IGFBP-3 Inhibits Cytokine-Induced Insulin Resistance and Early Manifestations of Atherosclerosis

Lathika Mohanraj, Ho Seong Kim, Wei Li, Qing Cai, Ki Eun Kim, Hye Jung Shin, Yong Jae Lee, Woo Jung Lee, Jung Hyun Kim, Youngman Oh

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22 Citations (Scopus)

Abstract

Metabolic syndrome is associated with visceral obesity, insulin resistance and an increased risk of cardiovascular diseases. Visceral fat tissue primarily consists of adipocytes that secrete cytokines leading to a state of systemic inflammation in obese conditions. One of the IGF-independent functions of IGFBP-3 is its role as an anti-inflammatory molecule. Our study in obese adolescents show a decrease in total IGFBP-3 levels and increase in proteolyzed IGFBP-3 in circulation when compared to their normal counterparts and establishes a positive correlation between IGFBP-3 proteolysis and adiposity parameters as well as insulin resistance. In human adipocytes, we show that IGFBP-3 inhibits TNF-α-induced NF-κB activity in an IGF-independent manner, thereby restoring the deregulated insulin signaling and negating TNF-α-induced inhibition of glucose uptake. IGFBP-3 further inhibits TNF-α, CRP and high glucose-induced NF-κB activity in human aortic endothelial cells (HAECs) and subsequently suppresses monocyte adhesion to HAEC through the IGFBP-3 receptor. In conclusion, these findings suggest that reduced levels of IGFBP-3 in circulation and reduced expression of IGFBP-3 in macrophages in obesity may result in suppression of its anti-inflammatory functions and therefore IGFBP-3 may present itself as a therapeutic for obesity-induced insulin resistance and for events occurring in the early stages of atherosclerosis.

Original languageEnglish
Article numbere55084
JournalPloS one
Volume8
Issue number1
DOIs
Publication statusPublished - 2013 Jan 28

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All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Mohanraj, L., Kim, H. S., Li, W., Cai, Q., Kim, K. E., Shin, H. J., Lee, Y. J., Lee, W. J., Kim, J. H., & Oh, Y. (2013). IGFBP-3 Inhibits Cytokine-Induced Insulin Resistance and Early Manifestations of Atherosclerosis. PloS one, 8(1), [e55084]. https://doi.org/10.1371/journal.pone.0055084