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Leptin and Obesity

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Leptin

Part of the book series: Endocrine Updates ((ENDO,volume 25))

Abstract

Serum leptin levels are increased in obesity in proportion to the amount of body fat. Gender and fat distribution into subcutanous or visceral adipose tissue depots contribute to greater serum leptin in women than men of equivalent fat mass. Serum leptin circulates in the plasma in association with a binding protein comprised of the extracellular domain of the leptin receptor. The postprandial surge in insulin and glucose stimulate leptin synthesis and a diurnal pattern in serum leptin. Hexosamine biosynthesis and adipocyte size contribute to greater leptin synthesis in adipocytes of obese subjects. Leptin resistance describes the inability of leptin to reduce food intake and decrease body weight in obese subjects with elevated leptin levels. Selective leptin resistance results in some systems remaining responsive to the elevated leptin in obesity. Selective leptin resistance contributes to obesity related hypertension and may contribute to other metabolic complications in obesity.

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References

  1. G. C. Kennedy, The role of depot fat in the hypothalamic control of food intake in the rat. Proc R Soc B, 140:578–592 (1953).

    Article  CAS  Google Scholar 

  2. G. R. Hervey, The effects of lesions in the hypothalamus in parabiotic rats. J Physiol, 145:336–352 (1959).

    PubMed  CAS  Google Scholar 

  3. D. L. Coleman, Obese and diabetes: two mutant genes causing diabetes-obesity syndromes in mice. Diabetologia, 14:141–148 (1978).

    Article  PubMed  CAS  Google Scholar 

  4. Y. Zhang, R. Proenca, M. Maffei, M. Barone, L. Leopold and J. M. Friedman, Positional cloning of the mouse obese gene and its human homologue. Nature, 372:425–432 (1994).

    Article  PubMed  CAS  Google Scholar 

  5. R. V. Considine and J. F. Caro, Leptin and the regulation of body weight. Int J Biochem Cell Biol, 29:1255–1272 (1997).

    Article  PubMed  CAS  Google Scholar 

  6. W. F. Blum, P. Englaro, A. M. Attanasio, W. Kiess and W. Rascher, Human and clinical perspectives on leptin. Proc Nutr Soc, 57:477–485 (1998).

    Article  PubMed  CAS  Google Scholar 

  7. M. Maffei, J. Halaas, E. Ravussin, R. E. Pratley, G. H. Lee, Y. Zhang, H. Fei, S. Kim, R. Lallone, S. Ranganathan, P. A. Kern and J. M. Friedman, Leptin levels in human and rodent: measurement of plasma leptin and ob RNA in obese and weight-reduced subjects. Nat Med, 1:1155–1161 (1995).

    Article  PubMed  CAS  Google Scholar 

  8. R. V. Considine, M. K. Sinha, M. L. Heiman, A. Kriauciunas, T. W. Stephens, M. R. Nyce, J. P. Ohannesian, C. C. Marco, L. J. McKee, T. L. Bauer and J. F. Caro, Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med, 334:292–295 (1996).

    Article  PubMed  CAS  Google Scholar 

  9. M. Rosenbaum and R. L. Leibel, Clinical Review 107. Role of gonadal steroids in the sexual dimorphisms in body composition and circulating concentrations of leptin. J Clin Endocrinol Metab, 84:1784–1789 (1999).

    Article  PubMed  CAS  Google Scholar 

  10. C. T. Montague, J. B. Prins, L. Sanders, J. E. Digby and S. O’Rahilly, Depot and sex-specific differences in human leptin mRNA expression. Diabetes, 46:342–347 (1997).

    PubMed  CAS  Google Scholar 

  11. A. M. Lefebvre, M. Laville, N. Veg, J. P. Riou, L. van Gaal, J. Auwerx and H. Vidal, Depot-specific differences in adipose tissue gene expression in lean and obese subjects. Diabetes, 47:98–103 (1998).

    PubMed  CAS  Google Scholar 

  12. V. Van Harmelen, S. Reynisdotir, P. Eriksson, A. Thome, J. Hoffstedt, F. Lonnqvist and P. Arner, Leptin secretion from subcutaneous and visceral adipose tissue of women. Diabetes, 47:913–917 (1998).

    PubMed  Google Scholar 

  13. L. B. Williams, R. L. Fawcett, A. S. Waechter, P. Zhang, B. E. Kogon, R. M. Jones, M. Inman, J. Huse and R. V. Considine, Leptin production in adipocytes from morbidly obese subjects: stimulation by dexamethasone, inhibition with troglitazone and influence of gender. J Clin Endocrinol Metab, 85:2678–2684 (2000).

