The DOI matches its Crossref record; 290 of the 290 references it cites were found in a registry or an index.
The inflammation highway: metabolism accelerates inflammatory traffic in obesity
Open accessAbstract
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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“Hypertrophy leads to multiple fold increase in infiltration of macrophages in WAT (55, 56), which promotes a pro-inflammatory and insulin resistant environment.”
From Metabolic impact of endogenously produced estrogens by adipose tissue in females and males across the lifespan (2025) · cites this paper as [56]
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“Conversely, macrophages that rely on fatty acid metabolism secrete anti-inflammatory cytokines and thus preserve insulin sensitivity of liver and adipose tissue (type M2) (167, 168).”
From Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease (2018) · cites this paper as [167]
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Pathophysiology of type 2 diabetes mellitus
Galicia-Garcia, U., Benito-Vicente, A., Jebari, S., Larrea-Sebal, A., Siddiqi, H., Uribe, K. B., Ostolaza, H., & Martín, C. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21176275 · Cited by 3,360
“Among them, patients with T2DM have higher levels of IL-1b, IL-6, IL-8, MCP-1, and other major cytokines in both monocytes and macrophages [130].”
BackgroundThe intestinal microbiota fuelling metabolic inflammation
Tilg, H., Zmora, N., Adolph, T. E., & Elinav, E. (2020) · Nature Reviews Immunology · doi:10.1038/s41577-019-0198-4 · Cited by 1,089
Inflammation and immunity in the pathogenesis of pulmonary arterial hypertension
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Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease
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Mitochondrial dysfunction in obesity
de Mello, A. H., Costa, A. B., Engel, J. D. G., & Rezin, G. T. (2018) · Life Sciences · doi:10.1016/j.lfs.2017.11.019 · Cited by 508
Metadata
- 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
- Venue
- Immunological Reviews
- Publisher
- Wiley
- Published
- 2012-08-14
- Volume
- 249
- Issue
- 1
- Pages
- 218-238
- ISSN
- 0105-2896 (ISSN-L)
- 1600-065X
- 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
- 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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