Article thumbnail
Location of Repository

The macrophage at the intersection of immunity and metabolism in obesity

By M Constantine Samaan


Obesity is a worldwide pandemic representing one of the major challenges that societies face around the globe. Identifying the mechanisms involved in its development and propagation will help the development of preventative and therapeutic strategies that may help control its rising rates

Topics: Review
Publisher: BioMed Central
OAI identifier:
Provided by: PubMed Central

Suggested articles


  1. (2009). [Chronic mild inflammation links obesity, metabolic syndrome, atherosclerosis and diabetes]. Vnitr Lek
  2. (2005). [Monocytes and macrophages–multifaced cell population involved in inflammation, atherosclerosis, and obesity]. Nippon Rinsho
  3. (2010). A: IL-4/STAT6 immune axis regulates peripheral nutrient metabolism and insulin sensitivity. Proc Natl Acad Sci USA
  4. (2004). A: Triglyceride-rich lipoproteins inhibit cholesterol efflux to apolipoprotein (apo) A1 from human macrophage foam cells. Atherosclerosis
  5. (2009). Adiponectin reduces lipid accumulation in macrophage foam cells. Atherosclerosis
  6. (2008). Adipose tissue inflammation and liver pathology in human obesity. Diabetes Metab
  7. (2009). Adipose tissue inflammation in obesity and metabolic syndrome. Discov Med
  8. (2010). Adipose tissue macrophages: their role in adipose tissue remodeling.
  9. (2003). Akira S: Toll-like receptors. Annual Review of Immunology
  10. (2004). al: PKC-theta knockout mice are protected from fat-induced insulin resistance.
  11. (2008). Araujo EP, de Souza CT: Diet-induced inflammation of the hypothalamus in obesity. Neuroimmunomodulation
  12. (2005). BK: Tumor Necrosis Factor-α Induces Skeletal Muscle Insulin Resistance in Healthy Human Subjects via Inhibition of Akt Substrate 160 Phosphorylation. Diabetes
  13. (1993). BM: Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science
  14. (1995). BM: Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance.
  15. (2009). Bouloumie A: Role of macrophage tissue infiltration in obesity and insulin resistance. Diabetes Metab
  16. (2009). Bruning JC: MyD88 signaling in the CNS is required for development of fatty acid-induced leptin resistance and diet-induced obesity. Cell Metab
  17. (2000). Cellular mechanisms of insulin resistance.
  18. (2011). Chawla A: Alternative macrophage activation and metabolism. Annu Rev Pathol
  19. (2009). Chemotactic cytokines, obesity and type 2 diabetes: in vivo and in vitro evidence for a possible causal correlation? Proc Nutr Soc
  20. (2001). CR: Insulin signalling and the regulation of glucose and lipid metabolism. Nature
  21. (2006). Diet and exercise reduce low-grade inflammation and macrophage infiltration in adipose tissue but not in skeletal muscle in severely obese subjects.
  22. (2010). Dietary and Genetic Obesity Promote Liver Inflammation and Tumorigenesis by Enhancing IL-6 and TNF Expression. Cell
  23. (2008). Differentiation and heterogeneity in the mononuclear phagocyte system. Mucosal Immunol
  24. (2009). Emerging Role of Adipose Tissue Hypoxia in Obesity and Insulin Resistance. Int J Obes (Lond)
  25. (2003). et al: Chronic inflammation in fat plays a crucial role
  26. (2009). et al: CXC ligand 5 is an adipose-tissue derived factor that links obesity to insulin resistance. Cell Metab
  27. (2007). et al: Macrophage PPAR gamma is required for normal skeletal muscle and hepatic insulin sensitivity and full antidiabetic effects of thiazolidinediones.
  28. (2007). et al: Macrophage-specific PPARgamma controls alternative activation and improves insulin resistance. Nature
  29. (2002). et al: Mechanism by Which Fatty Acids Inhibit Insulin Activation of Insulin Receptor Substrate-1 (IRS-1)-associated Phosphatidylinositol 3-Kinase Activity in Muscle.