    Article  PubMed  CAS  Google Scholar 

  14. C. S. Mantzoros, J. S. Flier and A. D. Rogol, A longitudinal assessment of hormonal and physical alterations during normal puberty in boys. V. Rising leptin levels may signal the onset of puberty. J Clin Endocrinol Metab, 82:1066–1070 (1997).

    Article  PubMed  CAS  Google Scholar 

  15. R. Sih, J. E. Morley, F. E. Kaiser, H. M. Perry III, P. Patrick and C. Ross, Testosterone replacement in older hypogonadal men: a 12-month randomized controlled trial. J Clin Endocrinol Metab, 82:1661–1667 (1997).

    Article  PubMed  CAS  Google Scholar 

  16. F. Jockenhovel, W. F. Blum, E. Vogel, P. Englaro, D. Muller-Wieland, D. Reinwein, W. Rascher and W Krone, Testosterone substitution normalizes elevated serum leptin levels in hypogonadal men. J Clin Endocrinol Metab, 82:2510–2513 (1997).

    Article  PubMed  CAS  Google Scholar 

  17. J. M. Fibers, H. Asscheman, J. C. Seidell, M. Frolich, A. E. Meinders and L. J. Gooren, Reversal of the sex difference in serum leptin levels upon cross-sex hormone administration in transsexuals. J Clin Endocrinol Metab, 82:3267–3270 (1997).

    Article  Google Scholar 

  18. X. Casabiell, V. Pineiro, R. Peino, M. Lage, J. P. Camina, R. Gallego, L. G. Vallejo, C. Dieguez and F. F. Casanueva, Gender differences in both spontaneous and stimulated leptin secretion by human omental adipose tissue in vitro: dexamethasone and estradiol stimulate leptin release in women, but not in men. J Clin Endocrinol Metab, 83:2149–2155 (1998).

    Article  PubMed  CAS  Google Scholar 

  19. V. Pineiro, X. Casabiell, R. Peino, M. Lage, J. P. Camina, C. Menendez, J. Baltar, C. Dieguez and F. F. Casanueva, Dihydrotestosterone, stanozol, androstenedione and dehydroepiandrosterone sulphate inhibit leptin secretion in female but not male samples of omental adipose tissue in vitro: lack of effect of testosterone. J Endocrinol, 160:425–432 (1999).

    Article  PubMed  CAS  Google Scholar 

  20. M. Sinha, J. P. Ohannesian, M. L. Heiman, A. Kriauciunas, T. W. Stephens, S. Magosin, C. Marco and J. F. Caro, Nocturnal rise of leptin in lean, obese, and non-insulin-dependent diabetes mellitus subjects. J Clin Invest, 97:1344–1347 (1996).

    PubMed  CAS  Google Scholar 

  21. D. A. Schoeller, L. K. Cella, M. K. Sinha and J. F. Caro, Entrainment of the diurnal rhythm of plasma leptin to meal timing. J Clin Invest, 100:1882–1887 (1997).

    PubMed  CAS  Google Scholar 

  22. J. Licinio, C. Mantzoros, A. B. Negrao, G. Cizza, M. L. Wong, P. B. Bongiomo, G. P. Chrousos, B. Karp, C. Allen, J. S. Flier and P. W. Gold, Human leptin levels are pulsatile and inversely related to pituitary-adrenal function. Nature Med, 3:575–579 (1997).

    Article  PubMed  CAS  Google Scholar 

  23. T. Utriainen, R. Malmstrom, S. Makimattila and H. Yki-Jarvinen, Supraphysiological hyperinsulinemia increases plasma leptin concentrations after 4 h in normal subjects. Diabetes, 45:1364–1366 (1996).

    PubMed  CAS  Google Scholar 

  24. M. F. Saad, A. Khan, A. Sharma, R. Michael, M. G. Road-Gabriel, R. Boyadjian, S. D. Jinagouda, G. M. Steil and V. Kamdar, Physiological insulinemia acutely modulates plasma leptin. Diabetes, 47:544–549 (1998).

    PubMed  CAS  Google Scholar 

  25. P. J. Havel, R. Townsend, L. Chaump and K. Teff, High fat meals reduce 24 h circulating leptin concentration in women. Diabetes, 48:334–341 (1999).

    PubMed  CAS  Google Scholar 

  26. L. Rossetti, Perspective: hexosamines and nutrient sensing. Endocrinol, 141:1922–1925 (2000).

    Article  CAS  Google Scholar 

  27. J. Wang, R. Liu, M. Hawkins, N. Barzilai and L. Rossetti, A nutrient-sensing pathway regulates leptin gene expression in muscle and fat. Nature, 393:684–688 (1998).

