Palabras clave
Leptina
Obesidad
Osteoporosis
Densidad ósea
Obesidad
Osteoporosis
Densidad ósea
Cómo citar
Rosero, R., Sierra, A., & Medina, A. (2017). Interacción de la leptina y el hueso en sujetos obesos. Protección vs. fragilidad. Revista Colombiana De Endocrinología, Diabetes &Amp; Metabolismo, 2(3), 14–21. https://doi.org/10.53853/encr.2.3.90
Resumen
La osteoporosis y la obesidad son dos de los desórdenes más frecuentes e importantes actualmente en endocrinología, con una prevalencia en aumento; ambas entidades alteran la configuración y mecánica del cuerpo y comparten características genéticas, con un progenitor común. Con el envejecimiento, la relación entre obesidad y baja densidad ósea se afianza, produciendo predominio de la adiposidad y osteoclastogénesis, que altera la función del osteoblasto, por el efecto protagónico de la leptina como modulador de la diferenciación de células mesenquimales a adipocitos y no a osteoblastos, lo que lleva a la expresión de la enfermedad.
En esta revisión queremos esclarecer fisiológicamente la estrecha relación entre estas dos condiciones (osteoporosis y obesidad) y establecer el papel estelar de las adipocinas en la patogenía de la osteoporosis.
Citas
1. Iwaniec UT, Dube MG, Boghossian S, Song H, Helferich WG, Turner RT, et al. Body mass influences cortical bone mass independent of leptin signaling. Bone. 2009;44(3):404-12. Epub 2008/12/20.
2. Tartaglia LA, Dembski M, Weng X, Deng N, Culpepper J, Devos R, et al. Identification and expression cloning of a leptin receptor, OB-R. Cell. 1995;83(7):1263-71. Epub 1995/12/29.
3. 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. The New England journal of medicine. 1999;341(12):879-84. Epub 1999/09/16.
4. Hebebrand J, Muller TD, Holtkamp K, Herpertz-Dahlmann B. The role of leptin in anorexia nervosa: clinical implications. Molecular psychiatry.2007;12(1):23-35. Epub 2006/10/25.
5. Pasco JA, Henry MJ, Kotowicz MA, Collier GR, Ball MJ, Ugoni AM, et al. Serum leptin levels are associated with bone mass in nonobese women. The Journal of clinical endocrinology and metabolism. 2001;86(5):1884-7. Epub 2001/05/10.
6. Friedman JM. Leptin, leptin receptors, and the control of body weight. Nutrition reviews. 1998;56(2 Pt 2):s38-46; discussion s54-75. Epub
1998/05/02.
7. Dardeno TA, Chou SH, Moon HS, Chamberland JP, Fiorenza CG, Mantzoros CS. Leptin in human physiology and therapeutics. Frontiers in neuroendocrinology. 2010;31(3):377-93. Epub 2010/07/06.
8. Simón E DBAS. Leptina y obesidad. Anales del sistema sanitario de Navarra. 2002;25:53-64.
9. Considine RV, Sinha MK, Heiman ML, Kriauciunas A, Stephens TW, Nyce MR, et al. Serum immunoreactive-leptin concentrations in normal-weight and obese humans. The New England journal of medicine. 1996;334(5):292-5. Epub 1996/02/01.
10. Chan JL, Heist K, DePaoli AM, Veldhuis JD, Mantzoros CS. The role of falling leptin levels in the neuroendocrine and metabolic adaptation to short-term starvation in healthy men. The Journal of clinical investigation. 2003;111(9):1409-21. Epub 2003/05/03.
11. Bjorbaek C, Elmquist JK, Michl P, Ahima RS, van Bueren A, McCall AL, et al. Expression of leptin receptor isoforms in rat brain microvessels. Endocrinology. 1998;139(8):3485-91. Epub 1998/07/29.
12. Ernst MB, Wunderlich CM, Hess S, Paehler M, Mesaros A, Koralov SB, et al. Enhanced Stat3 activation in POMC neurons provokes negative feedback inhibition of leptin and insulin signaling in obesity. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2009;29(37):11582-93. Epub 2009/09/18.
13. Gong L, Yao F, Hockman K, Heng HH, Morton GJ, Takeda K, et al. Signal transducer and activator of transcription-3 is required in hypothalamic agoutirelated protein/neuropeptide Y neurons for normal energy homeostasis. Endocrinology. 2008;149(7):3346-54. Epub 2008/04/12.
