More from my original research notes:
Leptin’s story isn’t a long one, but it’s extremely important. The first thing you need to know is that its importance is typically ignored in most diet books—which is a completely wrongheaded omission, because Leptin is an extremely critical hormone in terms of obesity, the complications of obesity, and weight loss. This is a topic that deserves to be discussed in far more detail than it typically is.
In 1994, a mutation in a specific mouse gene led to massive obesity and type II diabetes. This mutated gene was appropriately called the Ob gene (Ob being short for obese), and the mice were designated ob/ob—although there are other mutations involved that we’re not concerned with.
Normal mice without the defective gene produce a hormone that, when administered to ob/ob mice, causes them to lose weight, decrease body fat percentage, and reduce food intake (it suppresses appetite). The administration of this hormone even reverses the symptoms of type II diabetes[2-4]. It was called leptin after the Greek leptós, which, quite appropriately in this case, means “thin.”
This excited researchers a great deal, because it seemed as though a potential treatment for obesity in humans had been discovered.
As it turns out, humans also produce leptin, and those with the defective Ob gene are massively obese[5-6]. Before you start assuming obesity is genetic, however, be advised that this mutation is extremely rare in humans. In fact, it’s nearly non-existent. Even though you’re probably not carrying around this defective gene, however, you should know that leptin is still an important weight control hormone for “normal” people.
Leptin is produced mainly in the white fat cells of the body. The more fat cells you have, and the larger they get, the more leptin is produced[8-24]. As a result, leptin levels correlate with the amount of fat stored—although some researchers differ on this[25-26]. Even in extremely skinny people, leptin levels are associated with the amount of body fat present.
There’s also evidence of subcutaneous fat as the major leptin producer[13, 16-18, 22, 27-30]. A higher-than-normal amount of fat gives you an incredible advantage when you start your weight loss program because of the high levels of leptin produced. This is explained below, along with some other interesting properties of leptin.
– Increases metabolism[2-4, 31-34].
– Specifically increases fat burning[35-44].
– Prevents the formation and storage of fat[35, 40, 45-49].
– Women possess higher levels[12, 17, 23, 50-54], although there is some discrepancy.
– Regulates several hormones in the brain to decrease appetite and food intake[34, 56-79], and may independently cause decreased food intake[62, 80-82, 115].
– Reproductive effects: Improves fertility[83-89, 116], causes puberty to occur at a younger age in females with elevated levels[89-101, 117-119], and low levels inhibit the onset of puberty[94, 97, 101, 102].
– Appears to decrease desire for sweets[103-106].
– Increases the activity and production of immune system cells[107-108].
– Production decreases with age regardless of changes in fat mass[24, 109, 110].>
Leptin’s importance should be abundantly clear to you. When levels get low, you get hungry and your body stops burning fat. This may be the hormone that makes it nearly impossible to lose your love handles, hips, thighs, and belly.
When you’re dieting, the situation gets even worse, because most diets decrease levels of leptin[20, 111], making it difficult to maintain weight loss. The low leptin levels caused by dieting also make it very easy to regain the weight[111-113]. To neglect all consideration of leptin’s action when designing a diet is ridiculous, since nearly all researchers seem to agree that leptin is essential for weight maintenance.