    Article  PubMed  CAS  Google Scholar 

  28. D. A. McClain, T. Alexander, R. C. Cooksey and R. V. Considine, Hexosamines stimulate leptin production in transgenic mice. Endocrinol, 141:1999–2002 (2000).

    Article  CAS  Google Scholar 

  29. R. V. Considine, R. C. Cooksey, L. B. Williams, R. L. Fawcett, P. Zhang, W. T. Ambrosius, R. M. Whitfield, R. M. Jones, M. Inman, J. Huse and D. A. McClain, Hexosamines regulate leptin production in human subcutaneous adipocytes. J Clin Endo Metab, 85:3551–3556 (2000).

    Article  CAS  Google Scholar 

  30. M. K. Sinha, I. Opentanova, J. P. Ohannesian, J. W. Kolaczynski, M. L. Heiman, J. Hale, G. W. Becker, R. R. Bowsher, T. W. Stephens and J. F. Caro, Evidence of free and bound leptin in human circulation. Studies in lean and obese subjects and during short-term fasting. J Clin Invest, 98:1277–1282 (1996).

    PubMed  CAS  Google Scholar 

  31. K. L. Houseknecht, C. S. Mantzoros, R. Kuliawat, E. Hadro, J. S. Flier and B. B. Kahn, Evidence for leptin binding to proteins in serum of rodents and humans: modulation with obesity. Diabetes, 45:1638–1643 (1996).

    PubMed  CAS  Google Scholar 

  32. N. Lahlou, K. Clement, J. C. Carel, C. Vaisse, C. Lotton, Y. Le Bihan, A. Basdevant, Y. Lebouc, P. Froguel, M. Roger and B. Guy-Grand, Soluble leptin receptor in serum of subjects with complete resistance to leptin: relation to fat mass. Diabetes, 49:1347–1352 (2000).

    PubMed  CAS  Google Scholar 

  33. G. H. Lee, R. Proenca, J. M. Montez, K. M. Carroll, J. G. Darvishzadeh, J, I. Lee and J. M. Friedman, Abnormal splicing of the leptin receptor in diabetic mice. Nature, 379:632–635 (1996).

    Article  PubMed  CAS  Google Scholar 

  34. M. Maamra, M. Bidlingmaier, M. C. Postel-Vinay, Z. Wu, C. J. Strasburger and R. J. Ross, Generation of human soluble leptin receptor by proteolytic cleavage of membrane-anchored receptors. Endocrinol, 142:4389–4393 (2001).

    Article  CAS  Google Scholar 

  35. G. Brabant, H. Nave, B. Mayr, M. Behrend, V. van Harmelen and P. Arner, Secretion of free and protein-bound leptin from subcutaneous adipose tissue of lean and obese women. J Clin Endocrinol Metab, 87:3966–3970 (2002).

    Article  PubMed  CAS  Google Scholar 

  36. J. L. Chan, S. Bluher, N. Yiannakouris, M. A. Suchard, J. Kratzsch and C. S. Mantzoros, Regulation of circulating soluble leptin receptor levels by gender, adiposity, sex steroids, and leptin: observational and interventional studies in humans. Diabetes, 51:2105–2112 (2002).

    PubMed  CAS  Google Scholar 

  37. L. Huang, Z. Wang and C. Li, Modulation of circulating leptin levels by its soluble receptor. J Biol Chem, 276:6343–6349 (2001).

    Article  PubMed  CAS  Google Scholar 

  38. O. Zastrow, B, Seidel, W. Kiess, J. Thiery, E. Keller, A. Bottner and J. Kratzsch, The soluble leptin receptor is crucial for leptin action: evidence from clinical and experimental data. Int J Obes Relat Metab Disord, 27:1472–1478 (2003).

    Article  PubMed  CAS  Google Scholar 

  39. G. Yang, H. Ge, A. Boucher, X. Yu and C. Li, Modulation of direct leptin signaling by soluble leptin receptor. Mol Endocrinol, 18:1354–1362 (2004).

    Article  PubMed  CAS  Google Scholar 

  40. J. M, Friedman, Leptin, Leptin receptors, and the control of body weight. Nutr Rev, 56:S38–S48 (1998).

    Article  PubMed  CAS  Google Scholar 

  41. J. F. Caro, M. K. Sinha, J. W. Kolaczynski, P. L. Zhang and R. V. Considine, Leptin: the tale of an obesity gene. Diabetes, 45:1455–1462 (1996).

