Distinct macrophage populations direct inflammatory versus physiological changes in adipose tissue

Research output: Contribution to journalJournal articleResearchpeer-review

  • David A Hill
  • Hee-Woong Lim
  • Yong Hoon Kim
  • Wesley Y Ho
  • Yee Hoon Foong
  • Victoria L Nelson
  • Hoang C B Nguyen
  • Kavya Chegireddy
  • Jihoon Kim
  • Andreas Habertheuer
  • Prashanth Vallabhajosyula
  • Taku Kambayashi
  • Won, Kyoung Jae
  • Mitchell A Lazar

Obesity is characterized by an accumulation of macrophages in adipose, some of which form distinct crown-like structures (CLS) around fat cells. While multiple discrete adipose tissue macrophage (ATM) subsets are thought to exist, their respective effects on adipose tissue, and the transcriptional mechanisms that underlie the functional differences between ATM subsets, are not well understood. We report that obese fat tissue of mice and humans contain multiple distinct populations of ATMs with unique tissue distributions, transcriptomes, chromatin landscapes, and functions. Mouse Ly6c ATMs reside outside of CLS and are adipogenic, while CD9 ATMs reside within CLS, are lipid-laden, and are proinflammatory. Adoptive transfer of Ly6c ATMs into lean mice activates gene programs typical of normal adipocyte physiology. By contrast, adoptive transfer of CD9 ATMs drives gene expression that is characteristic of obesity. Importantly, human adipose tissue contains similar ATM populations, including lipid-laden CD9 ATMs that increase with body mass. These results provide a higher resolution of the cellular and functional heterogeneity within ATMs and provide a framework within which to develop new immune-directed therapies for the treatment of obesity and related sequela.

Original languageEnglish
JournalProceedings of the National Academy of Sciences of the United States of America
Volume115
Issue number22
Pages (from-to)E5096-E5105
ISSN0027-8424
DOIs
Publication statusPublished - 29 May 2018
Externally publishedYes

ID: 199325108