[expand title=”References (click to expand)”]
- 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 Dec 1;372(6505):425-32. Erratum in: Nature 1995 Mar 30;374(6521):479. -1-6-
- Pelleymounter MA, Cullen MJ, Baker MB, Hecht R, Winters D, Boone T, Collins F. Effects of the obese gene product on body weight regulation in ob/ob mice. Science. 1995 Jul 28;269(5223):540-3. -1-1-
- Halaas JL, Gajiwala KS, Maffei M, Cohen SL, Chait BT, Rabinowitz D, Lallone RL, Burley SK, Friedman JM. Weight-reducing effects of the plasma protein encoded by the obese gene. Science. 1995 Jul 28;269(5223):543-6. -1-2-
- Campfield LA, Smith FJ, Guisez Y, Devos R, Burn P. Recombinant mouse OB protein: evidence for a peripheral signal linking adiposity and central neural networks. Science. 1995 Jul 28;269(5223):546-9. -1-3-
- Montague CT, Farooqi IS, Whitehead JP, Soos MA, Rau H, Wareham NJ, Sewter CP, Digby JE, Mohammed SN, Hurst JA, Cheetham CH, Earley AR, Barnett AH, Prins JB, O’Rahilly S. Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature. 1997 Jun 26;387(6636):903-8. -1-7-
- Clement K, Vaisse C, Lahlou N, Cabrol S, Pelloux V, Cassuto D, Gourmelen M, Dina C, Chambaz J, Lacorte JM, Basdevant A, Bougneres P, Lebouc Y, Froguel P, Guy-Grand B. A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction. Nature. 1998 Mar 26;392(6674):398-401. -1-8-
- Carlsson B, Lindell K, Gabrielsson B, Karlsson C, Bjarnason R, Westphal O, Karlsson U, Sjostrom L, Carlsson LM. Obese (ob) gene defects are rare in human obesity. Obes Res. 1997 Jan;5(1):30-5. -3-86-
- Campfield LA, Smith FJ, Burn P. The OB protein (leptin) pathway–a link between adipose tissue mass and central neural networks. Horm Metab Res. 1996 Dec;28(12):619-32. Review. -1-4-
- Moinat M, Deng C, Muzzin P, Assimacopoulos-Jeannet F, Seydoux J, Dulloo AG, Giacobino JP. Modulation of obese gene expression in rat brown and white adipose tissues. FEBS Lett. 1995 Oct 9;373(2):131-4. -1-5-
- Klein S, Coppack SW, Mohamed-Ali V, Landt M. Adipose tissue leptin production and plasma leptin kinetics in humans. Diabetes. 1996 Jul;45(7):984-7. -2-1-
- Ronnemaa T, Karonen SL, Rissanen A, Koskenvuo M, Koivisto VA. Relation between plasma leptin levels and measures of body fat in identical twins discordant for obesity. Ann Intern Med. 1997 Jan 1;126(1):26-31. -2-4-
- Lonnqvist F, Nordfors L, Jansson M, Thorne A, Schalling M, Arner P. Leptin secretion from adipose tissue in women. Relationship to plasma levels and gene expression. J Clin Invest. 1997 May 15;99(10):2398-404. -2-5-
- Minocci A, Savia G, Lucantoni R, Berselli ME, Tagliaferri M, Calo G, Petroni ML, de Medici C, Viberti GC, Liuzzi A. Leptin plasma concentrations are dependent on body fat distribution in obese patients. Int J Obes Relat Metab Disord. 2000 Sep;24(9):1139-44. -2-7-
- Considine RV, Sinha MK, Heiman ML, Kriauciunas A, Stephens TW, Nyce MR, Ohannesian JP, Marco CC, McKee LJ, Bauer TL, et al. Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med. 1996 Feb 1;334(5):292-5. -2-8-
- Shimizu H, Shimomura Y, Hayashi R, Ohtani K, Sato N, Futawatari T, Mori M. Serum leptin concentration is associated with total body fat mass, but not abdominal fat distribution. Int J Obes Relat Metab Disord. 1997 Jul;21(7):536-41. -2-9-
- Fisher JS, Hickner RC, Racette SB, Binder EF, Landt M, Kohrt WM. Leptin response to insulin in humans is related to the lipolytic state of abdominal subcutaneous fat. J Clin Endocrinol Metab. 1999 Oct;84(10):3726-31. -2-10-