14. Santillán Benítez JG, Mendieta Zerón H, Ordóñez Quiroz Á, LM. GO. La leptina en la carcinogénesis mamaria. Vías de señalización. Química Viva. 2012;11(2):91-111.
15. Morrison CD. Leptin signaling in brain: A link between nutrition and cognition? Biochimica et biophysica acta. 2009;1792(5):401-8. Epub 2009/01/10.
16. Harvey J, McKay NG, Walker KS, Van der Kaay J, Downes CP, Ashford ML. Essential role of phosphoinositide 3-kinase in leptin-induced K(ATP) channel activation in the rat CRI-G1 insulinoma cell line. The Journal of biological chemistry. 2000;275(7):4660-9. Epub 2000/02/15.
17. Plum L, Ma X, Hampel B, Balthasar N, Coppari R, Munzberg H, et al. Enhanced PIP3 signaling in POMC neurons causes KATP channel activation and leads to diet-sensitive obesity. The Journal of clinical investigation. 2006;116(7):1886-901. Epub 2006/06/24.
18. Bjorbaek C, Buchholz RM, Davis SM, Bates SH, Pierroz DD, Gu H, et al. Divergent roles of SHP-2 in ERK activation by leptin receptors. The Journal of biological chemistry. 2001;276(7):4747-55. Epub 2000/11/22.
19. Rahmouni K, Sigmund CD, Haynes WG, Mark AL. Hypothalamic ERK mediates the anorectic and thermogenic sympathetic effects of leptin. Diabetes. 2009;58(3):536-42. Epub 2008/12/11.
20. Kim GS, Hong JS, Kim SW, Koh JM, An CS, Choi JY, et al. Leptin induces apoptosis via ERK/cPLA2/cytochrome c pathway in human bone marrow stromal cells. The Journal of biological chemistry. 2003;278(24):21920-9. Epub 2003/04/01.
21. Fruhbeck G. Intracellular signalling pathways activated by leptin. The Biochemical journal. 2006;393(Pt 1):7-20. Epub 2005/12/13.
22. ME. FVV. Señalización de la leptina. Revista de Educación Bioquímica. 2006;25(2):50-4.
23. Hamrick MW. Leptin and bone: A consensus emerging? IBMS BoneKEy. BoneKEy-Osteovision. 2007;4(3):99-107.
24. Rosen CJ, Bouxsein ML. Mechanisms of disease: is osteoporosis the obesity of bone? Nature clinical practice Rheumatology. 2006;2(1):35-43. Epub 2006/08/26.
25. Wren AM, Small CJ, Abbott CR, Jethwa PH, Kennedy AR, Murphy KG, et al. Hypothalamic actions of neuromedin U. Endocrinology. 2002;143(11):4227- 34. Epub 2002/10/26.
26. Yadav VK, Oury F, Suda N, Liu ZW, Gao XB, Confavreux C, et al. A serotonin-dependent mechanism explains the leptin regulation of bone mass, appetite, and energy expenditure. Cell. 2009;138(5):976-89. Epub 2009/09/10.
27. Hamrick MW, Della-Fera MA, Choi YH, Pennington C, Hartzell D, Baile CA. Leptin treatment induces loss of bone marrow adipocytes and increases bone formation in leptin-deficient ob/ob mice. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2005;20(6):994-1001. Epub 2005/05/11.
28. Holloway WR, Collier FM, Aitken CJ, Myers DE, Hodge JM, Malakellis M, et al. Leptin inhibits osteoclast generation. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2002;17(2):200-9. Epub 2002/01/29.
29. Cirmanová V, Bayer M, Stárka L, Zajícková K. The effect of leptin on Bone: An Evolving Concept of Action. 2008; 57 (Suppl. 1): 143-51. physiological research-ISSN 0865-8408
30. Burguera B, Couce ME, Curran GL, Jensen MD, Lloyd RV, Cleary MP, et al. Obesity is associated with a decreased leptin transport across the blood- brain barrier in rats. Diabetes. 2000;49(7):1219-23. Epub 2000/07/26.
31. Oswal A, Yeo G. Leptin and the control of body weight: a review of its diverse central targets, signaling mechanisms, and role in the pathogenesis of obesity. Obesity (Silver Spring). 2010;18(2):221-9. Epub 2009/08/01.
32. Turner RT, Kalra SP, Wong CP, Philbrick KA, Lindenmaier LB, Boghossian S, et al. Peripheral leptin regulates bone formation. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2013;28(1):22-34. Epub 2012/08/14.
