Human leptin: from an adipocyte hormone to an endocrine mediator.

Leptin is a mainly adipocyte-secreted protein that was discovered 5 years ago. Most of the research following this discovery focused on the role of leptin in body weight regulation, aiming to illuminate the pathophysiology of human obesity. However, more and more data are emerging that leptin is not only important in the regulation of food intake and energy balance, but that it also has a function as a metabolic and neuroendocrine hormone. It is now clear that it is especially involved in glucose metabolism, as well as in normal sexual maturation and reproduction. Besides this, interactions with the hypothalamic-pituitary-adrenal, thyroid and GH axes and even with haematopoiesis and the immune system have also been described. It has been shown that leptin secretion by the adipocyte is partly regulated by other hormones, such as insulin, cortisol, and sex steroids, mainly testosterone. Also, other hormones like thyroid hormone and GH are possibly involved in leptin synthesis. Leptin itself exerts effects on different endocrine axes, mainly on the hypothalamic-pituitary-gonadal axis and on insulin metabolism, but also on the hypothalamic-pituitary-adrenal, thyroid and GH axes. Leptin may thus be considered a new endocrine mediator, besides its obvious role in body weight regulation.

[1]  W. Rascher,et al.  Changes of Maternal Serum Leptin Levels during Pregnancy , 1998, Gynecologic and Obstetric Investigation.

[2]  N. Skakkebaek,et al.  Plasma leptin levels in healthy children and adolescents: dependence on body mass index, body fat mass, gender, pubertal stage, and testosterone. , 1997, The Journal of clinical endocrinology and metabolism.

[3]  P. Muzzin,et al.  Correction of obesity and diabetes in genetically obese mice by leptin gene therapy. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[4]  F. Chehab,et al.  Correction of the sterility defect in homozygous obese female mice by treatment with the human recombinant leptin , 1996, Nature Genetics.

[5]  C. Mantzoros,et al.  Journal of Clinical Endocrinology and Metabolism Printed in U.S.A. Copyright © 1997 by The Endocrine Society Leptin Concentrations in the Polycystic Ovary Syndrome* , 2022 .

[6]  M. Maffei,et al.  Positional cloning of the mouse obese gene and its human homologue , 1995, Nature.

[7]  M. Böni-Schnetzler,et al.  Leptin is suppressed during infusion of recombinant human insulin-like growth factor I (rhIGF I) in normal rats , 1999, Diabetologia.

[8]  K. Silver,et al.  The Gln223 Arg and Lys656 Asn Polymorphisms in the Human Leptin Receptor Do Not Associate With Traits Related to Obesity , 1997, Diabetes.

[9]  A. Spitzer,et al.  Placental Leptin: An Important New Growth Factor in Intrauterine and Neonatal Development? , 1997 .

[10]  G. Waeber,et al.  Leptin inhibits directly glucocorticoid secretion by normal human and rat adrenal gland. , 1998, Endocrinology.

[11]  W. Kohrt,et al.  Serum leptin levels are reduced in response to exercise training, but not hormone replacement therapy, in older women. , 1996, The Journal of clinical endocrinology and metabolism.

[12]  F. Cavagnini,et al.  Growth hormone in obesity , 1999, International Journal of Obesity.

[13]  W. Chung,et al.  Amino acid variants in the human leptin receptor: lack of association to juvenile onset obesity. , 1997, Biochemical and biophysical research communications.

[14]  F. Casanueva,et al.  Journal of Clinical Endocrinology and Metabolism Printed in U.S.A. Copyright © 1997 by The Endocrine Society Serum Leptin Levels in Normal Children: Relationship to Age, Gender, Body Mass Index, Pituitary-Gonadal Hormones, and Pubertal Stage* , 2022 .

[15]  Hongping,et al.  Leptin is a metabolic signal to the reproductive system. , 1996, Endocrinology.

