Current Osteoporosis Reports

, Volume 11, Issue 3, pp 194–202

Influence of Hormonal Appetite and Energy Regulators on Bone

  • Ee Cheng Khor
  • Natalie Kah Yun Wee
  • Paul A Baldock
Nutrition and Lifestyle in Osteoporosis (S Ferrari, Section Editor)

Abstract

Nutritional status is an essential component in determining whole body energy homeostasis. The balance between energy/food intake and metabolism is governed by a range of hormones secreted from various parts of the body. Their subsequent dissemination via the blood results in a wide range of biological responses including satiety, hunger, and glucose uptake. The roles of these systemic hormones also extend to bone regulation with animal and clinical studies establishing a relationship between these regulatory pathways. This review covers the gastrointestinal hormones, ghrelin, PYY, GIP, GLP-1, and GLP-2, and the adipokines, leptin, and adiponectin and their roles in regulating bone homeostasis. Their known actions are reviewed, with an emphasis upon recent advances in understanding. Taken together, this review outlines an expanding appreciation of the interactions between bone mass and the nutritional control of whole body energy balance by gut and adipose tissue.

Keywords

Energy Bone Ghrelin PYY GIP GLP Leptin Adiponectin 

References

Papers of particular interest, published recently, have been highlighted as: • Of importance, •• Of major importance

  1. 1.
    Clowes JA, Hannon RA, Yap TS, Hoyle NR, Blumsohn A, Eastell R. Effect of feeding on bone turnover markers and its impact on biological variability of measurements. Bone. 2002;30(6):886–90.PubMedCrossRefGoogle Scholar
  2. 2.
    Fantuzzi G. Adipose tissue, adipokines, and inflammation. J Allergy Clin Immunol. 2005;115(5):911–9. doi:10.1016/j.jaci.2005.02.023.PubMedCrossRefGoogle Scholar
  3. 3.
    Kershaw EE, Flier JS. Adipose tissue as an endocrine organ. J Clin Endocrinol Metab. 2004;89(6):2548–56. doi:10.1210/jc.2004-0395.PubMedCrossRefGoogle Scholar
  4. 4.
    Galic S, Oakhill JS, Steinberg GR. Adipose tissue as an endocrine organ. Mol Cell Endocrinol. 2010;316(2):129–39. doi:10.1016/j.mce.2009.08.018.PubMedCrossRefGoogle Scholar
  5. 5.
    Piya MK, McTernan PG, Kumar S. Adipokine inflammation and insulin resistance: the role of glucose, lipids and endotoxin. J Endocrinol. 2013;216(1):T1–T15. doi:10.1530/joe-12-0498.PubMedCrossRefGoogle Scholar
  6. 6.
    Matsubara M, Maruoka S, Katayose S. Inverse relationship between plasma adiponectin and leptin concentrations in normal-weight and obese women. Eur J Endocrinol. 2002;147(2):173–80. doi:10.1530/eje.0.1470173.PubMedCrossRefGoogle Scholar
  7. 7.
    Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature. 1999;402(6762):656–60. doi:10.1038/45230.PubMedCrossRefGoogle Scholar
  8. 8.
    Inui A, Asakawa A, Bowers CY, Mantovani G, Laviano A, Meguid MM, et al. Ghrelin, appetite, and gastric motility: the emerging role of the stomach as an endocrine organ. FASEB J Off Publ Fed Am Soc Exp Biol. 2004;18(3):439–56. doi:10.1096/fj.03-0641rev.Google Scholar
  9. 9.
    Williams DL, Cummings DE, Grill HJ, Kaplan JM. Meal-related ghrelin suppression requires postgastric feedback. Endocrinology. 2003;144(7):2765–7.PubMedCrossRefGoogle Scholar
  10. 10.
    Fukushima N, Hanada R, Teranishi H, Fukue Y, Tachibana T, Ishikawa H, et al. Ghrelin directly regulates bone formation. J Bone Miner Res. 2005;20(5):790–8. doi:10.1359/JBMR.041237.PubMedCrossRefGoogle Scholar
  11. 11.