33. Franek E, Nowak J, Safranow K, Adler G, Binczak-Kuleta A, Ciechanowicz A, et al. G(-2548)A leptin gene polymorphism in obese subjects is associated with serum leptin concentration and bone mass. Polskie Archiwum Medy- cyny Wewnetrznej. 2010;120(5):175-80. Epub 2010/05/27.
34. OMS. Nota descriptiva N°311. Obesidad y sobrepeso. Disponible en: http:// www.who.int/mediacentre/factsheets/fs311/es/index.html
35. Ministerio de la Protección Social. Encuesta Nacional de Salud, 2007.
36. Erazo M. Visión global en relación a la obesidad. Rev. Med. Clin, Condes. 2012; 23(2) 196-200
37. Acosta, K. La obesidad y su concentración según nivel socioeconómico en Colombia. Num 170, Julio , 2012.
38. Aranceta, j. Foz, M. Gil B, Jover, E. Mantilla, T. Millán, J. Monereo, S. Moreno, B. Documento de consenso: obesidad y riesgo cardiovascular. Clin Invest Arterioscl 2003;15(5):196-233
39. Papapietro, K, Massardo, T. Riffo, A. Díaz, E. Araya V, Adjemian, D. Montesinos, G. Castro, G. Disminución de masa ósea post-cirugía bariátrica con bypass en Y de Roux. Nutr Hosp. 2013;28:631-636. DOI:10.3305/ nh.2013.28.3.6400
40. Maor, G. Rochweger, M. Sege, Y. Phillips M. Leptin Acts as a Growth Factor on the Chondrocytes of Skeletal Growth Centers, Journal of bone and mineral research, Volume 17, Number 6, 2002
41. Rao, M. Schambelan, M. Tai, V. Abrams, D. Khatami, H. Havel, P. Sakkas, G. Mulligan,K. Assessing the Association between Leptin and Bone Mineral Density in HIV-InfectedMen. Hindawi Publishing Corporation AIDS Research and Treatment Volume 2012, Article ID 103072, 5 pages doi:10.1155/2012/103072
42. Friedman, J. Halaas, J. Leptin and the regulation of body weight in mammals, NATURE | VOL 395 | 22 OCTOBER 1998 | www.nature.com
43. Legiran, S. Brandi, M. Bone mass regulation of leptin and postmenopausal osteoporosis with obesity. Clinical Cases in Mineral and Bone Metabolism 2012; 9(3): 145-149
44. Anagnostis,P. Vakalopoulou,S. Charizopoulou, M. Kazantzidou, E. Chrysopoulou, T. Moka,E. Agapidou, A. Zournatzi, V. Garipidou, V. Is there any association between leptin levels and bone mineral density in haemophiliac men? Arch Med Sci 2013; 9, 3: 459-465
45. Coelho, M. Oliveira, T. Fernandes, R. Biochemistry of adipose tissue: an endocrine organ, Arch Med Sci 2, April / 2013
46. Kwon, H. Pessin, J. Adipokines mediate inflammation and insulin resistance, Front Endocrinol (Lausanne). 2013; 4: 71.
47. Coelho, M. Oliveira, T. Fernandes, R. Biochemistry of adipose tissue: an endocrine organ. Arch Med Sci 2013; 9, 2: 191-200 DOI: 10.5114/ aoms.2013.33181
48. Lazarenko OP, Rzonca SO, Suva LJ, Lecka-Czernik B. Netoglitazone is a PPAR- gamma ligand with selective effects on bone and fat. Bone. 2006;38(1):74- 84. Epub 2005/09/03.
49. Mantzoros, C. Magkos, F. Brinkoetter, M. Sienkiewicz, E. Dardeno, T. Kim, S. Hamnvik, OP. Koniaris, A. Leptin in human physiology and pathophysiology. Am J Physiol Endocrinol Metab 301: E567–E584, 2011.
50. Motyla, K. Rosena, C. Understanding leptin-dependent regulation of skeletal homeostasis, Biochimie. 2012 October; 94(10): 2089–2096. doi:10.1016/j. biochi.2012.04.015
51. Cao JJ, Gregoire BR, Gao H. High-fat diet decreases cancellous bone mass but has no effect on cortical bone mass in the tibia in mice. Bone.
2009;44(6):1097-104. Epub 2009/03/07.
