PMID- 26603191
OWN - NLM
STAT- MEDLINE
DCOM- 20161013
LR  - 20220409
IS  - 1932-7420 (Electronic)
IS  - 1550-4131 (Linking)
VI  - 23
IP  - 1
DP  - 2016 Jan 12
TI  - IL-18 Production from the NLRP1 Inflammasome Prevents Obesity and Metabolic 
      Syndrome.
PG  - 155-64
LID - S1550-4131(15)00481-7 [pii]
LID - 10.1016/j.cmet.2015.09.024 [doi]
AB  - Interleukin-18 (IL-18) is activated by Caspase-1 in inflammasome complexes and 
      has anti-obesity effects; however, it is not known which inflammasome regulates 
      this process. We found that mice lacking the NLRP1 inflammasome phenocopy mice 
      lacking IL-18, with spontaneous obesity due to intrinsic lipid accumulation. This 
      is exacerbated when the mice are fed a high-fat diet (HFD) or a high-protein 
      diet, but not when mice are fed a HFD with low energy density (high fiber). 
      Furthermore, mice with an activating mutation in NLRP1, and hence increased 
      IL-18, have decreased adiposity and are resistant to diet-induced metabolic 
      dysfunction. Feeding these mice a HFD further increased plasma IL-18 
      concentrations and strikingly resulted in loss of adipose tissue mass and fatal 
      cachexia, which could be prevented by genetic deletion of IL-18. Thus, NLRP1 is 
      an innate immune sensor that functions in the context of metabolic stress to 
      produce IL-18, preventing obesity and metabolic syndrome.
CI  - Copyright (c) 2016 Elsevier Inc. All rights reserved.
FAU - Murphy, Andrew J
AU  - Murphy AJ
AD  - Haematopoiesis and Leukocyte Biology, Baker IDI Heart and Diabetes Institute, 
      Melbourne 3004, Australia; Department of Immunology, Monash University, Melbourne 
      3004, Australia.
FAU - Kraakman, Michael J
AU  - Kraakman MJ
AD  - Haematopoiesis and Leukocyte Biology, Baker IDI Heart and Diabetes Institute, 
      Melbourne 3004, Australia.
FAU - Kammoun, Helene L
AU  - Kammoun HL
AD  - Haematopoiesis and Leukocyte Biology, Baker IDI Heart and Diabetes Institute, 
      Melbourne 3004, Australia; Cellular and Molecular Metabolism Laboratory, Baker 
      IDI Heart and Diabetes Institute, Melbourne 3004, Australia.
FAU - Dragoljevic, Dragana
AU  - Dragoljevic D
AD  - Haematopoiesis and Leukocyte Biology, Baker IDI Heart and Diabetes Institute, 
      Melbourne 3004, Australia; Department of Immunology, Monash University, Melbourne 
      3004, Australia.
FAU - Lee, Man K S
AU  - Lee MK
AD  - Haematopoiesis and Leukocyte Biology, Baker IDI Heart and Diabetes Institute, 
      Melbourne 3004, Australia; Department of Immunology, Monash University, Melbourne 
      3004, Australia.
FAU - Lawlor, Kate E
AU  - Lawlor KE
AD  - Division of Inflammation, The Walter and Eliza Hall Institute of Medical 
      Research, Parkville 3052, Australia; Department of Medical Biology, The 
      University of Melbourne, Parkville 3010, Australia.
FAU - Wentworth, John M
AU  - Wentworth JM
AD  - Division of Molecular Medicine, The Walter and Eliza Hall Institute of Medical 
      Research, Parkville 3052, Australia; Department of Medical Biology, The 
      University of Melbourne, Parkville 3010, Australia.
FAU - Vasanthakumar, Ajithkumar
AU  - Vasanthakumar A
AD  - Division of Immunology, The Walter and Eliza Hall Institute of Medical Research, 
      Parkville 3052, Australia; Department of Medical Biology, The University of 
      Melbourne, Parkville 3010, Australia.
FAU - Gerlic, Motti
AU  - Gerlic M
AD  - Department of Clinical Microbiology and Immunology, Sackler Faculty of Medicine, 
      Tel Aviv University, Tel Aviv 69978, Israel.
FAU - Whitehead, Lachlan W
AU  - Whitehead LW
AD  - Division of Systems Biology and Personalised Medicine, The Walter and Eliza Hall 
      Institute of Medical Research, Parkville 3052, Australia.