[16]  K. McCormick,et al.  Leptin does not affect adipocyte glucose metabolism: studies in fresh and cultured adipocytes. , 1998, Metabolism: clinical and experimental.

[17]  G. C. Kennedy,et al.  The role of depot fat in the hypothalamic control of food intake in the rat , 1953, Proceedings of the Royal Society of London. Series B - Biological Sciences.

[18]  K. Clément,et al.  A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction , 1998, Nature.

[19]  R. Considine,et al.  Serum immunoreactive-leptin concentrations in normal-weight and obese humans. , 1996, The New England journal of medicine.

[20]  K. Alberti,et al.  Augmented growth hormone (GH) secretory burst frequency and amplitude mediate enhanced GH secretion during a two-day fast in normal men. , 1992, The Journal of clinical endocrinology and metabolism.

[21]  N. Butte,et al.  Journal of Clinical Endocrinology and Metabolism Printed in U.S.A. Copyright © 1997 by The Endocrine Society Leptin in Human Reproduction: Serum Leptin Levels in Pregnant and Lactating Women , 2022 .

[22]  S. Radovick,et al.  The impact of reversible gonadal sex steroid suppression on serum leptin concentrations in children with central precocious puberty. , 1998, The Journal of clinical endocrinology and metabolism.

[23]  C. Ricordi,et al.  Journal of Clinical Endocrinology and Metabolism Printed in U.S.A. Copyright © 1999 by The Endocrine Society Leptin Suppression of Insulin Secretion and Gene Expression in Human Pancreatic Islets: Implications for the Development of Adipogenic Diabetes Me , 2022 .

[24]  T. Nakamura,et al.  Association of endogenous insulin secretion and mode of therapy with body fat and serum leptin levels in diabetic subjects. , 1998, Metabolism: clinical and experimental.

[25]  S. Melmed,et al.  Journal of Clinical Endocrinology and Metabolism Printed in U.S.A. Copyright © 1998 by The Endocrine Society Intact Leptin Receptor Is Selectively Expressed in Human Fetal Pituitary and Pituitary Adenomas and Signals Human Fetal Pituitary Growth Hormone S , 2022 .

[26]  T. Hyde,et al.  The hypothalamic leptin receptor in humans: identification of incidental sequence polymorphisms and absence of the db/db mouse and fa/fa rat mutations. , 1996, Diabetes.

[27]  K. Nakao,et al.  Nonadipose tissue production of leptin: Leptin as a novel placenta-derived hormone in humans , 1997, Nature Medicine.

[28]  S. Mudaliar,et al.  Lack of effect of leptin on glucose transport, lipoprotein lipase, and insulin action in adipose and muscle cells. , 1998, Endocrinology.

[29]  S. O’Rahilly,et al.  Depot- and sex-specific differences in human leptin mRNA expression: implications for the control of regional fat distribution. , 1997, Diabetes.

[30]  S. Refetoff,et al.  Thyroid dysfunction is not associated with alterations in serum leptin levels. , 1997, Thyroid : official journal of the American Thyroid Association.

[31]  D. Morgan,et al.  Effects of leptin on insulin sensitivity in normal rats. , 1997, Endocrinology.

[32]  R. Considine,et al.  Are leptin levels dependent on body fat distribution in obese men and women? , 1998, Eating and weight disorders : EWD.

[33]  J. Jørgensen,et al.  Differential effects of growth hormone and prednisolone on energy metabolism and leptin levels in humans. , 1998, Metabolism: clinical and experimental.

[34]  F. Escobar del Rey,et al.  Thyroid hormones influence serum leptin concentrations in the rat. , 1997, Endocrinology.

[35]  C. Mantzoros,et al.  A Longitudinal Assessment of Hormonal and Physical Alterations during Normal Puberty in Boys. v. Rising Leptin Levels May Signal the Onset of Puberty* , 2022 .

[36]  G G Klee,et al.  Thyroid dysfunction. , 1988, Endocrinology and metabolism clinics of North America.