    PubMed  CAS  Google Scholar 

  42. J. S. Flier, What’s in a name?In search of leptin’s physiologic role. J Clin Endocrinol Metab, 83:1407–1413 (1998).

    Article  PubMed  CAS  Google Scholar 

  43. R. S. Ahima, D. Prabakaran, C. Mantzoros, D. Qu, B. Lowell, E. Maratos-Flier and J. S. Flier, Role of leptin in the neuroendocrine response to fasting. Nature, 382:250–252 (1996).

    Article  PubMed  CAS  Google Scholar 

  44. J. W. Kolaczynski, R. V. Considine, J. Ohannesian, C. Marco, I. Opentanova, M. R. Nyce, M. Myint and J. F. Caro, Responses of leptin to short-term fasting and refeeding in humans:a link with ketogenesis but not ketones themselves. Diabetes, 45:1511–1515 (1996).

    PubMed  CAS  Google Scholar 

  45. G. Boden, X. Chen, M. Mozzoli and I. Ryan, Effect of fasting on serum leptin in normal human subjects. J Clin Endocrinol Metab, 81:3419–3423 (1996).

    Article  PubMed  CAS  Google Scholar 

  46. J. L. Chan, K. Heist, A. M. DePaoli, J. D. Veldhuis and C. S. Mantzoros, The role of falling leptin levels in the neuroendocrine and metabolic adaptation to short-term starvation in healthy men. J Clin Invest, 111:1409–1421 (2003).

    Article  PubMed  CAS  Google Scholar 

  47. V. A. Barr, D. Malide, M. J. Zamowski, S. I. Taylor and S. W. Cushman, Insulin stimulates both leptin secretion and production by white adipose tissue. Endocrinol, 138:4463–4472 (1997).

    Article  CAS  Google Scholar 

  48. R. L. Bradley and B. Cheatham, Regulation of ob gene expression and leptin secretion by insulin and dexamethasone in rat adipocytes. Diabetes, 48:272–278 (1999).

    PubMed  CAS  Google Scholar 

  49. B. S. Hamilton, D. Paglia, A. Y. M. Kwan and M. Deitel, Increased obese mRNA expression in omental fat cells from massively obese humans. Nat Med, 1:953–956 (1995).

    Article  PubMed  CAS  Google Scholar 

  50. K. Y. Guo, P. Halo, R. L. Leibel and Y. Zhang, Effects of obesity on the relationship of leptin mRNA expression and adipocyte size in anatomically distinct fat depots in mice. Am J Physiol Regul Integr Comp Physiol, 287:R112–Rl 19 (2004).

    PubMed  CAS  Google Scholar 

  51. F. Lonnqvist, L. Nordfors, M. Jansson, A. Thome, M. Schalling and P. Amer, Leptin secretion from adipose tissue of women. Relationship to plasma levels and gene expression. J Clin Invest, 99:2398–2404 (1997).

    PubMed  CAS  Google Scholar 

  52. P. Zhang, E. S. Klenk, M. A. Lazzaro, L. B. Williams and R. V. Considine, Hexosamines regulate leptin production in 3T3-L1 adipocytes through transcriptional mechanisms. Endocrinol, 143:99–106 (2002).

    Article  CAS  Google Scholar 

  53. G. S. Hotamisligil, P. Arner, J. F. Caro, R. L. Atkinson and B. M. Spiegelman, Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance. J Clin Invest, 95:2409–2415 (1995).

    PubMed  CAS  Google Scholar 

  54. E. A. Medina, K. L. Stanhope, T. M. Mizuno, C. V. Mobbs, F. Gregoire, N. E. Hubbard, K. L. Erickson and P. J. Havel, Effects of tumor necrosis factor alpha on leptin secretion and gene expression: relationship to changes of glucose metabolism in isolated rat adipocytes. Int J Obes Relat Metab Disord, 23:896–903 (1999).

    Article  PubMed  CAS  Google Scholar 

  55. R. L. Fawcett, A. S. Waechter, L. B. Williams, P. Zhang, R. Louie, R. M. Jones, M. Inman, J. Huse and R. V. Considine, TNFa inhibits leptin production in subcutaneous and omental adipocytes from morbidly obese humans. J Clin Endocrinol Metab, 85:530–535 (2000).

    Article  PubMed  CAS  Google Scholar 

  56. M. S. Zumbach, M. W. Boehme, P. Wahl, W. Stremmel, R. Ziegler and P. P. Nawroth, Tumor necrosis factor increases serum leptin levels in humans. J Clin Endocrinol Metab, 82:4080–4082 (1997).