    Sun Y, Ahmed S, Smith RG. Deletion of ghrelin impairs neither growth nor appetite. Mol Cell Biol. 2003;23(22):7973–81.PubMedCrossRefGoogle Scholar
  12. 12.
    Sun Y, Wang P, Zheng H, Smith RG. Ghrelin stimulation of growth hormone release and appetite is mediated through the growth hormone secretagogue receptor. Proc Natl Acad Sci U S A. 2004;101(13):4679–84. doi:10.1073/pnas.0305930101.PubMedCrossRefGoogle Scholar
  13. 13.
    Maccarinelli G, Sibilia V, Torsello A, Raimondo F, Pitto M, Giustina A, et al. Ghrelin regulates proliferation and differentiation of osteoblastic cells. J Endocrinol. 2005;184(1):249–56. doi:10.1677/joe.1.05837.PubMedCrossRefGoogle Scholar
  14. 14.
    •• van der Velde M, van der Eerden BC, Sun Y, Almering JM, van der Lely AJ, Delhanty PJ, et al. An age-dependent interaction with leptin unmasks ghrelin's bone-protective effects. Endocrinology. 2012;153(8):3593–602. doi:10.1210/en.2012-1277. This paper examines the skeletal effects that each ghrelin and leptin has and is one of the first studies that explains the interplay that these 2 hormones have on bone in vivo.PubMedCrossRefGoogle Scholar
  15. 15.
    Elefteriou F, Ahn JD, Takeda S, Starbuck M, Yang X, Liu X, et al. Leptin regulation of bone resorption by the sympathetic nervous system and CART. Nature. 2005;434(7032):514–20. http://www.nature.com/nature/journal/v434/n7032/suppinfo/nature03398_S1.html.PubMedCrossRefGoogle Scholar
  16. 16.
    Guerardel A, Tanko LB, Boutin P, Christiansen C, Froguel P. Obesity susceptibility CART gene polymorphism contributes to bone remodeling in postmenopausal women. Osteoporos Int: a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2006;17(1):156–7. doi:10.1007/s00198-005-2022-1
  17. 17.
    McLarnon A. Metabolism: age-dependent balance of leptin and ghrelin regulates bone metabolism. Nature Rev Endocrinol. 2012;8(9):504. doi:10.1038/nrendo.2012.116.CrossRefGoogle Scholar
  18. 18.
    Nouh O, Abd Elfattah MM, Hassouna AA. Association between ghrelin levels and BMD: a cross sectional trial. Gynecol Endocrinol. 2012;28(7):570–2. doi:10.3109/09513590.2011.593663.PubMedCrossRefGoogle Scholar
  19. 19.
    Wilasco MI, Goldani HA, Dornelles CT, Maurer RL, Kieling CO, Porowski M, et al. Ghrelin, leptin and insulin in healthy children: relationship with anthropometry, gender, and age distribution. Regul Pept. 2012;173(1–3):21–6. doi:10.1016/j.regpep.2011.08.013.PubMedCrossRefGoogle Scholar
  20. 20.
    Napoli N, Pedone C, Pozzilli P, Lauretani F, Bandinelli S, Ferrucci L, et al. Effect of ghrelin on bone mass density: the InChianti study. Bone. 2011;49(2):257–63. doi:10.1016/j.bone.2011.03.772.PubMedCrossRefGoogle Scholar
  21. 21.
    Pacifico L, Anania C, Poggiogalle E, Osborn JF, Prossomariti G, Martino F, et al. Relationships of acylated and des-acyl ghrelin levels to bone mineralization in obese children and adolescents. Bone. 2009;45(2):274–9. doi:10.1016/j.bone.2009.04.204.PubMedCrossRefGoogle Scholar
  22. 22.
