Inflammasome is a central player in the induction of obesity and insulin resistance

By R. Stienstra, J. V. van Diepen, C. Tack, M. Zaki, F. L. van de Veerdonk, Deshani Perera, G. Neale, G. Hooiveld, A. Hijmans, I. Vroegrijk and 6 more. Proceedings of the National Academy of Sciences of the United States of America, 2011

692 citations recorded by the source corpus.

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.

Subfields: Epidemiology, Immunology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/e31181ff6f7b41747e66f26202d7418bdc285bd1

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Citations in the corpus

NLRP3 inflammasome: From a danger signal sensor to a regulatory node of oxidative stress and inflammatory diseases (2015, background): “Compared with wild-type, ASC / mice are protected from liver steatosis, adipocyte hypertrophy and the HFD-induced insulin resistance [88].”
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Canonical Nlrp3 inflammasome links systemic low grade inflammation to functional decline in aging (2013, positive): “However, it has also been demonstrated that development of HFD-induced dysbiosis in a different strain of Asc mutant mice causes increased obesity (Henao-Mejia et al., 2012).”
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