TNF-α as an adipokine

Theron C. Gilliland, Guang William Wong

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Tumor necrosis factor alpha (TNF-α), a multifunctional cytokine and adipokine, exerts pleiotropic effects on many cell types and tissues. As an adipokine, this protein negatively regulates many aspects of glucose and lipid metabolism. Downstream targets of TNF-α down-regulate genes involved in the uptake and storage of free fatty acids and glucose in adipocytes. Additionally, TNF-α promotes insulin resistance by inducing serine phosphorylation of insulin receptor substrate 1 (IRS-1) and reducing the expression of IRS-1 mRNA, attenuating downstream insulin signaling. Reduction in insulin signaling results in decreased insulin-stimulated GLUT4 translocation to the plasma membrane, reducing glucose uptake into muscle and adipocytes. TNF-α also decreases the uptake of fatty acids into adipocytes while promoting lipolysis, thus contributing to dyslipidemia and exacerbating tissue insulin resistance. The increased levels of TNF-α found in obesity promote inflammation within the adipose compartment, which dysregulates the expression of adipokines (e.g., adiponectin) that promote insulin sensitivity. Collectively, TNF-α exerts a negative impact on whole-body insulin sensitivity and metabolism. Despite its importance, the therapeutic efficacy of blocking TNF-α is currently disputed. Understanding the many mechanisms of action of TNF-α will likely provide new avenues in treating metabolic disorders associated with diabetes and obesity.

Original languageEnglish (US)
Title of host publicationAdipokines
PublisherCRC Press
Pages119-127
Number of pages9
ISBN (Electronic)9781439879887
ISBN (Print)9781138114418
StatePublished - Apr 19 2016

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    Gilliland, T. C., & Wong, G. W. (2016). TNF-α as an adipokine. In Adipokines (pp. 119-127). CRC Press.