[37]  L. Aronne,et al.  Exonic and Intronic Sequence Variation in the Human Leptin Receptor Gene (LEPR) , 1997, Diabetes.

[38]  C. Mantzoros,et al.  Human leptin levels are pulsatile and inversely related to pituitary–ardenal function , 1997, Nature Medicine.

[39]  N. Barzilai,et al.  Intracerebroventricular Leptin Regulates Hepatic but Not Peripheral Glucose Fluxes* , 1998, The Journal of Biological Chemistry.

[40]  N. Hoggard,et al.  Leptin and leptin receptor mRNA and protein expression in the murine fetus and placenta. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[41]  J. Flier,et al.  Postnatal leptin surge and regulation of circadian rhythm of leptin by feeding. Implications for energy homeostasis and neuroendocrine function. , 1998, The Journal of clinical investigation.

[42]  J. Friedman,et al.  Longitudinal changes in maternal serum leptin concentrations, body composition, and resting metabolic rate in pregnancy. , 1998, American journal of obstetrics and gynecology.

[43]  H BRICAIRE,et al.  Journal of Endocrinology , 1939, Nature.

[44]  N. Sato,et al.  Estrogen increases in vivo leptin production in rats and human subjects. , 1997, The Journal of endocrinology.

[45]  P. Zimmet,et al.  Leptin: Is It Important in Diabetes? , 1996, Diabetic medicine : a journal of the British Diabetic Association.

[46]  K. Clément,et al.  Genetic studies of the leptin receptor gene in morbidly obese French Caucasian families , 1997, Human Genetics.

[47]  I. Chapman,et al.  Circulating leptin concentrations in polycystic ovary syndrome: relation to anthropometric and metabolic parameters , 1997, Clinical endocrinology.

[48]  M. Maffei,et al.  Positional cloning of the mouse obese gene and its human homologue , 1994, Nature.

[49]  E. Nieschlag,et al.  Strong association between serum levels of leptin and testosterone in men , 1997, Clinical endocrinology.

[50]  Johannes D. Veldhuis,et al.  Synchronicity of frequently sampled, 24-h concentrations of circulating leptin, luteinizing hormone, and estradiol in healthy women. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[51]  O. Boss,et al.  Induction of obesity and hyperleptinemia by central glucocorticoid infusion in the rat. , 1999, Diabetes.

[52]  L. Carlsson,et al.  Expression of functional leptin receptors in the human ovary. , 1997, The Journal of clinical endocrinology and metabolism.

[53]  G. Medley,et al.  Free leptin, bound leptin, and soluble leptin receptor in normal and diabetic pregnancies. , 1999, The Journal of clinical endocrinology and metabolism.

[54]  Y. Yoshimasa,et al.  Human leptin receptor gene in obese Japanese subjects: evidence against either obesity-causing mutations or association of sequence variants with obesity , 1997, Diabetologia.

[55]  J. Auwerx,et al.  Transient increase in obese gene expression after food intake or insulin administration , 1995, Nature.

[56]  A. Strosberg,et al.  A leptin missense mutation associated with hypogonadism and morbid obesity , 1998, Nature Genetics.

[57]  R. Casamitjana,et al.  Role of thyroid hormones on serum leptin levels. , 1998, European journal of endocrinology.

[58]  F. Casanueva,et al.  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. , 1998, The Journal of clinical endocrinology and metabolism.

[59]  A. Grossman,et al.  Obesity Results as a Consequence of Glucocorticoid Induced Leptin Resistance , 1996, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.

[60]  S. Woods,et al.  Specificity of Leptin Action on Elevated Blood Glucose Levels and Hypothalamic Neuropeptide Y Gene Expression in ob/ob Mice , 1996, Diabetes.

