The hindbrain is a site of energy balance action for prolactin-releasing peptide: feeding and thermic effects from GPR10 stimulation of the nucleus tractus solitarius/area postrema
- 164 Downloads
Prolactin-releasing peptide (PrRP) is a neuropeptide that suppresses food intake and increases body temperature when delivered to the forebrain ventricularly or parenchymally. However, PrRP’s receptor GPR10 is widely distributed throughout the brain with particularly high levels found in the dorsomedial hindbrain. Thus, we hypothesized that hindbrain-directed PrRP administration would affect energy balance and motivated feeding behavior.
To address this hypothesis, a range of behavioral and physiologic variables were measured in Sprague-Dawley rats that received PrRP delivered to the fourth ventricle (4V) or the nucleus of the solitary tract (NTS) at the level of the area postrema (AP).
4V PrRP delivery decreased chow intake and body weight, in part, through decreasing meal size in ad libitum maintained rats tested at dark onset. PrRP inhibited feeding when delivered to the nucleus tractus solitarius (NTS), but not to more ventral hindbrain structures. In addition, 4V as well as direct NTS administration of PrRP increased core temperature. By contrast, 4V PrRP did not reduce ad libitum intake of highly palatable food or the motivation to work for or seek palatable foods.
The dorsomedial hindbrain and NTS/AP, in particular, are sites of action in PrRP/GPR10-mediated control of chow intake, core temperature, and body weight.
KeywordsNTS Body temperature Reward Food intake Hyperthermia
We thank Zhi Yi Ong, Hallie Wald, and Amber Alhadeff for their assistance with experiments.
This study was funded by NIH R01 DK21397 (HJG) and T32 DK007314 (XSD).
Compliance with ethical standards
All procedures conformed to and received approval from the institutional standards of the University of Pennsylvania Animal Care and Use Committee.
Conflict of interest
The authors declare that they have no conflict of interest.
- Alhadeff AL, Mergler BD, Zimmer DJ, Turner CA, Reiner DJ, Schmidt HD, Grill HJ, Hayes MR (2017) Endogenous glucagon-like peptide-1 receptor signaling in the nucleus tractus solitarius is required for food intake control. Neuropsychopharmacology 42:1471–1479. https://doi.org/10.1038/npp.2016.246 CrossRefPubMedGoogle Scholar
- Choi DL, Davis JF, Magrisso IJ, Fitzgerald ME, Lipton JW, Benoit SC (2012) Orexin signaling in the paraventricular thalamic nucleus modulates mesolimbic dopamine and hedonic feeding in the rat. Neuroscience 210:243–248. https://doi.org/10.1016/j.neuroscience.2012.02.036 CrossRefPubMedPubMedCentralGoogle Scholar
- Dodd GT, Worth AA, Nunn N, Korpal AK, Bechtold DA, Allison MB, Myers MG Jr, Statnick MA, Luckman SM (2014) The Thermogenic effect of Leptin is dependent on a distinct population of prolactin-releasing peptide neurons in the dorsomedial hypothalamus. Cell Metab 20:639–649. https://doi.org/10.1016/j.cmet.2014.07.022 CrossRefPubMedPubMedCentralGoogle Scholar
- Ellacott KLJ, Donald EL, Clarkson P, Morten J, Masters D, Brennand J, Luckman SM (2005) Characterization of a naturally-occurring polymorphism in the UHR-1 gene encoding the putative rat prolactin-releasing peptide receptor. Peptides 26:675–681. https://doi.org/10.1016/j.peptides.2004.11.020 CrossRefPubMedGoogle Scholar
