Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Chronic increase of circulating galanin levels induces obesity and marked alterations in lipid metabolism similar to metabolic syndrome

International Journal of Obesity volume 33, pages 1381–1389 (2009)Cite this article

Abstract

Objective:

Galanin (GAL) has a role in the regulation of food intake by way of acting on the central nervous system in rodents. High serum GAL levels have been observed in obese human subjects, suggesting that peripheral GAL has a role in the regulation of energy balance and that elevated circulating GAL levels contribute to the development of obesity and obesity-associated metabolic impairments. Currently, it is not known how chronically increased levels of circulating GAL affect energy balance. The purpose of this study is to clarify the importance of chronically increased levels of circulating GAL on energy balance in a transgenic mouse model.

Research design and methods:

Male wild-type and homozygous galanin transgenic (GAL-Tg) mice were used to study the peripheral effects of a 10-fold increase in circulating GAL on food intake, body weight, lipid metabolism, hepatic steatosis, glucose homeostasis and energy expenditure.

Results:

In the absence of an orexigenic effect, GAL-Tg mice had increased body weight, visceral adiposity, total serum cholesterol, total serum triglycerides and hyperinsulinemia, as well as impaired glucose tolerance. Compared with wild-type mice, the obese phenotype observed in the GAL-Tg mice was attributed to decreased oxygen consumption and carbon dioxide production, and this effect was independent of any changes in food intake or horizontal activity. In this obese model, GAL contributed to the development of fatty liver disease, which was associated with impaired glucose tolerance, as well as a reduction in heat production and metabolic rate.

Conclusions:

Chronically elevated GAL may regulate body weight, metabolic rate, and lipid and carbohydrate metabolism through a mechanism that is independent of feeding regulation. The obese phenotype in the GAL-Tg mice is related to the reduced energy expenditure and insulin resistance. These findings support the hypothesis that increased circulating GAL levels contribute to the development of metabolic syndrome.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  1. Vrontakis ME, Torsello A, Friesen HG . Galanin. J Endocrinol Invest 1991; 14: 785–794.

    Article  CAS  PubMed  Google Scholar 

  2. Bartfai T, Hokfelt T, Langel U . Galanin -a neuroendocrine peptide. Crit Rev Neurobiol 1993; 7: 229–274.

    CAS  PubMed  Google Scholar 

  3. Crawley JN . Biological actions of galanin. Regul Pept 1995; 59: 1–16.

    Article  CAS  PubMed  Google Scholar 

  4. Vrontakis ME . Galanin: a biologically active peptide. Curr Drug Targets CNS Neurol Disord 2002; 1: 531–541.

    Article  CAS  PubMed  Google Scholar 

  5. Kaplan LM, Gabriel SM, Koenig JI, Sunday ME, Spindel ER, Martin JB et al. Galanin is an estrogen-inducible, secretory product of the rat anterior pituitary. Proc Natl Acad Sci USA 1988; 85: 7408–7412.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Vrontakis ME, Peden LM, Duckworth ML, Friesen HG . Isolation and characterization of a complementary DNA (galanin) clone from estrogen-induced pituitary tumor messenger RNA. J Biol Chem 1987; 262: 16755–16758.

    CAS  PubMed  Google Scholar 

  7. Branchek T, Smith KE, Walker MW . Molecular biology and pharmacology of galanin receptors. Ann NY Acad Sci 1998; 863: 94–107.

    Article  CAS  PubMed  Google Scholar 

  8. Wang S, He C, Hashemi T, Bayne M . Cloning and expressional characterization of a novel galanin receptor. Identification of different pharmacophores within galanin for the three galanin receptor subtypes. J Biol Chem 1997; 272: 31949–31952.

    Article  CAS  PubMed  Google Scholar 

  9. Crawley JN . The role of galanin in feeding behavior. Neuropeptides 1999; 33: 369–375.

    Article  CAS  PubMed  Google Scholar 

  10. Kyrkouli SE, Stanley BG, Leibowitz SF . Galanin: stimulation of feeding induced by medial hypothalamic injection of this novel peptide. Eur J Pharmacol 1986; 122: 159–160.

