipose tissue: composition, distribution, and link with lipid metabolism and fat mass loss. Diabetes 59:2817–2825PubMedPubMedCentralCrossRef Divoux A, Tordjman J, Lacasa D et al (2010) Fibrosis in human adipose tissue: composition, distribution, and link with lipid metabolism and fat mass loss. Diabetes 59:2817–2825PubMedPubMedCentralCrossRef
116.
go back to reference Kimura T, Kobayashi S, Hanihara-Tatsuzawa F, Sayama A, MaruYama T, Muta T (2014) Responses of macrophages to the danger signals released from necrotic cells. Int Immunol 26:697–704PubMedCrossRef Kimura T, Kobayashi S, Hanihara-Tatsuzawa F, Sayama A, MaruYama T, Muta T (2014) Responses of macrophages to the danger signals released from necrotic cells. Int Immunol 26:697–704PubMedCrossRef
118.
119.
go back to reference Gunasekaran MK, Viranaicken W, Girard AC et al (2013) Inflammation triggers high mobility group box 1 (HMGB1) secretion in adipose tissue, a potential link to obesity. Cytokine 64:103–111PubMedCrossRef Gunasekaran MK, Viranaicken W, Girard AC et al (2013) Inflammation triggers high mobility group box 1 (HMGB1) secretion in adipose tissue, a potential link to obesity. Cytokine 64:103–111PubMedCrossRef
120.
go back to reference Guzman-Ruiz R, Ortega F, Rodriguez A et al (2014) Alarmin high-mobility group B1 (HMGB1) is regulated in human adipocytes in insulin resistance and influences insulin secretion in beta-cells. Int J Obes 38:1545–1554CrossRef Guzman-Ruiz R, Ortega F, Rodriguez A et al (2014) Alarmin high-mobility group B1 (HMGB1) is regulated in human adipocytes in insulin resistance and influences insulin secretion in beta-cells. Int J Obes 38:1545–1554CrossRef
122.
go back to reference Voll RE, Herrmann M, Roth EA, Stach C, Kalden JR, Girkontaite I (1997) Immunosuppressive effects of apoptotic cells. Nature 390:350–351PubMedCrossRef Voll RE, Herrmann M, Roth EA, Stach C, Kalden JR, Girkontaite I (1997) Immunosuppressive effects of apoptotic cells. Nature 390:350–351PubMedCrossRef
123.
go back to reference Iyer SS, Pulskens WP, Sadler JJ et al (2009) Necrotic cells trigger a sterile inflammatory response through the Nlrp3 inflammasome. Proc Natl Acad Sci U S A 106:20388–20393PubMedPubMedCentralCrossRef Iyer SS, Pulskens WP, Sadler JJ et al (2009) Necrotic cells trigger a sterile inflammatory response through the Nlrp3 inflammasome. Proc Natl Acad Sci U S A 106:20388–20393PubMedPubMedCentralCrossRef
124.
go back to reference Erwig LP, Henson PM (2008) Clearance of apoptotic cells by phagocytes. Cell Death Differ 15:243–250PubMedCrossRef Erwig LP, Henson PM (2008) Clearance of apoptotic cells by phagocytes. Cell Death Differ 15:243–250PubMedCrossRef
125.
126.
go back to reference Feng D, Tang Y, Kwon H et al (2011) High-fat diet-induced adipocyte cell death occurs through a cyclophilin D intrinsic signaling pathway independent of adipose tissue inflammation. Diabetes 60:2134–2143PubMedPubMedCentralCrossRef Feng D, Tang Y, Kwon H et al (2011) High-fat diet-induced adipocyte cell death occurs through a cyclophilin D intrinsic signaling pathway independent of adipose tissue inflammation. Diabetes 60:2134–2143PubMedPubMedCentralCrossRef
127.
go back to reference Giordano A, Murano I, Mondini E et al (2013) Obese adipocytes show ultrastructural features of stressed cells and die of pyroptosis. J Lipid Res 54:2423–2436PubMedPubMedCentralCrossRef Giordano A, Murano I, Mondini E et al (2013) Obese adipocytes show ultrastructural features of stressed cells and die of pyroptosis. J Lipid Res 54:2423–2436PubMedPubMedCentralCrossRef
128.
