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

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

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.

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