- Van Harmelen V, Reynisdottir S, Eriksson P, Thorne A, Hoffstedt J, Lonnqvist F, Arner P. Leptin secretion from subcutaneous and visceral adipose tissue in women. Diabetes. 1998 Jun;47(6):913-7. -2-15-
- Hube F, Lietz U, Igel M, Jensen PB, Tornqvist H, Joost HG, Hauner H. Difference in leptin mRNA levels between omental and subcutaneous abdominal adipose tissue from obese humans. Horm Metab Res. 1996 Dec;28(12):690-3. -2-16-
- Taylor RW, Goulding A. Plasma leptin in relation to regional body fat in older New Zealand women. Aust N Z J Med. 1998 Jun;28(3):316-21. -2-17-
- Ostlund RE Jr, Yang JW, Klein S, Gingerich R. Relation between plasma leptin concentration and body fat, gender, diet, age, and metabolic covariates. J Clin Endocrinol Metab. 1996 Nov;81(11):3909-13. -2-20-
- Hickey MS, Considine RV, Israel RG, Mahar TL, McCammon MR, Tyndall GL, Houmard JA, Caro JF. Leptin is related to body fat content in male distance runners. Am J Physiol. 1996 Nov;271(5 Pt 1):E938-40. -2-21-
- Wauters M, Mertens I, Considine R, De Leeuw I, Van Gaal L. Are leptin levels dependent on body fat distribution in obese men and women? Eat Weight Disord. 1998 Sep;3(3):124-30. -2-25-
- Hassink SG, Sheslow DV, de Lancey E, Opentanova I, Considine RV, Caro JF. Serum leptin in children with obesity: relationship to gender and development. Pediatrics. 1996 Aug;98(2 Pt 1):201-3. -2-26-
- Moller N, O’Brien P, Nair KS. Disruption of the relationship between fat content and leptin levels with aging in humans. J Clin Endocrinol Metab. 1998 Mar;83(3):931-4. -2-43-
- Ranganathan S, Maffei M, Kern PA. Adipose tissue ob mRNA expression in humans: discordance with plasma leptin and relationship with adipose TNFalpha expression. J Lipid Res. 1998 Apr;39(4):724-30. -2-6-
- Garcia-Lorda P, Bullo M, Vila R, del Mar Grasa M, Alemany M, Salas-Salvado J. Leptin concentrations do not correlate with fat mass nor with metabolic risk factors in morbidly obese females. Diabetes Nutr Metab. 2001 Dec;14(6):329-36. -2-40-
- Johannsson G, Karlsson C, Lonn L, Marin P, Bjorntorp P, Sjostrom L, Carlsson B, Carlsson LM, Bengtsson BA. Serum leptin concentration and insulin sensitivity in men with abdominal obesity. Obes Res. 1998 Nov;6(6):416-21. -2-3-
- Cnop M, Landchild MJ, Vidal J, Havel PJ, Knowles NG, Carr DR, Wang F, Hull RL, Boyko EJ, Retzlaff BM, Walden CE, Knopp RH, Kahn SE. The concurrent accumulation of intra-abdominal and subcutaneous fat explains the association between insulin resistance and plasma leptin concentrations : distinct metabolic effects of two fat compartments. Diabetes. 2002 Apr;51(4):1005-15. -2-30-
- Takahashi M, Funahashi T, Shimomura I, Miyaoka K, Matsuzawa Y. Plasma leptin levels and body fat distribution. Horm Metab Res. 1996 Dec;28(12):751-2. -2-33-
- Montague CT, Prins JB, Sanders L, Digby JE, O’Rahilly S. Depot- and sex-specific differences in human leptin mRNA expression: implications for the control of regional fat distribution. Diabetes. 1997 Mar;46(3):342-7. -2-34-
- Elias CF, Lee C, Kelly J, Aschkenasi C, Ahima RS, Couceyro PR, Kuhar MJ, Saper CB, Elmquist JK. Leptin activates hypothalamic CART neurons projecting to the spinal cord. Neuron. 1998 Dec;21(6):1375-85. -3-50-
- Morley JE, Alshaher MM, Farr SA, Flood JF, Kumar VB. Leptin and neuropeptide Y (NPY) modulate nitric oxide synthase: further evidence for a role of nitric oxide in feeding. Peptides. 1999;20(5):595-600. -3-83-
- Barba G, Russo O, Siani A, Iacone R, Farinaro E, Gerardi MC, Russo P, Della Valle E, Strazzullo P. Plasma leptin and blood pressure in men: graded association independent of body mass and fat pattern. Obes Res. 2003 Jan;11(1):160-6. -2-39-
