Inflammatory pathways regulated by tumor necrosis receptor-associated factor 1 protect from metabolic consequences in diet-induced obesity short communication

Nathaly Anto Michel, Christian Colberg, Konrad Buscher, Björn Sommer, Akula Bala Pramod, Erik Ehinger, Bianca Dufner, Natalie Hoppe, Katharina Pfeiffer, Timoteo Marchini, Florian Willecke, Peter Stachon, Ingo Hilgendorf, Timo Heidt, Constantin Von Zur Muhlen, Dominik Von Elverfeldt, Dietmar Pfeifer, Roland Schüle, Ulrich Kintscher, Sebastian BrachsKlaus Ley, Christoph Bode, Andreas Zirlik, Dennis Wolf

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


Rationale: The coincidence of inflammation and metabolic derangements in obese adipose tissue has sparked the concept of met-inflammation. Previous observations, however, suggest that inflammatory pathways may not ultimately cause dysmetabolism. Objective: We have revisited the relationship between inflammation and metabolism by testing the role of TRAF (tumor necrosis receptor-associated factor)-1, an inhibitory adapter of inflammatory signaling of TNF (tumor necrosis factor)-a, IL (interleukin)-1ß, and TLRs (toll-like receptors). Methods and Results: Mice defcient for TRAF-1, which is expressed in obese adipocytes and adipose tissue lymphocytes, caused an expected hyperinflammatory phenotype in adipose tissue with enhanced adipokine and chemokine expression, increased leukocyte accumulation, and potentiated proinflammatory signaling in macrophages and adipocytes in a mouse model of diet-induced obesity. Unexpectedly, TRAF-1-/-mice were protected from metabolic derangements and adipocyte growth, failed to gain weight, and showed improved insulin resistance-an effect caused by increased lipid breakdown in adipocytes and UCP (uncoupling protein)-1-enabled thermogenesis. TRAF-1-dependent catabolic and proinflammatory cues were synergistically driven by ß3-adrenergic and inflammatory signaling and required the presence of both TRAF-1-defcient adipocytes and macrophages. In human obesity, TRAF-1-dependent genes were upregulated. Conclusions: Enhancing TRAF-1-dependent inflammatory pathways in a gain-of-function approach protected from metabolic derangements in diet-induced obesity. These fndings identify TRAF-1 as a regulator of dysmetabolism in mice and humans and question the pathogenic role of chronic inflammation in metabolism.

Original languageEnglish (US)
Pages (from-to)693-700
Number of pages8
JournalCirculation research
Issue number5
StatePublished - Mar 2018
Externally publishedYes


  • Adipocytes
  • Lipolysis
  • Metabolic syndrome
  • Mice
  • Obesity

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine


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