Language:

IL-18 Production from the NLRP1 Inflammasome Prevents Obesity and Metabolic Syndrome

Cell metabolism, 2016-01, Vol.23 (1), p.155-164 [Peer Reviewed Journal]

2016 Elsevier Inc. ;Copyright © 2016 Elsevier Inc. All rights reserved. ;ISSN: 1550-4131 ;EISSN: 1932-7420 ;DOI: 10.1016/j.cmet.2015.09.024 ;PMID: 26603191

Full text available

Citations Cited by

Actions
1. Add to My Research
2. Remove from My Research
3. E-mail
4. Print
5. Permalink
6. Citation
7. EasyBib
8. EndNote
9. RefWorks
10. Delicious
11. Export RIS
12. Export BibTeX

Title:
IL-18 Production from the NLRP1 Inflammasome Prevents Obesity and Metabolic Syndrome
Author: Murphy, Andrew J. ; Kraakman, Michael J. ; Kammoun, Helene L. ; Dragoljevic, Dragana ; Lee, Man K.S. ; Lawlor, Kate E. ; Wentworth, John M. ; Vasanthakumar, Ajithkumar ; Gerlic, Motti ; Whitehead, Lachlan W. ; DiRago, Ladina ; Cengia, Louise ; Lane, Rachael M. ; Metcalf, Donald ; Vince, James E. ; Harrison, Leonard C. ; Kallies, Axel ; Kile, Benjamin T. ; Croker, Ben A. ; Febbraio, Mark A. ; Masters, Seth L.
Subjects: Adaptor Proteins, Signal Transducing - genetics ; Adaptor Proteins, Signal Transducing - metabolism ; Animals ; Apoptosis Regulatory Proteins - genetics ; Apoptosis Regulatory Proteins - metabolism ; Body Weight ; Diet, High-Fat - adverse effects ; Inflammasomes - metabolism ; Interleukin-18 - biosynthesis ; Interleukin-18 - genetics ; Liver - metabolism ; Liver - pathology ; Male ; Metabolic Syndrome - metabolism ; Metabolic Syndrome - prevention & control ; Mice, Knockout ; Obesity - etiology ; Obesity - metabolism ; Obesity - prevention & control
Is Part Of: Cell metabolism, 2016-01, Vol.23 (1), p.155-164
Description: 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. [Display omitted] •Deletion of NLRP1 in mice leads to obesity and metabolic syndrome•NLRP1 obesity phenotype is related to the energy quotient of the diet•Loss of NLRP1 decreased IL-18 production and lipolysis•NLRP1 activation increased IL-18, prevented obesity, but was fatal on the high-fat diet Murphy et al. link the NLRP1 inflammasome to IL-18 production and show that mice lacking NLRP1 have defective lipolysis and become obese, as seen with IL-18 deficiency. NLRP1 activation prevents obesity but results in fatal fat loss and cachexia on a high-fat diet, which is rescued by deletion of IL-18.
Publisher: United States: Elsevier Inc
Language: English
Identifier: ISSN: 1550-4131
EISSN: 1932-7420
DOI: 10.1016/j.cmet.2015.09.024
PMID: 26603191
Source: Cell Press Free Archives
MEDLINE

Back to results list


INSPIRE LIBRARY - TON DUC THANG UNIVERSITY	(84-028) 37 755 057	Feedback
19 Nguyen Huu Tho St. Dist.7, HCM	thuvien@tdtu.edu.vn	Feedback

IL-18 Production from the NLRP1 Inflammasome Prevents Obesity and Metabolic Syndrome

2016 Elsevier Inc. ;Copyright © 2016 Elsevier Inc. All rights reserved. ;ISSN: 1550-4131 ;EISSN: 1932-7420 ;DOI: 10.1016/j.cmet.2015.09.024 ;PMID: 26603191

Searching Remote Databases, Please Wait