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.

  • Review Article
  • Published:

The role of 'adipotropins' and the clinical importance of a potential hypothalamic–pituitary–adipose axis

Nature Clinical Practice Endocrinology & Metabolism volume 2, pages 374–383 (2006)Cite this article

Abstract

Since adipocytes express specific receptors for pituitary hormones and hypothalamic releasing factors, adipose tissue has to be regarded as a fast-acting endocrine gland under the control of the brain. Expanding on this suggestion, the existence and clinical impact of a hypothalamic–pituitary–adipose axis is reviewed. The term 'adipotropins' is introduced in order to describe pituitary and hypothalamic hormones or releasing factors that directly target adipocytes by their specific receptors.

Key Points

  • Adipocytes express the specific receptors for nearly all known pituitary hormones and hypothalamic releasing factors

  • On this basis, the existence of a hypothalamic–pituitary–adipose axis has to be considered

  • Pituitary hormones and hypothalamic releasing factors can directly influence adipokine secretion and a wide variety of adipocyte functions

  • The name 'adipotropins' is suggested to characterize pituitary hormones and hypothalamic releasing factors that act on adipocytes via their specific receptors

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: Effects of an acute and prolonged stress reaction on adipocyte function and metabolism
Figure 2: 'Adipotropins' and the existence of a hypothalamic–pituitary–adipose axis

Similar content being viewed by others

References

  1. Wang Q et al. (1997) Interactions between leptin and hypothalamic neuropeptide Y neurons in the control of food intake and energy homeostasis in the rat. Diabetes 46: 335–341

    Article  CAS  Google Scholar 

  2. Qi Y et al. (2004) Adiponectin acts in the brain to decrease body weight. Nat Med 10: 524–529

    Article  CAS  Google Scholar 

  3. Schäffler A et al. (2005) Hypothesis paper: brain talks with fat—evidence for a hypothalamic–pituitary–adipose axis? Neuropeptides 39: 363–367

    Article  Google Scholar 

  4. Flint DJ et al. (2003) Effects of growth hormone and prolactin on adipose tissue development and function. Pituitary 6: 97–102

    Article  CAS  Google Scholar 

  5. Ling C et al. (2003) Identification of functional prolactin (PRL) receptor gene expression: PRL inhibits lipoprotein lipase activity in human white adipose tissue. J Clin Endocrinol Metab 88: 1804–1808

    Article  CAS  Google Scholar 

  6. Viengchareun S et al. (2004) Prolactin potentiates insulin-stimulated leptin expression and release from differentiated brown adipocytes. J Mol Endocrinol 33: 679–691

    Article  CAS  Google Scholar 

  7. Ling C and Billig H (2001) PRL receptor-mediated effects in female mouse adipocytes: PRL induces suppressors of cytokine signaling expression and suppresses insulin-induced leptin production in adipocytes in vitro. Endocrinology 142: 4880–4890

    Article  CAS  Google Scholar 

  8. Freemark M et al. (2001) Body weight and fat deposition in prolactin receptor-deficient mice. Endocrinology 142: 532–537

    Article  CAS  Google Scholar 

  9. Nilsson L et al. (2005) Prolactin and growth hormone regulate adiponectin secretion and receptor expression in adipose tissue. Biochem Biophys Res Commun 331: 1120–1126

    Article  CAS  Google Scholar 

  10. Hogan JC and Stephens JM (2005) The regulation of fatty acid synthase by STAT5A. Diabetes 54: 1968–1975

    Article  CAS  Google Scholar 

  11. Gualillo O et al. (1999) Prolactin stimulates leptin secretion by rat white adipose tissue. Endocrinology 140: 5149–5153

    Article  CAS  Google Scholar 

  12. Ling C et al. (2001) Increased resistin expression in the adipose tissue of male prolactin transgenic mice and in male mice with elevated androgen levels. FEBS Lett 507: 147–150

    Article  CAS  Google Scholar 

  13. Wu SL et al. (1999) Demonstration of thyrotropin receptor mRNA in orbital fat and eye muscle tissues from patients with Graves' ophthalmopathy by in situ hybridization. J Endocrinol Invest 22: 289–295

