AIM To investigate matrix metalloproteinase-11(MMP-11) expression in adipose tissue dysfunction, using in vitro and in vivo models of insulin resistance.METHODS Culture of mouse 3T3-L1 preadipocytes were induced to di...AIM To investigate matrix metalloproteinase-11(MMP-11) expression in adipose tissue dysfunction, using in vitro and in vivo models of 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 GraphP ad Prism Software.RESULTS MMP-11 m RNA expression levels were significantly higher in insulin resistant 3T3-L1 adipocytes compared to control cells(1.46±0.49vs0.83±0.21, respectively;P<0.00036). The increase in MMP-11 expression was observed even in the presence of TNF-α alone(3.79±1.11vs1±0.17, P<0.01) or hypoxia alone(1.79±0.7vs0.88±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 m RNA was upregulated in WAT from obese mice compared to lean mice(5.5±2.8vs1.1±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(Col6_α3), and fibroblast-specific protein 1.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.展开更多
文摘AIM To investigate matrix metalloproteinase-11(MMP-11) expression in adipose tissue dysfunction, using in vitro and in vivo models of 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 GraphP ad Prism Software.RESULTS MMP-11 m RNA expression levels were significantly higher in insulin resistant 3T3-L1 adipocytes compared to control cells(1.46±0.49vs0.83±0.21, respectively;P<0.00036). The increase in MMP-11 expression was observed even in the presence of TNF-α alone(3.79±1.11vs1±0.17, P<0.01) or hypoxia alone(1.79±0.7vs0.88±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 m RNA was upregulated in WAT from obese mice compared to lean mice(5.5±2.8vs1.1±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(Col6_α3), and fibroblast-specific protein 1.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.
