The necroptosis-inducing kinase RIPK3 dampens adipose tissue inflammation and glucose intolerance / Jérémie Gautheron, Mihael Vucur, Anne T. Schneider, Ilenia Severi, Christoph Roderburg, Sanchari Roy, Matthias Bartneck, Peter Schrammen, Mauricio Berriel Diaz, Josef Ehling, Felix Gremse, Felix Heymann, Christiane Koppe, Twan Lammers, Fabian Kiessling, Niels Van Best, Oliver Pabst, Gilles Courtois, Andreas Linkermann, Stefan Krautwald, Ulf P. Neumann, Frank Tacke, Christian Trautwein, Douglas R. Green, Thomas Longerich, Norbert Frey, Mark Luedde, Matthias Bluher, Stephan Herzig, Mathias Heikenwalder and Tom Luedde

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.

Saved in:
Persons: Gautheron, Jérémie [Author]; Vucur, Mihael [Author]; Schneider, Anne T. [Author]; Severi, Ilenia [Author]; Roderburg, Christoph [Author]; Roy, Sanchari [Author]; Bartneck, Matthias [Author]; Schrammen, Peter [Author]; Berriel Diaz, Mauricio [Author]; Ehling, Josef [Author]; Gremse, Felix [Author]; Heymann, Felix [Author]; Koppe, Christiane [Author]; Lammers, Twan [Author]; Kiessling, Fabian [Author]; Van Best, Niels [Author]; Pabst, Oliver [Author]; Courtois, Gilles [Author]; Linkermann, Andreas [Author]; Krautwald, Stefan [Author]; Neumann, Ulf P. [Author]; Tacke, Frank [Author]; Trautwein, Christian [Author]; Green, Douglas R. [Author]; Longerich, Thomas [Author]; Frey, Norbert [Author]; Luedde, Mark [Author]; Bluher, Matthias [Author]; Herzig, Stephan [Author]; Heikenwalder, Mathias [Author]; Luedde, Tom [Author]
Format: eArticle
Language(s):English
Publication:21 Jun 2016
Part of:Nature Communications 7(2016) Artikel-Nummer 11869, 16 Seiten
Subjects:Adipocytes
Adipose Tissue, White
Animals
Apoptosis
Body Mass Index
Caspase 8
Choline
Choline Deficiency
Diet, High-Fat
Gene Expression Regulation
Glucose Intolerance
Homeostasis
Humans
Inflammation
Insulin
Insulin Resistance
Intra-Abdominal Fat
Male
Mice
Necrosis
Obesity
Receptor-Interacting Protein Serine-Threonine Kinases
Notes:Gesehen am 14.05.2020
Physical description:16
ISSN:2041-1723
DOI:10.1038/ncomms11869