[61]  O. MacDougald,et al.  Regulated expression of the obese gene product (leptin) in white adipose tissue and 3T3-L1 adipocytes. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[62]  J Licinio,et al.  Human leptin deficiency caused by a missense mutation: multiple endocrine defects, decreased sympathetic tone, and immune system dysfunction indicate new targets for leptin action, greater central than peripheral resistance to the effects of leptin, and spontaneous correction of leptin-mediated defe , 1999, The Journal of clinical endocrinology and metabolism.

[63]  M. Reitman,et al.  Does Leptin Contribute to Diabetes Caused by Obesity? , 1996, Science.

[64]  J. Newcomer,et al.  Robust leptin secretory responses to dexamethasone in obese subjects. , 1997, The Journal of clinical endocrinology and metabolism.

[65]  R. Considine,et al.  Nocturnal rise of leptin in normal prepubertal and pubertal children and in patients with perinatal stalk-transection syndrome. , 1997, The Journal of clinical endocrinology and metabolism.

[66]  T. Saruta,et al.  Serum leptin concentrations in patients with thyroid disorders , 1998, Clinical endocrinology.

[67]  R. Huupponen,et al.  Correlation between circulating leptin and luteinizing hormone during the menstrual cycle in normal-weight women. , 1998, European journal of endocrinology.

[68]  J. Habener,et al.  Leptin Suppression of Insulin Secretion by the Activation of ATP-Sensitive K+ Channels in Pancreatic β-Cells , 1997, Diabetes.

[69]  S. Dagogo-Jack,et al.  Recombinant human insulin-like growth factor-I (IGF-I) therapy decreases plasma leptin concentration in patients with chronic renal insufficiency , 1998, International Journal of Obesity.

[70]  D. York,et al.  Effects of Leptin on Insulin Secretion From Isolated Rat Pancreatic Islets , 1998, Diabetes.

[71]  Rene Devos,et al.  Identification and expression cloning of a leptin receptor, OB-R , 1995, Cell.

[72]  A. Amsterdam,et al.  Leptin modulates the glucocorticoid-induced ovarian steroidogenesis. , 1999, Endocrinology.

[73]  C. Newgard,et al.  Direct antidiabetic effect of leptin through triglyceride depletion of tissues. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[74]  T. Hyde,et al.  Identification of Incidental Sequence Polymorphisms and Absence of the db/db Mouse and fa/fa Rat Mutations , 1996, Diabetes.

[75]  T. Tuomi,et al.  Serum and follicular fluid leptin during in vitro fertilization: relationship among leptin increase, body fat mass, and reduced ovarian response. , 1999, The Journal of clinical endocrinology and metabolism.

[76]  P. Herson,et al.  Leptin activates ATP‐sensitive potassium channels in the rat insulin‐secreting cell line, CRI‐G1 , 1997, The Journal of physiology.

[77]  S. O’Rahilly,et al.  Congenital leptin deficiency is associated with severe early-onset obesity in humans , 1997, Nature.

[78]  M. Kimura,et al.  Role of leptin in hypothalamic-pituitary function. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[79]  S. Mudaliar,et al.  Acute and Chronic Effect of Insulin on Leptin Production in Humans: Studies In Vivo and In Vitro , 1996, Diabetes.

[80]  R. Considine,et al.  Mutation screening and identification of a sequence variation in the human ob gene coding region. , 1996, Biochemical and biophysical research communications.

[81]  M. Laakso,et al.  Leptin concentrations, sex hormones, and cortisol in nondiabetic men. , 1997, The Journal of clinical endocrinology and metabolism.

[82]  R. Eckel,et al.  Isoproterenol and somatostatin decrease plasma leptin in humans: a novel mechanism regulating leptin secretion. , 1997, The Journal of clinical endocrinology and metabolism.

[83]  Y. Fukui,et al.  Reciprocal synaptic relations between CRF-immunoreactive- and TRH-immunoreactive neurons in the paraventricular nucleus of the rat hypothalamus , 1993, Brain Research.

