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Adapting to obesity with adipose tissue inflammation

Key Points

  • Adipocytes have an important role in sensing and managing energy status

  • Adipose tissue responds to overnutrition by mounting an immune response; however, the initial inflammatory trigger in adipose tissue is unknown

  • Inflammation induces insulin resistance through a variety of molecular mechanisms

  • The maladaptive responses that occur in long-term obesity are a result of chronic inflammation, particularly catecholamine resistance

  • Inflammatory pathways are intriguing therapeutic targets for metabolic disease; however, the clinical efficacy of drugs targeting these pathways has been disappointing

Abstract

Adipose tissue not only has an important role in the storage of excess nutrients but also senses nutrient status and regulates energy mobilization. An overall positive energy balance is associated with overnutrition and leads to excessive accumulation of fat in adipocytes. These cells respond by initiating an inflammatory response that, although maladaptive in the long run, might initially be a physiological response to the stresses obesity places on adipose tissue. In this Review, we characterize adipose tissue inflammation and review the current knowledge of what triggers obesity-associated inflammation in adipose tissue. We examine the connection between adipose tissue inflammation and the development of insulin resistance and catecholamine resistance and discuss the ensuing state of metabolic inflexibility. Finally, we review the current and potential new anti-inflammatory treatments for obesity-associated metabolic disease.

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Figure 1: Adaptive and maladaptive phases of inflammation in metabolic disease.
Figure 2: Initiators of obesity-associated inflammation in adipocytes.
Figure 3: Mechanisms underlying obesity-associated catecholamine resistance.

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S.M.R. and A.R.S. researched data for the article, contributed to discussion of the content, wrote the article and reviewed and/or edited the article before submission.

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Correspondence to Alan R. Saltiel.

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Glossary

Biogenic amines

Endogenous molecules with one or more amine groups; five important neurotransmitters are biogenic amines, including three catecholamines (dopamine, noradrenaline and adrenaline) as well as histamine and serotonin.

Mesenteric adipose tissue

A small membrane-like visceral fat depot connected to the intestine that expands into a large adipose depot surrounding the intestine during obesity.

Crown-like structures

These histological structures are observed in adipose tissue and are the result of immune cells surrounding dead adipocytes; as the immune cells pack into the spaces around the dead adipocytes and between the surrounding live adipocytes, they form a shape reminiscent of a crown.

Oxygen tension

The partial pressure of oxygen within a tissue, which is a measure of the amount of oxygen within the tissue.

Adipogenesis

The differentiation of pre-adipocytes (or other fibroblast-like cells) to make new adipocytes.

Type 2 or T helper 2 (TH2)

Type 2 cytokines, such as IL-4 and IL-13, are classified based on their secretion from TH2 cells (however, they are secreted from many other immune cells) and are typically anti-inflammatory and promote M2 macrophage differentiation; type 2 immunity is characterized by antibody-mediated immune responses.

Type 1 or T helper 1 (TH1)

Type 1 cytokines, such as IL-1β and tumour necrosis factor, are classified based on their secretion from TH1 cells (however, they are secreted from many other immune cells) and are typically pro-inflammatory; type 1 immunity is characterized by a phagocytic immune response.

Angiogenesis

The proliferation and migration of endothelial cells to form new blood vessels.

Metabolic inflexibility

A state in which responsiveness to catabolic and anabolic signals is reduced in adipocytes, leaving them unable to efficiently contract (mobilize nutrients) or expand (store nutrients).

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Reilly, S., Saltiel, A. Adapting to obesity with adipose tissue inflammation. Nat Rev Endocrinol 13, 633–643 (2017). https://doi.org/10.1038/nrendo.2017.90

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