    Cigdem Arica P, Kocael A, Tabak O, Taskin M, Zengin K, Uzun H. Plasma ghrelin, leptin, and orexin-A levels and insulin resistance after laparoscopic gastric band applications in morbidly obese patients. Minerva Medica. 2013;104(3):309–16.PubMedGoogle Scholar
  23. 23.
    •• Brzozowska MM, Sainsbury A, Eisman JA, Baldock PA, Center JR. Bariatric surgery, bone loss, obesity and possible mechanisms. Obes Rev. 2013;14(1):52–67. doi:10.1111/j.1467-789X.2012.01050.x. This review assesses the interactions between bariatric surgery, bone loss, and obesity. Obesity and bone loss has been widely overlooked; evidence suggests that continued bone loss is present in postbariatric surgery. This review extensively examines the current literature and suggests possible mechanisms that may be occurring.PubMedCrossRefGoogle Scholar
  24. 24.
    Shapses SA, Riedt CS. Bone, body weight, and weight reduction: what are the concerns? J Nutrition. 2006;136(6):1453–6.Google Scholar
  25. 25.
    Wong IP, Baldock PA, Herzog H. Gastrointestinal peptides and bone health. Curr Opin Endocrinol Diabetes Obes. 2010;17(1):44–50. doi:10.1097/MED.0b013e3283344a05.PubMedGoogle Scholar
  26. 26.
    Walsh JS, Henriksen DB. Feeding and bone. Arch Biochemis Biophys. 2010;503(1):11–9. doi:10.1016/j.abb.2010.06.020.CrossRefGoogle Scholar
  27. 27.
    •• Wong IPL, Driessler F, Khor EC, Shi Y-C, Hörmer B, Nguyen AD, et al. Peptide YY regulates bone remodeling in mice: a link between gut and skeletal biology. PLoS One. 2012;7(7):e40038. doi:10.1371/journal.pone.0040038. This study showed that PYY regulates bone remodelling via the osteoblastic Y1 receptor using knockout and transgenic mice.PubMedCrossRefGoogle Scholar
  28. 28.
    Wortley KE, Garcia K, Okamoto H, Thabet K, Anderson KD, Shen V, et al. Peptide YY regulates bone turnover in rodents. Gastroenterology. 2007;133(5):1534–43. doi:10.1053/j.gastro.2007.08.024.PubMedCrossRefGoogle Scholar
  29. 29.
    Yuzuriha H, Inui A, Asakawa A, Ueno N, Kasuga M, Meguid MM, et al. Gastrointestinal hormones (anorexigenic peptide YY and orexigenic ghrelin) influence neural tube development. FASEB J. 2007;21(9):2108–12. doi:10.1096/fj.06-7621com.PubMedCrossRefGoogle Scholar
  30. 30.
    Angelopoulos N, Goula A, Tolis G. Current knowledge in the neurophysiologic modulation of obesity. Metab Clin Exp. 2005;54(9):1202–17. doi:10.1016/j.metabol.2005.04.005.PubMedCrossRefGoogle Scholar
  31. 31.
    Misra M, Miller KK, Tsai P, Gallagher K, Lin A, Lee N, et al. Elevated peptide YY levels in adolescent girls with anorexia nervosa. J Clin Endocrinol Metabol. 2006;91(3):1027–33. doi:10.1210/jc.2005-1878.CrossRefGoogle Scholar
  32. 32.
    Howgate DJ, Graham SM, Leonidou A, Korres N, Tsiridis E, Tsapakis E. Bone metabolism in anorexia nervosa: molecular pathways and current treatment modalities. Osteoporo Int. 2013;24(2):407–21. doi:10.1007/s00198-012-2095-6.CrossRefGoogle Scholar
  33. 33.
    Scheid JL, Toombs RJ, Ducher G, Gibbs JC, Williams NI, De Souza MJ. Estrogen and peptide YY are associated with bone mineral density in premenopausal exercising women. Bone. 2011;49(2):194–201. doi:10.1016/j.bone.2011.04.011.PubMedCrossRefGoogle Scholar
  34. 34.
