The necroptosis-inducing kinase RIPK3 dampens adipose tissue inflammation and glucose intolerance

J. Gautheron, M. Vucur, A.T. Schneider, I. Severi, Twan Gerardus Gertudis Maria Lammers, LM. Heikenwalder, T. Luedde

Research output: Contribution to journalArticleAcademicpeer-review

62 Citations (Scopus)
143 Downloads (Pure)


Receptor-interacting protein kinase 3 (RIPK3) mediates necroptosis, a form of programmed cell death that promotes inflammation in various pathological conditions, suggesting that it might be a privileged pharmacological target. However, its function in glucose homeostasis and obesity has been unknown. Here we show that RIPK3 is over expressed in the white adipose tissue (WAT) of obese mice fed with a choline-deficient high-fat diet. Genetic inactivation of Ripk3 promotes increased Caspase-8-dependent adipocyte apoptosis and WAT inflammation, associated with impaired insulin signalling in WAT as the basis for glucose intolerance. Similarly to mice, in visceral WAT of obese humans, RIPK3 is overexpressed and correlates with the body mass index and metabolic serum markers. Together, these findings provide evidence that RIPK3 in WAT maintains tissue homeostasis and suppresses inflammation and adipocyte apoptosis, suggesting that systemic targeting of necroptosis might be associated with the risk of promoting insulin resistance in obese patients
Original languageEnglish
Article number11869
Pages (from-to)11869-
JournalNature communications
Issue number11869
Publication statusPublished - 2016


  • IR-103637
  • METIS-321015


Dive into the research topics of 'The necroptosis-inducing kinase RIPK3 dampens adipose tissue inflammation and glucose intolerance'. Together they form a unique fingerprint.

Cite this