Diet-induced adaptive thermogenesis requires neuropeptide FF receptor-2 signalling
Excess caloric intake results in increased fat accumulation and an increase in energy expenditure via diet-induced adaptive thermogenesis; however, the underlying mechanisms controlling these processes are unclear. Here we identify the neuropeptide FF receptor-2 (NPFFR2) as a critical regulator of diet-induced thermogenesis and bone homoeostasis. Npffr2(-/-) mice exhibit a stronger bone phenotype and when fed a HFD display exacerbated obesity associated with a failure in activating brown adipose tissue (BAT) thermogenic response to energy excess, whereas the activation of cold-induced BAT thermogenesis is unaffected. NPFFR2 signalling is required to maintain basal arcuate nucleus NPY mRNA expression. Lack of NPFFR2 signalling leads to a decrease in BAT thermogenesis under HFD conditions with significantly lower UCP-1 and PGC-1alpha levels in the BAT. Together, these data demonstrate that NPFFR2 signalling promotes diet-induced thermogenesis via a novel hypothalamic NPY-dependent circuitry thereby coupling energy homoeostasis with energy partitioning to adipose and bone tissue.
|ISBN||2041-1723 (Electronic) 2041-1723 (Linking)|
|Authors||Zhang, L.; Ip, C. K.; Lee, I. J.; Qi, Y.; Reed, F.; Karl, T.; Low, J. K.; Enriquez, R. F.; Lee, N. J.; Baldock, P. A.; Herzog, H.|
|Responsible Garvan Author|
|Publisher Name||Nature Communications|
|URL link to publisher's version||http://www.ncbi.nlm.nih.gov/pubmed/30413707|