    Article  PubMed  CAS  Google Scholar 

  57. S. R. Bornstein, J. Licinio, R. Tauchnitz, L. Engelmann, A. B. Negrao, P. Gold and G. P. Chrousos, Plasma leptin levels are increased in survivors of acute sepsis: associated loss of diurnal rhythm, in Cortisol and leptin secretion. J Clin Endocrinol Metab, 83:280–283 (1998).

    Article  PubMed  CAS  Google Scholar 

  58. H. Larsson and B, Ahren, Short-term dexamethasone treatment increases plasma leptin independently of changes in insulin sensitivity in healthy women. J Clin Endocrinol Metab, 81:4428–4432 (1996).

    Article  PubMed  CAS  Google Scholar 

  59. D. J. Wake and B. R. Walker, 11 beta-hydroxysteroid dehydrogenase type 1 in obesity and the metabolic syndrome. Mol Cell Endocrinol, 215:45–54 (2004).

    Article  PubMed  CAS  Google Scholar 

  60. P. De Vos, A. M. Lefebvre, I. Shrivo, J. C. Fruchart and J. Auwerx, Glucocorticoids induce the expression of the leptin gene through a non-classical mechanism of transcriptional activation. Eur J Biochem, 253:619–626 (1998).

    Article  PubMed  Google Scholar 

  61. C. T. Montague, I. S. Farooqi, J. P. Whitehead, M. A. Soos, H. Rau, N. J. Wareham, C. P. Sewter, J. E. Digby, S. N. Mohammed, J. A. Hurst, C. H. Cheetham, A. R. Early, A. H. Bamett, J. B. Prins and S. O’Rahilly, Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature, 387:903–908 (1997).

    Article  PubMed  CAS  Google Scholar 

  62. A. Strobel, T. Issad, L. Camoin, M. Ozata and A. D. Strosberg, A leptin missense mutation associated with hypogonadism and morbid obesity. Nat Genet, 18:213–215 (1998).

    Article  PubMed  CAS  Google Scholar 

  63. K. Clement, C. Vaisse, N. Lahlou, S. Cabrol, V. Pelloux, D. Cassuto, M. Gourmelen, C. Dina, J. Chambaz, J. M. Lacorte, A. Basdevant, P. Bougneres, Y. Lebouc, P. Froguel and B. Guy-Grand, A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction. Nature, 392:398–401 (1998).

    Article  PubMed  CAS  Google Scholar 

  64. R. C. Frederich, A. Hamann, S. Anderson, B. Lollmann, B. B. Lowell and J. S. Flier, Leptin levels reflect body lipid content in mice: evidence for diet-induced resistance to leptin action. Nat Med, 1:1311–1314 (1995).

    Article  PubMed  CAS  Google Scholar 

  65. M. A. Pelleymounter, M. J. Kullen, M. B. Baker, R. Hecht, D. Winters, T. Boone and F. Collins, Effects of the obese gene product on body weight regulation in ob/ob mice. Science, 269:540–543 (1995).

    Article  PubMed  CAS  Google Scholar 

  66. J. L. Halaas, K. S. Gajiwala, M. Maffei, S. L. Cohen, B. T. Chait, D. Rabinowitz, R. L. Lallone, S. K. Burley and J. M. Friedman, Weight-reducing effects of the plasma protein encoded by the obese gene. Science, 269:543–546 (1995).

    Article  PubMed  CAS  Google Scholar 

  67. L. A. Campfield, F. J. Smith, Y. Guisez, R. Devos and P. Burn, Recombinant mouse OB protein: evidence for a peripheral signal linking adiposity and central neural networks. Science, 269:546–549 (1995).

    Article  PubMed  CAS  Google Scholar 

  68. T. W. Stephens, M. Basinski, P. K. Bristow, J. M. Bue-Valleskey, S. G. Burgett, L. Craft, J. Hale, J. Hoffman, H. M. Hsiung, A. Kriauciunas, W. MacKellar, P. R. Rosteck Jr., B. Schoner, D. Smith, F. C. Tinsley, X. Y. Zhang and M. Heiman, The role of neuropeptide Y in the antiobesity action of the obese gene product. Nature, 377:530–532 (1995).

    Article  PubMed  CAS  Google Scholar 

  69. D. S. Weigle, T. R. Bukowski, D. C. Foster, S. Holderman, J. M. Kramer, G. Lasser, C. E. Lofton-Day, D. E. Prunkard, C. Raymond and J. L. Kuijper, Recombinant ob protein reduces feeding and body weight in the ob/ob mouse. J Clin Invest, 96:2065–2070 (1995).

