Abstract
The physiological function of the peptide galanin (Gal) remains to be established. It is known to exist in high concentrations within the hypothalamus and to modulate the secretion of specific hormones, as well as to potentiate food consumption. Our study provides evidence for an essential function of neuronal Gal, within a specific hypothalamic area, in stimulating the behavioral process of fat ingestion and body weight gain. Through analyses of peptide levels via RIA and of gene expression via in situ hybridization, a close positive association is established between Gal in the paraventricular nucleus (PVN), particularly its midlateral region, and fat ingestion. No such relationship is detected for Gal in other brain areas or between PVN Gal and ingestion of carbohydrate or protein, supporting the behavioral and anatomical specificity of this relationship. Through PVN injection studies with antisense oligonucleotides to Gal mRNA, a dramatic decline in fat ingestion and body weight suggests that endogenous Gal contributes to the natural appetite for fat. Thus, Gal in the PVN is identified as a neurochemical marker for fat ingestion and, consequently, body weight gain.
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Selected References
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- Akabayashi A., Wahlestedt C., Alexander J. T., Leibowitz S. F. Specific inhibition of endogenous neuropeptide Y synthesis in arcuate nucleus by antisense oligonucleotides suppresses feeding behavior and insulin secretion. Brain Res Mol Brain Res. 1994 Jan;21(1-2):55–61. doi: 10.1016/0169-328x(94)90377-8. [DOI] [PubMed] [Google Scholar]
- Armstrong S. A chronometric approach to the study of feeding behavior. Neurosci Biobehav Rev. 1980 Spring;4(1):27–53. doi: 10.1016/0149-7634(80)90024-x. [DOI] [PubMed] [Google Scholar]
- Beck B., Burlet A., Nicolas J. P., Burlet C. Galanin in the hypothalamus of fed and fasted lean and obese Zucker rats. Brain Res. 1993 Sep 24;623(1):124–130. doi: 10.1016/0006-8993(93)90019-j. [DOI] [PubMed] [Google Scholar]
- Bersani M., Johnsen A. H., Højrup P., Dunning B. E., Andreasen J. J., Holst J. J. Human galanin: primary structure and identification of two molecular forms. FEBS Lett. 1991 Jun 3;283(2):189–194. doi: 10.1016/0014-5793(91)80585-q. [DOI] [PubMed] [Google Scholar]
- Crawley J. N., Austin M. C., Fiske S. M., Martin B., Consolo S., Berthold M., Langel U., Fisone G., Bartfai T. Activity of centrally administered galanin fragments on stimulation of feeding behavior and on galanin receptor binding in the rat hypothalamus. J Neurosci. 1990 Nov;10(11):3695–3700. doi: 10.1523/JNEUROSCI.10-11-03695.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Flatt J. P. The difference in the storage capacities for carbohydrate and for fat, and its implications in the regulation of body weight. Ann N Y Acad Sci. 1987;499:104–123. doi: 10.1111/j.1749-6632.1987.tb36202.x. [DOI] [PubMed] [Google Scholar]
- Gabriel S. M., Kaplan L. M., Martin J. B., Koenig J. I. Tissue-specific sex differences in galanin-like immunoreactivity and galanin mRNA during development in the rat. Peptides. 1989 Mar-Apr;10(2):369–374. doi: 10.1016/0196-9781(89)90045-4. [DOI] [PubMed] [Google Scholar]
- Gabriel S. M., Koenig J. I., Washton D. L. Estrogen stimulation of galanin gene expression and galanin-like immunoreactivity in the rat and its blockade by the estrogen antagonist keoxifene (LY156758). Regul Pept. 1993 Jun 11;45(3):407–419. doi: 10.1016/0167-0115(93)90367-h. [DOI] [PubMed] [Google Scholar]
- Jhanwar-Uniyal M., Beck B., Jhanwar Y. S., Burlet C., Leibowitz S. F. Neuropeptide Y projection from arcuate nucleus to parvocellular division of paraventricular nucleus: specific relation to the ingestion of carbohydrate. Brain Res. 1993 Dec 17;631(1):97–106. doi: 10.1016/0006-8993(93)91192-u. [DOI] [PubMed] [Google Scholar]
- Jhanwar-Uniyal M., Chua S. C., Jr Critical effects of aging and nutritional state on hypothalamic neuropeptide Y and galanin gene expression in lean and genetically obese Zucker rats. Brain Res Mol Brain Res. 1993 Aug;19(3):195–202. doi: 10.1016/0169-328x(93)90026-l. [DOI] [PubMed] [Google Scholar]
- Kaplan L. M., Spindel E. R., Isselbacher K. J., Chin W. W. Tissue-specific expression of the rat galanin gene. Proc Natl Acad Sci U S A. 1988 Feb;85(4):1065–1069. doi: 10.1073/pnas.85.4.1065. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kyrkouli S. E., Stanley B. G., Leibowitz S. F. Galanin: stimulation of feeding induced by medial hypothalamic injection of this novel peptide. Eur J Pharmacol. 1986 Mar 11;122(1):159–160. doi: 10.1016/0014-2999(86)90175-5. [DOI] [PubMed] [Google Scholar]
