Inflammation links excess fat to insulin resistance: the role of the interleukin-1 family

C.J. Tack, R. Stienstra, L.A.B. Joosten, M.G. Netea

Research output: Contribution to journalArticleAcademicpeer-review

111 Citations (Scopus)


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.
Original languageEnglish
Pages (from-to)239-252
JournalImmunological reviews
Publication statusPublished - 2012


  • thioredoxin-interacting protein
  • type-2 diabetes-mellitus
  • necrosis-factor-alpha
  • subcutaneous adipose-tissue
  • beta-cell apoptosis
  • nf-kappa-b
  • tnf-alpha
  • innate immunity
  • receptor antagonist
  • metabolic syndrome

Fingerprint Dive into the research topics of 'Inflammation links excess fat to insulin resistance: the role of the interleukin-1 family'. Together they form a unique fingerprint.

Cite this