Current Diabetes Reports

, 17:87 | Cite as

The Immune System in Obesity: Developing Paradigms Amidst Inconvenient Truths

  • Madhur Agrawal
  • Philip A. Kern
  • Barbara S. Nikolajczyk
Obesity (J McCaffery, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Obesity


Purpose of Review

Adipose tissue (AT) houses both innate and adaptive immune systems that are crucial for preserving AT function and metabolic homeostasis. In this review, we summarize recent information regarding progression of obesity-associated AT inflammation and insulin resistance. We additionally consider alterations in AT distribution and the immune system in males vs. females and among different racial populations.

Recent Findings

Innate and adaptive immune cell-derived inflammation drives insulin resistance both locally and systemically. However, new evidence also suggests that the immune system is equally vital for adipocyte differentiation and protection from ectopic lipid deposition. Furthermore, roles of anti-inflammatory immune cells such as regulatory T cells, “M2-like” macrophages, eosinophils, and mast cells are being explored, primarily due to promise of immunotherapeutic applications. Both immune responses and AT distribution are strongly influenced by factors like sex and race, which have been largely underappreciated in the field of metabolically-associated inflammation, or meta-flammation.


More studies are required to recognize factors that switch inflammation from controlled to uncontrolled in obesity-associated pathogenesis and to integrate the combined effects of meta-flammation and immunometabolism. It is critical to recognize that the AT-associated immune system can be alternately beneficial and destructive; therefore, simply blocking immune responses early in obesity may not be the best clinical approach. The dearth of information on gender and race-associated disparities in metabolism, AT distribution, and the immune system suggest that a greater understanding of such differences will be critical to develop personalized treatments for obesity and the associated metabolic dysfunction.


Adipose tissue Obesity Innate immunity Adaptive immunity Gender Race Ethnicity 



Protein kinase B or PKB


Adipose tissue


Adenosine triphosphate


Brown adipose tissue


Body mass index


Regulatory B cell


C-C motif chemokine ligand 18


C-C motif chemokine ligand 2


C-C motif chemokine ligand 3


C-C motif chemokine ligand 4


C-C motif chemokine ligand 5


C-C motif chemokine ligand 7


CD11 antigen-like family member B/integrin subunit alpha M


CD11 antigen-like family member B/integrin subunit alpha M


Cluster of differentiation 14


Cluster of differentiation 206


Cluster of differentiation 3


Cluster of differentiation 301


Cluster of differentiation 4


Cluster of differentiation 45


Cluster of differentiation 69


Cluster of differentiation 8


Cyclic guanosine monophosphate


Crown-like structures


Collagen type I alpha 1 chain


Collagen type 3 alpha 1 chain


Collagen 6


Collagen type 6 alpha 1 chain


C-reactive protein


Cardiovascular disease


C-X-C motif chemokine ligand 1


C-X-C motif chemokine ligand 10


C-X-C motif chemokine ligand 8


Diet-induced obesity


EGF-like module-containing mucin-like hormone receptor-like 1


Fatty acid binding protein 4


Fibroblast growth factor 21


Forkhead box P3


GATA binding protein 3


Growth hormone


Guanylate cyclase 1 soluble subunit beta


Hemoglobin A1c or glycated hemoglobin


High-fat diet


Hypoxia-inducible factor 1 alpha subunit




Interferon gamma


Interleukin 10


Interleukin 13


Interleukin 1


Interleukin 3


Interleukin 33


Interleukin 4


Interleukin 5


Interleukin 6


Interleukin 8


IL-4 receptor subunit alpha


Intermuscular fat


Invariant natural killer T cells


Insulin resistance


Low-density lipoprotein




Monocyte chemotactic protein 1


Myogenic factor 6


Natural killer


Paired box 7


Protein kinase A


Peroxisome proliferator-activated receptor gamma


Protein kinase, cGMP-dependent, type I


Regulated upon activation, normally T-expressed, and presumably secreted/C-C motif chemokine ligand 5


Serum amyloid A3


Subcutaneous adipose tissue


Signal transducer and activator of transcription 6


Type 2 diabetes


Transforming growth factor beta


T helper 1


T helper 17


T helper 2


Toll-like receptor 13


Toll-like receptor 4


Toll-like receptor 7


Toll-like receptor 8


Tumor necrosis factor alpha


Regulatory T cells




Uncoupling protein 1


Visceral adipose tissue


Vascular endothelial growth factor


White adipose tissue


World Health Organization


Wild type



Barbara S. Nikolajczyk reports grants from the NIH (R01DK108056 and R01 DE025383). Philip A. Kern reports grants from the NIH (R01 DK107646, R01DK112282, and UL1TR001998).

Compliance with Ethical Standards

Conflict of Interest

Madhur Agrawal, Philip A. Kern, and Barbara S. Nikolajczyk declare that they have no conflicts of interest.

Human and Animal Rights and Informed Consent

All reported studies/experiments with human or animal subjects performed by the authors have been previously published and complied with all applicable ethical standards (including the Helsinki Declaration and its amendments, institutional/national research committee standards, and international/national/institutional guidelines).


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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Madhur Agrawal
    • 1
  • Philip A. Kern
    • 2
  • Barbara S. Nikolajczyk
    • 1
    • 3
    • 4
  1. 1.Department of MicrobiologyBoston University School of MedicineBostonUSA
  2. 2.Department of Medicine, Division of EndocrinologyUniversity of KentuckyLexingtonUSA
  3. 3.Department of PathologyBoston University School of MedicineBostonUSA
  4. 4.Department of Molecular and Cell BiologyBoston University Goldman School of Dental MedicineBostonUSA

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