Deletion of Proteinase Activated Receptor 2 (PAR2) Does Not Ameliorate Age‐Related Obesity

Abstract

The purpose of this study was to determine if proteinase activated receptor 2 (PAR2) plays a role in the development of age-related obesity and insulin resistance. Body composition and insulin action were assessed in 18-month old male PAR2 knockout (PAR2-KO) mice, age-matched male C57BL6 mice (AG), and young male C57BL6 mice (YG, 6 months old). Body composition was assessed by magnetic resonance spectroscopy (Bruker LF50 BCA Mini-Spec) and insulin action was assessed by glucose tolerance (GT), insulin tolerance (IT) and AICAR tolerance (AT) testing. Body mass was significantly higher in PAR2-KO and AG mice when compared to YG mice (P ≤.0001). Surprisingly, PAR2-KO mice weighed significantly more than AG mice (P=.042). Similar to body mass, epididymal white adipose tissue (EWAT) mass was significantly higher in PAR2-KO and AG mice when compared to YG mice (P ≤.0001). No significant differences in EWAT mass existed between PAR2-KO and AG mice (P=.95). Body composition analysis revealed that PAR2-KO and AG mice had significantly greater fat mass and higher body fat percentage than YG mice. Further, fat mass was significantly greater in PAR2-KO mice compared to AG mice (P=.045); however, only a trend for differences in body fat percentage was observed between PAR2-KO and AG mice (P=.09). No differences existed in lean body mass among the PAR2-KO, AG, and YG mice (P=.58). With regards to insulin action, area under the curve (AUC) for GT was significantly lower in PAR2-KO compared to AG mice (P =.0003) and YG mice (P=.001); however, no differences existed for the AUC for IT or AT indicating that PAR2-KO mice have greater insulin secretion rather than enhanced insulin sensitivity. In summary, age-related obesity does not appear to be dependent on PAR2 expression; in fact, an absence of PAR2 may increase adiposity with advancing age.