Nat Commun. 2018 Nov 9;9(1):4722. doi: 10.1038/s41467-018-06462-0.
Zhang, L; Ip, CK; Lee, IJ; Qi, Y; Reed, F; Karl, T; Low, JK; Enriquez, RF; Lee, NJ; Baldock, PA; Herzog, H
Neuroscience Division, Garvan Institute of Medical Research, St. Vincent's Hospital, Darlinghurst, NSW, Australia. St. Vincent's Clinical School, University of NSW, Sydney, NSW, Australia. School of Medicine, Western Sydney University, Sydney, NSW, Australia. Neuroscience Research Australia, Randwick, NSW, Australia. School of Medical Sciences, University of NSW, Sydney, NSW, Australia. Bone Biology Division, Garvan Institute of Medical Research, St Vincent's Hospital, Darlinghurst, NSW, Australia. Faculty of Medicine, University of NSW, Sydney, NSW, Australia.
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-1α 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.
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