A disintegrin and metalloproteinase domain-containing protein-12 levels in first-trimester pregnant women

WOS: 000444384300006Aim: In this prospective monocenter study, the authors aimed to investigate the correlations between levels of serum human disintegrin and metalloproteinase domain-containing protein 12 (ADAM12), pregnancy-associated plasma protein A (PAPP-A), serum-free beta hCG (f beta-hCG), and baby birth weights in two groups of pregnant women whose risks for trisomy 21 was found higher and lower than threshold value in first trimester screening test. Materials and Methods: Seventy-nine pregnant women were included the study. Using first trimester screening test, 40 of them were categorized as having above threshold risk (1/250) for trisomy 21 and, 39 of them were below threshold risk. ELISA method was used to measure the levels of serum ADAM12 and chemiluminescence method was used to measure the levels of PAPP-A and f beta-hCG. Results: In pregnant women at risk, ADAM12, PAPP-A multiple of median (MoM), and baby birth weights were found significantly lower than control group (p < 0.001, p < 0.001, and p = 0.029, respectively) while the levels of f beta-hCG MoM were higher than those of control group (p < 0.001). In the group of pregnant women having low birth weight (LBW) babies, ADAM12 levels were found lower than the group having normal birth weight babies (NBW) (p < 0.033). Also, the values of f beta-hCG MoM were found higher in comparison to NBW group (p < 0.029). A positive significant correlation was observed between ADAM12 concentrations and PAPP-A MoM (r = 0.630). Conclusions: Maternal serum ADAM12 levels are useful as biomarkers which support other screening parameters for predicting trisomy 21 risk. Additionally, maternal serum ADAM12 levels could be used for prediction of baby birth weights

Ablation of kallikrein 7 (KLK7) in adipose tissue ameliorates metabolic consequences of high fat diet-induced obesity by counteracting adipose tissue inflammation in vivo

Vaspin is an adipokine which improves glucose metabolism and insulin sensitivity in obesity. Kallikrein 7 (KLK7) is the first known protease target inhibited by vaspin and a potential target for the treatment of metabolic disorders. Here, we tested the hypothesis that inhibition of KLK7 in adipose tissue may beneficially affect glucose metabolism and adipose tissue function. Therefore, we have inactivated the Klk7 gene in adipose tissue using conditional gene-targeting strategies in mice. Klk7-deficient mice (ATKlk7 −/−) exhibited less weight gain, predominant expansion of subcutaneous adipose tissue and improved whole body insulin sensitivity under a high fat diet (HFD). ATKlk7 −/− mice displayed higher energy expenditure and food intake, most likely due to altered adipokine secretion including lower circulating leptin. Pro-inflammatory cytokine expression was significantly reduced in combination with an increased percentage of alternatively activated (anti-inflammatory) M2 macrophages in epigonadal adipose tissue of ATKlk7 −/−. Taken together, by attenuating adipose tissue inflammation, altering adipokine secretion and epigonadal adipose tissue expansion, Klk7 deficiency in adipose tissue partially ameliorates the adverse effects of HFD-induced obesity. In summary, we provide first evidence for a previously unrecognized role of KLK7 in adipose tissue with effects on whole body energy expenditure and insulin sensitivity