[84]  G. Tannenbaum,et al.  Leptin Is a Potent Stimulator of Spontaneous Pulsatile Growth Hormone (GH) Secretion and the GH Response to GH-Releasing Hormone* , 1998 .

[85]  P S Kalra,et al.  Interacting appetite-regulating pathways in the hypothalamic regulation of body weight. , 1999, Endocrine reviews.

[86]  K. Mounzih,et al.  Early Onset of Reproductive Function in Normal Female Mice Treated with Leptin , 1997, Science.

[87]  S. Lightman,et al.  Leptin and the pituitary–thyroid axis: a comparative study in lean, obese, hypothyroid and hyperthyroid subjects , 1998, Clinical endocrinology.

[88]  R. Vettor,et al.  Leptin and the hypothalamic-pituitary-adrenal axis activity in women with different obesity phenotypes , 1997, International Journal of Obesity.

[89]  P. Landais,et al.  Circulating Leptin in Normal Children and During the Dynamic Phase of Juvenile Obesity: Relation to Body Fatness, Energy Metabolism, Caloric Intake, and Sexual Dimorphism , 1997, Diabetes.

[90]  P. Beck‐Peccoz,et al.  Lack of effects of circulating thyroid hormone levels on serum leptin concentrations. , 1997, European journal of endocrinology.

[91]  H. Orskov,et al.  Serum leptin is increased in growth hormone-deficient adults: relationship to body composition and effects of placebo-controlled growth hormone therapy for 1 year. , 1997, Metabolism: clinical and experimental.

[92]  J. Kehayias,et al.  THE RELATIONSHIP BETWEEN GROWTH HORMONE KINETICS AND SARCOPENIA IN POSTMENOPAUSAL WOMEN : THE ROLE OF FAT MASS AND LEPTIN , 1998 .

[93]  J. Beavo,et al.  Leptin inhibits insulin secretion by activation of phosphodiesterase 3B. , 1998, The Journal of clinical investigation.

[94]  J. Friedman,et al.  Acute intravenous leptin infusion increases glucose turnover but not skeletal muscle glucose uptake in ob/ob mice. , 1999, Diabetes.

[95]  F. Casanueva,et al.  Serum immunoreactive-leptin levels are increased in patients with Cushing's syndrome. , 1996, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.

[96]  M. McCarthy,et al.  The circadian rhythm of leptin is preserved in growth hormone deficient hypopituitary adults , 1998, Clinical endocrinology.

[97]  J. Flier,et al.  Leptin inhibition of the hypothalamic-pituitary-adrenal axis in response to stress. , 1997, Endocrinology.

[98]  C. Mantzoros,et al.  Gender differences in leptin levels during puberty are related to the subcutaneous fat depot and sex steroids. , 1998, The American journal of physiology.

[99]  R. Lechan,et al.  Neuropeptide-Y-immunoreactive innervation of thyrotropin-releasing hormone-synthesizing neurons in the rat hypothalamic paraventricular nucleus. , 1990, Endocrinology.

[100]  M. Saad,et al.  Changes in plasma leptin during the menstrual cycle. , 1998, European journal of endocrinology.

[101]  C. Diéguez,et al.  Leptin levels and insulin sensitivity in obese and non-obese patients with polycystic ovary syndrome. , 1997, Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology.

[102]  G. Ramadori,et al.  Serum leptin levels in hypo- and hyperthyroidism. , 1998, The Journal of endocrinology.

[103]  F. Casanueva,et al.  Influence of endogenous leptin tone on the estrous cycle and luteinizing hormone pulsatility in female rats. , 1997, Neuroendocrinology.

[104]  R. Coleman,et al.  Leptin opposes insulin's effects on fatty acid partitioning in muscles isolated from obese ob/obmice. , 1999, American journal of physiology. Endocrinology and metabolism.