- Mistry AM, Swick AG, Romsos DR. Leptin rapidly lowers food intake and elevates metabolic rates in lean and ob/ob mice. J Nutr. 1997 Oct;127(10):2065-72. -3-32-
- William WN Jr, Ceddia RB, Curi R. Leptin controls the fate of fatty acids in isolated rat white adipocytes. J Endocrinol. 2002 Dec;175(3):735-44. -4-7-
- Fruhbeck G, Gomez-Ambrosi J. Depot-specific differences in the lipolytic effect of leptin on isolated white adipocytes. Med Sci Monit. 2002 Feb;8(2):BR47-55. -4-11-
- Fruhbeck G, Gomez-Ambrosi J, Salvador J. Leptin-induced lipolysis opposes the tonic inhibition of endogenous adenosine in white adipocytes. FASEB J. 2001 Feb;15(2):333-40. -4-13-
- Fruhbeck G, Aguado M, Martinez JA. In vitro lipolytic effect of leptin on mouse adipocytes: evidence for a possible autocrine/paracrine role of leptin. Biochem Biophys Res Commun. 1997 Nov 26;240(3):590-4. -4-19-
- Kamohara S, Burcelin R, Halaas JL, Friedman JM, Charron MJ. Acute stimulation of glucose metabolism in mice by leptin treatment. Nature. 1997 Sep 25;389(6649):374-7. -4-20-
- Ramsay TG. Porcine leptin alters insulin inhibition of lipolysis in porcine adipocytes in vitro. J Anim Sci. 2001 Mar;79(3):653-7. -4-22-
- Wang MY, Lee Y, Unger RH. Novel form of lipolysis induced by leptin. J Biol Chem. 1999 Jun 18;274(25):17541-4. -4-35-
- Siegrist-Kaiser CA, Pauli V, Juge-Aubry CE, Boss O, Pernin A, Chin WW, Cusin I, Rohner-Jeanrenaud F, Burger AG, Zapf J, Meier CA. Direct effects of leptin on brown and white adipose tissue. J Clin Invest. 1997 Dec 1;100(11):2858-64. -4-36-
- Fruhbeck G, Aguado M, Gomez-Ambrosi J, Martinez JA. Lipolytic effect of in vivo leptin administration on adipocytes of lean and ob/ob mice, but not db/db mice. Biochem Biophys Res Commun. 1998 Sep 8;250(1):99-102. -4-37-
- Wang ZW, Zhou YT, Lee Y, Higa M, Kalra SP, Unger RH. Hyperleptinemia depletes fat from denervated fat tissue. Biochem Biophys Res Commun. 1999 Jul 14;260(3):653-7. -4-39-
- Ramsay TG. Porcine leptin inhibits lipogenesis in porcine adipocytes. J Anim Sci. 2003 Dec;81(12):3008-17. -4-2-
- Ceddia RB, William WN Jr, Lima FB, Flandin P, Curi R, Giacobino JP. Leptin stimulates uncoupling protein-2 mRNA expression and Krebs cycle activity and inhibits lipid synthesis in isolated rat white adipocytes. Eur J Biochem. 2000 Oct;267(19):5952-8. -4-14-
- Ceddia RB, William WN Jr, Lima FB, Curi R. Leptin inhibits insulin-stimulated incorporation of glucose into lipids and stimulates glucose decarboxylation in isolated rat adipocytes. J Endocrinol. 1998 Sep;158(3):R7-9. -4-17-
- Elimam A, Kamel A, Marcus C. In vitro effects of leptin on human adipocyte metabolism. Horm Res. 2002;58(2):88-93. -4-25-
- Zhang HH, Kumar S, Barnett AH, Eggo MC. Intrinsic site-specific differences in the expression of leptin in human adipocytes and its autocrine effects on glucose uptake. J Clin Endocrinol Metab. 1999 Jul;84(7):2550-6. -4-26-
- Hellstrom L, Wahrenberg H, Hruska K, Reynisdottir S, Arner P. Mechanisms behind gender differences in circulating leptin levels. J Intern Med. 2000 Apr;247(4):457-62. -2-2-
- Song YM, Sheu WH, Lee WJ, Wu CJ, Kao CH. Plasma leptin concentrations are related to body fat mass and gender but not to thyroid dysfunction. Kaohsiung J Med Sci. 1999 Mar;15(3):119-26. -2-14-
- Couillard C, Mauriege P, Prud’homme D, Nadeau A, Tremblay A, Bouchard C, Despres JP. Plasma leptin concentrations: gender differences and associations with metabolic risk factors for cardiovascular disease. Diabetologia. 1997 Oct;40(10):1178-84. -2-24-.