52. Scheller, E. Song, J. Dishowitz, M. Hankenson,K. Krebsbac, K. A potential role for the myeloid lineage in leptin-regulated bone Metabolism. Horm Metab Res. 2012 January ; 44(1): 1–5. doi:10.1055/s-0031-1297971
53. Zhao, L. Jiang, H. Papasian, C. Maulik, D. Drees, B. Hamilton, J. Deng, H. Corre- lation of Obesity and Osteoporosis: Effect of Fat Mass on the Determination of Osteoporosis. Journal of bone and mineral research. Volume 23, Number 1, 2008
54. Batsis, J. Sahakyan, K. Singh, P. Bartels, S. Somer, V. Lopez-Jimenez, F. Leptin, Adiposity, and Mortality: Results from the National Health and Nutrition Examination Survey III, 1988 to 1994. Mayo Clinic Proceeding. 2015:90(4):481-491.
2. Tartaglia LA, Dembski M, Weng X, Deng N, Culpepper J, Devos R, et al. Identification and expression cloning of a leptin receptor, OB-R. Cell. 1995;83(7):1263-71. Epub 1995/12/29.
3. 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. The New England journal of medicine. 1999;341(12):879-84. Epub 1999/09/16.
4. Hebebrand J, Muller TD, Holtkamp K, Herpertz-Dahlmann B. The role of leptin in anorexia nervosa: clinical implications. Molecular psychiatry.2007;12(1):23-35. Epub 2006/10/25.
5. Pasco JA, Henry MJ, Kotowicz MA, Collier GR, Ball MJ, Ugoni AM, et al. Serum leptin levels are associated with bone mass in nonobese women. The Journal of clinical endocrinology and metabolism. 2001;86(5):1884-7. Epub 2001/05/10.
6. Friedman JM. Leptin, leptin receptors, and the control of body weight. Nutrition reviews. 1998;56(2 Pt 2):s38-46; discussion s54-75. Epub
1998/05/02.
7. Dardeno TA, Chou SH, Moon HS, Chamberland JP, Fiorenza CG, Mantzoros CS. Leptin in human physiology and therapeutics. Frontiers in neuroendocrinology. 2010;31(3):377-93. Epub 2010/07/06.
8. Simón E DBAS. Leptina y obesidad. Anales del sistema sanitario de Navarra. 2002;25:53-64.
9. Considine RV, Sinha MK, Heiman ML, Kriauciunas A, Stephens TW, Nyce MR, et al. Serum immunoreactive-leptin concentrations in normal-weight and obese humans. The New England journal of medicine. 1996;334(5):292-5. Epub 1996/02/01.
10. Chan JL, Heist K, DePaoli AM, Veldhuis JD, Mantzoros CS. The role of falling leptin levels in the neuroendocrine and metabolic adaptation to short-term starvation in healthy men. The Journal of clinical investigation. 2003;111(9):1409-21. Epub 2003/05/03.
11. Bjorbaek C, Elmquist JK, Michl P, Ahima RS, van Bueren A, McCall AL, et al. Expression of leptin receptor isoforms in rat brain microvessels. Endocrinology. 1998;139(8):3485-91. Epub 1998/07/29.
12. Ernst MB, Wunderlich CM, Hess S, Paehler M, Mesaros A, Koralov SB, et al. Enhanced Stat3 activation in POMC neurons provokes negative feedback inhibition of leptin and insulin signaling in obesity. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2009;29(37):11582-93. Epub 2009/09/18.
13. Gong L, Yao F, Hockman K, Heng HH, Morton GJ, Takeda K, et al. Signal transducer and activator of transcription-3 is required in hypothalamic agoutirelated protein/neuropeptide Y neurons for normal energy homeostasis. Endocrinology. 2008;149(7):3346-54. Epub 2008/04/12.
14. Santillán Benítez JG, Mendieta Zerón H, Ordóñez Quiroz Á, LM. GO. La leptina en la carcinogénesis mamaria. Vías de señalización. Química Viva. 2012;11(2):91-111.
15. Morrison CD. Leptin signaling in brain: A link between nutrition and cognition? Biochimica et biophysica acta. 2009;1792(5):401-8. Epub 2009/01/10.
16. Harvey J, McKay NG, Walker KS, Van der Kaay J, Downes CP, Ashford ML. Essential role of phosphoinositide 3-kinase in leptin-induced K(ATP) channel activation in the rat CRI-G1 insulinoma cell line. The Journal of biological chemistry. 2000;275(7):4660-9. Epub 2000/02/15.
