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Inflammatory lipid mediators in adipocyte function and obesity

Nature Reviews Endocrinology volume 6, pages 71–82 (2010)Cite this article

Subjects

Abstract

Survival of multicellular organisms depends on their ability to fight infection, metabolize nutrients, and store energy for times of need. Unsurprisingly, therefore, immunoregulatory and metabolic mechanisms interact in human conditions such as obesity. Both infiltrating immunoinflammatory cells and adipocytes play critical roles in the modulation of metabolic homeostasis, so it is important to understand factors that regulate both adipocyte and immune cell function. A currently favored paradigm for obesity-associated metabolic dysfunction is that chronic macronutrient and/or lipid overload (associated with adiposity) induces cellular stress that initiates and perpetuates an inflammatory cycle and pathophysiological signaling of immunoinflammatory cells and adipocytes. Many lipid mediators exert their biological effects by binding to cognate receptors, such as G-protein-coupled receptors and Toll-like receptors. This process is tightly regulated under normal physiological conditions, and any disruption can initiate disease processes. Observations that cellular lipid loading (associated with adiposity) initiates inflammatory events has encouraged studies on the role of lipid mediators. In this review, we speculate that lipid mediators act on important immune receptors to induce low-grade tissue inflammation, which leads to adipocyte and metabolic dysfunction.

Key Points

  • The idea that chronic low-grade inflammation underlies obesity and metabolic dysfunction has become credible in recent years

  • Clinical studies have shown that excess macronutrient intake promotes signs of inflammatory stress and leads to metabolic dysfunction

  • Metabolic dysfunction may not be just a disease of obesity but a disease of dysfunctional adipocytes, induced either by excess feeding (obesity), malnutrition, starvation or possibly an immunoinflammatory disorder

  • Elevation of the concentration of circulating and adipose-tissue-localized inflammatory lipid mediators contributes to inflammatory cell activation, adipocyte growth, development and dysfunction, which leads to metabolic disturbances

  • Lipid mediators might induce adipocyte dysfunction in obesity by over-stimulating or inhibiting cognate receptors, such as G-protein-coupled receptors and Toll-like receptors

  • Immune system modulation might provide a means to intervene and re-establish tolerance to the abnormal metabolic homeostasis that occurs in obesity

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Figure 1: Obesity, metabolic syndrome and inflammation citations as a function of year from 1995.
Figure 2: Inflammatory cells and adipocytes in adipose tissue in obesity.
Figure 3: Important lipid mediators in obesity and metabolic dysfunction.

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Authors and Affiliations

  1. School of Biomedical Sciences, The University of Queensland, Brisbane, 4072, QLD, Australia

    Abishek Iyer

  2. Institute for Molecular Bioscience, The University of Queensland, Brisbane, 4072, QLD, Australia

    David P. Fairlie

  3. Diamantina Institute for Cancer, Immunology and Metabolic Medicine, The University of Queensland, Brisbane, 4072, QLD, Australia

    Johannes B. Prins

  4. Department of Entomology and Cancer Center, University of California, Davis, 95616, CA, USA

    Bruce D. Hammock

  5. Faculty of Sciences, University of Southern Queensland, Toowoomba, 4350, QLD, Australia

    Lindsay Brown

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Correspondence to Lindsay Brown.

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Competing interests

J. B. Prins is founder and scientific director of Adipogen Pty Ltd, a spin-out company with initial shareholding by Queensland Government and The University of Queensland. Adipogen has patents in the field of anti-obesity therapeutics.

Bruce D. Hammond is the founder of Arête Therapeutics. This company is moving sEH inhibitors through clinical trials for treatment of hypertension, pain, metabolic disease, inflammation and other disorders. The other authors declare no competing interests.

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Iyer, A., Fairlie, D., Prins, J. et al. Inflammatory lipid mediators in adipocyte function and obesity. Nat Rev Endocrinol 6, 71–82 (2010). https://doi.org/10.1038/nrendo.2009.264

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