- Ellacott KLJ, Lawrence CB, Pritchard LE, Luckman SM (2003) Repeated administration of the anorectic factor prolactin-releasing peptide leads to tolerance to its effects on energy homeostasis. Am J Physiol Regul Integr Comp Physiol 285:R1005–R1010. https://doi.org/10.1152/ajpregu.00237.2003 CrossRefPubMedGoogle Scholar
- Fujii R, Fukusumi S, Hosoya M, Kawamata Y, Habata Y, Hinuma S, Sekiguchi M, Kitada C, Kurokawa T, Nishimura O, Onda H, Sumino Y, Fujino M (1999) Tissue distribution of prolactin-releasing peptide (PrRP) and its receptor. Regul Pept 83:1–10. https://doi.org/10.1016/S0167-0115(99)00028-2 CrossRefPubMedGoogle Scholar
- Hayes MR, Leichner TM, Zhao S, Lee GS, Chowansky A, Zimmer D, de Jonghe BC, Kanoski SE, Grill HJ, Bence KK (2011) Intracellular signals mediating the food intake-suppressive effects of hindbrain glucagon-like peptide-1 receptor activation. Cell Metab 13:320–330. https://doi.org/10.1016/j.cmet.2011.02.001 CrossRefPubMedPubMedCentralGoogle Scholar
- Horiuchi J, Saigusa T, Sugiyama N, Kanba S, Nishida Y, Sato Y, Hinuma S, Arita J (2002) Effects of prolactin-releasing peptide microinjection into the ventrolateral medulla on arterial pressure and sympathetic activity in rats. Brain Res 958:201–209. https://doi.org/10.1016/S0006-8993(02)03718-6 CrossRefPubMedGoogle Scholar
- Ibata Y, Iijima N, Kataoka Y, Kakihara K (2000) Morphological survey of prolactin-releasing peptide and its receptor with special reference to their functional roles in the brain. Neurosci Res 38(3):223–230. https://doi.org/10.1016/S0168-0102(00)00182-6
- Iijima N, Kataoka Y, Kakihara K, Bamba H, Tamada Y, Hayashi S, Matsuda T, Tanaka M, Honjyo H, Hosoya M, Hinuma S, Ibata Y (1999) Cytochemical study of prolactin-releasing peptide (PrRP) in the rat brain. Neuroreport 10:1713–1716. https://doi.org/10.1097/00001756-199906030-00016 CrossRefPubMedGoogle Scholar
- Kanoski SE, Zhao S, Guarnieri DJ, DiLeone RJ, Yan J, de Jonghe BC, Bence KK, Hayes MR, Grill HJ (2012) Endogenous leptin receptor signaling in the medial nucleus tractus solitarius affects meal size and potentiates intestinal satiation signals. AJP Endocrinol Metab 303:E496–E503. https://doi.org/10.1152/ajpendo.00205.2012 CrossRefGoogle Scholar
- Kataoka Y, Iijima N, Yano T, Kakihara K, Hayashi S, Hinuma S, Honjo H, Hayashi S, Tanaka M, Ibata Y (2001) Gonadal regulation of PrRP mRNA expression in the nucleus tractus solitarius and ventral and lateral reticular nuclei of the rat. Brain Res Mol Brain Res 87:42–47. https://doi.org/10.1016/S0169-328X(00)00280-1 CrossRefPubMedGoogle Scholar
- Kreisler AD, Davis EA, Rinaman L (2014) Differential activation of chemically identified neurons in the caudal nucleus of the solitary tract in non-entrained rats after intake of satiating vs. non-satiating meals. Physiol Behav 136:47–54. https://doi.org/10.1016/j.physbeh.2014.01.015 CrossRefPubMedGoogle Scholar
- Laurent P, Becker JAJ, Valverde O, Ledent C, de Kerchove d’Exaerde A, Schiffmann SN, Maldonado R, Vassart G, Parmentier M (2005) The prolactin-releasing peptide antagonizes the opioid system through its receptor GPR10. Nat Neurosci 8:1735–1741. https://doi.org/10.1038/nn1585 CrossRefPubMedGoogle Scholar
- Maletínská L, Nagelová V, Tichá A et al (2015) Novel lipidized analogs of prolactin-releasing peptide have prolonged half-lives and exert anti-obesity effects after peripheral administration. Int J Obes:986–993. https://doi.org/10.1038/ijo.2015.28
