Synergistic effects of Y2 and Y4 receptors on adiposity and bone mass revealed in double knockout XXXX .

@entity52465 @entity28 @entity19 @entity7298 @entity604 @entity43049 @entity36888
Neuropeptide Y regulates numerous physiological processes via at least five different Y receptors, but the specific roles of each receptor are still unclear. We previously demonstrated that @entity36888 knockout results in a lean phenotype, increased cancellous bone volume, and an increase in plasma @entity43049 ( @entity43049 ), a ligand for Y4 receptors. @entity43049 -overexpressing @entity19 are also known to have a lean phenotype. Deletion of the @entity52465 also produced a lean phenotype and increased plasma @entity43049 levels. We therefore hypothesized that part of the Y2 phenotype results from increased @entity43049 action on Y4 receptors and tested this in @entity43049 transgenic Y4(-/-) and Y2(-/-) Y4(-/-) double knockout @entity19 . Bone mass was not altered in Y4 knockout @entity19 . Surprisingly, despite significant @entity7298 , Y2(-/-) Y4(-/-) @entity19 retained a markedly lean phenotype, with reduced body weight, white adipose tissue mass, leptinemia, and insulinemia. Furthermore, bone volume was also increased threefold in Y2(-/-) Y4(-/-) @entity19 , and this was associated with enhanced osteoblastic activity. These changes were more pronounced than those observed in Y2(-/-) @entity19 , suggesting synergy between @entity36888 pathways. The lack of bone changes in @entity43049 @entity19 suggests that @entity43049 alone is not responsible for the bone mass increases but might play a major role in the lean phenotype. However, a synergistic interaction between Y2 and Y4 pathways seems to regulate bone volume and adiposity and could have important implications for possible interventions in @entity28 and for anabolic treatment of @entity604 .