    PubMed  CAS  Google Scholar 

  70. M. W. Schwartz, D. G. Baskin, T. R. Bukowski, J. L. Kuijper, D. Foster, G. Lasser, D. E. Prunkard, D. Porte Jr., S. C. Woods, R. J. Seeley and D. S. Weigle, Specificity of leptin action on elevated blood glucose levels and hypothalamic neuropeptide Y gene expression in ob/ob mice. Diabetes, 45:531–535 (1996).

    PubMed  CAS  Google Scholar 

  71. J. F. Caro, J. W. Kolaczynski, M. R. Nyce, J. P. Ohannesian, I. Opentanova, W. H. Goldman, R. B. Lynn, P. L. Zhang, M. K. Sinha and R. V. Considine, Decreased cerebrospinal fluid serum leptin ratio in obesity: a possible mechanism for leptin resistance. Lance, 348:159–161 (1996).

    Article  CAS  Google Scholar 

  72. M. W. Schwartz, E. Peskind, M. Raskind, E. J, Boyko and D. Porte Jr., Cerebrospinal fluid leptin levels;relationship to plasma levels and to adiposity in humans. Nat Med, 2:589–593 (1996).

    Article  PubMed  CAS  Google Scholar 

  73. W. A. Banks, A. J. Kastin, W. Huang, J. B. Jaspan and L. M. Maness, Leptin enters the brain by a saturable system independent of insulin. Peptides, 17:305–311 (1996).

    Article  PubMed  CAS  Google Scholar 

  74. M. Van Heek, D. S. Compton, C. F. France, R. P. Tedesco, A. B. Fawzi, M. P. Graziano, E. J. Sybertz, CD. Strader and H. R. Davis Jr., Diet-induced obese mice develop peripheral, but not central, resistance to leptin. J Clin Invest, 99:385–390 (1997).

    PubMed  Google Scholar 

  75. K. El-Haschimi, D. D. Pierroz, S. M. Hileman, C. Bjorbaek and J. S. Flier, Two defects contribute to hypothalamic leptin resistance in mice with diet-induced obesity. J Clin Invest, 105:1827–1832 (2000).

    PubMed  CAS  Google Scholar 

  76. W. A. Banks, A. B. Coon, S. M. Robinson, A. Moinuddin, J. M. Schultz, R. Nakaoke and J. E. Morley, Triglycerides induce leptin resistance at the blood-brain barrier. Diabetes, 53:1253–1260 (2004).

    PubMed  CAS  Google Scholar 

  77. H. Munzberg, J. S. Flier and C. Bjorbaek, Region-specific leptin resistance within the hypothalamus of diet-induced-obese mice. Endocrinol, 145:4880–4889 (2004).

    Article  CAS  Google Scholar 

  78. X. P. Chen, J. A. Losman and P. Rothman, SOCS proteins, regulators of intracellular signaling. Immunity, 13:287–290 (2000).

    Article  PubMed  CAS  Google Scholar 

  79. C. Bjorbaek, J. K. Elmquist, J. D. Frantz, S. E. Shoelson and J. S. Flier, Identification of SOCS-3 as a potential mediator of central leptin resistance. Mol Cell, 191:619–625 (1998).

    Article  Google Scholar 

  80. J. M. Zabolotny, K. K. Bence-Hanulec, A. Stricker-Krongrad, F. Haj, Y. Wang, Y. Minokoshi, Y. Kim, J. K. Elmquist, L. A. Tartaglia, B. B. Kahn and B. C. Neel, PTPIB regulates leptin signal transduction in vivo. Dev Cell, 2:489–495 (2002).

    Article  PubMed  CAS  Google Scholar 

  81. A. Cheng, N. Uetani, P. D. Simoncic, V. P. Chaubey, A. Lee-Loy, C. J. McGlade, B. P. Kennedy and M. L. Tremblay, Attenuation of leptin action and regulation of obesity by protein tyrosine phosphatase IB. Dev Cell, 2:497–503 (2002).

    Article  PubMed  CAS  Google Scholar 

  82. S. B. Heymsfield, A. S. Greenberg, K. Fujioka, R. M. Dixon, R Kusher, T. Hunt, J. A. Lubina, J. Patane, B. Self, P. Hunt and M. McCamish, Recombinant leptin for weight loss in obese and lean adults. JAMA, 282:1568–1575 (1999).

