Journal
IMMUNOLOGICAL REVIEWS
Volume 249, Issue -, Pages 239-252Publisher
WILEY
DOI: 10.1111/j.1600-065X.2012.01145.x
Keywords
insulin resistance; interleukin-1; autophagy; inflammasome; anakinra; visceral fat
Categories
Funding
- Netherlands DiabetesFonds
- Netherlands Organization for Scientific Research
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A growing body of evidence suggests that cytokines of the interleukin-1 (IL-1) family, particularly IL-1 beta but also IL-1Ra and IL-18, are involved in obesity-associated inflammation. IL-1 beta is produced via cleavage of pro-IL-1 beta by caspase-1, which in turn is activated by a multiprotein complex called the inflammasome. The components of the NLRP3 inflammasome are involved in sensing obesity-associated danger signals, both in mice and in human (obese) subjects, with caspase-1 seemingly the most crucial regulator. Autophagy is upregulated in obesity and may function as a mechanism to control IL-1 beta gene expression in adipose tissue to mitigate chronic inflammation. All these mechanisms are operative in human adipose tissue and appear to be more pronounced in human visceral compared to subcutaneous tissue. In animal studies, blocking caspase-1 activity results in decreased weight gain, decreased inflammation, and improved insulin sensitivity. Human intervention studies with IL-1Ra (anakinra) have reported beneficial effects in patients with diabetes, yet without significant changes in insulin sensitivity. Clearly, the IL-1 family of cytokines, especially IL-1 beta, plays an important role in obesity-associated inflammation and insulin resistance and may represent a therapeutic target to reverse the detrimental metabolic consequences of obesity.
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