Important role of NPY-Y4R signalling in the dual control of feeding and physical activity

The control of feeding and physical activity is tightly linked and coordinated. However the underlying mechanisms are unclear. One of the major regulatory systems of feeding behaviour involves neuropeptide Y (NPY) signalling, with the signalling mediated through NPY Y4 receptor also known to influence activity. Here we show that mice globally lacking the Npy4r (Npy4r−/−) in the absence of access to a running wheel behaved WT-like with regards to food intake, energy expenditure, respiratory exchange ratio and locomotion regardless of being fed on a chow or high fat diet. Interestingly however, when given the access to a running wheel, Npy4r−/− mice while having a comparable locomotor activity, showed significantly higher wheel-running activity than WT, again regardless of dietary conditions. This higher wheel-running activity in Npy4r−/−mice arose from an increased dark-phase running time rather than changes in number of running bouts or the running speed. Consistently, energy expenditure was higher in Npy4r−/− than WT mice. Importantly, food intake was reduced in Npy4r−/−mice under wheel access condition which was due to decreased feeding bouts rather than changes in meal size. Together, these findings demonstrate an important role of Npy4r signalling in the dual control of feeding and physical activity, particularly in the form of wheel-running activity.