Background: Visceral adipose tissue-derived serpin (vaspin) was identified in visceral adipose tissue (AT) of the Otsuka Long-Evans Tokushima Fatty rat and the serine protease kallikrein 7 (Klk7) has been identified as the first protease target. In mouse models, application of vaspin reduces food intake und improves glucose tolerance. In humans, expression of vaspin mRNA is associated with overweight, insulin resistance and Type-2-diabetes. Here, we investigated the role of Klk7 in the pathophysiology of obesity and related traits in an adipose tissue-specific Klk7 knock-out mouse.
Methods: Inactivation of the Klk7 gene in adipose tissue (Klk7aP2Cre mice) using conditional gene targeting strategies. Metabolic characterization of these mice under a standard and high-fat diet.
Results: Male Klk7aP2Cre mice under a standard chow diet exhibited significantly reduced body weight as well as slightly decreased body length in comparison to the control mice while the distribution of adipose tissue was unchanged. Furthermore, glucose-tolerance was significantly improved and insulin-tolerance was slightly amended when the Klk7 gene is inactivated in AT.
Under a high-fat diet, a significantly lower body weight was observed only for female Klk7aP2Cre mice, with a marginally lower body weight for male Klk7aP2Cre mice. We observed improved insulin-tolerance in male mice deficient of AT Klk7. Interestingly, both sexes exhibited differences in body fat distribution analyzed by Echo MRI and relative organ weight for the subcutaneous AT was strongly increased, while the visceral AT depot was reduced in the Klk7aP2Cre mice compared to controls.
Conclusion: In conclusion, these data reveal novel functions of the protease Klk7 in adipose tissue. AT specific Klk7 deficiency improved parameters of obesity and associated insulin-resistance.