Publications Search

Search for publications by author
Search for publications by abstract keyword(s)

Peripheral specific Y2 receptor knockdown protects mice from high fat diet induced obesity


Y2 receptors, particularly those in the brain, have been implicated in neuropeptide Y (NPY)-mediated effects on energy homeostasis and bone mass. Recent evidence also indicates a role for Y2 receptors in peripheral tissues in this process by promoting adipose tissue accretion, however their effects on energy balance remain unclear. Here we show that adult-onset conditional knockdown of Y2 receptors predominantly in peripheral tissues results in protection against diet induced obesity accompanied by significantly reduced weight gain, marked reduction in adiposity and improvements in glucose tolerance without any adverse effect on lean mass or bone. These changes occur in association with significant increases in energy expenditure, respiratory exchange ratio and physical activity and despite concurrent hyperphagia. On a chow diet knockdown of peripheral Y2 receptors results in increased respiratory exchange ratio and physical activity with no effect on lean or bone mass, but decreases energy expenditure without effecting body weight or food intake. These results suggest that peripheral Y2 receptor signalling is critical in the regulation of oxidative fuel selection and physical activity and protects against the diet-induced obesity. The lack of effects on bone mass seen in this model further indicates that bone mass is primarily controlled by non-peripheral Y2 receptors. This study provides evidence that novel drugs that target peripheral rather than central Y2 receptors could provide benefits for the treatment of obesity and glucose intolerance without adverse effects on lean and bone mass, with the additional benefit of avoiding side effects often associated with pharmaceuticals that act on the central nervous system.

Type Journal
Authors Shi, Y.C.; Lin, S.; Castillo, L.; Aljanova, A.; Enriquez, R.F.; Nguyen, A.D.; Baldock, P.A.; Zhang, L.; Bijker, M.; Macia, L.; Yulyaningsih, E.; Zhang, H.; Lau, J.; Sainsbury, A.; Herzog, H.
Responsible Garvan Author A/Prof Yanchuan Shi
Publisher Name Obesity
Published Date 2011-05-07
Published Volume 19
Published Issue 11
Published Pages 2137-48
Status Published in-print
DOI oby201199 [pii] 10.1038/oby.2011.99
URL link to publisher's version
OpenAccess link to author's accepted manuscript version