go back to reference Alkhouri N, Gornicka A, Berk MP et al (2010) Adipocyte apoptosis, a link between obesity, insulin resistance, and hepatic steatosis. J Biol Chem 285:3428–3438PubMedPubMedCentralCrossRef Alkhouri N, Gornicka A, Berk MP et al (2010) Adipocyte apoptosis, a link between obesity, insulin resistance, and hepatic steatosis. J Biol Chem 285:3428–3438PubMedPubMedCentralCrossRef
129.
go back to reference Coenen KR, Gruen ML, Chait A, Hasty AH (2007) Diet-induced increases in adiposity, but not plasma lipids, promote macrophage infiltration into white adipose tissue. Diabetes 56:564–573PubMedCrossRef Coenen KR, Gruen ML, Chait A, Hasty AH (2007) Diet-induced increases in adiposity, but not plasma lipids, promote macrophage infiltration into white adipose tissue. Diabetes 56:564–573PubMedCrossRef
130.
go back to reference Langin D, Dicker A, Tavernier G et al (2005) Adipocyte lipases and defect of lipolysis in human obesity. Diabetes 54:3190–3197PubMedCrossRef Langin D, Dicker A, Tavernier G et al (2005) Adipocyte lipases and defect of lipolysis in human obesity. Diabetes 54:3190–3197PubMedCrossRef
131.
go back to reference Bjorntorp P, Sjostrom L (1972) The composition and metabolism in vitro of adipose tissue fat cells of different sizes. Eur J Clin Investig 2:78–84CrossRef Bjorntorp P, Sjostrom L (1972) The composition and metabolism in vitro of adipose tissue fat cells of different sizes. Eur J Clin Investig 2:78–84CrossRef
132.
go back to reference Laurencikiene J, Skurk T, Kulyte A et al (2011) Regulation of lipolysis in small and large fat cells of the same subject. J Clin Endocrinol Metab 96:E2045–E2049PubMedCrossRef Laurencikiene J, Skurk T, Kulyte A et al (2011) Regulation of lipolysis in small and large fat cells of the same subject. J Clin Endocrinol Metab 96:E2045–E2049PubMedCrossRef
133.
go back to reference Langin D, Arner P (2006) Importance of TNFα and neutral lipases in human adipose tissue lipolysis. Trends Endocrinol Metab 17:314–320PubMedCrossRef Langin D, Arner P (2006) Importance of TNFα and neutral lipases in human adipose tissue lipolysis. Trends Endocrinol Metab 17:314–320PubMedCrossRef
134.
go back to reference Cifuentes M, Albala C, Rojas CV (2008) Differences in lipogenesis and lipolysis in obese and non-obese adult human adipocytes. Biol Res 41:197–204PubMedCrossRef Cifuentes M, Albala C, Rojas CV (2008) Differences in lipogenesis and lipolysis in obese and non-obese adult human adipocytes. Biol Res 41:197–204PubMedCrossRef
135.
136.
go back to reference Ryden M, Andersson DP, Bernard S, Spalding K, Arner P (2013) Adipocyte triglyceride turnover and lipolysis in lean and overweight subjects. J Lipid Res 54:2909–2913PubMedPubMedCentralCrossRef Ryden M, Andersson DP, Bernard S, Spalding K, Arner P (2013) Adipocyte triglyceride turnover and lipolysis in lean and overweight subjects. J Lipid Res 54:2909–2913PubMedPubMedCentralCrossRef
137.
go back to reference Wei Y, Wang D, Topczewski F, Pagliassotti MJ (2006) Saturated fatty acids induce endoplasmic reticulum stress and apoptosis independently of ceramide in liver cells. Am J Physiol Endocrinol Metab 291:E275–E281PubMedCrossRef Wei Y, Wang D, Topczewski F, Pagliassotti MJ (2006) Saturated fatty acids induce endoplasmic reticulum stress and apoptosis independently of ceramide in liver cells. Am J Physiol Endocrinol Metab 291:E275–E281PubMedCrossRef
138.
go back to reference Pal D, Dasgupta S, Kundu R et al (2012) Fetuin-A acts as an endogenous ligand of TLR4 to promote lipid-induced insulin resistance. Nat Med 18:1279–1285PubMedCrossRef Pal D, Dasgupta S, Kundu R et al (2012) Fetuin-A acts as an endogenous ligand of TLR4 to promote lipid-induced insulin resistance. Nat Med 18:1279–1285PubMedCrossRef
139.
