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Stienstra, Rinke, Joosten, Leo A B, Koenen, Tim, van Tits, Berry, van Diepen, Janna A, van den Berg, Sjoerd A A, Rensen, Patrick C N, Voshol, Peter J, Fantuzzi, Giamilla, Hijmans, Anneke, Kersten, Sander, Müller, Michael 
ORCID: https://orcid.org/0000-0002-5930-9905, van den Berg, Wim B, van Rooijen, Nico, Wabitsch, Martin, Kullberg, Bart-Jan, van der Meer, Jos W M, Kanneganti, Thirumala, Tack, Cees J and Netea, Mihai G
(2010)
The inflammasome-mediated caspase-1 activation controls adipocyte differentiation and insulin sensitivity.
Cell Metabolism, 12 (6).
pp. 593-605.
ISSN 1550-4131
Abstract
Obesity-induced inflammation originating from expanding adipose tissue interferes with insulin sensitivity. Important metabolic effects have been recently attributed to IL-1β and IL-18, two members of the IL-1 family of cytokines. Processing of IL-1β and IL-18 requires cleavage by caspase-1, a cysteine protease regulated by a protein complex called the inflammasome. We demonstrate that the inflammasome/caspase-1 governs adipocyte differentiation and insulin sensitivity. Caspase-1 is upregulated during adipocyte differentiation and directs adipocytes toward a more insulin-resistant phenotype. Treatment of differentiating adipocytes with recombinant IL-1β and IL-18, or blocking their effects by inhibitors, reveals that the effects of caspase-1 on adipocyte differentiation are largely conveyed by IL-1β. Caspase-1 and IL-1β activity in adipose tissue is increased both in diet-induced and genetically induced obese animal models. Conversely, mice deficient in caspase-1 are more insulin sensitive as compared to wild-type animals. In addition, differentiation of preadipocytes isolated from caspase-1(-/-) or NLRP3(-/-) mice resulted in more metabolically active fat cells. In vivo, treatment of obese mice with a caspase-1 inhibitor significantly increases their insulin sensitivity. Indirect calorimetry analysis revealed higher fat oxidation rates in caspase-1(-/-) animals. In conclusion, the inflammasome is an important regulator of adipocyte function and insulin sensitivity, and caspase-1 inhibition may represent a novel therapeutic target in clinical conditions associated with obesity and insulin resistance.
| Item Type: | Article |
|---|---|
| Additional Information: | Copyright © 2010 Elsevier Inc. All rights reserved. |
| Uncontrolled Keywords: | adipocytes,animals,calorimetry, indirect,carrier proteins,caspase 1,cell differentiation,enzyme activation,histological techniques,immunoblotting,inflammasomes,insulin resistance,interleukin-18,interleukin-1beta,mice,mice, knockout,obesity,polymerase chain reaction,sdg 3 - good health and well-being ,/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being |
| Faculty \ School: | Faculty of Medicine and Health Sciences > Norwich Medical School |
| UEA Research Groups: | Faculty of Medicine and Health Sciences > Research Groups > Nutrition and Preventive Medicine Faculty of Medicine and Health Sciences > Research Groups > Gastroenterology and Gut Biology Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health |
| Depositing User: | Pure Connector |
| Date Deposited: | 10 Jun 2014 20:46 |
| Last Modified: | 06 Jun 2024 14:46 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/47673 |
| DOI: | 10.1016/j.cmet.2010.11.011 |
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