The ominous triad of adipose tissue dysfunction: inflammation, fibrosis, and impaired angiogenesis
Clair Crewe, … , Yu Aaron An, Philipp E. Scherer
Clair Crewe, … , Yu Aaron An, Philipp E. Scherer
Published January 3, 2017
Citation Information: J Clin Invest. 2017;127(1):74-82. https://doi.org/10.1172/JCI88883.
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The ominous triad of adipose tissue dysfunction: inflammation, fibrosis, and impaired angiogenesis

Abstract

There are three dominant contributors to the pathogenesis of dysfunctional adipose tissue (AT) in obesity: unresolved inflammation, inappropriate extracellular matrix (ECM) remodeling and insufficient angiogenic potential. The interactions of these processes during AT expansion reflect both a linear progression as well as feed-forward mechanisms. For example, both inflammation and inadequate angiogenic remodeling can drive fibrosis, which can in turn promote migration of immune cells into adipose depots and impede further angiogenesis. Therefore, the relationship between the members of this triad is complex but important for our understanding of the pathogenesis of obesity. Here we untangle some of these intricacies to highlight the contributions of inflammation, angiogenesis, and the ECM to both “healthy” and “unhealthy” AT expansion.

Authors

Clair Crewe, Yu Aaron An, Philipp E. Scherer

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Figure 2

The role of senescence in obesity-associated AT dysfunction.

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The role of senescence in obesity-associated AT dysfunction. Chronic obe...
Chronic obesity can cause AT oxidative stress, DNA damage, and increased exposure to high glucose and ceramide concentrations. These deleterious factors can drive cellular senescence in many cells types. Adipocyte and endothelial cell senescence have been specifically studied in the context of obesity. Mature adipocytes and endothelial cells as well as their precursors can undergo senescence and take on the SASP. SASP factors can promote AT dysfunction through dysregulation of AT ECM remodeling, inflammation, and angiogenesis.