[105]  I. Yokota,et al.  Serum leptin concentration in cord blood: relationship to birth weight and gender. , 1997, The Journal of clinical endocrinology and metabolism.

[106]  G. Paolisso,et al.  Lack of association between changes in plasma leptin concentration and in food intake during the menstrual cycle , 1999, European journal of clinical investigation.

[107]  U. Keller,et al.  Effects of glucocorticoids and of growth hormone on serum leptin concentrations in man. , 1996, European journal of endocrinology.

[108]  E. Ravussin,et al.  Leptin levels in human and rodent: Measurement of plasma leptin and ob RNA in obese and weight-reduced subjects , 1995, Nature Medicine.

[109]  W. Scherbaum,et al.  Evidence for a Novel Peripheral Action of Leptin as a Metabolic Signal to the Adrenal Gland: Leptin Inhibits Cortisol Release Directly , 1997, Diabetes.

[110]  J. F. Caro,et al.  Leptin is normal in PCOS, an editorial about three "negative" papers. , 1997, The Journal of clinical endocrinology and metabolism.

[111]  A. Mizuno,et al.  Leptin affects pancreatic endocrine functions through the sympathetic nervous system. , 1998, Endocrinology.

[112]  P. Zimmet,et al.  Hyperleptinaemia: the Missing Link in the Metabolic Syndrome? , 1997, Diabetic medicine : a journal of the British Diabetic Association.

[113]  L. Slieker,et al.  Regulation of Expression of ob mRNA and Protein by Glucocorticoids and cAMP (*) , 1996, The Journal of Biological Chemistry.

[114]  M. Pelleymounter,et al.  Effects of the obese gene product on body weight regulation in ob/ob mice. , 1995, Science.

[115]  S. Kahn,et al.  Evidence That Plasma Leptin and Insulin Levels are Associated With Body Adiposity Via Different Mechanisms , 1997, Diabetes Care.

[116]  M. Wabitsch,et al.  Contribution of androgens to the gender difference in leptin production in obese children and adolescents. , 1997, The Journal of clinical investigation.

[117]  P. McKeigue,et al.  Leptin receptor gene variation and obesity: lack of association in a white British male population. , 1997, Human molecular genetics.

[118]  P. Deurenberg,et al.  Serum leptin levels during recombinant human GH therapy in adults with GH deficiency. , 1997, European journal of endocrinology.

[119]  W. Scherbaum,et al.  Leptin down-regulates the steroid producing system in the adrenal. , 1998, Endocrine research.

[120]  R. Seeley,et al.  Identification of targets of leptin action in rat hypothalamus. , 1996, The Journal of clinical investigation.

[121]  R. Steiner,et al.  Leptin is a metabolic gate for the onset of puberty in the female rat. , 1997, Endocrinology.

[122]  R. Holman,et al.  UKPDS 20: plasma leptin, obesity, and plasma insulin in type 2 diabetic subjects. , 1997, The Journal of clinical endocrinology and metabolism.

[123]  J. Little,et al.  Leptin levels do not change acutely with food administration in normal or obese subjects, but are negatively correlated with pituitary‐adrenal activity , 1997, Clinical endocrinology.

[124]  B. Scheithauer,et al.  The Journal of Clinical Endocrinology & Metabolism Printed in U.S.A. Copyright © 1999 by The Endocrine Society Leptin and Leptin Receptor Expression in Normal and Neoplastic Human Pituitary: Evidence of a Regulatory Role for Leptin on Pituitary Cell Proli , 2022 .

[125]  S. Yen,et al.  Hypoleptinemia in women athletes: absence of a diurnal rhythm with amenorrhea. , 1997, The Journal of clinical endocrinology and metabolism.

[126]  K. Mounzih,et al.  Leptin treatment rescues the sterility of genetically obese ob/ob males. , 1997, Endocrinology.

[127]  B. Voerman,et al.  Changes in subcutaneous and visceral fat mass during growth hormone replacement therapy in adult men. , 1996, International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity.

