Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Alerts
  • Advertising/recruitment
  • Subscribe
  • Contact
  • Current Issue
  • Past Issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Author's Takes
  • Reviews
    • View all reviews ...
    • Tumor Microenvironment (Mar 2021)
    • 100th Anniversary of Insulin's Discovery (Jan 2021)
    • Hypoxia-inducible factors in disease pathophysiology and therapeutics (Oct 2020)
    • Latency in Infectious Disease (Jul 2020)
    • Immunotherapy in Hematological Cancers (Apr 2020)
    • Big Data's Future in Medicine (Feb 2020)
    • Mechanisms Underlying the Metabolic Syndrome (Oct 2019)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Commentaries
    • Concise Communication
    • Editorials
    • Viewpoint
    • Top read articles
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Author's Takes
  • In-Press Preview
  • Commentaries
  • Concise Communication
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Alerts
  • Advertising/recruitment
  • Subscribe
  • Contact
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.
View: Text | PDF
Review Series

The ominous triad of adipose tissue dysfunction: inflammation, fibrosis, and impaired angiogenesis

  • Text
  • PDF
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

×

Figure 1

The complex contributions of angiogenesis, inflammation, and fibrosis in healthy and unhealthy AT expansion.

Options: View larger image (or click on image) Download as PowerPoint
The complex contributions of angiogenesis, inflammation, and fibrosis in...
Hypoxia during early AT expansion induces stress signaling that facilitates angiogenesis via upregulation of an array of genes including VEGF, initiates inflammatory cell infiltration, and induces organized ECM remodeling to encourage appropriate AT expansion. However, persistent stress signaling translates into injury signaling, caused by long-term and severe hypoxia. This hypoxic condition fails to induce VEGF, resulting in impaired angiogenesis. Limited oxygen supply also triggers chronic low-grade inflammation predominantly characterized by proinflammatory macrophage infiltration. Upregulation of HIF-1α also increases the fibrotic program in AT. The integrated responses among those three factors promote significant hypotrophy in adipose tissue, and the consequence is an unhealthy AT expansion as well as obesity-associated metabolic consequences.

Copyright © 2021 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts