The inflammation highway: metabolism accelerates inflammatory traffic in obesity

Authors

  • Amy R. Johnson,

    1. Department of Nutrition, Gillings School of Global Public Health and School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
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  • J. Justin Milner,

    1. Department of Nutrition, Gillings School of Global Public Health and School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
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  • Liza Makowski

    Corresponding author
    • Department of Nutrition, Gillings School of Global Public Health and School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
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Correspondence to:

Liza Makowski

Department of Nutrition

2203 McGavran-Greenberg Hall CB#7461

University of North Carolina at Chapel Hill

Chapel Hill, NC 27599, USA

Tel.: +1 919 843 4383

Fax: +1 919 966 7216

e-mail: liza.makowski@unc.edu

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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