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

  • Nat Commun. 2018 Nov 9;9(1):4722. doi: 10.1038/s41467-018-06462-0.
Lei Zhang  1  2 ,  Chi Kin Ip  1 ,  I-Chieh J Lee  1 ,  Yue Qi  1 ,  Felicia Reed  1 ,  Tim Karl  3  4  5 ,  Jac Kee Low  4 ,  Ronaldo F Enriquez  1  6 ,  Nicola J Lee  1  2 ,  Paul A Baldock  5  6  7 ,  Herbert Herzog  8  9  10
Affiliations
  • 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. [email protected].
  • 9. School of Medical Sciences, University of NSW, Sydney, NSW, Australia. [email protected].
  • 10. Faculty of Medicine, University of NSW, Sydney, NSW, Australia. [email protected].
PMID: 30413707 DOI: 10.1038/s41467-018-06462-0
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.