[128]  J. Hyde,et al.  Upregulation of leptin receptor gene expression in the anterior pituitary of human growth hormone-releasing hormone transgenic mice. , 1998, Endocrinology.

[129]  C. Bouchard,et al.  Plasma leptin concentrations: gender differences and associations with metabolic risk factors for cardiovascular disease , 1997, Diabetologia.

[130]  D. Porte,et al.  Cerebrospinal fluid leptin levels: Relationship to plasma levels and to adiposity in humans , 1996, Nature Medicine.

[131]  R. Leibel,et al.  Effects of gender, body composition, and menopause on plasma concentrations of leptin. , 1996, The Journal of clinical endocrinology and metabolism.

[132]  C. Saper,et al.  From Lesions to Leptin Hypothalamic Control of Food Intake and Body Weight , 1999, Neuron.

[133]  J. Habener,et al.  Leptin receptors expressed on pancreatic beta-cells. , 1996, Biochemical and biophysical research communications.

[134]  Judith E. Adams,et al.  Relationship between growth hormone (GH) status, serum leptin and body composition in healthy and GH deficient elderly subjects , 1997, Clinical endocrinology.

[135]  L. Seoane,et al.  Leptin increases in vivo GH responses to GHRH and GH-releasing peptide-6 in food-deprived rats. , 2000, European journal of endocrinology.

[136]  M. Saad,et al.  Journal of Clinical Endocrinology and Metabolism Printed in U.S.A. Copyright © 1997 by The Endocrine Society Sexual Dimorphism in Plasma Leptin Concentration* , 2022 .

[137]  F. Casanueva,et al.  Regulation of in vivo growth hormone secretion by leptin. , 1997, Endocrinology.

[138]  Johan Auwerx,et al.  Depot-Specific Differences in Adipose Tissue Gene Expression in Lean and Obese Subjects , 1998, Diabetes.

[139]  R. Stolk,et al.  The acute effect of dexamethasone on plasma leptin concentrations and the relationships between fasting leptin, the IGF‐I/IGFBP system, dehydroepiandrosterone, androstenedione and testosterone in an elderly population , 1998, Clinical endocrinology.

[140]  C. Newgard,et al.  β-Cell Function in Normal Rats Made Chronically Hyperleptinemic by Adenovirus-Leptin Gene Therapy , 1997, Diabetes.

[141]  C. Mantzoros,et al.  Short-term hyperthyroidism has no effect on leptin levels in man. , 1997, The Journal of clinical endocrinology and metabolism.

[142]  M. Reitman,et al.  Hyperleptinemia of Pregnancy Associated with the Appearance of a Circulating Form of the Leptin Receptor* , 1997, The Journal of Biological Chemistry.

[143]  S. Chua,et al.  Effects of exogenous gonadal steroids on leptin homeostasis in rats. , 1999, Obesity research.

[144]  W. Blum,et al.  Dexamethasone Induces an Acute and Sustained Rise in Circulating Leptin Levels in Normal Human Subjects , 1996, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.

[145]  Serum immunoreactive leptin concentrations in women with polycystic ovary syndrome. , 1996, The Journal of clinical endocrinology and metabolism.

[146]  R. Lang,et al.  Radiommunological measurement of leptin in plasma of obese and diabetic human subjects. , 1996, Endocrinology.

[147]  M. Polansky,et al.  Effects of prolonged hyperinsulinemia on serum leptin in normal human subjects. , 1997, The Journal of clinical investigation.

[148]  F. Escobar del Rey,et al.  Thyroid Hormones Influence Serum Leptin Concentrations in the Rat. , 1997, Endocrinology.

[149]  S. Haffner,et al.  Leptin concentrations in women in the San Antonio Heart Study: effect of menopausal status and postmenopausal hormone replacement therapy. , 1997, American journal of epidemiology.

