Peroxisome proliferator-activated receptor γcontrols ingestive behavior, agouti-related protein, and neuropeptide Y mRNA in the arcuate hypothalamus

Xjohn T. Garretson, Brett J.W. Teubner, Kevin L. Grove, Almira Vazdarjanova, Vitaly Ryu, Timothy J. Bartness

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


Peroxisome proliferator-activated receptor γ (PPARγ) is clinically targeted for type II diabetes treatment; however, rosiglitazone (ROSI), a PPARγ agonist, increases food intake and body/fat mass as side-effects. Mechanisms for these effects and the role of PPARγ in feeding are not understood. Therefore, we tested this role in Siberian hamsters, a model of human energy balance, and C57BL/6 mice. We tested the following: (1) how ROSI and/or GW9662 (2-chloro-5-nitro-N-phenylbenzamide;PPARγ antagonist) injected intraperitoneally or into the third ventricle (3V) affected Siberian hamster feeding behaviors; (2) whether food deprivation (FD) co-increases agouti-related protein (AgRP) and PPARγ mRNAexpression in Siberian hamsters and mice; (3) whether intraperitoneally administered ROSI increases AgRP andNPYin ad libitum-fed animals; (4) whether intraperitoneally administeredPPARγ antagonism blocks FD-induced increases in AgRP and NPY; and finally, (5) whether intraperitoneally administered PPAR γ modulation affects plasma ghrelin. Third ventricular and intraperitoneally administered ROSI increased food hoarding and intake for 7 d, an effect attenuated by 3V GW9662, and also prevented (intraperitoneal) FD-induced feeding. FD hamsters and mice increased AgRP within the arcuate hypothalamic nucleus with concomitant increases in PPAR γ exclusively within AgRP/NPY neurons. ROSI increased AgRP and NPY similarly to FD, and GW9662 prevented FD-induced increases in AgRP and NPY in both species. Neither ROSI nor GW9662 affected plasma ghrelin. Thus, we demonstrated that PPAR γ activation is sufficient to trigger food hoarding/intake, increase AgRP/NPY, and possibly is necessary for FD-induced increases in feeding and AgRP/NPY. These findings provide initial evidence that FD-induced increases in AgRP/NPY may be a direct PPARγ-dependent process that controls ingestive behaviors.

Original languageEnglish (US)
Pages (from-to)4571-4581
Number of pages11
JournalJournal of Neuroscience
Issue number11
StatePublished - 2015


  • AgRP
  • Arcuate
  • Food hoarding
  • Ingestive behavior
  • NPY
  • PPAR gamma

ASJC Scopus subject areas

  • Neuroscience(all)


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