| Inflammasome is a central player in the induction of obesity and insulin resistance. | |
| | |
MedLine Citation:
|
PMID: 21876127 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Inflammation plays a key role in the pathogenesis of obesity. Chronic overfeeding leads to macrophage infiltration in the adipose tissue, resulting in proinflammatory cytokine production. Both microbial and endogenous danger signals trigger assembly of the intracellular innate immune sensor Nlrp3, resulting in caspase-1 activation and production of proinflammatory cytokines IL-1β and IL-18. Here, we showed that mice deficient in Nlrp3, apoptosis-associated speck-like protein, and caspase-1 were resistant to the development of high-fat diet-induced obesity, which correlated with protection from obesity-induced insulin resistance. Furthermore, hepatic triglyceride content, adipocyte size, and macrophage infiltration in adipose tissue were all reduced in mice deficient in inflammasome components. Monocyte chemoattractant protein (MCP)-1 is a key molecule that mediates macrophage infiltration. Indeed, defective inflammasome activation was associated with reduced MCP-1 production in adipose tissue. Furthermore, plasma leptin and resistin that affect energy use and insulin sensitivity were also changed by inflammasome-deficiency. Detailed metabolic and molecular phenotyping demonstrated that the inflammasome controls energy expenditure and adipogenic gene expression during chronic overfeeding. These findings reveal a critical function of the inflammasome in obesity and insulin resistance, and suggest inhibition of the inflammasome as a potential therapeutic strategy. |
| | |
Authors:
|
Rinke Stienstra; Janna A van Diepen; Cees J Tack; Md Hasan Zaki; Frank L van de Veerdonk; Deshani Perera; Geoffrey A Neale; Guido J Hooiveld; Anneke Hijmans; Irene Vroegrijk; Sjoerd van den Berg; Johannes Romijn; Patrick C N Rensen; Leo A B Joosten; Mihai G Netea; Thirumala-Devi Kanneganti |
Related Documents
:
|
15316307 - Atherosclerosis and systemic lupus erythematosus. 7542057 - Role of heat shock protein 65/60 in the pathogenesis of atherosclerosis. 20060487 - 15-hete protects rat pulmonary arterial smooth muscle cells from apoptosis via the pi3k... 2654377 - Leukotrienes. biology and role in disease. 16169197 - Inhibitors of arachidonic acid metabolism act synergistically to signal apoptosis in ne... 17195067 - Wp760, a melanoma selective drug. |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2011-08-29 |
Journal Detail:
|
Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 108 ISSN: 1091-6490 ISO Abbreviation: Proc. Natl. Acad. Sci. U.S.A. Publication Date: 2011 Sep |
Date Detail:
|
Created Date: 2011-09-14 Completed Date: 2011-11-09 Revised Date: 2012-03-13 |
Medline Journal Info:
|
Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: United States |
Other Details:
|
Languages: eng Pagination: 15324-9 Citation Subset: IM |
Affiliation:
|
Department of Medicine, Radboud University Nijmegen Medical Centre, and Nijmegen Institute for Infection, Inflammation and Immunity, 6525 GA Nijmegen, The Netherlands. |
| Data Bank Information | |
Bank Name/Acc. No.:
|
GEO/GSE25205 |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Adipocytes
/
drug effects,
metabolism,
pathology Adipose Tissue / pathology Animals Carrier Proteins / metabolism Caspase 1 / metabolism Cell Movement / drug effects Cholesterol / blood Cytoskeletal Proteins / deficiency, metabolism Dietary Fats / administration & dosage, pharmacology Energy Metabolism / drug effects Fatty Liver / complications, pathology, prevention & control Glucose Clamp Technique Humans Hyperinsulinism / complications, pathology Hypertrophy Inflammasomes / metabolism* Insulin Resistance* Macrophages / drug effects, pathology Male Mice Obesity / blood, complications, metabolism* Triglycerides / blood |
| Grant Support | |
ID/Acronym/Agency:
|
AI088177/AI/NIAID NIH HHS; AR056296/AR/NIAMS NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/CIAS1 protein, mouse; 0/Carrier Proteins; 0/Cytoskeletal Proteins; 0/Dietary Fats; 0/Inflammasomes; 0/Pycard protein, mouse; 0/Triglycerides; 57-88-5/Cholesterol; EC 3.4.22.36/Caspase 1 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Asymmetric dispersal allows an upstream region to control population structure throughout a species'...
Next Document: Convergent evolution of two mammalian neuronal enhancers by sequential exaptation of unrelated retro...