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Microbiota, Inflammation and Obesity

  • Yolanda SanzEmail author
  • Angela Moya-Pérez
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 817)

Abstract

Interactions between metabolism and immunity play a pivotal role in the development of obesity-associated chronic co-morbidities. Obesity involves impairment of immune function affecting both the innate and adaptive immune system. This leads to increased risk of infections as well as chronic low-grade inflammation, which in turn causes metabolic dysfunction (e.g. insulin resistance) and chronic disease (e.g. type-2 diabetes). Gut microbiota has emerged as one of the key factors regulating early events triggering inflammation associated with obesity and metabolic dysfunction. This effect seems to be related to diet- and obesity-associated changes in gut microbiota composition and to increased translocation of immunogenic bacterial products, which activate innate and adaptive immunity in the gut and beyond, contributing to an increase in inflammatory tone. Innate immune receptors, like Toll-like receptors (TLRs), are known to be up-regulated in the tissue affected by most inflammatory disorders and activated by both specific microbial components and dietary lipids. This triggers several signaling transduction pathways (e.g. JNK and IKKβ/NF-κB), leading to inflammatory cytokine and chemokine (TNF-α, IL-1, MCP1) production and to inflammatory cell recruitment, causing insulin resistance. T-cell differentiation into effector inflammatory or regulatory T cells also depends on the type of TLR activated and on cytokine production, which in turn depends upon gut microbiota-diet interactions. Here, we update and discuss our current understanding of how gut microbiota could contribute to defining whole-body metabolism by influencing diverse components of the innate and adaptive immune system, both locally and systemically.

Keywords

Insulin Resistance Adipose Tissue Adaptive Immune System Metabolic Dysfunction Adipose Tissue Inflammation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

BMI

Body mass index

ER

Endoplasmic reticulum

ERK

Extracellular signal-regulated kinase

ERS

Endoplasmic reticulum stress

FetA

Fetuin-A

HFD

High-fat diet

IKK

Inhibitory κB kinase

IL

Interleukin

IL-1Ra

IL-1 receptor antagonist

iNOS

Inducible nitric oxide synthase

IR

Insulin receptor

IRF

Interferon regulatory transcription factor

IRS

Insulin receptor substrate

IRS-1

Insulin receptor substrate 1

LPS

Lipopolysaccharide

LTA

Lipoteichoic acids

M1

“Classically activated” macrophages

M2

“Alternative activated” macrophages

MAPKs

Mitogen-activated protein kinases

M-cells

Microfold cells

MCP

Monocyte chemotactic protein

MDP

Muramyl dipeptide

Meso-DAP

d-Glutamyl-meso-diaminopimelic acid

MHC

Major histocompatibility complex

NF- κB

Nuclear factor-κB

NKT

Natural killer T

NLRs

Nod-like receptor family

NOD

Nucleotide oligomerization domain

NOS2

Nitric-oxide synthase 2

PGN

Peptidoglycan

PI3K

Phosphatidylinositol 3-kinase

PI3-K

Phosphatidylinositol 3-kinase

RHM

Recruited hepatic macrophage

ROS

Reactive oxygen species

SAA3

Serum amyloid A3 protein

SFA

Saturated fatty acid

SOC

Suppressor of cytokine signaling

STAT3

Signal transducer and activator of transcription 3

TH1

T helper 1

TLRs

Toll-like receptor family

TNF

Tumor necrosis factor

Tregs

Regulatory T

ZO

Zonula occludens

Notes

Acknowledgements

This work was supported by grants AGL2011-25169 and Consolider Fun-C-Food CSD2007-00063 from the Spanish Ministry of Economy and Competitiveness (MINECO, Spain). The scholarship of A Moya from MINECO is fully acknowledged.

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Copyright information

© Springer New York 2014

Authors and Affiliations

  1. 1.Microbial Ecology, Nutrition & HealthNational Research Council (IATA-CSIC)PaternaSpain

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