    Batterham RL, Cohen MA, Ellis SM, Le Roux CW, Withers DJ, Frost GS, et al. Inhibition of food intake in obese subjects by Peptide YY3–36. N Engl J Med. 2003;349(10):941–8. doi:10.1056/NEJMoa030204.PubMedCrossRefGoogle Scholar
  35. 35.
    Reid IR. Relationships among body mass, its components, and bone. Bone. 2002;31(5):547–55.PubMedCrossRefGoogle Scholar
  36. 36.
    Utz AL, Lawson EA, Misra M, Mickley D, Gleysteen S, Herzog DB, et al. Peptide YY (PYY) levels and bone mineral density (BMD) in women with anorexia nervosa. Bone. 2008;43(1):135–9. doi:10.1016/j.bone.2008.03.007.PubMedCrossRefGoogle Scholar
  37. 37.
    Misra M, Prabhakaran R, Miller KK, Goldstein MA, Mickley D, Clauss L, et al. Prognostic indicators of changes in bone density measures in adolescent girls with anorexia nervosa-II. J Clin Endocrinol Metabol. 2008;93(4):1292–7. doi:10.1210/jc.2007-2419.CrossRefGoogle Scholar
  38. 38.
    Clowes JA, Khosla S, Eastell R. Potential role of pancreatic and enteric hormones in regulating bone turnover. J Bone Min Res. 2005;20(9):1497–506. doi:10.1359/JBMR.050524.CrossRefGoogle Scholar
  39. 39.
    Asmar M, Holst JJ. Glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide: new advances. Curr Opin Endocrinol Diabetes Obes. 2010;17(1):57–62. doi:10.1097/MED.0b013e3283339051.PubMedGoogle Scholar
  40. 40.
    Paschetta E, Hvalryg M, Musso G. Glucose-dependent insulinotropic polypeptide: from pathophysiology to therapeutic opportunities in obesity-associated disorders. Obes Rev. 2011;12(10):813–28. doi:10.1111/j.1467-789X.2011.00897.x.PubMedCrossRefGoogle Scholar
  41. 41.
    Tsukiyama K, Yamada Y, Yamada C, Harada N, Kawasaki Y, Ogura M, et al. Gastric inhibitory polypeptide as an endogenous factor promoting new bone formation after food ingestion. Mol Endocrinol. 2006;20(7):1644–51. doi:10.1210/me.2005-0187.PubMedCrossRefGoogle Scholar
  42. 42.
    Xie D, Zhong Q, Ding KH, Cheng H, Williams S, Correa D, et al. Glucose-dependent insulinotropic peptide-overexpressing transgenic mice have increased bone mass. Bone. 2007;40(5):1352–60. doi:10.1016/j.bone.2007.01.007.PubMedCrossRefGoogle Scholar
  43. 43.
    Xie D, Cheng H, Hamrick M, Zhong Q, Ding K-H, Correa D, et al. Glucose-dependent insulinotropic polypeptide receptor knockout mice have altered bone turnover. Bone. 2005;37(6):759–69. doi:10.1016/j.bone.2005.06.021.PubMedCrossRefGoogle Scholar
  44. 44.
    Gaudin-Audrain C, Irwin N, Mansur S, Flatt PR, Thorens B, Basle M, et al. Glucose-dependent insulinotropic polypeptide receptor deficiency leads to modifications of trabecular bone volume and quality in mice. Bone. 2013;53(1):221–30. doi:10.1016/j.bone.2012.11.039.PubMedCrossRefGoogle Scholar
  45. 45.
    Nuche-Berenguer B, Moreno P, Esbrit P, Dapia S, Caeiro JR, Cancelas J, et al. Effect of GLP-1 treatment on bone turnover in normal, type 2 diabetic, and insulin-resistant states. Calcif Tissue Int. 2009;84(6):453–61. doi:10.1007/s00223-009-9220-3.PubMedCrossRefGoogle Scholar
  46. 46.
