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.
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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
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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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Sanz, Y., Moya-Pérez, A. (2014). Microbiota, Inflammation and Obesity. In: Lyte, M., Cryan, J. (eds) Microbial Endocrinology: The Microbiota-Gut-Brain Axis in Health and Disease. Advances in Experimental Medicine and Biology(), vol 817. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-0897-4_14
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