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Adipokines in inflammation and metabolic disease

Key Points

  • Adipose tissue functions as an energy-storage and endocrine organ, thereby coordinating energy supply and demand at the level of the whole organism.

  • Adipose tissue is comprised of distinct cell populations that are engaged in complex crosstalk pathways.

  • Obesity and inflammation can alter the metabolic status of adipose tissue depots. Highly inflamed, metabolically dysfunctional adipose tissue is characterized by macrophage infiltration, capillary rarefaction and adipocyte necrosis.

  • Adipokines and adipose tissue-derived factors carry out inter-tissue communication functions. Adipokines are mainly secreted by adipocytes, whereas adipose tissue-derived factors can be secreted by cells in addition to or other than adipocytes (for example, interleukin-6, which is secreted by both adipocytes and macrophages).

  • Inflammatory factors are secreted by metabolically dysfunctional adipocytes and innate immune cells that infiltrate obese adipose tissues.

  • Anti-inflammatory adipokines are secreted by metabolically normal adipocytes to attenuate inflammation and coordinate fuel use by metabolically active tissues.

Abstract

The worldwide epidemic of obesity has brought considerable attention to research aimed at understanding the biology of adipocytes (fat cells) and the events occurring in adipose tissue (fat) and in the bodies of obese individuals. Accumulating evidence indicates that obesity causes chronic low-grade inflammation and that this contributes to systemic metabolic dysfunction that is associated with obesity-linked disorders. Adipose tissue functions as a key endocrine organ by releasing multiple bioactive substances, known as adipose-derived secreted factors or adipokines, that have pro-inflammatory or anti-inflammatory activities. Dysregulated production or secretion of these adipokines owing to adipose tissue dysfunction can contribute to the pathogenesis of obesity-linked complications. In this Review, we focus on the role of adipokines in inflammatory responses and discuss their potential as regulators of metabolic function.

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Figure 1: Adipose tissue depots.
Figure 2: Components of adipose tissue.
Figure 3: Phenotypic modulation of adipose tissue.

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Acknowledgements

The authors are funded by US National Institutes of Health grants (AG34972, HL86785, AG15052 and HL81587).

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Glossary

Insulin resistance

A condition characterized by the inability of cells (in the muscle, liver and fat) to respond appropriately to endogenous insulin, resulting in increased blood glucose levels.

Crown-like structure

An aggregation of single or fused macrophages (also referred to as multinucleated giant cells) around a single adipocyte in adipose tissue. These structures are typically associated with obesity, adipose tissue dysfunction and chronic inflammation.

M1 or 'classically activated' macrophage

A macrophage that is activated by Toll-like receptor ligands (such as lipopolysaccharide) and interferon-γ, and that expresses inducible nitric oxide synthase and nitric oxide, as well as other pro-inflammatory factors.

M2 or 'alternatively activated' macrophage

A macrophage that is stimulated by interleukin-4 (IL-4) or IL-13, and that expresses arginase 1, the mannose receptor CD206 and the IL-4 receptor α-chain.

The metabolic syndrome

A disorder characterized by the presence of at least three of the following features: large waist circumference (men: ≥40 inches; women: ≥35 inches), high levels of circulating triglycerides (≥150 mg dl−1), low levels of high-density lipoprotein (men: <40 mg dl−1; women: <50 mg dl−1), high fasting blood glucose (100 mg dl−1) and high blood pressure (≥130/85 mm Hg). Together, these conditions increase the risk of heart disease, stroke and type 2 diabetes.

Stromal vascular fraction

Non-adipocyte components of adipose tissue, including monocytes, macrophages, vascular cells, pre-adipocytes, T cells and mesenchymal stem cells.

Foam cell

A macrophage in the arterial wall that ingests oxidized low-density lipoprotein and assumes a foamy appearance. These cells secrete various substances involved in atherosclerotic plaque growth.

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Ouchi, N., Parker, J., Lugus, J. et al. Adipokines in inflammation and metabolic disease. Nat Rev Immunol 11, 85–97 (2011). https://doi.org/10.1038/nri2921

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