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Inflammation, Cytokines and Insulin Resistance: A Clinical Perspective

Abstract

Obesity and obesity-related disorders have dramatically increased globally in the last decades. These entities are commonly associated with a state of insulin resistance and the relationship between extensive lipid deposition and insulin resistance is widely accepted. The underlying mechanisms for insulin resistance, however, are still incompletely understood. Evidence from experimental research and human studies in the last years has suggested that innate immune pathways and inflammatory mechanisms also might play a role. Insulin resistance in case of obesity is commonly accompanied by low-grade systemic inflammation and adipose tissue inflammation. The expression of various pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1 and IL-6 is increased in adipose tissue and its expression linked to systemic inflammation and accompanying insulin resistance. Weight loss reduces this enhanced cytokine expression in the adipose tissue and thereby improves systemic inflammation. Whereas there is also substantial evidence that pro-inflammatory cytokines, certain members of the inflammasome and various transcription factors such as nuclear factor-κB play a major role in animal models of insulin resistance and type 2 diabetes, human studies neutralizing certain pro-inflammatory cytokines suggest so far that not all pro-inflammatory cytokines are of equal clinical importance. First clinical studies favor an important role for IL-1 family members and probably IL-6 but not for TNF-α in insulin-resistant states. Although we still have missing links in the understanding of insulin resistance, certain inflammatory pathways have also evolved in humans as central players.

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Acknowledgments

This work was supported by the Christian Doppler Society.

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Correspondence to Herbert Tilg.

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Wieser, V., Moschen, A.R. & Tilg, H. Inflammation, Cytokines and Insulin Resistance: A Clinical Perspective. Arch. Immunol. Ther. Exp. 61, 119–125 (2013). https://doi.org/10.1007/s00005-012-0210-1

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Keywords

  • Innate immunity
  • Type 2 diabetes
  • Adipocytokines
  • Anti-cytokine therapies