FAU - DiRago, Ladina
AU  - DiRago L
AD  - Division of Cancer and Hematology, The Walter and Eliza Hall Institute of Medical 
      Research, Parkville 3052, Australia.
FAU - Cengia, Louise
AU  - Cengia L
AD  - Division of Cancer and Hematology, The Walter and Eliza Hall Institute of Medical 
      Research, Parkville 3052, Australia.
FAU - Lane, Rachael M
AU  - Lane RM
AD  - Division of ACRF Chemical Biology, The Walter and Eliza Hall Institute of Medical 
      Research, Parkville 3052, Australia.
FAU - Metcalf, Donald
AU  - Metcalf D
AD  - Division of Cancer and Hematology, The Walter and Eliza Hall Institute of Medical 
      Research, Parkville 3052, Australia; Department of Medical Biology, The 
      University of Melbourne, Parkville 3010, Australia.
FAU - Vince, James E
AU  - Vince JE
AD  - Division of Inflammation, The Walter and Eliza Hall Institute of Medical 
      Research, Parkville 3052, Australia; Department of Medical Biology, The 
      University of Melbourne, Parkville 3010, Australia.
FAU - Harrison, Leonard C
AU  - Harrison LC
AD  - Division of Molecular Medicine, The Walter and Eliza Hall Institute of Medical 
      Research, Parkville 3052, Australia; Department of Medical Biology, The 
      University of Melbourne, Parkville 3010, Australia.
FAU - Kallies, Axel
AU  - Kallies A
AD  - Division of Immunology, The Walter and Eliza Hall Institute of Medical Research, 
      Parkville 3052, Australia; Department of Medical Biology, The University of 
      Melbourne, Parkville 3010, Australia.
FAU - Kile, Benjamin T
AU  - Kile BT
AD  - Division of ACRF Chemical Biology, The Walter and Eliza Hall Institute of Medical 
      Research, Parkville 3052, Australia; Department of Medical Biology, The 
      University of Melbourne, Parkville 3010, Australia.
FAU - Croker, Ben A
AU  - Croker BA
AD  - Division of Hematology/Oncology, Boston Children's Hospital, Harvard Medical 
      School, Boston, MA 02115, USA.
FAU - Febbraio, Mark A
AU  - Febbraio MA
AD  - Cellular and Molecular Metabolism Laboratory, Baker IDI Heart and Diabetes 
      Institute, Melbourne 3004, Australia; Division of Diabetes and Metabolism, Garvan 
      Institute of Medical Research, Darlinghurst 2010, Australia.
FAU - Masters, Seth L
AU  - Masters SL
AD  - Division of Inflammation, The Walter and Eliza Hall Institute of Medical 
      Research, Parkville 3052, Australia; Department of Medical Biology, The 
      University of Melbourne, Parkville 3010, Australia. Electronic address: 
      masters@wehi.edu.au.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151022
PL  - United States
TA  - Cell Metab
JT  - Cell metabolism
JID - 101233170
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (Inflammasomes)
RN  - 0 (Interleukin-18)
RN  - 0 (NALP1 protein, mouse)
SB  - IM
CIN - Cell Metab. 2016 Jan 12;23(1):6-7. PMID: 26771112
MH  - Adaptor Proteins, Signal Transducing/genetics/*metabolism
MH  - Animals
MH  - Apoptosis Regulatory Proteins/genetics/*metabolism
MH  - Body Weight
MH  - Diet, High-Fat/adverse effects
MH  - Inflammasomes/*metabolism
MH  - Interleukin-18/*biosynthesis/genetics
MH  - Liver/metabolism/pathology
MH  - Male
MH  - Metabolic Syndrome/*metabolism/prevention & control
MH  - Mice, Knockout
MH  - Obesity/etiology/*metabolism/prevention & control
EDAT- 2015/11/26 06:00
MHDA- 2016/10/14 06:00
CRDT- 2015/11/26 06:00
PHST- 2015/01/21 00:00 [received]
PHST- 2015/06/03 00:00 [revised]
PHST- 2015/09/23 00:00 [accepted]
PHST- 2015/11/26 06:00 [entrez]
PHST- 2015/11/26 06:00 [pubmed]
PHST- 2016/10/14 06:00 [medline]
AID - S1550-4131(15)00481-7 [pii]
AID - 10.1016/j.cmet.2015.09.024 [doi]
PST - ppublish
SO  - Cell Metab. 2016 Jan 12;23(1):155-64. doi: 10.1016/j.cmet.2015.09.024. Epub 2015 
      Oct 22.