- Niskanen LK, Haffner S, Karhunen LJ, Turpeinen AK, Miettinen H, Uusitupa MI. Serum leptin in obesity is related to gender and body fat topography but does not predict successful weight loss. Eur J Endocrinol. 1997 Jul;137(1):61-7. -2-32-
- Vettor R, De Pergola G, Pagano C, Englaro P, Laudadio E, Giorgino F, Blum WF, Giorgino R, Federspil G. Gender differences in serum leptin in obese people: relationships with testosterone, body fat distribution and insulin sensitivity. Eur J Clin Invest. 1997 Dec;27(12):1016-24. -2-45-
- Jensen MD, Hensrud D, O’Brien PC, Nielsen S. Collection and interpretation of plasma leptin concentration data in humans. Obes Res. 1999 May;7(3):241-5. -2-22-
- Di Marzo V, Goparaju SK, Wang L, Liu J, Batkai S, Jarai Z, Fezza F, Miura GI, Palmiter RD, Sugiura T, Kunos G. Leptin-regulated endocannabinoids are involved in maintaining food intake. Nature. 2001 Apr 12;410(6830):822-5. -3-5-
- Baskin DG, Seeley RJ, Kuijper JL, Lok S, Weigle DS, Erickson JC, Palmiter RD, Schwartz MW. Increased expression of mRNA for the long form of the leptin receptor in the hypothalamus is associated with leptin hypersensitivity and fasting. Diabetes. 1998 Apr;47(4):538-43. -3-6-
- Backberg M, Hervieu G, Wilson S, Meister B. Orexin receptor-1 (OX-R1) immunoreactivity in chemically identified neurons of the hypothalamus: focus on orexin targets involved in control of food and water intake. Eur J Neurosci. 2002 Jan;15(2):315-28. -3-7-
- Sahu A. Evidence suggesting that galanin (GAL), melanin-concentrating hormone (MCH), neurotensin (NT), proopiomelanocortin (POMC) and neuropeptide Y (NPY) are targets of leptin signaling in the hypothalamus. Endocrinology. 1998 Feb;139(2):795-8. -3-8-
- Kristensen P, Judge ME, Thim L, Ribel U, Christjansen KN, Wulff BS, Clausen JT, Jensen PB, Madsen OD, Vrang N, Larsen PJ, Hastrup S. Hypothalamic CART is a new anorectic peptide regulated by leptin. Nature. 1998 May 7;393(6680):72-6. -3-14-
- Baskin DG, Breininger JF, Schwartz MW. Leptin receptor mRNA identifies a subpopulation of neuropeptide Y neurons activated by fasting in rat hypothalamus. Diabetes. 1999 Apr;48(4):828-33. -3-15-
- Mercer JG, Moar KM, Rayner DV, Trayhurn P, Hoggard N. Regulation of leptin receptor and NPY gene expression in hypothalamus of leptin-treated obese (ob/ob) and cold-exposed lean mice. FEBS Lett. 1997 Feb 3;402(2-3):185-8. -3-16-
- Schwartz MW, Baskin DG, Bukowski TR, Kuijper JL, Foster D, Lasser G, Prunkard DE, Porte D Jr, Woods SC, Seeley RJ, Weigle DS. Specificity of leptin action on elevated blood glucose levels and hypothalamic neuropeptide Y gene expression in ob/ob mice. Diabetes. 1996 Apr;45(4):531-5. -3-18-
- Elmquist JK. Hypothalamic pathways underlying the endocrine, autonomic, and behavioral effects of leptin. Physiol Behav. 2001 Nov-Dec;74(4-5):703-8. Review. -3-20-
- Stephens TW, Basinski M, Bristow PK, Bue-Valleskey JM, Burgett SG, Craft L, Hale J, Hoffmann J, Hsiung HM, Kriauciunas A, et al. The role of neuropeptide Y in the antiobesity action of the obese gene product. Nature. 1995 Oct 12;377(6549):530-2. -3-21-
- Mercer JG, Hoggard N, Williams LM, Lawrence CB, Hannah LT, Morgan PJ, Trayhurn P. Coexpression of leptin receptor and preproneuropeptide Y mRNA in arcuate nucleus of mouse hypothalamus. J Neuroendocrinol. 1996 Oct;8(10):733-5. -3-23-
- Cheung CC, Clifton DK, Steiner RA. Proopiomelanocortin neurons are direct targets for leptin in the hypothalamus. Endocrinology. 1997 Oct;138(10):4489-92. -3-24-
- Schwartz MW, Seeley RJ, Campfield LA, Burn P, Baskin DG. Identification of targets of leptin action in rat hypothalamus. J Clin Invest. 1996 Sep 1;98(5):1101-6. -3-26-
- Shimada M, Tritos NA, Lowell BB, Flier JS, Maratos-Flier E. Mice lacking melanin-concentrating hormone are hypophagic and lean. Nature. 1998 Dec 17;396(6712):670-4. -3-29-