    Article  CAS  PubMed  Google Scholar 

  11. Menendez JA, Atrens DM, Leibowitz SF . Metabolic effects of galanin injections into the paraventricular nucleus of the hypothalamus. Peptides 1992; 13: 323–327.

    Article  CAS  PubMed  Google Scholar 

  12. Rada P, Mark GP, Hoebel BG . Galanin in the hypothalamus raises dopamine and lowers acetylcholine release in the nucleus accumbens: a possible mechanism for hypothalamic initiation of feeding behavior. Brain Res 1998; 798: 1–6.

    Article  CAS  PubMed  Google Scholar 

  13. Tempel DL, Leibowitz KJ, Leibowitz SF . Effects of PVN galanin on macronutrient selection. Peptides 1988; 9: 309–314.

    Article  CAS  PubMed  Google Scholar 

  14. Smith BK, Berthoud HR, York DA, Bray GA . Differential effects of baseline macronutrient preferences on macronutrient selection after galanin, NPY, and an overnight fast. Peptides 1997; 18: 207–211.

    Article  CAS  PubMed  Google Scholar 

  15. Smith BK, York DA, Bray GA . Chronic cerebroventricular galanin does not induce sustained hyperphagia or obesity. Peptides 1994; 15: 1267–1272.

    Article  CAS  PubMed  Google Scholar 

  16. Baranowska B, Radzikowska M, Wasilewska-Dziubinska E, Kaplinski A, Roguski K, Plonowski A . Neuropeptide Y, leptin, galanin and insulin in women with polycystic ovary syndrome. Gynecol Endocrinol 1999; 13: 344–351.

    Article  CAS  PubMed  Google Scholar 

  17. Baranowska B, Radzikowska M, Wasilewska-Dziubinska E, Roguski K, Borowiec M . Disturbed release of gastrointestinal peptides in anorexia nervosa and in obesity. Diabetes Obes Metab 2000; 2: 99–103.

    Article  CAS  PubMed  Google Scholar 

  18. Baranowska B, Wasilewska-Dziubinska E, Radzikowska M, Plonowski A, Roguski K . Neuropeptide Y, galanin, and leptin release in obese women and in women with anorexia nervosa. Metabolism 1997; 46: 1384–1389.

    Article  CAS  PubMed  Google Scholar 

  19. Wynick D, Hammond PJ, Akinsanya KO, Bloom SR . Galanin regulates basal and estrogen-stimulated lactotroph function. Nature 1993; 364: 529–532.

    Article  CAS  PubMed  Google Scholar 

  20. Bauer FE, Ginsberg L, Venetikou M, MacKay DJ, Burrin JM, Bloom SR . Growth hormone release in man induced by galanin, a new hypothalamic peptide. Lancet 1986; 2: 192–195.

    Article  CAS  PubMed  Google Scholar 

  21. Murakami Y, Ohshima K, Mochizuki T, Yanaihara N . Effect of human galanin on growth hormone prolactin, and antidiuretic hormone secretion in normal men. J Clin Endocrinol Metab 1993; 77: 1436–1438.

    CAS  PubMed  Google Scholar 

  22. Perumal P, Vrontakis ME . Transgenic mice over-expressing galanin exhibit pituitary adenomas and increased secretion of galanin, prolactin and growth hormone. J Endocrinol 2003; 179: 145–154.

    Article  CAS  PubMed  Google Scholar 

  23. Kim ER, Leckstrom A, Mizuno TM . Impaired anorectic effect of leptin in neurotensin receptor 1-deficient mice. Behav Brain Res 2008; 194: 66–71.

    Article  CAS  PubMed  Google Scholar 

  24. Olsson B, Bohlooly YM, Fitzgerald SM, Frick F, Ljungberg A, Ahren B et al. Bovine growth hormone transgenic mice are resistant to diet-induced obesity but develop hyperphagia, dyslipidemia, and diabetes on a high-fat diet. Endocrinology 2005; 146: 920–930.

    Article  CAS  PubMed  Google Scholar 

  25. Lang R, Gundlach AL, Kofler B . The galanin peptide family: receptor pharmacology, pleiotropic biological actions, and implications in health and disease. Pharmacol Ther 2007; 115: 177–207.

