The Inhibitory Innate Immune Sensor NLRP12 Maintains a Threshold against Obesity by Regulating Gut Microbiota Homeostasis.
Cell Host Microbe
; 24(3): 364-378.e6, 2018 09 12.
Article
em En
| MEDLINE
| ID: mdl-30212649
ABSTRACT
In addition to high-fat diet (HFD) and inactivity, inflammation and microbiota composition contribute to obesity. Inhibitory immune receptors, such as NLRP12, dampen inflammation and are important for resolving inflammation, but their role in obesity is unknown. We show that obesity in humans correlates with reduced expression of adipose tissue NLRP12. Similarly, Nlrp12-/- mice show increased weight gain, adipose deposition, blood glucose, NF-κB/MAPK activation, and M1-macrophage polarization. Additionally, NLRP12 is required to mitigate HFD-induced inflammasome activation. Co-housing with wild-type animals, antibiotic treatment, or germ-free condition was sufficient to restrain inflammation, obesity, and insulin tolerance in Nlrp12-/- mice, implicating the microbiota. HFD-fed Nlrp12-/- mice display dysbiosis marked by increased obesity-associated Erysipelotrichaceae, but reduced Lachnospiraceae family and the associated enzymes required for short-chain fatty acid (SCFA) synthesis. Lachnospiraceae or SCFA administration attenuates obesity, inflammation, and dysbiosis. These findings reveal that Nlrp12 reduces HFD-induced obesity by maintaining beneficial microbiota.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
3_ND
Base de dados:
MEDLINE
Assunto principal:
Peptídeos e Proteínas de Sinalização Intracelular
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Microbioma Gastrointestinal
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Obesidade
Limite:
Adult
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Aged
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Animals
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Cell Host Microbe
Ano de publicação:
2018
Tipo de documento:
Article