Cellular and molecular players in adipose tissue inflammation in the development of obesity-induced insulin resistance

Biochim Biophys Acta. 2014 Mar;1842(3):446-62. doi: 10.1016/j.bbadis.2013.05.017. Epub 2013 May 22.


There is increasing evidence showing that inflammation is an important pathogenic mediator of the development of obesity-induced insulin resistance. It is now generally accepted that tissue-resident immune cells play a major role in the regulation of this obesity-induced inflammation. The roles that adipose tissue (AT)-resident immune cells play have been particularly extensively studied. AT contains most types of immune cells and obesity increases their numbers and activation levels, particularly in AT macrophages (ATMs). Other pro-inflammatory cells found in AT include neutrophils, Th1 CD4 T cells, CD8 T cells, B cells, DCs, and mast cells. However, AT also contains anti-inflammatory cells that counter the pro-inflammatory immune cells that are responsible for the obesity-induced inflammation in this tissue. These anti-inflammatory cells include regulatory CD4 T cells (Tregs), Th2 CD4 T cells, and eosinophils. Hence, AT inflammation is shaped by the regulation of pro- and anti-inflammatory immune cell homeostasis, and obesity skews this balance towards a more pro-inflammatory status. Recent genetic studies revealed several molecules that participate in the development of obesity-induced inflammation and insulin resistance. In this review, the cellular and molecular players that participate in the regulation of obesity-induced inflammation and insulin resistance are discussed, with particular attention being placed on the roles of the cellular players in these pathogeneses. This article is part of a Special Issue entitled: Modulation of Adipose Tissue in Health and Disease.

Keywords: ABCA; AIM; APC; ASC; AT; AT macrophage; ATM; ATP-binding cassette transporter; Adipose tissue; Adipose tissue immune cell; Apoptosis inhibitor of macrophage; BLT; BM; BMT; Bregs; C-C chemokine receptor type 2; C-X-C motif chemokine 5; C-X-C motif receptor 2; CCL5; CCR2; CLSs; CTLs; CX3C chemokine receptor 1; CX3CR1; CXCL5; CXCR2; Casp1; Caspase 1; Chemokine (C-C motif) ligand 5; DAMPs; DC; Damage-associated molecular pattern molecules; Dendritic cells; ECM; FABP; FFA; Free fatty acids; G-protein coupled receptor 120; GFP; GLUT4; GPR120; Glucose transporter type 4; HFD; HMGB1; IKKb; IR; IRS; Insulin receptor substrate; Insulin resistance; JNKs; Jun N-terminal kinases; KLF4; Krueppel-like factor 4; MAPK; MCP-1; MGL1; MHC; MPO; Major histocompatibility complex; NE; NFkB; NKT; NLS; NOD-like receptor family, pyrin domain containing 3; Natural Killer T cell; Nlrp3; Obesity-induced Inflammation; PBMC; PKC; PPAR; PRRs; Pattern recognition receptors; Protein kinase C; RAGs; RANTES; ROS; Reactive oxygen species; Recombination activating genes; Regulated on Activation Normal T cell Expressed and Secreted; SOCS1; SVC; Sorbin and SH3 domain-containing protein 1; Sorbs1; Suppressor of cytokine signaling 1; T cell receptors; T2D; TAMs; TCRs; TLR; TNF; TZDs; Toll-like receptors; Treg; Tumor necrosis factors; Type 2 Diabetes; adipose tissue; antigen-presenting cell; apoptotic speck protein containing a caspase recruitment domain; bone marrow; bone marrow transplantation; crown-like structures; cytotoxic T cells; double stranded DNA; dsDNA; extracellular matrix; fatty-acid-binding protein; green fluorescent protein; high fat diet; high-mobility group box 1; inhibitor of κB kinase-β; insulin receptor; leukotriene B4 receptor; macrophage galactose-type lectin 1; mitogen-activated protein kinase; monocyte chemotactic protein-1; myeloperoxidase; neutrophil elastase; nuclear factor kappa-light-chain-enhancer of activated B cells; nuclear localization sequence; peripheral blood mononuclear cell; peroxisome proliferator-activated receptors; regulator T cells; regulatory B cells; stromal vascular cell; thiazolidinediones; tumor-associated macrophages.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adipose Tissue / immunology*
  • Adipose Tissue / metabolism
  • Adipose Tissue / pathology
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Humans
  • Inflammation / immunology
  • Inflammation / metabolism*
  • Inflammation / pathology
  • Insulin Resistance / genetics*
  • Insulin Resistance / immunology
  • Kruppel-Like Factor 4
  • Macrophages / cytology
  • Macrophages / immunology
  • Neutrophils / immunology
  • Neutrophils / metabolism
  • Obesity / immunology*
  • Obesity / metabolism
  • Obesity / pathology
  • Th1 Cells / immunology
  • Th1 Cells / metabolism