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Nat Commun. 2018 Nov 9;9(1):4722. doi: 10.1038/s41467-018-06462-0.

Diet-induced adaptive thermogenesis requires neuropeptide FF receptor-2 signalling.

Zhang L1,2, Ip CK1, Lee IJ1, Qi Y1, Reed F1, Karl T3,4,5, Low JK4, Enriquez RF1,6, Lee NJ1,2, Baldock PA5,6,7, Herzog H8,9,10.

Author information

1
Neuroscience Division, Garvan Institute of Medical Research, St. Vincent's Hospital, Darlinghurst, NSW, Australia.
2
St. Vincent's Clinical School, University of NSW, Sydney, NSW, Australia.
3
School of Medicine, Western Sydney University, Sydney, NSW, Australia.
4
Neuroscience Research Australia, Randwick, NSW, Australia.
5
School of Medical Sciences, University of NSW, Sydney, NSW, Australia.
6
Bone Biology Division, Garvan Institute of Medical Research, St Vincent's Hospital, Darlinghurst, NSW, Australia.
7
Faculty of Medicine, University of NSW, Sydney, NSW, Australia.
8
Neuroscience Division, Garvan Institute of Medical Research, St. Vincent's Hospital, Darlinghurst, NSW, Australia. h.herzog@garvan.org.au.
9
School of Medical Sciences, University of NSW, Sydney, NSW, Australia. h.herzog@garvan.org.au.
10
Faculty of Medicine, University of NSW, Sydney, NSW, Australia. h.herzog@garvan.org.au.

Abstract

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.

PMID:
30413707
PMCID:
PMC6226433
DOI:
10.1038/s41467-018-06462-0
[Indexed for MEDLINE]
Free PMC Article

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