17. Plum L, Ma X, Hampel B, Balthasar N, Coppari R, Munzberg H, et al. Enhanced PIP3 signaling in POMC neurons causes KATP channel activation and leads to diet-sensitive obesity. The Journal of clinical investigation. 2006;116(7):1886-901. Epub 2006/06/24.
18. Bjorbaek C, Buchholz RM, Davis SM, Bates SH, Pierroz DD, Gu H, et al. Divergent roles of SHP-2 in ERK activation by leptin receptors. The Journal of biological chemistry. 2001;276(7):4747-55. Epub 2000/11/22.
19. Rahmouni K, Sigmund CD, Haynes WG, Mark AL. Hypothalamic ERK mediates the anorectic and thermogenic sympathetic effects of leptin. Diabetes. 2009;58(3):536-42. Epub 2008/12/11.
20. Kim GS, Hong JS, Kim SW, Koh JM, An CS, Choi JY, et al. Leptin induces apoptosis via ERK/cPLA2/cytochrome c pathway in human bone marrow stromal cells. The Journal of biological chemistry. 2003;278(24):21920-9. Epub 2003/04/01.
21. Fruhbeck G. Intracellular signalling pathways activated by leptin. The Biochemical journal. 2006;393(Pt 1):7-20. Epub 2005/12/13.
22. ME. FVV. Señalización de la leptina. Revista de Educación Bioquímica. 2006;25(2):50-4.
23. Hamrick MW. Leptin and bone: A consensus emerging? IBMS BoneKEy. BoneKEy-Osteovision. 2007;4(3):99-107.
24. Rosen CJ, Bouxsein ML. Mechanisms of disease: is osteoporosis the obesity of bone? Nature clinical practice Rheumatology. 2006;2(1):35-43. Epub 2006/08/26.
25. Wren AM, Small CJ, Abbott CR, Jethwa PH, Kennedy AR, Murphy KG, et al. Hypothalamic actions of neuromedin U. Endocrinology. 2002;143(11):4227- 34. Epub 2002/10/26.
26. Yadav VK, Oury F, Suda N, Liu ZW, Gao XB, Confavreux C, et al. A serotonin-dependent mechanism explains the leptin regulation of bone mass, appetite, and energy expenditure. Cell. 2009;138(5):976-89. Epub 2009/09/10.
27. Hamrick MW, Della-Fera MA, Choi YH, Pennington C, Hartzell D, Baile CA. Leptin treatment induces loss of bone marrow adipocytes and increases bone formation in leptin-deficient ob/ob mice. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2005;20(6):994-1001. Epub 2005/05/11.
28. Holloway WR, Collier FM, Aitken CJ, Myers DE, Hodge JM, Malakellis M, et al. Leptin inhibits osteoclast generation. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2002;17(2):200-9. Epub 2002/01/29.
29. Cirmanová V, Bayer M, Stárka L, Zajícková K. The effect of leptin on Bone: An Evolving Concept of Action. 2008; 57 (Suppl. 1): 143-51. physiological research-ISSN 0865-8408
30. Burguera B, Couce ME, Curran GL, Jensen MD, Lloyd RV, Cleary MP, et al. Obesity is associated with a decreased leptin transport across the blood- brain barrier in rats. Diabetes. 2000;49(7):1219-23. Epub 2000/07/26.
31. Oswal A, Yeo G. Leptin and the control of body weight: a review of its diverse central targets, signaling mechanisms, and role in the pathogenesis of obesity. Obesity (Silver Spring). 2010;18(2):221-9. Epub 2009/08/01.
32. Turner RT, Kalra SP, Wong CP, Philbrick KA, Lindenmaier LB, Boghossian S, et al. Peripheral leptin regulates bone formation. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2013;28(1):22-34. Epub 2012/08/14.
33. Franek E, Nowak J, Safranow K, Adler G, Binczak-Kuleta A, Ciechanowicz A, et al. G(-2548)A leptin gene polymorphism in obese subjects is associated with serum leptin concentration and bone mass. Polskie Archiwum Medy- cyny Wewnetrznej. 2010;120(5):175-80. Epub 2010/05/27.