    Article  CAS  Google Scholar 

  14. Ludgate M et al. (1998) The thyrotropin receptor in thyroid eye disease. Thyroid 8: 411–413

    Article  CAS  Google Scholar 

  15. Valyasevi RW et al. (2002) Stimulation of adipogenesis, peroxisome proliferator-activated receptor-gamma (PPARγ), and thyrotropin receptor by PPARγ agonist in human orbital preadipocyte fibroblasts. J Clin Endocrinol Metab 87: 2352–2358

    CAS  PubMed  Google Scholar 

  16. Valyasevi RW et al. (1999) Differentiation of human orbital preadipocyte fibroblasts induces expression of functional thyrotropin receptor. J Clin Endocrinol Metab 84: 2557–2562

    CAS  PubMed  Google Scholar 

  17. Sorisky A et al. (2000) TSH receptor in adipose cells. Horm Metab Res 32: 468–474

    Article  CAS  Google Scholar 

  18. Shimura H et al. (1998) Analysis of differentiation-induced expression mechanisms of thyrotropin receptor gene in adipocytes. Mol Endocrinol 12: 1473–1486

    Article  CAS  Google Scholar 

  19. Bell A et al. (2002) TSH signaling and cell survival in 3T3-L1 preadipocytes. Am J Physiol Cell Physiol 283: C1056–C1064

    Article  CAS  Google Scholar 

  20. Menendez C et al. (2003) TSH stimulates leptin secretion by a direct effect on adipocytes. J Endocrinol 176: 7–12

    Article  CAS  Google Scholar 

  21. Shintani M et al. (1999) Thyrotropin decreases leptin production in rat adipocytes. Metabolism 48: 1570–1574

    Article  CAS  Google Scholar 

  22. Yaturu S et al. (2004) Changes in adipocyte hormones leptin, resistin, and adiponectin in thyroid dysfunction. J Cell Biochem 93: 491–496

    Article  CAS  Google Scholar 

  23. Santini F et al. (2004) Serum concentrations of adiponectin and leptin in patients with thyroid dysfunctions. J Endocrinol Invest 27: RC5–RC7

    Article  CAS  Google Scholar 

  24. Janson A et al. (1998) Presence of thyrotropin receptor in infant adipocytes. Pediatr Res 43: 555–558

    Article  CAS  Google Scholar 

  25. Janson A et al. (1995) Effects of stimulatory and inhibitory thyrotropin receptor antibodies on lipolysis in infant adipocytes. J Clin Endocrinol Metab 80: 1712–1716

    CAS  PubMed  Google Scholar 

  26. Heufelder AE (2000) Pathogenesis of ophthalmopathy in autoimmune thyroid disease. Rev Endocr Metab Disord 1: 87–95

    Article  CAS  Google Scholar 

  27. Jyonouchi SC et al. (2001) Interleukin-6 stimulates thyrotropin receptor expression in human orbital preadipocyte fibroblasts from patients with Graves' ophthalmopathy. Thyroid 11: 929–934

    Article  CAS  Google Scholar 

  28. Valyasevi RW et al. (2001) Effect of tumor necrosis factor-α, interferon-γ, and transforming growth factor-β on adipogenesis and expression of thyrotropin receptor in human orbital preadipocyte fibroblasts. J Clin Endocrinol Metab 86: 903–908

    CAS  PubMed  Google Scholar 

  29. Bell A et al. (2003) TSH stimulates IL-6 secretion from adipocytes in culture. Arterioscler Thromb Vasc Biol 23: 65–66

    Article  Google Scholar 

  30. Bahn RS et al. (1998) Thyrotropin receptor expression in cultured Graves' orbital preadipocyte fibroblasts is stimulated by thyrotropin. Thyroid 8: 193–196

    Article  CAS  Google Scholar 

  31. Starkey K et al. (2003) Peroxisome proliferator-activated receptor-γ in thyroid eye disease: contraindication for thiazolidinedione use? J Clin Endocrinol Metab 88: 55–59

    Article  CAS  Google Scholar 

  32. Vikman K et al. (1991) Expression and regulation of growth hormone (GH) receptor messenger ribonucleic acid (mRNA) in rat adipose tissue, adipocytes, and adipocyte precursor cells: GH regulation of GH receptor mRNA. Endocrinology 129: 1155–1161

    Article  CAS  Google Scholar 

  33. Hellgren G et al. (2001) Growth hormone receptor interaction with JAK proteins differs between tissues. J Interferon Cytokine Res 21: 75–83