    • Pacheco-Pantoja EL, Ranganath LR, Gallagher JA, Wilson PJ, Fraser WD. Receptors and effects of gut hormones in three osteoblastic cell lines. BMC Physiol. 2011;11:12. doi:10.1186/1472-6793-11-12. This paper outlines the response of cell lines to GLP-2 and explains that osteoblastic maturation may be a factor in explaining the different responses observed.PubMedCrossRefGoogle Scholar
  47. 47.
    Henriksen DB, Alexandersen P, Bjarnason NH, Vilsboll T, Hartmann B, Henriksen EE, et al. Role of gastrointestinal hormones in postprandial reduction of bone resorption. J Bone Miner Res. 2003;18(12):2180–9. doi:10.1359/jbmr.2003.18.12.2180.PubMedCrossRefGoogle Scholar
  48. 48.
    Henriksen DB, Alexandersen P, Byrjalsen I, Hartmann B, Bone HG, Christiansen C, et al. Reduction of nocturnal rise in bone resorption by subcutaneous GLP-2. Bone. 2004;34(1):140–7.PubMedCrossRefGoogle Scholar
  49. 49.
    Henriksen DB, Alexandersen P, Hartmann B, Adrian CL, Byrjalsen I, Bone HG, et al. Disassociation of bone resorption and formation by GLP-2: a 14-day study in healthy postmenopausal women. Bone. 2007;40(3):723–9. doi:10.1016/j.bone.2006.09.025.PubMedCrossRefGoogle Scholar
  50. 50.
    Henriksen DB, Alexandersen P, Hartmann B, Adrian CL, Byrjalsen I, Bone HG, et al. Four-month treatment with GLP-2 significantly increases hip BMD: a randomized, placebo-controlled, dose-ranging study in postmenopausal women with low BMD. Bone. 2009;45(5):833–42. doi:10.1016/j.bone.2009.07.008.PubMedCrossRefGoogle Scholar
  51. 51.
    Dicembrini I, Mannucci E, Rotella CM. Bone: incretin hormones perceiver or receiver? Exp Diabetes Res. 2012;2012:519784. doi:10.1155/2012/519784.PubMedCrossRefGoogle Scholar
  52. 52.
    Askov-Hansen C, Jeppesen PB, Lund P, Hartmann B, Holst JJ, Henriksen DB. Effect of glucagon-like peptide-2 exposure on bone resorption: effectiveness of high concentration versus prolonged exposure. Regul Pept. 2012;181C:4–8. doi:10.1016/j.regpep.2012.11.002.Google Scholar
  53. 53.
    Considine RV, Sinha MK, Heiman ML, Kriauciunas A, Stephens TW, Nyce MR, et al. Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med. 1996;334(5):292–5. doi:10.1056/NEJM199602013340503.PubMedCrossRefGoogle Scholar
  54. 54.
    Chen H, Charlat O, Tartaglia LA, Woolf EA, Weng X, Ellis SJ, et al. Evidence that the diabetes gene encodes the leptin receptor: identification of a mutation in the leptin receptor gene in db/db Mice. Cell. 1996;84(3):491–5. doi:10.1016/S0092-8674(00)81294-5.PubMedCrossRefGoogle Scholar
  55. 55.
    Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature. 1994;372(6505):425–32.PubMedCrossRefGoogle Scholar
  56. 56.
    Baldock PA, Sainsbury A, Allison S, Lin EJ, Couzens M, Boey D, et al. Hypothalamic control of bone formation: distinct actions of leptin and y2 receptor pathways. J Bone Miner Res. 2005;20(10):1851–7. doi:10.1359/JBMR.050523.PubMedCrossRefGoogle Scholar
  57. 57.
    Baldock PA, Allison S, McDonald MM, Sainsbury A, Enriquez RF, Little DG, et al. Hypothalamic regulation of cortical bone mass: opposing activity of Y2 receptor and leptin pathways. J Bone Miner Res. 2006;21(10):1600–7. doi:10.1359/jbmr.060705.PubMedCrossRefGoogle Scholar
  58. 58.