  30. (2009). et al: Muscle inflammatory response and insulin resistance: synergistic interaction between macrophages and fatty acids leads to impaired insulin action.
  31. (2008). et al: 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
  32. (2010). Ferrante AW Jr: C-C chemokine receptor 2 (CCR2) regulates the hepatic recruitment of myeloid cells that promote obesity-induced hepatic steatosis. Diabetes
  33. (2003). Ferrante AW Jr: Obesity is associated with macrophage accumulation in adipose tissue.
  34. (2006). Flier JS: TLR4 links innate immunity and fatty acid induced insulin resistance.
  35. FO: Alternative activation of macrophages: mechanism and functions.
  36. (2000). Free Fatty Acids and Pathogenesis of Type 2 Diabetes Mellitus. Trends in Endocrinology and Metabolism
  37. (2007). Fruhbeck G: Proinflammatory cytokines in obesity: impact of type 2 diabetes mellitus and gastric bypass. Obes Surg
  38. (2003). Funahashi T: Importance of adipocytokines in obesity-related diseases. Horm Res
  39. (2007). Getting to the site of inflammation: the leukocyte adhesion cascade updated. Nat Rev Immunol
  40. (2005). Global burden of obesity in
  41. (2009). Gordon S: Alternative activation of macrophages: immune function and cellular biology. Immunobiology
  42. (2002). H: Adipose tissue gene expression in patients with a loss of function mutation in the leptin receptor. Int J Obes Relat Metab Disord
  43. (2004). HA: Intramyocellular lipid content in type 2 diabetes patients compared with overweight sedentary men and highly trained endurance athletes.
  44. HL: Induction of regulatory T cells decreases adipose inflammation and alleviates insulin resistance in ob/ob mice.
  45. (2002). Hotamisligil GS: A central role for JNK in obesity and insulin resistance. Nature
  46. (2008). Hotamisligil GS: A predominant role for parenchymal c-Jun amino terminal kinase (JNK) in the regulation of systemic insulin sensitivity. PLoS One
  47. (2005). Hotamisligil GS: Inflammation, stress, and diabetes.
  48. (2003). Hotamisligil GS: Obesity-induced inflammatory changes in adipose tissue.
  49. (2009). Human adipose tissue macrophages: m1 and m2 cell surface markers in subcutaneous and omental depots and after weight loss.
  50. (2002). Impairment of Insulin Signaling in Human Skeletal Muscle Cells by Co-Culture With Human Adipocytes. Diabetes
  51. (2008). Inflammation and endoplasmic reticulum stress in obesity and diabetes.
  52. (2003). Inflammation and the IKK beta/I kappa B/NFkappa B axis in obesity- and diet-induced insulin resistance.
  53. (2007). Inflammation, obesity and comorbidities: the role of diet. Public Health Nutr
  54. (2003). Inflammatory pathways and insulin action.
  55. (2009). Inhibition of the chemokine (CC motif) ligand 2/chemokine (C-C motif) receptor 2 pathway attenuates hyperglycaemia and inflammation in a mouse model of hepatic steatosis and lipoatrophy. Diabetologia
  56. (2001). Insulin stimulates PKCzeta -mediated phosphorylation of insulin receptor substrate-1 (IRS-1). A self-attenuated mechanism to negatively regulate the function of IRS proteins.
  57. (2008). IS: HIF-1alpha protein rather than mRNA as a marker of hypoxia in adipose tissue in obesity: focus on “inflammation is associated with a decrease of lipogenic factors in omental fat in women,” by Poulain-Godefroy et al.
  58. (2007). Jr: Obesity-induced inflammation: a metabolic dialogue in the language of inflammation.
  59. (2010). Klip A: NOD2 activation induces muscle cell-autonomous innate immune responses and insulin resistance. Endocrinology
  60. (2009). Klip A: Palmitateand lipopolysaccharide-activated macrophages evoke contrasting insulin responses in muscle cells.
  61. (2007). Konturek PC: Adiponectin, resistin and subclinical inflammation–the metabolic burden in Launois Bensaude Syndrome, a rare form of obesity.
