| Summary: | Increased plasma and adipose tissue protease activity is observed in patients with type 2 diabetes and obesity. It has been proposed that specific proteases contribute to the link between obesity, adipose tissue inflammation and metabolic diseases. We have recently shown that ablation of the serine protease kallikrein-related peptidase 7 (<i>Klk7</i>) specifically in adipose tissue preserves systemic insulin sensitivity and protects mice from obesity-related AT inflammation. Here, we investigated whether whole body <i>Klk7</i> knockout (<i>Klk7<sup>−/−</sup></i>) mice develop a phenotype distinct from that caused by reduced <i>Klk7</i> expression in adipose tissue. Compared to littermate controls, <i>Klk7<sup>−/−</sup></i> mice gain less body weight and fat mass both under chow and high fat diet (HFD) feeding, are hyper-responsive to exogenous insulin and exhibit preserved adipose tissue function due to adipocyte hyperplasia and lower inflammation. <i>Klk7<sup>−/−</sup></i> mice exhibit increased adipose tissue thermogenesis, which is not related to altered thyroid function. These data strengthen our recently proposed role of <i>Klk7</i> in the regulation of body weight, energy metabolism, and obesity-associated adipose tissue dysfunction. The protective effects of <i>Klk7</i> deficiency in obesity are likely linked to a significant limitation of adipocyte hypertrophy. In conclusion, our data indicate potential application of specific KLK7 inhibitors to regulate KLK7 activity in the development of obesity and counteract obesity-associated inflammation and metabolic diseases.
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