    Article  CAS  Google Scholar 

  34. Barnard R et al. (1990) Soluble forms of the rabbit adipose tissue and liver growth hormone receptors are antigenically identical, but the integral membrane forms differ. Biochem J 267: 471–477

    Article  CAS  Google Scholar 

  35. Nam SY and Lobie PE (2000) The mechanism of effect of growth hormone on preadipocyte and adipocyte function. Obes Rev 1: 73–86

    Article  CAS  Google Scholar 

  36. Nam SY and Marcus C (2000) Growth hormone and adipocyte function in obesity. Horm Res 53 (Suppl 1): 87–97

    CAS  PubMed  Google Scholar 

  37. Wabitsch M et al. (1996) Mitogenic and antiadipogenic properties of human growth hormone in differentiating human adipocyte precursor cells in primary culture. Pediatr Res 40: 450–456

    Article  CAS  Google Scholar 

  38. Kralisch S et al. (2005) Hormonal regulation of the novel adipocytokine visfatin in 3T3-L1 adipocytes. J Endocrinol 185: R1–R8

    Article  CAS  Google Scholar 

  39. Delhanty PJ et al. (2002) Growth hormone rapidly induces resistin gene expression in white adipose tissue of spontaneous dwarf (SDR) rats. Endocrinology 143: 2445–2448

    Article  CAS  Google Scholar 

  40. Cone RD et al. (1996) The melanocortin receptors: agonists, antagonists, and the hormonal control of pigmentation. Recent Prog Horm Res 51: 287–317

    CAS  PubMed  Google Scholar 

  41. Boston BA and Cone RD (1996) Characterization of melanocortin receptor subtype expression in murine adipose tissues and in the 3T3-L1 cell line. Endocrinology 137: 2043–2050

    Article  CAS  Google Scholar 

  42. Norman D et al. (2003) ACTH and α-MSH inhibit leptin expression and secretion in 3T3-L1 adipocytes: model for a central-peripheral melanocortin-leptin pathway. Mol Cell Endocrinol 200: 99–109

    Article  CAS  Google Scholar 

  43. Cho KJ et al. (2005) Signaling pathways implicated in α-melanocyte stimulating hormone-induced lipolysis in 3T3-L1 adipocytes. J Cell Biochem 96: 869–878

    Article  CAS  Google Scholar 

  44. Morimoto C et al. (1998) Antilipolytic actions of insulin on basal and hormone-induced lipolysis in rat adipocytes. J Lipid Res 39: 957–962

    CAS  PubMed  Google Scholar 

  45. Izawa T et al. (1994) Increase in cytosolic free Ca2 in corticotropin-stimulated white adipocytes. Am J Physiol 266 (3 Pt 1): E418–E426

    Google Scholar 

  46. Xue B et al. (1998) The agouti gene product inhibits lipolysis in human adipocytes via a Ca2-dependent mechanism. FASEB J 12: 1391–1396

    Article  CAS  Google Scholar 

  47. Shirakura S et al. (1990) Activation of glucose transport by activatory receptor agonists of adenlyate cyclase in rat adipocytes. Comp Biochem Physiol A 97: 81–86

    Article  CAS  Google Scholar 

  48. Marette A et al. (1990) Mechanism of norepinephrin stimulation of glucose transport in isolated rat brown adipocytes. Int J Obes 14: 857–867

    CAS  PubMed  Google Scholar 

  49. Kuroda M et al. (1987) Regulation of insulin-stimulated glucose transport in the isolated rat adipocyte. cAMP-independent effects of lipolytic and antilipolytic agents. J Biol Chem 262: 245–253

    CAS  PubMed  Google Scholar 

  50. Friedberg M et al. (2003) Modulation of 11 β-hydroxysteroid dehydrogenase type 1 in mature human subcutaneous adipocytes by hypothalamic messengers. J Clin Endocrinol Metab 88: 385–393

    Article  CAS  Google Scholar 

  51. Bradley RL et al. (2005) Neuropeptides, including neuropeptide Y and melanocortins, mediate lipolysis in murine adipocytes. Obes Res 13: 653–661

