Journal
INTERNATIONAL IMMUNOPHARMACOLOGY
Volume 42, Issue -, Pages 209-217Publisher
ELSEVIER
DOI: 10.1016/j.intimp.2016.11.019
Keywords
Hypoxia; Inflammation; Insulin resistance; 3T3-L1 adipocytes; Bilobalide
Categories
Funding
- University Grants Commission, Govt. of India
- KSCSTE
- DBT
- CSIR [NaPAHA CSC 0130]
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Obesity leads to inflammation and insulin resistance in adipose tissue. Hypoxia, observed in obese adipose tissue is suggested as a major cause of inflammation and insulin resistance in obesity. However, the role of hypoxia in adipose tissue during obesity and insulin resistance was not well established. Here we mainly explored the crosstalk between hypoxia induced inflammation, and insulin resistance and also secretion of angiogenic factors in 3T3-L1 adipocytes and possible reversal with bilobalide. Hypoxia for 24 h significantly (P <= 0.05) increased the secretion of MCP-1 (4.59 fold), leptin (2.96 fold) and reduced adiponectin secretion (2.93 fold). In addition, the mRNA level of resistin (6.8 fold) and TLR4 receptors (8.8 fold) was upregulated in hypoxic adipocytes. The release of inflammatory cytokines and expression of TLR4 receptors led to activation of and NF-kappa B signalling. We further investigated the effects of JNK and NF-kappa B activation on insulin signalling receptors. The present study showed increased (P <= 0.05) serine 307 phosphorylation of IRS-1 (1.9 fold) and decreased expression of IRS-2 (0.53 fold) in hypoxic group showing hypoxia induced impairment in insulin signalling. Hypoxia significantly (P <= 0.05) increased basal glucose uptake (3.3 fold) as well as GLUT-1 expression in adipocytes indicating GLUT-1 mediated glucose uptake. Hypoxia for 24 h significantly increased (P <= 0.05) the expression of angiogenic factors. Bilobalide protected adipocytes from hypoxia induced inflammation and insulin resistance mainly by reducing inflammatory adipokine secretion, improving adiponectin secretion, reducing NF-kappa B/JNK activation, and inhibiting serine phosphorylation of IRS-1 receptors of insulin signalling pathway. (C) 2016 Elsevier B.V. All rights reserved.
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