go back to reference Chait A, Kim F (2010) Saturated fatty acids and inflammation: who pays the toll? Arterioscler Thromb Vasc Biol 30:692–693PubMedCrossRef Chait A, Kim F (2010) Saturated fatty acids and inflammation: who pays the toll? Arterioscler Thromb Vasc Biol 30:692–693PubMedCrossRef
140.
go back to reference Anderson EK, Hill AA, Hasty AH (2012) Stearic acid accumulation in macrophages induces Toll-like receptor 4/2-independent inflammation leading to endoplasmic reticulum stress-mediated apoptosis. Arterioscler Thromb Vasc Biol 32:1687–1695PubMedPubMedCentralCrossRef Anderson EK, Hill AA, Hasty AH (2012) Stearic acid accumulation in macrophages induces Toll-like receptor 4/2-independent inflammation leading to endoplasmic reticulum stress-mediated apoptosis. Arterioscler Thromb Vasc Biol 32:1687–1695PubMedPubMedCentralCrossRef
141.
go back to reference Boden G, Duan X, Homko C et al (2008) Increase in endoplasmic reticulum stress-related proteins and genes in adipose tissue of obese, insulin-resistant individuals. Diabetes 57:2438–2444PubMedPubMedCentralCrossRef Boden G, Duan X, Homko C et al (2008) Increase in endoplasmic reticulum stress-related proteins and genes in adipose tissue of obese, insulin-resistant individuals. Diabetes 57:2438–2444PubMedPubMedCentralCrossRef
143.
go back to reference Caspar-Bauguil S, Kolditz CI, Lefort C et al (2015) Fatty acids from fat cell lipolysis do not activate an inflammatory response but are stored as triacylglycerols in adipose tissue macrophages. Diabetologia 58:2627–2636PubMedCrossRef Caspar-Bauguil S, Kolditz CI, Lefort C et al (2015) Fatty acids from fat cell lipolysis do not activate an inflammatory response but are stored as triacylglycerols in adipose tissue macrophages. Diabetologia 58:2627–2636PubMedCrossRef
144.
go back to reference Choque B, Catheline D, Rioux V, Legrand P (2014) Linoleic acid: between doubts and certainties. Biochimie 96:14–21PubMedCrossRef Choque B, Catheline D, Rioux V, Legrand P (2014) Linoleic acid: between doubts and certainties. Biochimie 96:14–21PubMedCrossRef
145.
go back to reference Zhang J, Gao Z, Yin J, Quon MJ, Ye J (2008) S6K directly phosphorylates IRS-1 on Ser-270 to promote insulin resistance in response to TNF-α signaling through IKK2. J Biol Chem 283:35375–35382PubMedPubMedCentralCrossRef Zhang J, Gao Z, Yin J, Quon MJ, Ye J (2008) S6K directly phosphorylates IRS-1 on Ser-270 to promote insulin resistance in response to TNF-α signaling through IKK2. J Biol Chem 283:35375–35382PubMedPubMedCentralCrossRef
146.
go back to reference Jager J, Gremeaux T, Cormont M, Le Marchand-Brustel Y, Tanti JF (2007) Interleukin-1β-induced insulin resistance in adipocytes through down-regulation of insulin receptor substrate-1 expression. Endocrinology 148:241–251PubMedPubMedCentralCrossRef Jager J, Gremeaux T, Cormont M, Le Marchand-Brustel Y, Tanti JF (2007) Interleukin-1β-induced insulin resistance in adipocytes through down-regulation of insulin receptor substrate-1 expression. Endocrinology 148:241–251PubMedPubMedCentralCrossRef
147.
go back to reference Olholm J, Paulsen SK, Cullberg KB, Richelsen B, Pedersen SB (2010) Anti-inflammatory effect of resveratrol on adipokine expression and secretion in human adipose tissue explants. Int J Obes 34:1546–1553CrossRef Olholm J, Paulsen SK, Cullberg KB, Richelsen B, Pedersen SB (2010) Anti-inflammatory effect of resveratrol on adipokine expression and secretion in human adipose tissue explants. Int J Obes 34:1546–1553CrossRef
148.
go back to reference Dandona P, Aljada A, Mohanty P et al (2001) Insulin inhibits intranuclear nuclear factor κB and stimulates IκB in mononuclear cells in obese subjects: evidence for an anti-inflammatory effect? J Clin Endocrinol Metab 86:3257–3265PubMed Dandona P, Aljada A, Mohanty P et al (2001) Insulin inhibits intranuclear nuclear factor κB and stimulates IκB in mononuclear cells in obese subjects: evidence for an anti-inflammatory effect? J Clin Endocrinol Metab 86:3257–3265PubMed
149.
