Cited by 603Adipokines, Inflammation, and Metabolic DiseasesAdipose Tissue and MetabolismPeroxisome Proliferator-Activated Receptors

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The inflammation highway: metabolism accelerates inflammatory traffic in obesity

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Johnson, Amy R., Justin Milner, J., Makowski, Liza·2012·Immunological Reviews

DOI 10.1111/j.1600-065x.2012.01151.xPMC PMC3422768

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Abstract

Summary: As humans evolved, perhaps the two strongest selection determinants of survival were a robust immune response able to clear bacterial, viral, and parasitic infection and an ability to efficiently store nutrients to survive times when food sources were scarce. These traits are not mutually exclusive. It is now apparent that critical proteins necessary for regulating energy metabolism, such as peroxisome proliferator‐activated receptors, Toll‐like receptors, and fatty acid‐binding proteins, also act as links between nutrient metabolism and inflammatory pathway activation in immune cells. Obesity in humans is a symptom of energy imbalance: the scale has been tipped such that energy intake exceeds energy output and may be a result, in part, of evolutionary selection toward a phenotype characterized by efficient energy storage. As discussed in this review, obesity is a state of low‐grade, chronic inflammation that promotes the development of insulin resistance and diabetes. Ironically, the formation of systemic and/or local, tissue‐specific insulin resistance upon inflammatory cell activation may actually be a protective mechanism that co‐evolved to repartition energy sources within the body during times of stress during infection. However, the point has been reached where a once beneficial adaptive trait has become detrimental to the health of the individual and an immense public health and economic burden. This article reviews the complex relationship between obesity, insulin resistance/diabetes, and inflammation, and although the liver, brain, pancreas, muscle, and other tissues are relevant, we focus specifically on how the obese adipose microenvironment can promote immune cell influx and sustain damaging inflammation that can lead to the onset of insulin resistance and diabetes. Finally, we address how substrate metabolism may regulate the immune response and discuss how fuel uptake and metabolism may be a targetable approach to limit or abrogate obesity‐induced inflammation.

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T-Cell Accumulation and Regulated on Activation, Normal T Cell Expressed and Secreted Upregulation in Adipose Tissue in Obesity
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Inhibition of protein kinase Cε prevents hepatic insulin resistance in nonalcoholic fatty liver disease
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10.1172/JCI20514 · DOI · Paper page
10.1111/j.1469-7793.2003.00335.x · DOI · Paper page

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See all 603

Authors: Johnson, A. R., Justin Milner, J., & Makowski, L.
Affiliations: University of North Carolina at Chapel Hill (US)
Department of Nutrition Gillings School of Global Public Health and School of Medicine University of North Carolina at Chapel Hill Chapel Hill NC USA
Corresponding author: Makowski, Liza
ORCID: Johnson, Amy R.
Makowski, Liza
Venue: Immunological Reviews
Publisher: Wiley
Published: 2012-08-14
Volume: 249
Issue: 1
Pages: 218-238
ISSN: 0105-2896 (ISSN-L)
1600-065X
DOI: 10.1111/j.1600-065x.2012.01151.x
PMC: PMC3422768
OpenAlex: W1968604913
Cited by: 603
References: 290
Citations by year: 2026: 9 · 2025: 25 · 2024: 26 · 2023: 38 · 2022: 40 · 2021: 57 · 2020: 46 · 2019: 67 · 2018: 47 · 2017: 62 · 2016: 51 · 2015: 41 · 2014: 46 · 2013: 42 · 2012: 4
FWCI: 5.31
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Immunological Reviews (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Institute on Alcohol Abuse and Alcoholism (AA017376, K99AA017376, R00AA017376)
National Cancer Institute (P50CA058223)
National Institute of Diabetes and Digestive and Kidney Diseases (P30DK034987, P30DK056350)
National Institute of Environmental Health Sciences (U01ES019472, ES019472)
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
Keywords: obesity, low-grade inflammation, insulin resistance, type 2 diabetes, adipose tissue microenvironment, immune cell infiltration, energy metabolism, peroxisome proliferator-activated receptors, Toll-like receptors, fatty acid binding protein, substrate metabolism, immune regulation
MeSH terms: Adipose Tissue, Animals, B-Lymphocytes, Energy Intake, Diabetes Mellitus, Energy Metabolism, Humans, Inflammation, Insulin Resistance, Macrophages, Obesity, T-Lymphocytes, Peroxisome Proliferator-Activated Receptors, Fatty Acid-Binding Proteins, Toll-Like Receptors

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The inflammation highway: metabolism accelerates inflammatory traffic in obesity

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