@article{10.1371/journal.pone.0055084, doi = {10.1371/journal.pone.0055084}, author = {Mohanraj, Lathika AND Kim, Ho-Seong AND Li, Wei AND Cai, Qing AND Kim, Ki Eun AND Shin, Hye-Jung AND Lee, Yong-Jae AND Lee, Woo Jung AND Kim, Jung Hyun AND Oh, Youngman}, journal = {PLOS ONE}, publisher = {Public Library of Science}, title = {IGFBP-3 Inhibits Cytokine-Induced Insulin Resistance and Early Manifestations of Atherosclerosis}, year = {2013}, month = {01}, volume = {8}, url = {https://doi.org/10.1371/journal.pone.0055084}, pages = {1-13}, 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.}, number = {1}, }