go back to reference Han JM, Patterson SJ, Speck M, Ehses JA, Levings MK (2014) Insulin inhibits IL-10-mediated regulatory T cell function: implications for obesity. J Immunol 192:623–629PubMedCrossRef Han JM, Patterson SJ, Speck M, Ehses JA, Levings MK (2014) Insulin inhibits IL-10-mediated regulatory T cell function: implications for obesity. J Immunol 192:623–629PubMedCrossRef
150.
go back to reference Jansen HJ, Stienstra R, van Diepen JA et al (2013) Start of insulin therapy in patients with type 2 diabetes mellitus promotes the influx of macrophages into subcutaneous adipose tissue. Diabetologia 56:2573–2581PubMedCrossRef Jansen HJ, Stienstra R, van Diepen JA et al (2013) Start of insulin therapy in patients with type 2 diabetes mellitus promotes the influx of macrophages into subcutaneous adipose tissue. Diabetologia 56:2573–2581PubMedCrossRef
151.
go back to reference Pedersen DJ, Guilherme A, Danai LV et al (2015) A major role of insulin in promoting obesity-associated adipose tissue inflammation. Mol Metab 4:507–518PubMedPubMedCentralCrossRef Pedersen DJ, Guilherme A, Danai LV et al (2015) A major role of insulin in promoting obesity-associated adipose tissue inflammation. Mol Metab 4:507–518PubMedPubMedCentralCrossRef
152.
go back to reference Mauer J, Chaurasia B, Plum L et al (2010) Myeloid cell-restricted insulin receptor deficiency protects against obesity-induced inflammation and systemic insulin resistance. PLoS Genet 6:e1000938PubMedPubMedCentralCrossRef Mauer J, Chaurasia B, Plum L et al (2010) Myeloid cell-restricted insulin receptor deficiency protects against obesity-induced inflammation and systemic insulin resistance. PLoS Genet 6:e1000938PubMedPubMedCentralCrossRef
153.
go back to reference Han S, Liang CP, DeVries-Seimon T et al (2006) Macrophage insulin receptor deficiency increases ER stress-induced apoptosis and necrotic core formation in advanced atherosclerotic lesions. Cell Metab 3:257–266PubMedCrossRef Han S, Liang CP, DeVries-Seimon T et al (2006) Macrophage insulin receptor deficiency increases ER stress-induced apoptosis and necrotic core formation in advanced atherosclerotic lesions. Cell Metab 3:257–266PubMedCrossRef
154.
155.
go back to reference Olefsky JM, Reaven GM (1976) Insulin binding to monocytes and total mononuclear leukocytes from normal and diabetic patients. J Clin Endocrinol Metab 43:226–231PubMedCrossRef Olefsky JM, Reaven GM (1976) Insulin binding to monocytes and total mononuclear leukocytes from normal and diabetic patients. J Clin Endocrinol Metab 43:226–231PubMedCrossRef
156.
go back to reference de Rekeneire N, Peila R, Ding J et al (2006) Diabetes, hyperglycemia, and inflammation in older individuals: the health, aging and body composition study. Diabetes Care 29:1902–1908PubMedCrossRef de Rekeneire N, Peila R, Ding J et al (2006) Diabetes, hyperglycemia, and inflammation in older individuals: the health, aging and body composition study. Diabetes Care 29:1902–1908PubMedCrossRef
157.
go back to reference Venneri MA, Giannetta E, Panio G et al (2015) Chronic inhibition of PDE5 limits pro-inflammatory monocyte–macrophage polarization in streptozotocin-induced diabetic mice. PLoS One 10:e0126580PubMedPubMedCentralCrossRef Venneri MA, Giannetta E, Panio G et al (2015) Chronic inhibition of PDE5 limits pro-inflammatory monocyte–macrophage polarization in streptozotocin-induced diabetic mice. PLoS One 10:e0126580PubMedPubMedCentralCrossRef
158.
go back to reference Lin Y, Berg AH, Iyengar P et al (2005) The hyperglycemia-induced inflammatory response in adipocytes: the role of reactive oxygen species. J Biol Chem 280:4617–4626PubMedCrossRef Lin Y, Berg AH, Iyengar P et al (2005) The hyperglycemia-induced inflammatory response in adipocytes: the role of reactive oxygen species. J Biol Chem 280:4617–4626PubMedCrossRef
159.
