An inflammatory micro-environment promotes human adipocyte apoptosis

Mol Cell Endocrinol. 2011 Jun 6;339(1-2):105-13. doi: 10.1016/j.mce.2011.04.004. Epub 2011 Apr 9.


Obesity-associated macrophage infiltration into adipose tissue is responsible for both local and systemic inflammation. Recent findings suggest fat cell apoptosis as an initiator of macrophage recruitment. Here, we investigated the effects of an inflammatory micro-environment on fat cells using human THP-1 macrophages and SGBS adipocytes. Macrophage-secreted factors induced insulin resistance, inhibited insulin-stimulated Akt phosphorylation, and induced apoptosis of adipocytes. The apoptosis-inducing effect was even more pronounced in direct co-cultures of adipocytes and macrophages. Our data suggest a link between insulin resistance and apoptosis sensitivity. Accordingly, pharmacological and genetic inhibition of insulin signaling at the level of Akt2 sensitized adipocytes to apoptosis induction by macrophage-secreted factors. In conclusion, we describe here a novel interaction of macrophages and fat cells, i.e. induction of apoptosis. Our data suggest a feed-forward cycle in which macrophages further drive the inflammatory process by inducing insulin resistance and concomitant apoptosis of adipocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / drug effects
  • Adipocytes / pathology*
  • Adipocytes / physiology
  • Adipose Tissue / drug effects
  • Adipose Tissue / metabolism
  • Adipose Tissue / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Apoptosis*
  • CD11c Antigen / metabolism
  • Cells, Cultured
  • Chromones / pharmacology
  • Coculture Techniques
  • Culture Media, Conditioned
  • Cytokines / metabolism
  • Female
  • Humans
  • Inflammation / pathology
  • Insulin / pharmacology
  • Insulin Resistance
  • MAP Kinase Signaling System / drug effects
  • Macrophages / metabolism
  • Macrophages / pathology
  • Male
  • Middle Aged
  • Morpholines / pharmacology
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors
  • Proto-Oncogene Proteins c-akt / metabolism


  • CD11c Antigen
  • Chromones
  • Culture Media, Conditioned
  • Cytokines
  • Insulin
  • Morpholines
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • Proto-Oncogene Proteins c-akt