Aim
To investigate matrix metalloproteinase-11 (MMP-11) expression in adipose tissue dysfunction, using in vitro and in vivo models of insulin resistance.
Conclusion
Our results indicate that dysregulation of MMP-11 expression is an early process in the adipose tissue dysfunction, which leads to obesity and obesity-related insulin resistance.
Methods
Culture of mouse 3T3-L1 preadipocytes were induced to differentiation into mature 3T3-L1 adipocytes. Cellular insulin resistance was induced by treating differentiated cultured adipocytes with hypoxia and/or tumor necrosis factor (TNF)-α, and transcriptional changes were analyzed in each condition thereafter. For the in vivo studies, MMP-11 expression levels were measured in white adipose tissue (WAT) from C57BL/6J mice that underwent low fat diet or high-fat feeding in order to induce obesity and obesity-related insulin resistance. Statistical analysis was carried out with GraphPad Prism Software.
Results
MMP-11 mRNA expression levels were significantly higher in insulin resistant 3T3-L1 adipocytes compared to control cells (1.46 ± 0.49 vs 0.83 ± 0.21, respectively; P < 0.00036). The increase in MMP-11 expression was observed even in the presence of TNF-α alone (3.79 ± 1.11 vs 1 ± 0.17, P < 0.01) or hypoxia alone (1.79 ± 0.7 vs 0.88 ± 0.1, P < 0.00023). The results obtained in in vitro experiments were confirmed in the in vivo model of insulin resistance. In particular, MMP-11 mRNA was upregulated in WAT from obese mice compared to lean mice (5.5 ± 2.8 vs 1.1 ± 0.7, respectively; P < 3.72E-08). The increase in MMP-11 levels in obese mice was accompanied by the increase in typical markers of fibrosis, such as collagen type VI alpha 3 (Col6α3), and fibroblast-specific protein 1.