Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • 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 ...
    • Aging (Upcoming)
    • Next-Generation Sequencing in Medicine (Jun 2022)
    • New Therapeutic Targets in Cardiovascular Diseases (Mar 2022)
    • Immunometabolism (Jan 2022)
    • Circadian Rhythm (Oct 2021)
    • Gut-Brain Axis (Jul 2021)
    • Tumor Microenvironment (Mar 2021)
    • 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
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
Obesity induces a phenotypic switch in adipose tissue macrophage polarization
Carey N. Lumeng, … , Jennifer L. Bodzin, Alan R. Saltiel
Carey N. Lumeng, … , Jennifer L. Bodzin, Alan R. Saltiel
Published January 2, 2007
Citation Information: J Clin Invest. 2007;117(1):175-184. https://doi.org/10.1172/JCI29881.
View: Text | PDF
Research Article

Obesity induces a phenotypic switch in adipose tissue macrophage polarization

  • Text
  • PDF
Abstract

Adipose tissue macrophages (ATMs) infiltrate adipose tissue during obesity and contribute to insulin resistance. We hypothesized that macrophages migrating to adipose tissue upon high-fat feeding may differ from those that reside there under normal diet conditions. To this end, we found a novel F4/80+CD11c+ population of ATMs in adipose tissue of obese mice that was not seen in lean mice. ATMs from lean mice expressed many genes characteristic of M2 or “alternatively activated” macrophages, including Ym1, arginase 1, and Il10. Diet-induced obesity decreased expression of these genes in ATMs while increasing expression of genes such as those encoding TNF-α and iNOS that are characteristic of M1 or “classically activated” macrophages. Interestingly, ATMs from obese C-C motif chemokine receptor 2–KO (Ccr2-KO) mice express M2 markers at levels similar to those from lean mice. The antiinflammatory cytokine IL-10, which was overexpressed in ATMs from lean mice, protected adipocytes from TNF-α–induced insulin resistance. Thus, diet-induced obesity leads to a shift in the activation state of ATMs from an M2-polarized state in lean animals that may protect adipocytes from inflammation to an M1 proinflammatory state that contributes to insulin resistance.

Authors

Carey N. Lumeng, Jennifer L. Bodzin, Alan R. Saltiel

×

Figure 6

IL-10 prevents the effects of TNF-α on adipocytes.

Options: View larger image (or click on image) Download as PowerPoint
IL-10 prevents the effects of TNF-α on adipocytes.
(A) IL-10 decreases M...
(A) IL-10 decreases MCP-1 secretion by adipocytes. 3T3-L1 adipocytes were treated with media with or without IL-10 (20 ng/ml) for 16 hours. Conditioned media was then removed and assayed for MCP-1 levels by ELISA. n = 5 independent samples per condition. Data are expressed as mean ± SD. (B) IL-10 protects adipocytes from TNF-α–induced downregulation of insulin receptor and glucose transporter 4 (GLUT4) expression. 3T3-L1 cells were treated with or without IL-10 for 24 hours prior to treatment with or without TNF-α (17 ng/ml for 6 hours). Lysates were prepared and immunoblots probed with antibodies against the insulin receptor (IR) and GLUT4. (C) IL-10 maintains IRS levels despite treatment with TNF-α. Adipocytes were treated as described for B and lysates examined for IRS1 tyrosine phosphorylation induced by insulin (INS; 100 nM for 5 minutes) after immunoprecipitation of IRS1. IRS serine phosphorylation at Ser307 was evaluated using specific antibodies.

Copyright © 2022 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts