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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

Abstract

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.

Summary

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.

Keywords

Adipose tissue Obesity Innate immunity Adaptive immunity Gender Race Ethnicity 

Abbreviations

Akt

Protein kinase B or PKB

AT

Adipose tissue

ATP

Adenosine triphosphate

BAT

Brown adipose tissue

BMI

Body mass index

Bregs

Regulatory B cell

CCL18

C-C motif chemokine ligand 18

CCL2

C-C motif chemokine ligand 2

CCL3

C-C motif chemokine ligand 3

CCL4

C-C motif chemokine ligand 4

CCL5

C-C motif chemokine ligand 5

CCL7

C-C motif chemokine ligand 7

CD11b

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

CD11c

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

CD14

Cluster of differentiation 14

CD206

Cluster of differentiation 206

CD3

Cluster of differentiation 3

CD301

Cluster of differentiation 301

CD4

Cluster of differentiation 4

CD45

Cluster of differentiation 45

CD69

Cluster of differentiation 69

CD8

Cluster of differentiation 8

cGMP

Cyclic guanosine monophosphate

CLS

Crown-like structures

Col1a1

Collagen type I alpha 1 chain

Col3a1

Collagen type 3 alpha 1 chain

Col6

Collagen 6

Col6a1

Collagen type 6 alpha 1 chain

CRP

C-reactive protein

CVD

Cardiovascular disease

CXCL1

C-X-C motif chemokine ligand 1

CXCL10

C-X-C motif chemokine ligand 10

CXCL8

C-X-C motif chemokine ligand 8

DIO

Diet-induced obesity

F4/80

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

FABP4

Fatty acid binding protein 4

FGF21

Fibroblast growth factor 21

Foxp3

Forkhead box P3

GATA3

GATA binding protein 3

GH

Growth hormone

GUCYB3

Guanylate cyclase 1 soluble subunit beta

HbA1C

Hemoglobin A1c or glycated hemoglobin

HFD

High-fat diet

HIF1

Hypoxia-inducible factor 1 alpha subunit

IFN

Interferon

IFNg

Interferon gamma

IL-10

Interleukin 10

IL-13

Interleukin 13

IL-1

Interleukin 1

IL-3

Interleukin 3

IL-33

Interleukin 33

IL-4

Interleukin 4

IL-5

Interleukin 5

IL-6

Interleukin 6

IL-8

Interleukin 8

IL4ra

IL-4 receptor subunit alpha

IMAT

Intermuscular fat

iNKT

Invariant natural killer T cells

IR

Insulin resistance

LDL

Low-density lipoprotein

LPS

Lipopolysaccharide

MCP-1

Monocyte chemotactic protein 1

Myf6

Myogenic factor 6

NK

Natural killer

PAX7

Paired box 7

PKA

Protein kinase A

PPARγ

Peroxisome proliferator-activated receptor gamma

PRKG1

Protein kinase, cGMP-dependent, type I

RANTES

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

SAA3

Serum amyloid A3

SAT

Subcutaneous adipose tissue

STAT6

Signal transducer and activator of transcription 6

T2D

Type 2 diabetes

TGF

Transforming growth factor beta

Th1

T helper 1

Th17

T helper 17

Th2

T helper 2

TLR13

Toll-like receptor 13

TLR4

Toll-like receptor 4

TLR7

Toll-like receptor 7

TLR8

Toll-like receptor 8

TNF

Tumor necrosis factor alpha

Tregs

Regulatory T cells

TZDs

Thiazolidinediones

UCP1

Uncoupling protein 1

VAT

Visceral adipose tissue

VEGF

Vascular endothelial growth factor

WAT

White adipose tissue

WHO

World Health Organization

WT

Wild type

Notes

Acknowledgments

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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