    Article  CAS  Google Scholar 

  52. Boston BA (1999) The role of melanocortins in adipocyte function. Ann NY Acad Sci 885: 75–84

    Article  CAS  Google Scholar 

  53. Hoggard N et al. (2004) Regulation of adipose tissue leptin secretion by α-melanocyte-stimulating hormone and agouti-related protein: further evidence of an interaction between leptin and the melanocortin signalling system. J Mol Endocrinol 32: 145–153

    Article  CAS  Google Scholar 

  54. Boland D and Goren HJ (1987) Binding and structural properties of oxytocin receptors in isolated rat epididymal adipocytes. Regul Pept 18: 7–18

    Article  CAS  Google Scholar 

  55. Gimpl G and Fahrenholz F (2001) The oxytocin receptor system: structure, function, and regulation. Physiol Rev 81: 629–683

    Article  CAS  Google Scholar 

  56. Egan JJ et al. (1990) Insulin, oxytocin, and vasopressin stimulate protein kinase C activity in adipocyte plasma membranes. Proc Natl Acad Sci USA 87: 1052–1056

    Article  CAS  Google Scholar 

  57. Krieger-Brauer HI and Kather H (1995) The stimulus-sensitive H2O2-generating system present in human fat-cell plasma membranes is multireceptor-linked and under antagonistic control by hormones and cytokines. Biochem J 307: 543–548

    Article  CAS  Google Scholar 

  58. Axelrod L et al. (1986) Prostacyclin production by isolated rat adipocytes: evidence for cyclic adenosine 3',5'-monophosphate-dependent and independent mechanisms and for a selective effect of insulin. Endocrinology 119: 2233–2239

    Article  CAS  Google Scholar 

  59. Cheng K and Larner J (1985) Unidirectional actions of insulin and Ca2-dependent hormones on adipocyte pyruvate dehydrogenase. J Biol Chem 260: 5279–5285

    CAS  PubMed  Google Scholar 

  60. Blackmore PF and Augert G (1989) Effect of hormones on cytosolic free calcium in adipocytes. Cell Calcium 10: 561–567

    Article  CAS  Google Scholar 

  61. Hernandez A and Obregon MJ (1995) Presence of growth factors-induced type III iodothyronine 5-deiodinase in cultured rat brown adipocytes. Endocrinology 136: 4543–4550

    Article  CAS  Google Scholar 

  62. Seres J et al. (2004) Corticotropin-releasing hormone system in human adipose tissue. J Clin Endocrinol Metab 89: 965–970

    Article  CAS  Google Scholar 

  63. Hochberg Z et al. (2004) Hypothalamic regulation of adiposity: the role of 11β-hydroxysteroid dehydrogenase type 1. Horm Metab Res 36: 365–369

    Article  CAS  Google Scholar 

  64. Murdoch WJ (1995) Immunolocalization of a gonadotropin-releasing hormone receptor site in murine endometrium that mediates apoptosis. Cell Tissue Res 282: 527–529

    Article  CAS  Google Scholar 

  65. Dodt C et al. (2003) Sympathetic control of white adipose tissue in lean and obese humans. Acta Physiol Scand 177: 351–357

    Article  CAS  Google Scholar 

  66. Turtzo LC et al. (2002) Completing the loop: neuron-adipocyte interactions and the control of energy homeostasis. Horm Metab Res 34: 607–615

    Article  CAS  Google Scholar 

  67. Grunfeld C et al. (1985) Characterization of adrenocorticotropin receptors that appear when 3T3-L1 cells differentiate into adipocytes. Endocrinology 116: 113–117

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Associate Professor,

    Andreas Schäffler, Jürgen Schölmerich & Christa Buechler

  2. Professor and Director,

    Andreas Schäffler, Jürgen Schölmerich & Christa Buechler

  3. Senior Scientist in the Department of Internal Medicine I, University of Regensburg, Germany

    Andreas Schäffler, Jürgen Schölmerich & Christa Buechler

Authors
  1. Andreas Schäffler
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jürgen Schölmerich
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Christa Buechler
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Andreas Schäffler.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Schäffler, A., Schölmerich, J. & Buechler, C. The role of 'adipotropins' and the clinical importance of a potential hypothalamic–pituitary–adipose axis. Nat Rev Endocrinol 2, 374–383 (2006). https://doi.org/10.1038/ncpendmet0197

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ncpendmet0197

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing