Nlrp1b1 negatively modulates obesity-induced inflammation by promoting IL-18 production

Obesity-induced inflammation, triggered by lipid-mediated activation of the Nlrp3 inflammasome, results in glucose metabolism alterations and type 2 diabetes. This knowledge has been generated using animals deficient for any of the different components of this inflammasome (Caspase-1, Asc or Nlrp3)...

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Bibliographic Details
Published in:Scientific reports 2019-09, Vol.9 (1), p.13815-12, Article 13815
Main Authors: Salazar-León, Jonathan, Valdez-Hernández, Ana Laura, García-Jiménez, Sara, Román-Domínguez, Luis, Huanosta-Murillo, Enrique, Bonifaz, Laura C, Pérez-Martínez, Leonor, Pedraza-Alva, Gustavo
Format: Article
Language:English
Subjects:
3T3-L1 Cells
Adipose tissue
Alleles
Animals
Apoptosis Regulatory Proteins - genetics
Caspase
Caspase-1
Diabetes
Diabetes mellitus
Diabetes mellitus (non-insulin dependent)
Diet, High-Fat - adverse effects
Disease Models, Animal
Glucose
Glucose Intolerance - genetics
Glucose Intolerance - immunology
Glucose metabolism
Glucose tolerance
High fat diet
Inflammasomes
Inflammation
Insulin
Insulin Resistance - genetics
Insulin Resistance - immunology
Interleukin 18
Interleukin-18 - metabolism
Intolerance
Lipolysis
Metabolism
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Transgenic
Obesity
Obesity - chemically induced
Obesity - complications
Obesity - genetics
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Summary:Obesity-induced inflammation, triggered by lipid-mediated activation of the Nlrp3 inflammasome, results in glucose metabolism alterations and type 2 diabetes. This knowledge has been generated using animals deficient for any of the different components of this inflammasome (Caspase-1, Asc or Nlrp3) in the C57BL/6 background. Unlike C57BL/6 mice, which carry allele 2 of the Nlrp1b gene (Nlrp1b2), Balb/c mice that carry allele 1 (Nlrp1b1) are less prone to develop alterations in the glucose metabolism when fed with a high fat diet. However, the molecular bases for these metabolic differences are unknown. Here we show that the Nlrp1b1 allele down regulates the adipose tissue inflammatory response attenuating glucose intolerance and insulin resistance in obese C57BL/mice. Our results indicate that the positive effects of the Nlrp1b1 inflammasome on glucose tolerance and insulin sensitivity involve IL-18-mediated effects on lipolysis, pointing out that differential expression of allelic variants of genes coding for inflammasome components might control susceptibility or resistance to develop diabetes in obese individuals.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-019-49546-7