Endocrinology, Vol 127, 730-737, Copyright © 1990 by Endocrine Society

ARTICLES

Increased hypothalamic content of preproneuropeptide Y messenger ribonucleic acid in genetically obese Zucker rats and its regulation by food deprivation

G Sanacora, M Kershaw, JA Finkelstein and JD White
Department of Medicine, State University of New York, Stony Brook 11794.

Neuropeptide Y (NPY) is a potent orexigenic agent capable of producing hyperphagia and obesity. NPY-containing neurons project from the hypothalmic arcuate nucleus to the paraventricular nucleus, an area known to be sensitive to the orexigenic effects of NPY. In this study we investigated the possibility that preproNPY messenger RNA (mRNA) content may be altered in obese Zucker rats compared to that of their lean littermates. Total RNA was isolated from hypothalamic dissections from male and female, obese and lean Zucker rats. RNA was also isolated from dissections of: olfactory bulb, entorhinal cortex, hippocampus, and striatum of female obese and lean rats. PreproNPY mRNA content was determined by solution hybridization-RNase protection analysis. The results revealed a 2- to 3-fold increase in preproNPY mRNA levels in the hypothalamus of obese animals compared to lean. The increase was observed in both sexes and was specific to the hypothalamus. In situ hybridization localized this increase to the arcuate nucleus. An additional RNase protection study was pursued to investigate the effects of 72 h food deprivation on hypothalamic preproNPY mRNA levels in lean and obese animals. Lean animals displayed an approximate 2-fold increase in preproNPY mRNA content, whereas obese animals showed no significant increase after food deprivation. These data are consistent with the hypothesis that NPY projections within the hypothalamus are involved in regulating feeding behavior and weight gain, and that disturbed regulation of hypothalamic NPY expression may play a role in the etiology of obesity in the genetically obese Zucker rat.

This article has been cited by other articles:

				E. E. Ladenheim, N. L. Hamilton, R. R. Behles, S. Bi, L. L. Hampton, J. F. Battey, and T. H. Moran Factors Contributing to Obesity in Bombesin Receptor Subtype-3-Deficient Mice Endocrinology, March 1, 2008; 149(3): 971 - 978. [Abstract] [Full Text] [PDF]

				C. Wang, E. Bomberg, C. Billington, A. Levine, and C. M. Kotz Brain-derived neurotrophic factor in the hypothalamic paraventricular nucleus reduces energy intake Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2007; 293(3): R1003 - R1012. [Abstract] [Full Text] [PDF]

				S. Mashiko, A. Ishihara, H. Iwaasa, H. Sano, J. Ito, A. Gomori, Z. Oda, R. Moriya, H. Matsushita, M. Jitsuoka, et al. A Pair-Feeding Study Reveals That a Y5 Antagonist Causes Weight Loss in Diet-Induced Obese Mice by Modulating Food Intake and Energy Expenditure Mol. Pharmacol., February 1, 2007; 71(2): 602 - 608. [Abstract] [Full Text] [PDF]

				A. Ishihara, A. Kanatani, S. Mashiko, T. Tanaka, M. Hidaka, A. Gomori, H. Iwaasa, N. Murai, S.-i. Egashira, T. Murai, et al. A neuropeptide Y Y5 antagonist selectively ameliorates body weight gain and associated parameters in diet-induced obese mice PNAS, May 2, 2006; 103(18): 7154 - 7158. [Abstract] [Full Text] [PDF]

				L. Ste. Marie, S. Luquet, T. B. Cole, and R. D. Palmiter Modulation of neuropeptide Y expression in adult mice does not affect feeding PNAS, December 20, 2005; 102(51): 18632 - 18637. [Abstract] [Full Text] [PDF]

				S. Stanley, K. Wynne, B. McGowan, and S. Bloom Hormonal Regulation of Food Intake Physiol Rev, October 1, 2005; 85(4): 1131 - 1158. [Abstract] [Full Text] [PDF]