    Article  PubMed  CAS  Google Scholar 

  83. C. J. Hukshorn, W. H. M. Saris, S. Westerterp-Plantenga, A. R. Farid, F. J. Smith, L. A. Campfield, Weekly subcutaneous pegylated recombinant native human leptin (PEG-OB)administration in obese men. J Clin Endocrinol Metab, 85:4003–4009 (2000).

    Article  PubMed  CAS  Google Scholar 

  84. W. G. Haynes, D. A. Morgan, S. A. Walsh, A. L. Mark and W. I. Sivitz, Receptor-mediated regional sympathetic nerve activation by leptin. J Clin Invest, 100:270–278 (1997).

    PubMed  CAS  Google Scholar 

  85. J. C. Dunbar, Y. Hu and H. Lu, Intracerebroventricular leptin increases lumbar and renal sympathetic nerve activity and blood pressure in normal rats. Diabetes, 46:2040–2043 (1997).

    PubMed  CAS  Google Scholar 

  86. G. F. DiBona, The sympathetic nervous system and hypertension:recent developments. Hypertension, 43:147–150 (2004).

    Article  PubMed  CAS  Google Scholar 

  87. A. L. Mark, R. A. Shaffer, M. L. Correia, D. A. Morgan, CD. Sigmund and W. G. Haynes, Contrasting blood pressure effects of obesity in leptin-deficient ob/ob mice and agouti yellow obese mice. J Hypertens, 17:1949–1953 (1999).

    Article  PubMed  CAS  Google Scholar 

  88. M. Aizawa-Abe, Y. Ogawa, H. Masuzaki, K. Ebihara, N. Satoh, H, Iwai, N. Matsuoka, T. Hayashi, K. Hosoda, G. Inoue, Y. Yoshimasa and K. Nakao, Pathophysiological role of leptin in obesity-related hypertension. J Clin Invest, 105:1243–1252 (2000).

    PubMed  CAS  Google Scholar 

  89. K. Rahnnouni, D. A. Morgan, G. M. Morgan, A. L. Mark and W. G. Haynes, Role of selective leptin resistance in diet-induced obesity hypertension. Diabetes, 54:2012–2018 (2005).

    Google Scholar 

  90. C. Bjorbaek and B. B. Kahn, Leptin signaling in the central nervous system and the periphery. Recent Prog Horn Res, 59:305–331 (2004).

    Article  CAS  Google Scholar 

  91. M. Nakata, T. Yada, N. Soejima and I. Maruyama, Leptin promotes aggregation of human platelets via the long form of its receptor. Diabetes, 48:426–429 (1999).

    PubMed  CAS  Google Scholar 

  92. S. Konstantinides, K. Shafer, S. Koschnick and D. J. Loskutoff, Leptin-dependent platelet aggregation and arterial thrombosis suggests a mechanism for atherothrombotic disease in obesity. J Clin Invest, 108:1533–1540 (2001).

    Article  PubMed  CAS  Google Scholar 

  93. A. Bouloumie, T. Marumo, M. Lafontan and R. Busse, Leptin induces oxidative stress in human endothelial cells. FASEB J, 13:1231–1238 (1999).

    PubMed  CAS  Google Scholar 

  94. S. L Yamagishi, D. Edelstein, X. L. Du, Y. Kaneda, M. Guzman and M. Brownlee, Leptin induces mitochondrial superoxide production and monocyte chemoattractant protein-1 expression in aortic endothelial cells by increasing fatty acid oxidation via protein kinase A. J Biol Chem, 276:25096–25100 (2001).

    Article  PubMed  CAS  Google Scholar 

  95. R. H. Unger, Longevity, lipotoxicity and leptin: the adipocyte defense against feasting and famine. Biochimie, 87:57–64 (2005).

    Article  PubMed  CAS  Google Scholar 

  96. Y. Lee, M. Y. Wang, T. Kakuma, Z. W. Wang, E. Babcock, K. McCorkle, M. Higa, Y. T. Zhou and R. H. Unger, Liporegulation in diet-induced obesity. The antisteatotic role of hyperleptinemia. J Biol Chem, 276:5629–5635 (2001).

    Article  PubMed  CAS  Google Scholar 

  97. R. B. Ceddia, Direct metabolic regulation in skeletal muscle and fat tissue by leptin: implications for glucose and fatty acids homeostasis. Int J Obes Relat Metab Disord, Epub ahead of print (2005).

    Google Scholar 

  98. G. Brabant, G. Muller, R. Horn, C. Anderwald, M. Roden and H. Nave, Hepatic leptin signaling in obesity. FASEB J, 19:1048–1050 (2005).

