title: Peroxisome proliferator-activated receptor γ controls ingestive behavior, agouti-related protein, and neuropeptide Y mRNA in the arcuate hypothalamus.
abstract: 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 mRNA expression in Siberian hamsters and mice; (3) whether intraperitoneally administered ROSI increases AgRP and NPY in ad libitum-fed animals; (4) whether intraperitoneally administered PPARγ antagonism blocks FD-induced increases in AgRP and NPY; and finally, (5) whether intraperitoneally administered PPARγ 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 PPARγ 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 PPARγ 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.
authors: Neuroscience Institute, Center for Obesity Reversal, Georgia State University, Atlanta, Georgia 30303.
authors: John T
authors: http://orcid.org/0000-0002-9594-8632
authors: JT
authors: Garretson
authors: Department of Biology, and.
authors: Brett J W
authors: BJ
authors: Teubner
authors: Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, Oregon 97006.
authors: Kevin L
authors: KL
authors: Grove
authors: Department of Pharmacology and Toxicology, Georgia Regents University, Augusta, Georgia 30912, and Charlie Norwood Veterans Administration Medical Center, Augusta, Georgia 30901.
authors: Almira
authors: A
authors: Vazdarjanova
authors: Department of Biology, and Center for Obesity Reversal, Georgia State University, Atlanta, Georgia 30303.
authors: Vitaly
authors: http://orcid.org/0000-0001-8068-4577
authors: V
authors: Ryu
authors: Neuroscience Institute, Department of Biology, and Center for Obesity Reversal, Georgia State University, Atlanta, Georgia 30303, bartness@gsu.edu.
authors: Timothy J
authors: TJ
authors: Bartness
mesh_terms: D054369:Agouti-Related Protein / Q000096:biosynthesis*; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000378:metabolism*; D006224:Cricetinae; D005247:Feeding Behavior / Q000502:physiology* / Q000523:psychology; D051379:Mice; D008810:Mice, Inbred C57BL; D009478:Neuropeptide Y / Q000096:biosynthesis*; D047495:PPAR gamma / Q000096:biosynthesis*; D017111:Phodopus; D012333:RNA, Messenger / Q000096:biosynthesis*
chemical_list: D054369:Agouti-Related Protein; C515199:Agrp protein, mouse; D009478:Neuropeptide Y; D047495:PPAR gamma; D012333:RNA, Messenger
keywords: AgRP; NPY; PPAR gamma; arcuate; food hoarding; ingestive behavior