				K. A. Takahashi and R. D. Cone Fasting Induces a Large, Leptin-Dependent Increase in the Intrinsic Action Potential Frequency of Orexigenic Arcuate Nucleus Neuropeptide Y/Agouti-Related Protein Neurons Endocrinology, March 1, 2005; 146(3): 1043 - 1047. [Abstract] [Full Text] [PDF]

				K. Wynne, S. Stanley, B. McGowan, and S. Bloom Appetite control J. Endocrinol., February 1, 2005; 184(2): 291 - 318. [Abstract] [Full Text] [PDF]

				C. B. Kaelin, A. W. Xu, X.-Y. Lu, and G. S. Barsh Transcriptional Regulation of Agouti-Related Protein (Agrp) in Transgenic Mice Endocrinology, December 1, 2004; 145(12): 5798 - 5806. [Abstract] [Full Text] [PDF]

				E. Itateyama, S. Chiba, T. Sakata, and H. Yoshimatsu Hypothalamic Neuronal Histamine in Genetically Obese Animals: Its Implication of Leptin Action in the Brain Experimental Biology and Medicine, November 1, 2003; 228(10): 1132 - 1137. [Abstract] [Full Text] [PDF]

				S. Kumano, H. Matsumoto, Y. Takatsu, J. Noguchi, C. Kitada, and T. Ohtaki Changes in Hypothalamic Expression Levels of Galanin-Like Peptide in Rat and Mouse Models Support That It Is a Leptin-Target Peptide Endocrinology, June 1, 2003; 144(6): 2634 - 2643. [Abstract] [Full Text] [PDF]

				A. K. Hewson, L. Y.C. Tung, D. W. Connell, L. Tookman, and S. L. Dickson The Rat Arcuate Nucleus Integrates Peripheral Signals Provided by Leptin, Insulin, and a Ghrelin Mimetic Diabetes, December 1, 2002; 51(12): 3412 - 3419. [Abstract] [Full Text] [PDF]

				C. L. Chaffer and M. J. Morris The Feeding Response to Melanin-Concentrating Hormone Is Attenuated by Antagonism of the NPY Y1-Receptor in the Rat Endocrinology, January 1, 2002; 143(1): 191 - 197. [Abstract] [Full Text] [PDF]

				J. Kamegai, H. Tamura, T. Shimizu, S. Ishii, H. Sugihara, and I. Wakabayashi Chronic Central Infusion of Ghrelin Increases Hypothalamic Neuropeptide Y and Agouti-Related Protein mRNA Levels and Body Weight in Rats Diabetes, November 1, 2001; 50(11): 2438 - 2443. [Abstract] [Full Text] [PDF]

				J. M. Overton, T. D. Williams, J. B. Chambers, and M. E. Rashotte Cardiovascular and metabolic responses to fasting and thermoneutrality are conserved in obese Zucker rats Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2001; 280(4): R1007 - R1015. [Abstract] [Full Text] [PDF]

				A. Kanatani, M. Hata, S. Mashiko, A. Ishihara, O. Okamoto, Y. Haga, T. Ohe, T. Kanno, N. Murai, Y. Ishii, et al. A Typical Y1 Receptor Regulates Feeding Behaviors: Effects of a Potent and Selective Y1 Antagonist, J-115814 Mol. Pharmacol., March 1, 2001; 59(3): 501 - 505. [Abstract] [Full Text]

				M. Shintani, Y. Ogawa, K. Ebihara, M. Aizawa-Abe, F. Miyanaga, K. Takaya, T. Hayashi, G. Inoue, K. Hosoda, M. Kojima, et al. Ghrelin, an Endogenous Growth Hormone Secretagogue, Is a Novel Orexigenic Peptide That Antagonizes Leptin Action Through the Activation of Hypothalamic Neuropeptide Y/Y1 Receptor Pathway Diabetes, February 1, 2001; 50(2): 227 - 232. [Abstract] [Full Text]

