Conditional inactivation of limbic neuropeptide y-1 receptors increases vulnerability to diet-induced obesity in male mice

Silvia Paterlini, Riccardo Panelli, Laura Gioiosa, Stefano Parmigiani, Paolo Franceschini, Ilaria Bertocchi, Alessandra Oberto, Alessandro Bartolomucci, Carola Eva, Paola Palanza

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


NPY and its Y1 cognate receptor (Y1R) have been shown to be involved in the regulation of stress, anxiety, depression and energy homeostasis. We previously demonstrated that conditional knockout of Npy1r gene in the excitatory neurons of the forebrain of adolescent male mice (Npy1rrfb mice) decreased body weight growth and adipose tissue and increased anxiety. In the present study, we used the same conditional system to examine whether the targeted disruption of the Npy1r gene in limbic areas might affect susceptibility to obesity and associated disorders during adulthood in response to a 3-week high-fat diet (HFD) regimen. We demonstrated that following HFD exposure, Npy1rrfb male mice showed increased body weight, visceral adipose tissue, and blood glucose levels, hyperphagia and a dysregulation of calory intake as compared to control Npy1r2lox mice. These results suggest that low expression of Npy1r in limbic areas impairs habituation to high caloric food and causes high susceptibility to diet-induced obesity and glucose intolerance in male mice, uncovering a specific contribution of the limbic Npy1r gene in the dysregulation of the eating/satiety balance.

Original languageEnglish (US)
Article number8745
JournalInternational journal of molecular sciences
Issue number16
StatePublished - Aug 2 2021

Bibliographical note

Funding Information:
Funding: This work was supported by the Italian Ministry of University and Research (MIUR) [PRIN 2008 PLKP3E_002 and PRIN 2010 7MSMA4_005], The “Neuroscience program” by Compagnia di San Paolo and the Cariplo Foundation (grant 2013-0786, 1 February 2014).

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.


  • Food intake
  • Glucose intolerance
  • High fat diet
  • NPY
  • Obesity
  • Y1R
  • Eating
  • Obesity/etiology
  • Male
  • Receptors, Neuropeptide Y/genetics
  • Gene Knockout Techniques
  • Limbic System/metabolism
  • Animals
  • Diet, High-Fat
  • Glucose Intolerance/etiology
  • Mice

PubMed: MeSH publication types

  • Journal Article


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