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The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance

Dixit, Vishwa Deep ; Vandanmagsar, Bolormaa ; Youm, Yun-Hee ; Ravussin, Anthony ; Galgani, Jose E ; Stadler, Krisztian ; Mynatt, Randall L ; Ravussin, Eric ; Stephens, Jacqueline M

Nature medicine, 2011-02, Vol.17 (2), p.179-188 [Periódico revisado por pares]

United States: Nature Publishing Group

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Título:
The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance
Autor: Dixit, Vishwa Deep ; Vandanmagsar, Bolormaa ; Youm, Yun-Hee ; Ravussin, Anthony ; Galgani, Jose E ; Stadler, Krisztian ; Mynatt, Randall L ; Ravussin, Eric ; Stephens, Jacqueline M
Assuntos: Adipose Tissue - metabolism ; Adipose Tissue - physiopathology ; Animals ; Carrier Proteins - physiology ; Caspase 1 - physiology ; Cell receptors ; Cellular biology ; Complications and side effects ; Disease Models, Animal ; Female ; Glucose Tolerance Test ; Humans ; Inflammasomes - physiology ; Inflammation ; Inflammation - metabolism ; Inflammation - physiopathology ; Inflammatory diseases ; Insulin - physiology ; Insulin resistance ; Insulin Resistance - physiology ; Interleukin-1beta - physiology ; Macrophages - physiology ; Male ; Mice ; Mice, Inbred C57BL ; NLR Family, Pyrin Domain-Containing 3 Protein ; Obesity ; Obesity - metabolism ; Obesity - physiopathology ; Physiological aspects ; Proteins ; Reverse Transcriptase Polymerase Chain Reaction ; Risk factors ; Signal transduction
É parte de: Nature medicine, 2011-02, Vol.17 (2), p.179-188
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Descrição: The emergence of chronic inflammation during obesity in the absence of overt infection or well-defined autoimmune processes is a puzzling phenomenon. The Nod-like receptor (NLR) family of innate immune cell sensors, such as the nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (Nlrp3, but also known as Nalp3 or cryopyrin) inflammasome are implicated in recognizing certain nonmicrobial originated 'danger signals' leading to caspase-1 activation and subsequent interleukin-1β (IL-1β) and IL-18 secretion. We show that calorie restriction and exercise-mediated weight loss in obese individuals with type 2 diabetes is associated with a reduction in adipose tissue expression of Nlrp3 as well as with decreased inflammation and improved insulin sensitivity. We further found that the Nlrp3 inflammasome senses lipotoxicity-associated increases in intracellular ceramide to induce caspase-1 cleavage in macrophages and adipose tissue. Ablation of Nlrp3 in mice prevents obesity-induced inflammasome activation in fat depots and liver as well as enhances insulin signaling. Furthermore, elimination of Nlrp3 in obese mice reduces IL-18 and adipose tissue interferon-γ (IFN-γ) expression, increases naive T cell numbers and reduces effector T cell numbers in adipose tissue. Collectively, these data establish that the Nlrp3 inflammasome senses obesity-associated danger signals and contributes to obesity-induced inflammation and insulin resistance.
Editor: United States: Nature Publishing Group
Idioma: Inglês

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The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance

Dixit, Vishwa Deep ; Vandanmagsar, Bolormaa ; Youm, Yun-Hee ; Ravussin, Anthony ; Galgani, Jose E ; Stadler, Krisztian ; Mynatt, Randall L ; Ravussin, Eric ; Stephens, Jacqueline M

United States: Nature Publishing Group

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