				P. D. Raposinho, E. Castillo, V. D'alleves, P. Broqua, F. P. Pralong, and M. L. Aubert Chronic Blockade of the Melanocortin 4 Receptor Subtype Leads to Obesity Independently of Neuropeptide Y Action, with No Adverse Effects on the Gonadotropic and Somatotropic Axes Endocrinology, December 1, 2000; 141(12): 4419 - 4427. [Abstract] [Full Text] [PDF]

				M. E. Bell, S. Bhatnagar, S. F. Akana, S. Choi, and M. F. Dallman Disruption of Arcuate/Paraventricular Nucleus Connections Changes Body Energy Balance and Response to Acute Stress J. Neurosci., September 1, 2000; 20(17): 6707 - 6713. [Abstract] [Full Text] [PDF]

				A. Kanatani, S. Mashiko, N. Murai, N. Sugimoto, J. Ito, T. Fukuroda, T. Fukami, N. Morin, D. J. MacNeil, L. H. T. Van der Ploeg, et al. Role of the Y1 Receptor in the Regulation of Neuropeptide Y-Mediated Feeding: Comparison of Wild-Type, Y1 Receptor-Deficient, and Y5 Receptor-Deficient Mice Endocrinology, March 1, 2000; 141(3): 1011 - 1016. [Abstract] [Full Text] [PDF]

				A. Inui Transgenic Approach to the Study of Body Weight Regulation Pharmacol. Rev., March 1, 2000; 52(1): 35 - 62. [Abstract] [Full Text] [PDF]

				P. J. Larsen, M. Tang-Christensen, C. E. Stidsen, K. Madsen, M. S. Smith, and J. L. Cameron Activation of Central Neuropeptide Y Y1 Receptors Potently Stimulates Food Intake in Male Rhesus Monkeys J. Clin. Endocrinol. Metab., October 1, 1999; 84(10): 3781 - 3791. [Abstract] [Full Text] [PDF]

				T. M. Mizuno, H. Makimura, J. Silverstein, J. L. Roberts, T. Lopingco, and C. V. Mobbs Fasting Regulates Hypothalamic Neuropeptide Y, Agouti-Related Peptide, and Proopiomelanocortin in Diabetic Mice Independent of Changes in Leptin or Insulin Endocrinology, October 1, 1999; 140(10): 4551 - 4557. [Abstract] [Full Text]

				K. E. Zakrzewska, A. Sainsbury, I. Cusin, J. Rouru, B. Jeanrenaud, and F. Rohner-Jeanrenaud Selective Dependence of Intracerebroventricular Neuropeptide Y-Elicited Effects on Central Glucocorticoids Endocrinology, July 1, 1999; 140(7): 3183 - 3187. [Abstract] [Full Text]

				M. W Schwartz, D. G Baskin, K. J Kaiyala, and S. C Woods Model for the regulation of energy balance and adiposity by the central nervous system Am. J. Clinical Nutrition, April 1, 1999; 69(4): 584 - 596. [Abstract] [Full Text] [PDF]

				E. E. Muller, V. Locatelli, and D. Cocchi Neuroendocrine Control of Growth Hormone Secretion Physiol Rev, April 1, 1999; 79(2): 511 - 607. [Abstract] [Full Text] [PDF]

				S. P. Kalra, M. G. Dube, S. Pu, B. Xu, T. L. Horvath, and P. S. Kalra Interacting Appetite-Regulating Pathways in the Hypothalamic Regulation of Body Weight Endocr. Rev., February 1, 1999; 20(1): 68 - 100. [Abstract] [Full Text]

				M. J. Cunningham, D. K. Clifton, and R. A. Steiner Leptin's Actions on the Reproductive Axis: Perspectives and Mechanisms Biol Reprod, February 1, 1999; 60(2): 216 - 222. [Abstract] [Full Text] [PDF]