- Maniscalco JW, Zheng H, Gordon PJ, Rinaman L (2015) Negative energy balance blocks neural and behavioral responses to acute stress by “silencing” central glucagon-like peptide 1 signaling in rats. J Neurosci 35:10701–10714. https://doi.org/10.1523/JNEUROSCI.3464-14.2015 CrossRefPubMedPubMedCentralGoogle Scholar
- Matsumoto H, Maruyama M, Noguchi J, Horikoshi Y, Fujiwara K, Kitada C, Hinuma S, Onda H, Nishimura O, Inoue K, Fujino M (2000) Stimulation of corticotropin-releasing hormone-mediated adrenocorticotropin secretion by central administration of prolactin-releasing peptide in rats. Neurosci Lett 285:234–238. https://doi.org/10.1016/S0304-3940(00)01077-6 CrossRefPubMedGoogle Scholar
- Mera T, Fujihara H, Kawasaki M, Hashimoto H, Saito T, Shibata M, Saito J, Oka T, Tsuji S, Onaka T, Ueta Y (2006) Prolactin-releasing peptide is a potent mediator of stress responses through the hypothalamic paraventricular nucleus. Neuroscience 141:1069–1086. https://doi.org/10.1016/j.neuroscience.2006.04.023 CrossRefPubMedGoogle Scholar
- Mikulášková B, Zemenová J, Pirník Z, Pražienková V, Bednárová L, Železná B, Maletínská L, Kuneš J (2015) Effect of palmitoylated prolactin-releasing peptide on food intake and neural activation after different routes of peripheral administration in rats. Peptides 75:109–117. https://doi.org/10.1016/j.peptides.2015.11.005 CrossRefPubMedGoogle Scholar
- Olszewski PK, Klockars A, Levine AS (2016) Oxytocin: a conditional anorexigen whose effects on appetite depend on the physiological, behavioural and social contexts. J Neuroendocrinol 28(4). https://doi.org/10.1111/jne.12376
- Roland BL, Sutton SW, Wilson SJ, Luo L, Pyati J, Huvar R, Erlander MG, Lovenberg TW (1999) Anatomical distribution of prolactin-releasing peptide and its receptor suggests additional functions in the central nervous system and periphery. Endocrinology 140:5736–5745. https://doi.org/10.1210/endo.140.12.7211 CrossRefPubMedGoogle Scholar
- Samson WK, Keown C, Samson CK, Samson HW, Lane B, Baker JR, Taylor MM (2003) Prolactin-releasing peptide and its homolog RFRP-1 act in hypothalamus but not in anterior pituitary gland to stimulate stress hormone secretion. Endocrine 20:59–66. https://doi.org/10.1385/ENDO:20:1-2:59 CrossRefPubMedGoogle Scholar
- Seal LJ, Small CJ, Dhillo WS, Stanley SA, Abbott CR, Ghatei MA, Bloom SR (2001) PRL-releasing peptide inhibits food intake in male rats via the dorsomedial hypothalamic nucleus and not the paraventricular hypothalamic nucleus. Endocrinology 142:4236–4243. https://doi.org/10.1210/en.142.10.4236 CrossRefPubMedGoogle Scholar
- Smith GP (2000) The controls of eating: a shift from nutritional homeostasis to behavioral neuroscience. Nutrition 16(10):814-820. https://doi.org/10.1016/S0899-9007(00)00457-3
- Thompson RH, Canteras NS, Swanson LW (1996) Organization of projections from the dorsomedial nucleus of the hypothalamus: a PHA-L study in the rat. J Comp Neurol 376:143–173. https://doi.org/10.1002/(SICI)1096-9861(19961202)376:1<143::AID-CNE9>3.0.CO;2-3 CrossRefPubMedGoogle Scholar
- Watanabe T, Mikio S, Yuki Y, et al (2005) Mutated G-protein-coupled receptor GPR10 is responsible for the hyperphagia/dyslipidaemia/obesity locus of Dmo1 in the OLETF rat. Clin Exp Pharmacol Physiol 32(5-6):355–366. https://doi.org/10.1111/j.1440-1681.2005.04196.x