  62. (1999). Leukocyte adhesion molecules in atherogenesis. Clin Chim Acta
  63. (2003). Loskutoff DJ: Monocyte chemoattractant protein 1 in obesity and insulin resistance.
  64. (2009). Loss of Kupffer cells in diet-induced obesity is associated with increased hepatic steatosis, STAT3 signaling, and further decreases in insulin signaling. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
  65. (2005). M: IKK-beta links inflammation to obesityinduced insulin resistance. Nat Med
  66. M: JNK1 and IKKβ: molecular links between obesity and metabolic dysfunction.
  67. (2007). Macrophage heterogeneity and tissue lipids.
  68. (2007). Macrophagesecreted factors impair human adipogenesis: involvement of proinflammatory state in preadipocytes. Endocrinology
  69. (2009). Markers of inflammation and hemodynamic measurements in obesity: Copenhagen City Heart Study. Am J Hypertens
  70. (1999). Mechanisms of TNF-alpha-induced insulin resistance. Exp Clin Endocrinol Diabetes
  71. (2002). Medzhitov R: Innate Immune Recognition. Annual Review of Immunology
  72. (2007). Medzhitov R: Innate immunity–cross-talk with adaptive immunity through pattern recognition receptors and cytokines. Curr Opin Immunol
  73. (2000). MF: The c-Jun NH(2)-terminal kinase promotes insulin resistance during association with insulin receptor substrate-1 and phosphorylation of Ser(307).
  74. (1984). Mitchinson MJ: Monocytic origin of foam cells in human atherosclerotic plaques. Atherosclerosis
  75. (2009). MJ: Examination of ‘lipotoxicity’ in skeletal muscle of high-fat fed and ob/ob mice.
  76. (2003). Molecular mechanisms of inflammation in obesity-linked insulin resistance.
  77. (2000). Molecular mechanisms of insulin resistance and the role of the adipocyte.
  78. (2005). Monocyte Chemoattractant
  79. (2006). Monocyte chemotactic protein-1 is a potential player in the negative cross-talk between adipose tissue and skeletal muscle. Endocrinology
  80. (2008). MP: Adipocyte dysfunctions linking obesity to insulin resistance and type 2 diabetes. Nat Rev Mol Cell Biol
  81. (2011). MP: Body mass index-independent inflammation in omental adipose tissue associated with insulin resistance in morbid obesity. Surgery for Obesity and Related Diseases
  82. (2008). MP: Leptin resistance: a possible interface of inflammation and metabolism in obesity-related cardiovascular disease.
  83. (2011). National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 2.7 million participants. The Lancet
  84. (2008). Neels JG: Ablation of CD11c-positive cells normalizes insulin sensitivity in obese insulin resistant animals. Cell Metab
  85. (2008). Neutrophils transiently infiltrate intra-abdominal fat early in the course of high-fat feeding.
  86. (1999). O’Rahilly S: Effects of recombinant leptin therapy in a child with congenital leptin deficiency.
  87. (2009). O’Rahilly S: Leptin: a pivotal regulator of human energy homeostasis.
  88. (2006). Obin MS: Obesity and the role of adipose tissue in inflammation and metabolism.
  89. (1997). of 9IkB Kinases Essential for NF-kB Activation. Science
  90. (2007). Olefsky JM: 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.
  91. (2009). Olefsky JM: Glucocorticoids and thiazolidinediones interfere with adipocytemediated macrophage chemotaxis and recruitment.
  92. (2006). Olefsky JM: Inflamed fat: what starts the fire?
  93. (2008). Olefsky JM: Insulin sensitivity: modulation by nutrients and inflammation.
  94. (2005). PA: Expression of CD68 and macrophage chemoattractant protein-1 genes in human adipose and muscle tissues: association with cytokine expression, insulin resistance, and reduction by pioglitazone. Diabetes
  95. (1999). Penicaud L: A role for preadipocytes as macrophage-like cells.