    PubMed  CAS  Google Scholar 

  99. Z. Wang, Y. T. Zhou, T. Kakuma, Y. Lee, S. P. Kalra, P. S. Kalra, W. Pan and R. H, Unger, Leptin resistance of adipocytes in obesity: role of suppressors of cytokine signaling. Biochem Biophys Res Commun, 277:20–26 (2000).

    Article  PubMed  CAS  Google Scholar 

  100. J. Rieusset, K. Bouzakri, E. Chevillotte, N. Ricard, D, Jacquet, J. P. Bastard, M. Laville and H. Vidal, Suppressor of cytokine signaling 3 expression and insulin resistance in skeletal muscle of obese and type 2 diabetic patients. Diabetes, 53:2232–2241 (2004).

    PubMed  CAS  Google Scholar 

  101. H. Shi, I. Tzameli, C. Bjorbaek and J. S. Flier, Suppressor of cytokine signaling 3 is a physiological regulator of adipocyte insulin signaling. J Biol Chem, 279:34744–34740 (2004).

    Google Scholar 

  102. D. L. Krebs and D. J. Hilton, SOCS proteins: negative regulators of cytokine signaling. Stem Cells, 19:378–387 (2001).

    Article  PubMed  CAS  Google Scholar 

  103. B. Emanuelli, P. Peraldi, C. Filloux, D. Sawka-Verhelle, D. Hilton and E. Van Obberghen, SOCS-3 is an insulin-induced negative regulator of insulin signaling. J Biol Chem, 275:15985–15991 (2000).

    Article  PubMed  CAS  Google Scholar 

  104. G. Fruhbeck, M. Aguado and J. A. Martinez, In vitro lipolytic effect of leptin on mouse adipocytes:evidence for a possible autocrine/paracrine role of leptin. Biochem Biophys Res Commun, 240:590–594 (1997).

    Article  PubMed  CAS  Google Scholar 

  105. C. A. Siegrist-Kaiser, V. Pauli, C. E. Juge-Aubry, O. Boss, A. Pernin, W. W. Chin, I. Cusin, F. Rohner-Jeanrenaud, A. G. Burger, J. Zapf and C. A. Meier, Direct effects of leptin on brown and white adipose tissue. J Clin Invest, 100:2858–2864 (1997).

    Article  PubMed  CAS  Google Scholar 

  106. M. Y. Wang, Y. Lee and R. H, Unger, Novel form of lipolysis induced by leptin, J Biol Chem, 274:17541–17544 (1999).

    Article  PubMed  CAS  Google Scholar 

  107. Y. B. Kim, S. Uotani, D. D. Pierroz, J. S, Flier and B. B. Kahn, In vivo administration of leptin activates signal transduction directly in insulin-sensitive tissue: overlapping but distinct pathways from insulin. Endocrinol, 141:2328–2339 (2000).

    Article  CAS  Google Scholar 

  108. C. Perez, C. Fernandez-Galaz, T. Fernandez-Agullo, C. Arribas, A. Andres, M. Ros and J. M. Carrascosa, Leptin impairs insulin signaling in rat adipocytes. Diabetes, 53:347–353 (2004).

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Cellular and Integrative Physiology, Indianapolis, IN

    Lauren N. Bell & Robert V. Considine

  2. Department of Medicine, Indiana Univerisity, Indianapolis, IN

    Lauren N. Bell & Robert V. Considine

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  1. Lauren N. Bell
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Editors and Affiliations

  1. Texas Tech University School of Medicine, Lubbock, Texas, USA

    V. Daniel Castracane PhD (Professor Emeritus and Director of Laboratory Operations) (Professor Emeritus and Director of Laboratory Operations)

  2. Foundation for Blood Research, P. O. Box 190, Scarborough, ME, USA

    V. Daniel Castracane PhD (Professor Emeritus and Director of Laboratory Operations) (Professor Emeritus and Director of Laboratory Operations)

  3. Department of Biological Sciences, Purdue University Calumet, Hammond, Indiana, USA

    Michael C. Henson PhD (Professor and Head) (Professor and Head)

  4. Dept. of Obstetrics and Gynecology, School of Medicine, Tulane University Health Sciences, New Orleans, LA, USA

    Michael C. Henson PhD (Professor and Head) (Professor and Head)

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Bell, L.N., Considine, R.V. (2006). Leptin and Obesity. In: Castracane, V.D., Henson, M.C. (eds) Leptin. Endocrine Updates, vol 25. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-31416-7_3

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  • DOI: https://doi.org/10.1007/978-0-387-31416-7_3

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