34. OMS. Nota descriptiva N°311. Obesidad y sobrepeso. Disponible en: http:// www.who.int/mediacentre/factsheets/fs311/es/index.html
35. Ministerio de la Protección Social. Encuesta Nacional de Salud, 2007.
36. Erazo M. Visión global en relación a la obesidad. Rev. Med. Clin, Condes. 2012; 23(2) 196-200
37. Acosta, K. La obesidad y su concentración según nivel socioeconómico en Colombia. Num 170, Julio , 2012.
38. Aranceta, j. Foz, M. Gil B, Jover, E. Mantilla, T. Millán, J. Monereo, S. Moreno, B. Documento de consenso: obesidad y riesgo cardiovascular. Clin Invest Arterioscl 2003;15(5):196-233
39. Papapietro, K, Massardo, T. Riffo, A. Díaz, E. Araya V, Adjemian, D. Montesinos, G. Castro, G. Disminución de masa ósea post-cirugía bariátrica con bypass en Y de Roux. Nutr Hosp. 2013;28:631-636. DOI:10.3305/ nh.2013.28.3.6400
40. Maor, G. Rochweger, M. Sege, Y. Phillips M. Leptin Acts as a Growth Factor on the Chondrocytes of Skeletal Growth Centers, Journal of bone and mineral research, Volume 17, Number 6, 2002
41. Rao, M. Schambelan, M. Tai, V. Abrams, D. Khatami, H. Havel, P. Sakkas, G. Mulligan,K. Assessing the Association between Leptin and Bone Mineral Density in HIV-InfectedMen. Hindawi Publishing Corporation AIDS Research and Treatment Volume 2012, Article ID 103072, 5 pages doi:10.1155/2012/103072
42. Friedman, J. Halaas, J. Leptin and the regulation of body weight in mammals, NATURE | VOL 395 | 22 OCTOBER 1998 | www.nature.com
43. Legiran, S. Brandi, M. Bone mass regulation of leptin and postmenopausal osteoporosis with obesity. Clinical Cases in Mineral and Bone Metabolism 2012; 9(3): 145-149
44. Anagnostis,P. Vakalopoulou,S. Charizopoulou, M. Kazantzidou, E. Chrysopoulou, T. Moka,E. Agapidou, A. Zournatzi, V. Garipidou, V. Is there any association between leptin levels and bone mineral density in haemophiliac men? Arch Med Sci 2013; 9, 3: 459-465
45. Coelho, M. Oliveira, T. Fernandes, R. Biochemistry of adipose tissue: an endocrine organ, Arch Med Sci 2, April / 2013
46. Kwon, H. Pessin, J. Adipokines mediate inflammation and insulin resistance, Front Endocrinol (Lausanne). 2013; 4: 71.
47. Coelho, M. Oliveira, T. Fernandes, R. Biochemistry of adipose tissue: an endocrine organ. Arch Med Sci 2013; 9, 2: 191-200 DOI: 10.5114/ aoms.2013.33181
48. Lazarenko OP, Rzonca SO, Suva LJ, Lecka-Czernik B. Netoglitazone is a PPAR- gamma ligand with selective effects on bone and fat. Bone. 2006;38(1):74- 84. Epub 2005/09/03.
49. Mantzoros, C. Magkos, F. Brinkoetter, M. Sienkiewicz, E. Dardeno, T. Kim, S. Hamnvik, OP. Koniaris, A. Leptin in human physiology and pathophysiology. Am J Physiol Endocrinol Metab 301: E567–E584, 2011.
50. Motyla, K. Rosena, C. Understanding leptin-dependent regulation of skeletal homeostasis, Biochimie. 2012 October; 94(10): 2089–2096. doi:10.1016/j. biochi.2012.04.015
51. Cao JJ, Gregoire BR, Gao H. High-fat diet decreases cancellous bone mass but has no effect on cortical bone mass in the tibia in mice. Bone.
2009;44(6):1097-104. Epub 2009/03/07.
52. Scheller, E. Song, J. Dishowitz, M. Hankenson,K. Krebsbac, K. A potential role for the myeloid lineage in leptin-regulated bone Metabolism. Horm Metab Res. 2012 January ; 44(1): 1–5. doi:10.1055/s-0031-1297971
53. Zhao, L. Jiang, H. Papasian, C. Maulik, D. Drees, B. Hamilton, J. Deng, H. Corre- lation of Obesity and Osteoporosis: Effect of Fat Mass on the Determination of Osteoporosis. Journal of bone and mineral research. Volume 23, Number 1, 2008
54. Batsis, J. Sahakyan, K. Singh, P. Bartels, S. Somer, V. Lopez-Jimenez, F. Leptin, Adiposity, and Mortality: Results from the National Health and Nutrition Examination Survey III, 1988 to 1994. Mayo Clinic Proceeding. 2015:90(4):481-491.
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