  96. (2001). Penicaud L: Altered macrophage-like functions of preadipocytes in inflammation and genetic obesity.
  97. (2007). Pothoulakis C: Obesity, innate immunity and gut inflammation. Curr Opin Gastroenterol
  98. (1998). RB: The anti-inflammatory agents aspirin and salicylate inhibit the activity of I(kappa)B kinase-beta.
  99. (2007). Recognition of microorganisms and activation of the immune response. Nature
  100. (2003). Resistin and type 2 diabetes: regulation of resistin expression by insulin and rosiglitazone and the effects of recombinant resistin on lipid and glucose metabolism in human differentiated adipocytes.
  101. (2005). Role of endoplasmic reticulum stress and c-Jun NH2-terminal kinase pathways in inflammation and origin of obesity and diabetes. Diabetes
  102. (1997). Role of pro- and anti-inflammatory cytokines during inflammation: experimental and clinical findings. J Biol Regul Homeost Agents
  103. (2006). Rondinone CM: PKCtheta is a key player in the development of insulin resistance.
  104. (2009). S: Alternative activation of macrophages: an immunologic functional perspective. Annu Rev Immunol
  105. (2007). SA: Obesity and inflammation: II. Curr Gastroenterol Rep
  106. (2007). SA: Obesity and inflammation: III. Curr Gastroenterol Rep
  107. (2007). Saltiel AR: Increased inflammatory properties of adipose tissue macrophages recruited during diet-induced obesity. Diabetes
  108. (2007). Saltiel AR: Obesity induces a phenotypic switch in adipose tissue macrophage polarization.
  109. (2008). Saltiel AR: Phenotypic switching of adipose tissue macrophages with obesity is generated by spatiotemporal differences in macrophage subtypes. Diabetes
  110. (2009). Saltiel AR: T-ing up inflammation in fat. Nat Med
  111. (2008). Schrauwen-Hinderling VB: Lipid accumulation in nonadipose tissue and lipotoxicity. Physiol Behav
  112. (2009). Schwartz MW: Does hypothalamic inflammation cause obesity? Cell Metab
  113. sheet: Obesity and overweight.
  114. (2007). Shulman GI: Inhibition of protein kinase Cepsilon prevents hepatic insulin resistance in nonalcoholic fatty liver disease.
  115. (2004). Skeletal muscle lipid accumulation in obesity, insulin resistance, and type 2 diabetes. Pediatr Diabetes
  116. (2001). Skeletal Muscle Lipid Content and Insulin Resistance: Evidence for a Paradox in Endurance-Trained Athletes.
  117. (2009). Spriet LL: Regulation of skeletal muscle mitochondrial fatty acid metabolism in lean and obese individuals.
  118. (2007). Stulnig TM: Adipose tissue macrophages. Immunology Letters
  119. (2007). Stulnig TM: Human adipose tissue macrophages are of an antiinflammatory phenotype but capable of excessive pro-inflammatory mediator production.
  120. (2007). The macrophage: past, present and future.
  121. (2006). The mononuclear phagocyte system. Curr Opin Immunol
  122. (2006). Toll-like Receptor-2 Is Essential for the Development of Palmitate-induced Insulin Resistance in Myotubes.
  123. (2004). Unraveling the multiple roles of leptin in inflammation and autoimmunity.
  124. (2003). Unravelling mononuclear phagocyte heterogeneity. Nat Rev Immunol 10(6):453-460.
  125. (2009). Vignes S: [Inflammation, adipokines and obesity]. Rev Med Interne
  126. (2011). W: Conditioned medium from hypoxia-treated adipocytes renders muscle cells insulin resistant.
  127. (2010). Weight loss and lipolysis promote a dynamic immune response in murine adipose tissue.
  128. (2004). Wood IS: Adipokines: inflammation and the pleiotropic role of white adipose tissue.
  129. (2005). Wood IS: Signalling role of adipose tissue: adipokines and inflammation in obesity. Biochem Soc Trans
  130. (2007). Yeh ET: Obesity, inflammation, and vascular disease: the role of the adipose tissue as an endocrine organ. Subcell Biochem

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.