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Linking Inflammation, Obesity and Diabetes

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Metabolic Syndrome

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Abstract

Overnutrition disrupts normal adipose tissue function. Dysfunctional lipid metabolism leads to an increase in circulating free fatty acids, initiating inflammatory signaling cascades and increased immune cell activity in metabolic tissue. A feedback loop of pro-inflammatory cytokines exacerbates this chronic inflammatory state, driving further immune cell infiltration, cytokine secretion, and activation of inflammasome complexes. This disrupts the insulin signaling cascade and is causative of defects in hepatic and skeletal muscle glucose homeostasis, resulting in systemic insulin resistance and ultimately the development of type 2 diabetes. This chapter will focus on the initiation of the inflammatory response in obesity and describe the impact of this on metabolic tissue, with a particular emphasis on the development of insulin resistance and type 2 diabetes. We will also review current and prospective treatment and intervention strategies and the biological mechanisms through which these function.

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Abbreviations

ADP:

Adenosine diphosphate

AMP:

Adenosine monophosphate

AMPK:

AMP-activated protein kinase

ASC:

Apoptosis-associated speck-like protein containing a CARD

ATM:

Adipose tissue macrophages

ATP:

Adenosine triphosphate

BAT:

Brown adipose tissue

BMI:

Body mass index

BMM:

Bone marrow macrophages

CCR:

C–C chemokine receptor

CLS:

Crown-like structures

DAG:

Diacylglycerols

DAMPs:

Danger-associated molecular patterns

DC:

Dendritic cell

DGAT:

Diacylglycerol acyltransferase

DHA:

Docosahexaenoic acid

DIO:

Diet-induced obesity

ECM:

Extracellular matrix

EPA:

Eicosapentaenoic acid

FA:

Fatty acids

FFA:

Free fatty acids

Fiaf:

Fasting-induced adipocyte factor

GLUT:

Glucose transporter type

GPR:

G protein-coupled receptor

HFD:

High-fat diet

ICAM:

Intercellular adhesion molecule

IKK:

IκB kinase

IL:

Interleukin

IR:

Insulin resistance

IRS:

Insulin receptor substrate

IS:

Insulin sensitivity

IκB:

Inhibitor of κB

JNK:

c-Jun N-terminal kinase

LPS:

Lipopolysaccharide

MAPK:

Mitogen-activated protein kinase

MCP:

Monocyte chemoattractant protein

MetS:

Metabolic syndrome

MHC:

Major histocompatibility complex

MUFA:

Monounsaturated fatty acids

NF-κB:

Nuclear factor kappa B

NLR:

NOD-like receptor

PI3K:

Phosphatidylinositol 3-kinase

PKB:

Protein kinase B

PKC:

Protein kinase C

PPAR:

Peroxisome proliferator-activated receptor

PUFA:

Polyunsaturated fatty acids

R:

Receptor

RA:

Receptor antagonist

SCFA:

Short-chain fatty acid

SFA:

Saturated fatty acids

SOCS:

Suppressor of cytokine signaling

SVF:

Stromal vascular fraction

T2D:

Type 2 diabetes

TAG:

Triacylglycerol

TH :

T helper

TLR:

Toll-like receptor

TNF:

Tumor necrosis factor

TNFR:

Tumor necrosis factor receptor

Treg:

Regulatory T cell

TZDs:

Thiazolidinediones

UCP-1:

Uncoupling protein 1

WAT:

White adipose tissue

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  1. University College Dublin, Dublin, County Dublin, Ireland

    Maeve A. McArdle, Elaine B. Kennedy & Helen M. Roche

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    Rexford S. Ahima

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McArdle, M.A., Kennedy, E.B., Roche, H.M. (2015). Linking Inflammation, Obesity and Diabetes. In: Ahima, R. (eds) Metabolic Syndrome. Springer, Cham. https://doi.org/10.1007/978-3-319-12125-3_29-1

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