    Hamrick MW, Pennington C, Newton D, Xie D, Isales C. Leptin deficiency produces contrasting phenotypes in bones of the limb and spine. Bone. 2004;34(3):376–83. doi:10.1016/j.bone.2003.11.020.PubMedCrossRefGoogle Scholar
  59. 59.
    Lee NJ, Wong IP, Baldock PA, Herzog H. Leptin as an endocrine signal in bone. Curr Osteoporos Rep. 2008;6(2):62–6.PubMedCrossRefGoogle Scholar
  60. 60.
    Vaisse C, Halaas JL, Horvath CM, Darnell Jr JE, Stoffel M, Friedman JM. Leptin activation of Stat3 in the hypothalamus of wild-type and ob/ob mice but not db/db mice. Nat Genet. 1996;14(1):95–7. doi:10.1038/ng0996-95.PubMedCrossRefGoogle Scholar
  61. 61.
    Ducy P, Amling M, Takeda S, Priemel M, Schilling AF, Beil FT, et al. Leptin inhibits bone formation through a hypothalamic relay: a central control of bone mass. Cell. 2000;100(2):197–207. doi:10.1016/S0092-8674(00)81558-5.PubMedCrossRefGoogle Scholar
  62. 62.
    Iwaniec UT, Boghossian S, Lapke PD, Turner RT, Kalra SP. Central leptin gene therapy corrects skeletal abnormalities in leptin-deficient ob/ob mice. Peptides. 2007;28(5):1012–9. doi:10.1016/j.peptides.2007.02.001.PubMedCrossRefGoogle Scholar
  63. 63.
    Takeda S, Elefteriou F, Levasseur R, Liu X, Zhao L, Parker KL, et al. Leptin regulates bone formation via the sympathetic nervous system. Cell. 2002;111(3):305–17. doi:10.1016/S0092-8674(02)01049-8.PubMedCrossRefGoogle Scholar
  64. 64.
    Kajimura D, Hinoi E, Ferron M, Kode A, Riley KJ, Zhou B, et al. Genetic determination of the cellular basis of the sympathetic regulation of bone mass accrual. J Exp Med. 2011;208(4):841–51. doi:10.1084/jem.20102608.PubMedCrossRefGoogle Scholar
  65. 65.
    Wilding JP, Gilbey SG, Bailey CJ, Batt RA, Williams G, Ghatei MA, et al. Increased neuropeptide-Y messenger ribonucleic acid (mRNA) and decreased neurotensin mRNA in the hypothalamus of the obese (ob/ob) mouse. Endocrinology. 1993;132(5):1939–44. doi:10.1210/en.132.5.1939.PubMedCrossRefGoogle Scholar
  66. 66.
    Stephens TW, Basinski M, Bristow PK, Bue-Valleskey JM, Burgett SG, Craft L, et al. The role of neuropeptide Y in the antiobesity action of the obese gene product. Nature. 1995;377(6549):530–2.PubMedCrossRefGoogle Scholar
  67. 67.
    Baldock PA, Allison SJ, Lundberg P, Lee NJ, Slack K, Lin E-JD, et al. Novel role of Y1 receptors in the coordinated regulation of bone and energy homeostasis. J Biolog Chemis. 2007;282(26):19092–102. doi:10.1074/jbc.M700644200.CrossRefGoogle Scholar
  68. 68.
    Baldock PA, Lee NJ, Driessler F, Lin S, Allison S, Stehrer B, et al. Neuropeptide Y knockout mice reveal a central role of NPY in the coordination of bone mass to body weight. PLoS One. 2009;4(12):e8415. doi:10.1371/journal.pone.0008415.PubMedCrossRefGoogle Scholar
  69. 69.