    Article  CAS  PubMed  Google Scholar 

  26. Crawley JN, Mufson EJ, Hohmann JG, Teklemichael D, Steiner RA, Holmberg K et al. Galanin overexpressing transgenic mice. Neuropeptides 2002; 36: 145–156.

    Article  CAS  PubMed  Google Scholar 

  27. Cai A, Hayes JD, Patel N, Hyde JF . Targeted overexpression of galanin in lactotrophs of transgenic mice induces hyperprolactinemia and pituitary hyperplasia. Endocrinolog. 1999; 140: 4955–4964.

    Article  CAS  Google Scholar 

  28. Hohmann JG, Krasnow SM, Teklemichael DN, Clifton DK, Wynick D, Steiner RA . Neuroendocrine profiles in galanin-overexpressing and knockout mice. Neuroendocrinology 2003; 77: 354–366.

    Article  CAS  PubMed  Google Scholar 

  29. Abramov U, Florén A, Echevarria DJ, Brewer A, Manuzon H, Robinson JK et al. Regulation of feeding by galnon. Neuropeptides 2004; 38: 55–61.

    Article  CAS  PubMed  Google Scholar 

  30. Giustina A, Brogan R, Conley L, Godi D, Manelli F, Wehrenberg WB . Acute and chronic galanin administration decreases hypothalamic galanin synthesis in both male and female adult rats. evidence for a long-loop galanin autofeedback. Metabolism 2000; 49: 778–783.

    Article  CAS  PubMed  Google Scholar 

  31. Frick F, Bohlooly YM, Linden D, Olsson B, Tornell J, Eden S et al. Long-term growth hormone excess induces marked alterations in lipoprotein metabolism in mice. Am J Physiol Endocrinol Metab 2001; 281: E1230–E1239.

    Article  CAS  PubMed  Google Scholar 

  32. Heffernan MA, Thorburn AW, Fam B, Summers R, Conway-Campbell B, Waters MJ et al. Increase of fat oxidation and weight loss in obese mice caused by chronic treatment with human growth hormone or a modified C-terminal fragment. Int J Obes Relat Metab Disord 2001; 25: 1442–1449.

    Article  CAS  PubMed  Google Scholar 

  33. Moore Jr JP, Cai A, Maley BE, Jennes L, Hyde JF . Galanin within the normal and hyperplastic anterior pituitary gland. localization, secretion, and functional analysis in normal and human growth hormone-releasing hormone transgenic mice. Endocrinology 1999; 140: 1789–1799.

    Article  CAS  PubMed  Google Scholar 

  34. Fleenor D, Oden J, Kelly PA, Mohan S, Alliouachene S, Pende M et al. Roles of the lactogens and somatogens in perinatal and postnatal metabolism and growth. studies of a novel mouse model combining lactogen resistance and growth hormone deficiency. Endocrinology 2005; 146: 103–112.

    Article  CAS  PubMed  Google Scholar 

  35. Beck B . Hypothalamic galanin and early state of hyperphagia in obese Zucker rats. Appetite 2007; 48: 206–210.

    Article  CAS  PubMed  Google Scholar 

  36. Odorizzi M, Fernette B, Angel E, Burlet C, Tankosic P, Burlet A . Galanin receptor antagonists decrease fat preference in Brattleboro rat. Neuropharmacology 2002; 42: 134–141.

    Article  CAS  PubMed  Google Scholar 

  37. Yun R, Dourmashkin JT, Hill J, Gayles EC, Fried SK, Leibowitz SF . PVN galanin increases fat storage and promotes obesity by causing muscle to utilize carbohydrate more than fat. Peptides 2005; 26: 2265–2273.

    Article  CAS  PubMed  Google Scholar 

  38. Leibowitz SF, Dourmashkin JT, Chang GQ, Hill JO, Gayles EC, Fried SK et al. Acute high-fat diet paradigms link galanin to triglycerides and their transport and metabolism in muscle. Brain Res 2004; 1008: 168–178.

    Article  CAS  PubMed  Google Scholar 

  39. Wynick D, Small CJ, Bloom SR, Pachnis V . Targeted disruption of the murine galanin gene. Ann NY Acad Sci 1998; 863: 22–47.