- Proulx K, Richard D, Walker CD. Leptin regulates appetite-related neuropeptides in the hypothalamus of developing rats without affecting food intake. Endocrinology. 2002 Dec;143(12):4683-92. -3-35-
- Hosoi T, Okuma Y, Nomura Y. Leptin regulates interleukin-1beta expression in the brain via the STAT3-independent mechanisms. Brain Res. 2002 Sep 13;949(1-2):139-46. -3-38-
- Korner J, Savontaus E, Chua SC Jr, Leibel RL, Wardlaw SL. Leptin regulation of Agrp and Npy mRNA in the rat hypothalamus. J Neuroendocrinol. 2001 Nov;13(11):959-66. -3-42-
- Niimi M, Sato M, Taminato T. Neuropeptide Y in central control of feeding and interactions with orexin and leptin. Endocrine. 2001 Mar;14(2):269-73. -3-47-
- Schwartz MW, Erickson JC, Baskin DG, Palmiter RD. Effect of fasting and leptin deficiency on hypothalamic neuropeptide Y gene transcription in vivo revealed by expression of a lacZ reporter gene. Endocrinology. 1998 May;139(5):2629-35. -3-49-
- Hosoi T, Okuma Y, Nomura Y. Leptin induces IL-1 receptor antagonist expression in the brain. Biochem Biophys Res Commun. 2002 Jun 7;294(2):215-9. -3-58-
- Funahashi H, Hori T, Shimoda Y, Mizushima H, Ryushi T, Katoh S, Shioda S. Morphological evidence for neural interactions between leptin and orexin in the hypothalamus. Regul Pept. 2000 Aug 25;92(1-3):31-5. -3-60-
- Goldstone AP, Mercer JG, Gunn I, Moar KM, Edwards CM, Rossi M, Howard JK, Rasheed S, Turton MD, Small C, Heath MM, O’Shea D, Steere J, Meeran K, Ghatei MA, Hoggard N, Bloom SR. Leptin interacts with glucagon-like peptide-1 neurons to reduce food intake and body weight in rodents. FEBS Lett. 1997 Sep 29;415(2):134-8. -3-73-
- Dryden S, King P, Pickavance L, Doyle P, Williams G. Divergent effects of intracerebroventricular and peripheral leptin administration on feeding and hypothalamic neuropeptide Y in lean and obese (fa/fa) Zucker rats. Clin Sci (Lond). 1999 Mar;96(3):307-12. -3-81-
- Cohen P, Zhao C, Cai X, Montez JM, Rohani SC, Feinstein P, Mombaerts P, Friedman JM. Selective deletion of leptin receptor in neurons leads to obesity. J Clin Invest. 2001 Oct;108(8):1113-21. -3-94-
- Pinto S, Roseberry AG, Liu H, Diano S, Shanabrough M, Cai X, Friedman JM, Horvath TL. Rapid rewiring of arcuate nucleus feeding circuits by leptin. Science. 2004 Apr 2;304(5667):110-5. -3-45-
- Brunner L, Nick HP, Cumin F, Chiesi M, Baum HP, Whitebread S, Stricker-Krongrad A, Levens N. Leptin is a physiologically important regulator of food intake. Int J Obes Relat Metab Disord. 1997 Dec;21(12):1152-60. -3-72-
- Rentsch J, Levens N, Chiesi M. Recombinant ob-gene product reduces food intake in fasted mice. Biochem Biophys Res Commun. 1995 Sep 5;214(1):131-6. -3-87-
- Rosenbaum M, Nicolson M, Hirsch J, Heymsfield SB, Gallagher D, Chu F, Leibel RL. Effects of gender, body composition, and menopause on plasma concentrations of leptin. J Clin Endocrinol Metab. 1996 Sep;81(9):3424-7. -2-35-
- Giovambattista A, Suescun MO, Nessralla CC, Franca LR, Spinedi E, Calandra RS. Modulatory effects of leptin on leydig cell function of normal and hyperleptinemic rats. Neuroendocrinology. 2003 Nov;78(5):270-9. -4-3-
- Mounzih K, Lu R, Chehab FF. Leptin treatment rescues the sterility of genetically obese ob/ob males. Endocrinology. 1997 Mar;138(3):1190-3. -3-70-
- Pralong FP, Gonzales C, Voirol MJ, Palmiter RD, Brunner HR, Gaillard RC, Seydoux J, Pedrazzini T. The neuropeptide Y Y1 receptor regulates leptin-mediated control of energy homeostasis and reproductive functions. FASEB J. 2002 May;16(7):712-4. Epub 2002 Mar 12. -3-107-
- Barash IA, Cheung CC, Weigle DS, Ren H, Kabigting EB, Kuijper JL, Clifton DK, Steiner RA. Leptin is a metabolic signal to the reproductive system. Endocrinology 1996; 137:3144-3147.