				K. Meeran, D. O’Shea, C. M. B. Edwards, M. D. Turton, M. M. Heath, I. Gunn, S. Abusnana, M. Rossi, C. J. Small, A. P. Goldstone, et al. Repeated Intracerebroventricular Administration of Glucagon-Like Peptide-1-(7-36) Amide or Exendin-(9-39) Alters Body Weight in the Rat Endocrinology, January 1, 1999; 140(1): 244 - 250. [Abstract] [Full Text]

				M. Jang and D. R. Romsos Neuropeptide Y and Corticotropin-Releasing Hormone Concentrations within Specific Hypothalamic Regions of Lean but Not Ob/ob Mice Respond to Food-Deprivation and Refeeding J. Nutr., December 1, 1998; 128(12): 2520 - 2525. [Abstract] [Full Text]

				N. A. Tritos, J. K. Elmquist, J. W. Mastaitis, J. S. Flier, and E. Maratos-Flier Characterization of Expression of Hypothalamic Appetite-Regulating Peptides in Obese Hyperleptinemic Brown Adipose Tissue-Deficient (Uncoupling Protein-Promoter-Driven Diphtheria Toxin A) Mice Endocrinology, November 1, 1998; 139(11): 4634 - 4641. [Abstract] [Full Text] [PDF]

				T. J. Kowalski, T. A. Houpt, J. Jahng, N. Okada, S. C. Chua Jr., and G. P. Smith Ontogeny of neuropeptide Y expression in response to deprivation in lean Zucker rat pups Am J Physiol Regulatory Integrative Comp Physiol, August 1, 1998; 275(2): R466 - R470. [Abstract] [Full Text] [PDF]

				M. W. Schwartz, J. C. Erickson, D. G. Baskin, and R. D. Palmiter Effect of Fasting and Leptin Deficiency on Hypothalamic Neuropeptide Y Gene Transcription in Vivo Revealed by Expression of a lacZ Reporter Gene Endocrinology, May 1, 1998; 139(5): 2629 - 2635. [Abstract] [Full Text] [PDF]

				A. Ishihara, T. Tanaka, A. Kanatani, T. Fukami, M. Ihara, and T. Fukuroda A potent neuropeptide Y antagonist, 1229U91, suppressed spontaneous food intake in Zucker fatty rats Am J Physiol Regulatory Integrative Comp Physiol, May 1, 1998; 274(5): R1500 - R1504. [Abstract] [Full Text] [PDF]

				A. Stricker-Krongrad, R. Kozak, C. Burlet, J. P. Nicolas, and B. Beck Physiological regulation of hypothalamic neuropeptide Y release in lean and obese rats Am J Physiol Regulatory Integrative Comp Physiol, December 1, 1997; 273(6): R2112 - R2116. [Abstract] [Full Text] [PDF]

				G. Legradi, C. H. Emerson, R. S. Ahima, J. S. Flier, and R. M. Lechan Leptin Prevents Fasting-Induced Suppression of Prothyrotropin-Releasing Hormone Messenger Ribonucleic Acid in Neurons of the Hypothalamic Paraventricular Nucleus Endocrinology, June 1, 1997; 138(6): 2569 - 2576. [Abstract] [Full Text] [PDF]

				R. A. Kesterson, D. Huszar, C. A. Lynch, R. B. Simerly, and R. D. Cone Induction of Neuropeptide Y Gene Expression in the Dorsal Medial Hypothalamic Nucleus in Two Models of the Agouti Obesity Syndrome Mol. Endocrinol., May 1, 1997; 11(5): 630 - 637. [Abstract] [Full Text]

				C. L. M. Bivens and D. H. Olster Abnormal Estrous Cyclicity and Behavioral Hyporesponsiveness to Ovarian Hormones in Genetically Obese Zucker Female Rats Endocrinology, January 1, 1997; 138(1): 143 - 148. [Abstract] [Full Text] [PDF]