Inflammation; Macrophages; Microbiota; NLRP3; Obesity; Type 2 diabetes; Inflammasomes; NLR Family, Pyrin Domain-Containing 3 Protein; Humans; Inflammasomes/metabolism; Inflammation/metabolism; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism; Obesity/complications; Diabetes Mellitus, Type 2/etiology; Gastrointestinal Microbiome; Diabetes Mellitus, Type 2; Medicine (all)
Abstract :
[en] Type 2 diabetes is characterized by chronic hyperglycaemia in a context of insulin resistance and ?-cell dysfunction. A chronic low-grade inflammation is observed in obesity and has been associated with the development of metabolic disorders. The molecular mechanisms underlying this inflammation are not fully understood. Production of interleukin-1 beta by macrophages infiltrating insulin-sensitive tissues and pancreatic islets plays a major role in the pathogenesis of type 2 diabetes. This pro-inflammatory cytokine is produced through the activation of the NLRP3 inflammasome in response to danger signals that accumulate during obesity, including saturated fatty acids. The composition of the intestinal microbiota differs in obese subjects compared with lean individuals, particularly in response to high saturated fat diet. These modifications could trigger a chronic low-grade inflammation and promote the emergence of type 2 diabetes. The microbiota could therefore constitutes a therapeutic target in the prevention and management of metabolic abnormalities associated with obesity. [fr] Le diabète de type 2 est caractérisé par une hyperglycémie chronique survenant dans un contexte de résistance à l’insuline et de déficit de sécrétion d’insuline par les cellules ? du pancréas. Un état inflammatoire chronique à bas bruit est observé dans l’obésité et est associé au développement d’anomalies métaboliques. Les mécanismes moléculaires à l’origine de cette inflammation ne sont pas encore bien compris. La production d’interleukine-1 bêta par les macrophages infiltrant les tissus cibles de l’insuline et les îlots pancréatiques joue un rôle important dans la pathogénie du diabète de type 2. Cette cytokine pro-inflammatoire est produite via l’activation de l’inflammasome NLRP3 en réponse à divers signaux de danger s’accumulant avec l’obésité, dont les acides gras saturés. La composition du microbiote intestinal diffère chez les sujets obèses par rapport aux individus minces, notamment en réponse à une alimentation riche en graisses saturées. Ces modifications pourraient entraîner le déclenchement d’un état inflammatoire chronique et favoriser l’émergence d’un diabète de type 2. Le microbiote pourrait, dès lors, constituer une cible thérapeutique dans la prévention et la prise en charge des anomalies métaboliques associées à l’obésité.
Disciplines :
Endocrinology, metabolism & nutrition
Author, co-author :
Esser, Nathalie ; Centre Hospitalier Universitaire de Liège - CHU > > Service de diabétologie, nutrition, maladies métaboliques
PAQUOT, Nicolas ; Centre Hospitalier Universitaire de Liège - CHU > > Service de diabétologie, nutrition, maladies métaboliques
Language :
French
Title :
Inflammation, obésité et diabète de type 2. Rôle de l’inflammasome NLRP3 et du microbiote intestinal.
Alternative titles :
[en] Inflammation, obesity and type 2 diabetes. Role of the NLRP3 inflammasome and gut microbiota.
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