    Baldock PA, Sainsbury A, Couzens M, Enriquez RF, Thomas GP, Gardiner EM, et al. Hypothalamic Y2 receptors regulate bone formation. J Clin Invest. 2002;109(7):915–21. doi:10.1172/JCI14588.PubMedGoogle Scholar
  70. 70.
    •• Wong IPL, Nguyen AD, Khor EC, Enriquez RF, Eisman JA, Sainsbury A, et al. Neuropeptide Y is a critical modulator of Leptin's regulation of cortical bone. J Bone Miner Res. 2013;28(4):886–98. doi:10.1002/jbmr.1786. This study showed the contribution of NPY in the cortical bone phenotype of ob/ob mice.PubMedCrossRefGoogle Scholar
  71. 71.
    Cornish J, Callon KE, Bava U, Lin C, Naot D, Hill BL, et al. Leptin directly regulates bone cell function in vitro and reduces bone fragility in vivo. J Endocrinol. 2002;175(2):405–15.PubMedCrossRefGoogle Scholar
  72. 72.
    Lee YJ, Park JH, Ju SK, You KH, Ko JS, Kim HM. Leptin receptor isoform expression in rat osteoblasts and their functional analysis. FEBS Lett. 2002;528(1–3):43–7.PubMedCrossRefGoogle Scholar
  73. 73.
    Steppan CM, Crawford DT, Chidsey-Frink KL, Ke H, Swick AG. Leptin is a potent stimulator of bone growth in ob/ob mice. Regul Pept. 2000;92(1–3):73–8. doi:10.1016/S0167-0115(00)00152-X.PubMedCrossRefGoogle Scholar
  74. 74.
    Nakajima R, Inada H, Koike T, Yamano T. Effects of leptin to cultured growth plate chondrocytes. Horm Res. 2003;60(2):91–8.PubMedCrossRefGoogle Scholar
  75. 75.
    Reseland JE, Syversen U, Bakke I, Qvigstad G, Eide LG, Hjertner O, et al. Leptin is expressed in and secreted from primary cultures of human osteoblasts and promotes bone mineralization. J Bone Miner Res. 2001;16(8):1426–33. doi:10.1359/jbmr.2001.16.8.1426.PubMedCrossRefGoogle Scholar
  76. 76.
    Burguera B, Hofbauer LC, Thomas T, Gori F, Evans GL, Khosla S, et al. Leptin reduces ovariectomy-induced bone loss in rats. Endocrinology. 2001;142(8):3546–53. doi:10.1210/en.142.8.3546.PubMedCrossRefGoogle Scholar
  77. 77.
    Jackson MA, Iwaniec UT, Turner RT, Wronski TJ, Kalra SP. Effects of increased hypothalamic leptin gene expression on ovariectomy-induced bone loss in rats. Peptides. 2011;32(8):1575–80. doi:10.1016/j.peptides.2011.04.029.PubMedCrossRefGoogle Scholar
  78. 78.
    •• Turner RT, Kalra SP, Wong CP, Philbrick KA, Lindenmaier LB, Boghossian S, et al. Peripheral leptin regulates bone formation. J Bone Miner Res. 2013;28(1):22–34. doi:10.1002/jbmr.1734. The role of peripheral leptin signalling in bone remodelling was revisited in this study.PubMedCrossRefGoogle Scholar
  79. 79.
    Williams LM. Hypothalamic dysfunction in obesity. Proc Nutr Soc. 2012;71(4):521–33. doi:10.1017/S002966511200078X.PubMedCrossRefGoogle Scholar
  80. 80.
    Hamrick MW, Ding KH, Ponnala S, Ferrari SL, Isales CM. Caloric restriction decreases cortical bone mass but spares trabecular bone in the mouse skeleton: implications for the regulation of bone mass by body weight. J Bone Miner Res. 2008;23(6):870–8. doi:10.1359/jbmr.080213.PubMedCrossRefGoogle Scholar
  81. 81.
