Nutrigenomics pp 121-137 | Cite as

Chronic Inflammation and Metabolic Stress

  • Carsten Carlberg
  • Stine Marie Ulven
  • Ferdinand Molnár


Macrophages are associated with various tissues and either derive from monocytes circulating in the blood or from self-renewing embryonal cell populations. They show a large variety of stimulus- and tissue-specific functions, of which the extremes are pro-inflammatory M1-type and anti-inflammatory M2-type macrophages. M1 macrophages are key cells in the initiation of the acute inflammatory response, while M2 macrophages are resolving inflammation and coordinate tissue repair. However, tissue inflammation is not only caused by bacterial infection or tissue injury but may also derive from changes in the concentration of nutrients and metabolites. In this case, the immune system cannot cope the primary stimulus, so that chronic inflammation develops. This metabolic stress, in contrast to infectious or traumatic stress, is often caused by lipid overload in the blood and in adipose tissue. This again is a hallmark of age-related metabolic diseases, such as obesity, insulin resistance and atherosclerosis. For example, hypercholesterolemia (Sect.  11.3) causes stress to macrophages and their associated cells. Moreover, perturbations of the homeostasis of nutrient metabolism dys-regulate functions of the liver.

In this chapter, we will present monocytes and macrophages as the key players in acute and chronic inflammation. We will provide molecular and cellular details of examples of metabolic stress, such as disturbance of reverse cholesterol transport and ER stress. In this context, we will discuss macrophages as important therapeutic targets.


Monocytes M1- and M2-type macrophages Dendritic cells Cytokines Acute inflammation Chronic inflammation Cholesterol crystals Inflammasome Reverse cholesterol transport LDL HDL Metabolic stress ER stress LXR PPAR 

Additional Reading

  1. Fu S, Watkins SM, Hotamisligil GS (2012) The role of endoplasmic reticulum in hepatic lipid homeostasis and stress signaling. Cell Metab 15:623–634CrossRefPubMedGoogle Scholar
  2. Lawrence T, Natoli G (2011) Transcriptional regulation of macrophage polarization: enabling diversity with identity. Nat Rev Immunol 11:750–761CrossRefPubMedGoogle Scholar
  3. Tabas I, Glass CK (2013) Anti-inflammatory therapy in chronic disease: challenges and opportunities. Science 339:166–172CrossRefPubMedPubMedCentralGoogle Scholar
  4. Tall AR, Yvan-Charvet L (2015) Cholesterol, inflammation and innate immunity. Nat Rev Immunol 15:104–116CrossRefPubMedPubMedCentralGoogle Scholar
  5. Wynn TA, Chawla A, Pollard JW (2013) Macrophage biology in development, homeostasis and disease. Nature 496:445–455CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Carsten Carlberg
    • 1
  • Stine Marie Ulven
    • 2
  • Ferdinand Molnár
    • 3
  1. 1.Institute of BiomedicineUniversity of Eastern FinlandKuopioFinland
  2. 2.Department of NutritionUniversity of OsloOsloNorway
  3. 3.School of PharmacyUniversity of Easterm FinlandKuopioFinland

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