title: NPY modulates PYY function in the regulation of energy balance and glucose homeostasis.
abstract: OBJECTIVE
  Both the neuronal-derived neuropeptide Y (NPY) and the gut hormone peptide YY (PYY) have been implicated in the regulation of energy balance and glucose homeostasis. However, despite similar affinities for the same Y receptors, the co-ordinated actions of these two peptides in energy and glucose homeostasis remain largely unknown.
  
  
  METHODS
  To investigate the mechanisms and possible interactions between PYY with NPY in the regulation of these processes, we utilized NPY/PYY single and double mutant mouse models and examined parameters of energy balance and glucose homeostasis.
  
  
  RESULTS
  PYY(-/-) mice exhibited increased fasting-induced food intake, enhanced fasting and oral glucose-induced serum insulin levels, and an impaired insulin tolerance, - changes not observed in NPY(-/-) mice. Interestingly, whereas PYY deficiency-induced impairment in insulin tolerance remained in NPY(-/-) PYY(-/-) mice, effects of PYY deficiency on fasting-induced food intake and serum insulin concentrations at baseline and after the oral glucose bolus were absent in NPY(-/-) PYY(-/-) mice, suggesting that NPY signalling may be required for PYY's action on insulin secretion and fasting-induced hyperphagia. Moreover, NPY(-/-) PYY(-/-) , but not NPY(-/-) or PYY(-/-) mice had significantly decreased daily food intake, indicating interactive control by NPY and PYY on spontaneous food intake. Furthermore, both NPY(-/-) and PYY(-/-) mice showed significantly reduced respiratory exchange ratio during the light phase, with no additive effects observed in NPY(-/-) PYY(-/-) mice, indicating that NPY and PYY may regulate oxidative fuel selection via partly shared mechanisms. Overall, physical activity and energy expenditure, however, are not significantly altered by NPY and PYY single or double deficiencies.
  
  
  CONCLUSIONS
  These findings show significant and diverse interactions between NPY and PYY signalling in the regulation of different aspects of energy balance and glucose homeostasis.
authors.affiliation: Neuroscience Research Program, Garvan Institute of Medical Research, St Vincent's Hospital, Darlinghurst, Sydney, New South Wales, Australia.
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.forename: A D
authors.initials: AD
authors.lastname: Nguyen
authors.forename: I-C J
authors.initials: IC
authors.lastname: Lee
authors.forename: E
authors.initials: E
authors.lastname: Yulyaningsih
authors.forename: S J
authors.initials: SJ
authors.lastname: Riepler
authors.forename: B
authors.initials: B
authors.lastname: Stehrer
authors.forename: R F
authors.initials: RF
authors.lastname: Enriquez
authors.forename: S
authors.initials: S
authors.lastname: Lin
authors.forename: Y-C
authors.initials: YC
authors.lastname: Shi
authors.forename: P A
authors.initials: PA
authors.lastname: Baldock
authors.forename: A
authors.initials: A
authors.lastname: Sainsbury
authors.forename: H
authors.initials: H
authors.lastname: Herzog
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D004435:Eating; D004734:Energy Metabolism; D005215:Fasting / Q000097:blood; D005951:Glucose Tolerance Test; D006706:Homeostasis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity; D009478:Neuropeptide Y / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D019894:Peptide YY / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D009478:Neuropeptide Y; D019894:Peptide YY