    Farooqi IS, Jebb SA, Langmack G, Lawrence E, Cheetham CH, Prentice AM, et al. Effects of recombinant leptin therapy in a child with congenital leptin deficiency. N Engl J Med. 1999;341(12):879–84. doi:10.1056/NEJM199909163411204.PubMedCrossRefGoogle Scholar
  82. 82.
    Ahmadi F, Salari S, Maziar S, Esfahanian F, Khazaeipour Z, Ranjbarnovin N. Relationship between serum leptin levels and bone mineral density and bone metabolic markers in patients on hemodialysis. Saudi J Kidney Dis Transpl. 2013;24(1):41–7.Google Scholar
  83. 83.
    Zhao H-Z, Bi Y-F, Ma L-Y, Zhao L, Wang T-G, Zhang L-Z, et al. The effects of bisphenol A (BPA) exposure on fat mass and serum leptin concentrations have no impact on bone mineral densities in nonobese premenopausal women. Clin Biochemis. 2012;45(18):1602–6. doi:10.1016/j.clinbiochem.2012.08.024.CrossRefGoogle Scholar
  84. 84.
    Thomas T, Burguera B, Melton III LJ, Atkinson EJ, O'Fallon WM, Riggs BL, et al. Role of serum leptin, insulin, and estrogen levels as potential mediators of the relationship between fat mass and bone mineral density in men versus women. Bone. 2001;29(2):114–20.PubMedCrossRefGoogle Scholar
  85. 85.
    Sienkiewicz E, Magkos F, Aronis KN, Brinkoetter M, Chamberland JP, Chou S, et al. Long-term metreleptin treatment increases bone mineral density and content at the lumbar spine of lean hypoleptinemic women. Metab Clin Exp. 2011;60(9):1211–21. doi:10.1016/j.metabol.2011.05.016.PubMedCrossRefGoogle Scholar
  86. 86.
    Conroy R, Girotra M, Shane E, McMahon DJ, Pavlovich KH, Leibel RL, et al. Leptin administration does not prevent the bone mineral metabolism changes induced by weight loss. Metab Clin Exp. 2011;60(9):1222–6. doi:10.1016/j.metabol.2011.02.010.PubMedCrossRefGoogle Scholar
  87. 87.
    Hu E, Liang P, Spiegelman BM. AdipoQ is a novel adipose-specific gene dysregulated in obesity. J Biologic Chemis. 1996;271(18):10697–703.CrossRefGoogle Scholar
  88. 88.
    Berner HS, Lyngstadaas SP, Spahr A, Monjo M, Thommesen L, Drevon CA, et al. Adiponectin and its receptors are expressed in bone-forming cells. Bone. 2004;35(4):842–9. doi:10.1016/j.bone.2004.06.008.PubMedCrossRefGoogle Scholar
  89. 89.
    Luo X-H, Guo L-J, Yuan L-Q, Xie H, Zhou H-D, Wu X-P, et al. Adiponectin stimulates human osteoblasts proliferation and differentiation via the MAPK signaling pathway. Exp Cell Res. 2005;309(1):99–109. doi:10.1016/j.yexcr.2005.05.021.PubMedCrossRefGoogle Scholar
  90. 90.
    Shinoda Y, Yamaguchi M, Ogata N, Akune T, Kubota N, Yamauchi T, et al. Regulation of bone formation by adiponectin through autocrine/paracrine and endocrine pathways. J Cell Biochemis. 2006;99(1):196–208. doi:10.1002/jcb.20890.CrossRefGoogle Scholar
  91. 91.
    Zhang Y, Zhou P, Kimondo JW. Adiponectin and osteocalcin: relation to insulin sensitivity. Biochem Cell Biol. 2012;90(5):613–20. doi:10.1139/o2012-022.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Ee Cheng Khor
    • 1
  • Natalie Kah Yun Wee
    • 1
  • Paul A Baldock
    • 1
  1. 1.Bone Regulation, Neuroscience Research DivisionGarvan Institute of Medical ResearchSydneyAustralia

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