go back to reference Morohoshi M, Fujisawa K, Uchimura I, Numano F (1996) Glucose-dependent interleukin 6 and tumor necrosis factor production by human peripheral blood monocytes in vitro. Diabetes 45:954–959PubMedCrossRef Morohoshi M, Fujisawa K, Uchimura I, Numano F (1996) Glucose-dependent interleukin 6 and tumor necrosis factor production by human peripheral blood monocytes in vitro. Diabetes 45:954–959PubMedCrossRef
160.
go back to reference Parathath S, Grauer L, Huang LS et al (2011) Diabetes adversely affects macrophages during atherosclerotic plaque regression in mice. Diabetes 60:1759–1769PubMedPubMedCentralCrossRef Parathath S, Grauer L, Huang LS et al (2011) Diabetes adversely affects macrophages during atherosclerotic plaque regression in mice. Diabetes 60:1759–1769PubMedPubMedCentralCrossRef
161.
go back to reference Chen J, Jing G, Xu G, Shalev A (2014) Thioredoxin-interacting protein stimulates its own expression via a positive feedback loop. Mol Endocrinol 28:674–680PubMedPubMedCentralCrossRef Chen J, Jing G, Xu G, Shalev A (2014) Thioredoxin-interacting protein stimulates its own expression via a positive feedback loop. Mol Endocrinol 28:674–680PubMedPubMedCentralCrossRef
162.
go back to reference Devi TS, Lee I, Huttemann M, Kumar A, Nantwi KD, Singh LP (2012) TXNIP links innate host defense mechanisms to oxidative stress and inflammation in retinal Muller glia under chronic hyperglycemia: implications for diabetic retinopathy. Exp Diabetes Res 2012:438238PubMedPubMedCentralCrossRef Devi TS, Lee I, Huttemann M, Kumar A, Nantwi KD, Singh LP (2012) TXNIP links innate host defense mechanisms to oxidative stress and inflammation in retinal Muller glia under chronic hyperglycemia: implications for diabetic retinopathy. Exp Diabetes Res 2012:438238PubMedPubMedCentralCrossRef
163.
go back to reference Park YJ, Yoon SJ, Suh HW et al (2013) TXNIP deficiency exacerbates endotoxic shock via the induction of excessive nitric oxide synthesis. PLoS Pathog 9:e1003646PubMedPubMedCentralCrossRef Park YJ, Yoon SJ, Suh HW et al (2013) TXNIP deficiency exacerbates endotoxic shock via the induction of excessive nitric oxide synthesis. PLoS Pathog 9:e1003646PubMedPubMedCentralCrossRef
164.
go back to reference Stienstra R, Joosten LA, Koenen T et al (2010) The inflammasome-mediated caspase-1 activation controls adipocyte differentiation and insulin sensitivity. Cell Metab 12:593–605PubMedPubMedCentralCrossRef Stienstra R, Joosten LA, Koenen T et al (2010) The inflammasome-mediated caspase-1 activation controls adipocyte differentiation and insulin sensitivity. Cell Metab 12:593–605PubMedPubMedCentralCrossRef
165.
go back to reference Sabater D, Arriaran S, Romero Mdel M et al (2014) Cultured 3T3L1 adipocytes dispose of excess medium glucose as lactate under abundant oxygen availability. Sci Rep 4:3663PubMedCrossRef Sabater D, Arriaran S, Romero Mdel M et al (2014) Cultured 3T3L1 adipocytes dispose of excess medium glucose as lactate under abundant oxygen availability. Sci Rep 4:3663PubMedCrossRef
166.
go back to reference DiGirolamo M, Newby FD, Lovejoy J (1992) Lactate production in adipose tissue: a regulated function with extra-adipose implications. FASEB J 6:2405–2412PubMed DiGirolamo M, Newby FD, Lovejoy J (1992) Lactate production in adipose tissue: a regulated function with extra-adipose implications. FASEB J 6:2405–2412PubMed
167.
Metadata
Title
Adipose tissue macrophages: going off track during obesity
Authors
Lily Boutens
Rinke Stienstra
Publication date
01-05-2016
Publisher
Springer Berlin Heidelberg
Published in
Diabetologia / Issue 5/2016
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-016-3904-9

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