    Article  CAS  PubMed  Google Scholar 

  40. Zorrilla EP, Brennan M, Sabino V, Lu X, Bartfai T . Galanin type 1 receptor knockout mice show altered responses to high-fat diet and glucose challenge. Physiol Behav 2007; 91: 479–485.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Adams AC, Clapham JC, Wynick D, Speakman JR . Feeding behaviour in galanin knockout mice supports a role of galanin in fat intake and preference. J Neuroendocrinol 2008; 20: 199–206.

    Article  CAS  PubMed  Google Scholar 

  42. Nagase H, Bray GA, York DA . Effect of galanin and enterostatin on sympathetic nerve activity to interscapular brown adipose tissue. Brain Res 1996; 709: 44–50.

    Article  CAS  PubMed  Google Scholar 

  43. degli Uberti EC, Ambrosio MR, Bondanelli M, Trasforini G, Margutti A, Valentini A et al. Human galanin reduces plasma norepinephrine levels in man. J Clin Endocrinol Metab 1995; 80: 1894–1898.

    CAS  PubMed  Google Scholar 

  44. Dentin R, Pegorier JP, Benhamed F, Foufelle F, Ferre P, Fauveau V et al. Hepatic glucokinase is required for the synergistic action of ChREBP and SREBP-1c on glycolytic and lipogenic gene expression. J Biol Chem 2004; 279: 20314–20326.

    Article  CAS  PubMed  Google Scholar 

  45. Kohjima M, Enjoji M, Higuchi N, Kato M, Kotoh K, Yoshimoto T et al. Re-evaluation of fatty acid metabolism-related gene expression in nonalcoholic fatty liver disease. Int J Mol Med 2007; 20: 351–358.

    CAS  PubMed  Google Scholar 

  46. Gaysinskaya VA, Karatayev O, Chang GQ, Leibowitz SF . Increased caloric intake after a high-fat preload: relation to circulating triglycerides and orexigenic peptides. Physiol Behav 2007; 91: 142–153.

    Article  CAS  PubMed  Google Scholar 

  47. Leibowitz SF . Regulation and effects of hypothalamic galanin: relation to dietary fat, alcohol ingestion, circulating lipids and energy homeostasis. Neuropeptides 2005; 39: 327–332.

    Article  CAS  PubMed  Google Scholar 

  48. Chang GQ, Karatayev O, Davydova Z, Leibowitz SF . Circulating triglycerides impact on orexigenic peptides and neuronal activity in hypothalamus. Endocrinology 2004; 145: 3904–3912.

    Article  CAS  PubMed  Google Scholar 

  49. Plaisier CL, Kyttälä M, Weissglas-Volkov D, Sinsheimer JS, Huertas-Vazquez A, Riba L et al. Galanin preproprotein is associated with elevated plasma triglycerides. Arterioscler Thromb Vasc Biol 2009; 29: 147–152.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by the National Science and Engineer Research Council of Canada (NSERC) and Manitoba Institute of Child Health (MICH) to MEV, and Canada Research Chair (CRC) and Canada Foundation for Innovation (CFI) to TMM. NJP was a recipient of the Manitoba Health Research Council (MHRC) Doctoral Studentship. We would like to thank Lin Zhang for his help with the graph electronic formation.

Author information

Authors and Affiliations

  1. Department of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, Manitoba, Canada

    N J Poritsanos, M-E Lautatzis & M Vrontakis

  2. Department of Physiology, University of Manitoba, Winnipeg, Manitoba, Canada

    N J Poritsanos & T M Mizuno

Authors
  1. N J Poritsanos
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. T M Mizuno
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M-E Lautatzis
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M Vrontakis
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M Vrontakis.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Poritsanos, N., Mizuno, T., Lautatzis, ME. et al. Chronic increase of circulating galanin levels induces obesity and marked alterations in lipid metabolism similar to metabolic syndrome. Int J Obes 33, 1381–1389 (2009). https://doi.org/10.1038/ijo.2009.187

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ijo.2009.187

Keywords

This article is cited by

Search

Advanced search

Quick links