- Chehab FF, Lim ME, Lu R. Correction of the sterility defect homozygous obese female mice by treatment with the human recombinant leptin. Nat Genet 1996; 12:318-320.
- Strobel A, Issad T, Camoin L, Ozata M, Strosberg AD. A leptin missense mutation associated with hypogonadism and morbid obesity. Nat Genet 1998; 139:2284-2286.
- Tezuka M, Irahara M, Ogura K, Kiyokawa M, Tamura T, Matsuzaki T, Yasui T, Aono T. Effects of leptin on gonadotropin secretion in juvenile female rat pituitary cells. Eur J Endocrinol. 2002 Feb;146(2):261-6. -4-12-
- Kiess W, Reich A, Meyer K, Glasow A, Deutscher J, Klammt J, Yang Y, Muller G, Kratzsch J. A role for leptin in sexual maturation and puberty? Horm Res. 1999;51 Suppl 3:55-63. Review. -3-103-
- Gueorguiev M, Goth ML, Korbonits M. Leptin and puberty: a review. Pituitary. 2001 Jan-Apr;4(1-2):79-86. Review. -3-104-
- Ahima RS, Dushay J, Flier SN, Prabakaran D, Flier JS. Leptin accelerates the onset of puberty in normal female mice. J Clin Invest. 1997 Feb 1;99(3):391-5. -3-106-
- Yura S, Ogawa Y, Sagawa N, Masuzaki H, Itoh H, Ebihara K, Aizawa-Abe M, Fujii S, Nakao K. Accelerated puberty and late-onset hypothalamic hypogonadism in female transgenic skinny mice overexpressing leptin. J Clin Invest. 2000 Mar;105(6):749-55. -3-108-
- Bronson FH. Puberty in female mice is not associated with increases in either body fat or leptin. Endocrinology. 2001 Nov;142(11):4758-61. -3-109-
- Chehab FF, Mounzih K, Lu R, Lim ME. Early onset of reproductive function in normal female mice treated with leptin. Science. 1997 Jan 3;275(5296):88-90. -3-114-
- Cheung CC, Thornton JE, Kuijper JL, Weigle DS, Clifton DK, Steiner RA. Leptin is a metabolic gate for the onset of puberty in the female rat. Endocrinology. 1997 Feb;138(2):855-8. -3-115-
- Cheung CC, Thornton JE, Nurani SD, Clifton DK, Steiner RA. A reassessment of leptin’s role in triggering the onset of puberty in the rat and mouse. Neuroendocrinology. 2001 Jul;74(1):12-21. -3-116-
- Mantzoros CS, Flier JS, Rogol AD. 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. 1997 Apr;82(4):1066-70. -3-117-
- Gruaz NM, Lalaoui M, Pierroz DD, Englaro P, Sizonenko PC, Blum WF, Aubert ML. Chronic administration of leptin into the lateral ventricle induces sexual maturation in severely food-restricted female rats. J Neuroendocrinol. 1998 Aug;10(8):627-33. -3-119-
- Brandao CM, Lombardi MT, Nishida SK, Hauache OM, Vieira JG. Serum leptin concentration during puberty in healthy nonobese adolescents. Braz J Med Biol Res. 2003 Oct;36(10):1293-6.
