Obesity is a major public health problem worldwide, and it is associated with an increased
risk of developing type 2 diabetes. It is now commonly accepted that chronic inflammation
associated with obesity induces insulin resistance and β-cell dysfunction in diabetic
patients. Obesity-associated inflammation is characterized by increased abundance
of macrophages and enhanced production of inflammatory cytokines in adipose tissue.
Adipose tissue macrophages are suggested to be the major source of local and systemic
inflammatory mediators such as tumor necrosis factor α, interleukin (IL)-1β, and IL-6.
These cytokines induce insulin resistance in insulin target tissues by activating
the suppressors of cytokine signaling proteins, several kinases such as c-Jun N-terminal
kinase, IκB kinase β, and protein kinase C, inducible nitric oxide synthase, extracellular
signal-regulated kinase, and protein tyrosine phosphatases such as protein tyrosine
phosphatase 1B. These activated factors impair the insulin signaling at the insulin
receptor and the insulin receptor substrates levels. The same process most likely
occurs in the pancreas as it contains a pool of tissue-resident macrophages. High
concentrations of glucose or palmitate via the chemokine production promote further
immune cell migration and infiltration into the islets. These events ultimately induce
inflammatory responses leading to the apoptosis of the pancreatic β cells. In this
review, the cellular and molecular players that participate in the regulation of obesity-induced
inflammation are discussed, with particular attention being placed on the roles of
the molecular players linking inflammation to insulin resistance and β-cell dysfunction.
Abbreviations:
AMPK (AMP-activated protein kinase), ATM (adipose tissue macrophages), CCL (chemokine (C-C motif) ligand), CCR2 (chemokine (C-C motif) receptor 2), CX3CL1 (chemokine (C-X3-C motif) ligand 1), CX3CR1 (chemokine (C-X3-C motif) receptor), CXCL (CXC chemokine ligand), DAG (diacylglycerol), ER (endoplasmic reticulum), ERK (extracellular signal-regulated kinase), FFA (free fatty acid), GLUT (glucose transporter), HFD (high-fat diet), IAPP (islet amyloid polypeptide), IFN-γ (interferon gamma), IKKβ (IκB kinase β), IL-6 (interleukin 6), IL-1β (interleukin 1 β), IL-10 (interleukin 10), IL-4 (interleukin 4), IL-13 (interleukin 13), iNOS (inducible nitric oxide synthase), IRE1 (inositol-requiring protein 1), IRS (insulin receptor substrate), JNK (c-Jun N-terminal kinase), LAR (leukocyte antigen related), LPS (lipopolysaccharide), LTB4 (leukotriene B4), MAPK (mitogen-activated protein kinase), MCP-1 (monocyte chemotactic protein 1), mTORC (mammalian target of rapamycin complex), MyD88 (myeloid differentiation primary response gene 88), NF-κB (nuclear factor kappa B), NK cell (natural killer cells), NLRs (NOD-like receptors), NLRP3 (NLR pyrin domain containing 3), NO (nitric oxide), PAMPs (pathogen-associated molecular patterns), PDX-1 (pancreatic and duodenal homeobox 1), PI3-kinase (phosphoinositide (PI) 3-kinase), PKC (protein kinase C), PP2A (protein phosphatase 2A), PRRs (pattern recognition receptors), PTEN (phosphatase and tensin homolog), PTPs (protein tyrosine phosphatases), PTP1B (protein tyrosine phosphatase 1B), ROS (reactive oxygen species), SHIP2 (SH2 domain-containing inositol-5-phosphatase 2), SOCS (suppressors of cytokine signaling), T2D (type 2 diabetes), Th1 (T-helper 1), TLR4 (toll-like receptor 4), TNF-α (tumor necrosis factor α), TRAF2 (TNF receptor–associated factor 2), Treg cell (regulatory T cell), TSC1 (tuberous sclerosis 1), TSC2 (tuberous sclerosis 2), UPR (unfolded protein response), WAT (white adipose tissue)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: September 05, 2015
Accepted:
August 31,
2015
Received in revised form:
August 29,
2015
Received:
July 13,
2015
Footnotes
Hadi Khodabandehloo, Sattar Gorgani-Firuzjaee, and Ghodratollah Panahi contributed equally to this work.
Identification
Copyright
© 2016 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
