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

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Abstract

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
Volume7
Issue number11869
DOIs
Publication statusPublished - 2016

Fingerprint

Receptor-Interacting Protein Serine-Threonine Kinases
adipose tissues
White Adipose Tissue
Glucose Intolerance
glucose
Protein Kinases
Adipose Tissue
Phosphotransferases
Tissue
Inflammation
proteins
apoptosis
Glucose
homeostasis
insulin
Adipocytes
mice
Tissue homeostasis
Homeostasis
obesity

Keywords

  • IR-103637
  • METIS-321015

Cite this

Gautheron, J., Vucur, M., Schneider, A. T., Severi, I., Lammers, T. G. G. M., Heikenwalder, LM., & Luedde, T. (2016). The necroptosis-inducing kinase RIPK3 dampens adipose tissue inflammation and glucose intolerance. Nature communications, 7(11869), 11869-. [11869]. https://doi.org/10.1038/ncomms11869
Gautheron, J. ; Vucur, M. ; Schneider, A.T. ; Severi, I. ; Lammers, Twan Gerardus Gertudis Maria ; Heikenwalder, LM. ; Luedde, T. / The necroptosis-inducing kinase RIPK3 dampens adipose tissue inflammation and glucose intolerance. In: Nature communications. 2016 ; Vol. 7, No. 11869. pp. 11869-.
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abstract = "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",
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Gautheron, J, Vucur, M, Schneider, AT, Severi, I, Lammers, TGGM, Heikenwalder, LM & Luedde, T 2016, 'The necroptosis-inducing kinase RIPK3 dampens adipose tissue inflammation and glucose intolerance' Nature communications, vol. 7, no. 11869, 11869, pp. 11869-. https://doi.org/10.1038/ncomms11869

The necroptosis-inducing kinase RIPK3 dampens adipose tissue inflammation and glucose intolerance. / Gautheron, J.; Vucur, M.; Schneider, A.T.; Severi, I.; Lammers, Twan Gerardus Gertudis Maria; Heikenwalder, LM.; Luedde, T.

In: Nature communications, Vol. 7, No. 11869, 11869, 2016, p. 11869-.

Research output: Contribution to journalArticleAcademicpeer-review

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AU - Gautheron, J.

AU - Vucur, M.

AU - Schneider, A.T.

AU - Severi, I.

AU - Lammers, Twan Gerardus Gertudis Maria

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AU - Luedde, T.

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AB - 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

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