- Leibowitz S. F., Kim T. Impact of a galanin antagonist on exogenous galanin and natural patterns of fat ingestion. Brain Res. 1992 Dec 18;599(1):148–152. doi: 10.1016/0006-8993(92)90863-5. [DOI] [PubMed] [Google Scholar]
- Leibowitz S. F., Lucas D. J., Leibowitz K. L., Jhanwar Y. S. Developmental patterns of macronutrient intake in female and male rats from weaning to maturity. Physiol Behav. 1991 Dec;50(6):1167–1174. doi: 10.1016/0031-9384(91)90578-c. [DOI] [PubMed] [Google Scholar]
- Leibowitz S. F. Neurochemical-neuroendocrine systems in the brain controlling macronutrient intake and metabolism. Trends Neurosci. 1992 Dec;15(12):491–497. doi: 10.1016/0166-2236(92)90101-d. [DOI] [PubMed] [Google Scholar]
- Levin M. C., Sawchenko P. E., Howe P. R., Bloom S. R., Polak J. M. Organization of galanin-immunoreactive inputs to the paraventricular nucleus with special reference to their relationship to catecholaminergic afferents. J Comp Neurol. 1987 Jul 22;261(4):562–582. doi: 10.1002/cne.902610408. [DOI] [PubMed] [Google Scholar]
- Lin L., Gehlert D. R., York D. A., Bray G. A. Effect of enterostatin on the feeding responses to galanin and NPY. Obes Res. 1993 May;1(3):186–192. doi: 10.1002/j.1550-8528.1993.tb00610.x. [DOI] [PubMed] [Google Scholar]
- McHugh P. R., Moran T. H., Barton G. N. Satiety: a graded behavioural phenomenon regulating caloric intake. Science. 1975 Oct 10;190(4210):167–169. doi: 10.1126/science.1166310. [DOI] [PubMed] [Google Scholar]
- Melander T., Hökfelt T., Rökaeus A. Distribution of galaninlike immunoreactivity in the rat central nervous system. J Comp Neurol. 1986 Jun 22;248(4):475–517. doi: 10.1002/cne.902480404. [DOI] [PubMed] [Google Scholar]
- Menéndez J. A., Atrens D. M., Leibowitz S. F. Metabolic effects of galanin injections into the paraventricular nucleus of the hypothalamus. Peptides. 1992 Mar-Apr;13(2):323–327. doi: 10.1016/0196-9781(92)90116-k. [DOI] [PubMed] [Google Scholar]
- Merchenthaler I., López F. J., Negro-Vilar A. Anatomy and physiology of central galanin-containing pathways. Prog Neurobiol. 1993 Jun;40(6):711–769. doi: 10.1016/0301-0082(93)90012-h. [DOI] [PubMed] [Google Scholar]
- Okada S., York D. A., Bray G. A., Mei J., Erlanson-Albertsson C. Differential inhibition of fat intake in two strains of rat by the peptide enterostatin. Am J Physiol. 1992 Jun;262(6 Pt 2):R1111–R1116. doi: 10.1152/ajpregu.1992.262.6.R1111. [DOI] [PubMed] [Google Scholar]
- Rolls B. J., Shide D. J. The influence of dietary fat on food intake and body weight. Nutr Rev. 1992 Oct;50(10):283–290. doi: 10.1111/j.1753-4887.1992.tb02466.x. [DOI] [PubMed] [Google Scholar]
- Schwartz M. W., Figlewicz D. P., Baskin D. G., Woods S. C., Porte D., Jr Insulin in the brain: a hormonal regulator of energy balance. Endocr Rev. 1992 Aug;13(3):387–414. doi: 10.1210/edrv-13-3-387. [DOI] [PubMed] [Google Scholar]
- Shor-Posner G., Ian C., Brennan G., Cohn T., Moy H., Ning A., Leibowitz S. F. Self-selecting albino rats exhibit differential preferences for pure macronutrient diets: characterization of three subpopulations. Physiol Behav. 1991 Dec;50(6):1187–1195. doi: 10.1016/0031-9384(91)90581-8. [DOI] [PubMed] [Google Scholar]
- Tatemoto K., Rökaeus A., Jörnvall H., McDonald T. J., Mutt V. Galanin - a novel biologically active peptide from porcine intestine. FEBS Lett. 1983 Nov 28;164(1):124–128. doi: 10.1016/0014-5793(83)80033-7. [DOI] [PubMed] [Google Scholar]
- Tempel D. L., Leibowitz K. J., Leibowitz S. F. Effects of PVN galanin on macronutrient selection. Peptides. 1988 Mar-Apr;9(2):309–314. doi: 10.1016/0196-9781(88)90265-3. [DOI] [PubMed] [Google Scholar]
- Tempel D. L., Leibowitz S. F. Diurnal variations in the feeding responses to norepinephrine, neuropeptide Y and galanin in the PVN. Brain Res Bull. 1990 Dec;25(6):821–825. doi: 10.1016/0361-9230(90)90177-2. [DOI] [PubMed] [Google Scholar]
- Tempel D. L., Leibowitz S. F. Galanin inhibits insulin and corticosterone release after injection into the PVN. Brain Res. 1990 Dec 17;536(1-2):353–357. doi: 10.1016/0006-8993(90)90050-l. [DOI] [PubMed] [Google Scholar]
- Uniyal S. K., Sati O. P. Triterpenoid saponins from roots of Clematis grata. Phytochemistry. 1992 Apr;31(4):1427–1428. doi: 10.1016/0031-9422(92)80310-b. [DOI] [PubMed] [Google Scholar]
- Wade G. N., Schneider J. E. Metabolic fuels and reproduction in female mammals. Neurosci Biobehav Rev. 1992 Summer;16(2):235–272. doi: 10.1016/s0149-7634(05)80183-6. [DOI] [PubMed] [Google Scholar]
- de Castro J. M. Circadian rhythms of the spontaneous meal pattern, macronutrient intake, and mood of humans. Physiol Behav. 1987;40(4):437–446. doi: 10.1016/0031-9384(87)90028-x. [DOI] [PubMed] [Google Scholar]