- Weimann E, Blum WF, Witzel C, Schwidergall S, Bohles HJ. Hypoleptinemia in female and male elite gymnasts. Eur J Clin Invest. 1999 Oct;29(10):853-60. -3-113-
- Shigemura N, Ohta R, Kusakabe Y, Miura H, Hino A, Koyano K, Nakashima K, Ninomiya Y. Leptin modulates behavioral responses to sweet substances by influencing peripheral taste structures. Endocrinology. 2004 Feb;145(2):839-47. Epub 2003 Oct 30. -3-63-
- Kawai K, Sugimoto K, Nakashima K, Miura H, Ninomiya Y. Leptin as a modulator of sweet taste sensitivities in mice. Proc Natl Acad Sci U S A. 2000 Sep 26;97(20):11044-9. -3-99-
- Shigemura N, Miura H, Kusakabe Y, Hino A, Ninomiya Y. Expression of leptin receptor (Ob-R) isoforms and signal transducers and activators of transcription (STATs) mRNAs in the mouse taste buds. Arch Histol Cytol. 2003 Aug;66(3):253-60. -3-100-
- Han Z, Yan JQ, Luo GG, Liu Y, Wang YL. Leptin receptor expression in the basolateral nucleus of amygdala of conditioned taste aversion rats. World J Gastroenterol. 2003 May;9(5):1034-7. -3-102-
- Martin-Romero C, Santos-Alvarez J, Goberna R, Sanchez-Margalet V. Human leptin enhances activation and proliferation of human circulating T lymphocytes. Cell Immunol. 2000 Jan 10;199(1):15-24. -4-16-
- Lord GM, Matarese G, Howard JK, Baker RJ, Bloom SR, Lechler RI. Leptin modulates the T-cell immune response and reverses starvation-induced immunosuppression. Nature. 1998 Aug 27;394(6696):897-901. -4-38-
- Sasai K, Oba K, Nakano H, Metori S. [Effect of age, gender, and body fat distribution on serum leptin concentrations] Nippon Ronen Igakkai Zasshi. 1999 Dec;36(12):874-80. Japanese. -2-27-
- Scarpace PJ, Tumer N. Peripheral and hypothalamic leptin resistance with age-related obesity. Physiol Behav. 2001 Nov-Dec;74(4-5):721-7. -3-46-
- Ahima RS, Kelly J, Elmquist JK, Flier JS. Distinct physiologic and neuronal responses to decreased leptin and mild hyperleptinemia. Endocrinology. 1999 Nov;140(11):4923-31. -3-30-
- Filozof CM, Murua C, Sanchez MP, Brailovsky C, Perman M, Gonzalez CD, Ravussin E. Low plasma leptin concentration and low rates of fat oxidation in weight-stable post-obese subjects. Obes Res. 2000 May;8(3):205-10. -2-28-
- Muzzin P, Eisensmith RC, Copeland KC, Woo SL. Correction of obesity and diabetes in genetically obese mice by leptin gene therapy. Proc Natl Acad Sci U S A. 1996 Dec 10;93(25):14804-8. -3-80-
- Meister B. Control of food intake via leptin receptors in the hypothalamus. Vitam Horm. 2000;59:265-304. Review. -3-1-
- Heini AF, Lara-Castro C, Kirk KA, Considine RV, Caro JF, Weinsier RL. Association of leptin and hunger-satiety ratings in obese women. Int J Obes Relat Metab Disord. 1998 Nov;22(11):1084-7.
- Lado-Abeal J, Norman RL. Leptin and reproductive function in males. Semin Reprod Med. 2002 May;20(2):145-51. Review.
- Sun C, Yu C, Wang S. Study on the effects of leptin on puberty development in children. Zhonghua Yu Fang Yi Xue Za Zhi. 2001 Sep;35(5):293-6.
- Ellis KJ, Nicolson M. Leptin levels and body fatness in children: effects of gender, ethnicity, and sexual development. Pediatr Res. 1997 Oct;42(4):484-8.
- Blum WF, Englaro P, Hanitsch S, Juul A, Hertel NT, Muller J, Skakkebaek NE, Heiman ML, Birkett M, Attanasio AM, Kiess W, Rascher W. Plasma leptin levels in healthy children and adolescents: dependence on body mass index, body fat mass, gender, pubertal stage, and testosterone. J Clin Endocrinol Metab. 1997 Sep;82(9):2904-10.