[150]  L. Spicer,et al.  Adipose obese gene product, leptin, inhibits bovine ovarian thecal cell steroidogenesis. , 1998, Biology of reproduction.

[151]  B. Ahrén,et al.  Plasma Leptin Levels Correlate to Islet Function Independently of Body Fat in Postmenopausal Women , 1996, Diabetes.

[152]  V. Emilsson,et al.  Expression of the Functional Leptin Receptor mRNA in Pancreatic Islets and Direct Inhibitory Action of Leptin on Insulin Secretion , 1997, Diabetes.

[153]  S. Haffner,et al.  Plasma leptin in non‐diabetic Asian Indians: association with abdominal adiposity , 1997, Diabetic medicine : a journal of the British Diabetic Association.

[154]  C. Mantzoros,et al.  Role of leptin in the neuroendocrine response to fasting , 1996, Nature.

[155]  S. Haffner,et al.  Leptin Concentrations in Diabetic and Nondiabetic Mexican-Americans , 1996, Diabetes.

[156]  L. Kaplan,et al.  Increase in plasma leptin and Lep mRNA concentrations by food intake is dependent on insulin. , 1998, Metabolism: clinical and experimental.

[157]  T. Saruta,et al.  Regulation of expression of leptin mRNA and secretion of leptin by thyroid hormone in 3T3-L1 adipocytes. , 1997, Biochemical and biophysical research communications.

[158]  D. Smith,et al.  Leptin rapidly suppresses insulin release from insulinoma cells, rat and human islets and, in vivo, in mice. , 1997, The Journal of clinical investigation.

[159]  C. Diéguez,et al.  Leptin inhibits in vitro hypothalamic somatostatin secretion and somatostatin mRNA levels. , 1997, Endocrinology.

[160]  J. Camiña,et al.  Sex-based differences in serum leptin concentrations from umbilical cord blood at delivery. , 1997, European journal of endocrinology.

[161]  E. Ravussin,et al.  Structure and sequence variation at the human leptin receptor gene in lean and obese Pima Indians. , 1997, Human molecular genetics.

[162]  R. Vettor,et al.  Serum leptin in obese women with polycystic ovary syndrome is correlated with body weight and fat distribution but not with androgen and insulin levels. , 1998, Metabolism: clinical and experimental.

[163]  G. Brabant,et al.  Determinants of serum leptin levels in Cushing's syndrome. , 1998, The Journal of clinical endocrinology and metabolism.

[164]  M. Roden,et al.  Failure of leptin to affect basal and insulin-stimulated glucose metabolism of rat skeletal muscle in vitro , 1998, Diabetologia.

[165]  G. Müller,et al.  Leptin Impairs Metabolic Actions of Insulin in Isolated Rat Adipocytes* , 1997, The Journal of Biological Chemistry.

[166]  Thomas Madej,et al.  Threading analysis suggests that the obese gene product may be a helical cytokine , 1995, FEBS letters.

[167]  J. Seidell,et al.  Reversal of the sex difference in serum leptin levels upon cross-sex hormone administration in transsexuals. , 1997, The Journal of clinical endocrinology and metabolism.

[168]  R. Huupponen,et al.  Serum leptin concentrations in women with polycystic ovary syndrome. , 1997, The Journal of clinical endocrinology and metabolism.

[169]  Plasma leptin and acute serotoninergic stimulation of the corticotropic axis in women who are normal weight or obese. , 1997, Obesity research.

[170]  J. Bue-Valleskey,et al.  The role of neuropeptide Y in the antiobesity action of the obese gene product , 1995, Nature.

[171]  E. Mannucci,et al.  Relationship between leptin and oestrogens in healthy women. , 1998, European journal of endocrinology.

[172]  R. Valcavi,et al.  Influence of thyroid status on serum immunoreactive leptin levels. , 1997, The Journal of clinical endocrinology and metabolism.

[173]  B. Falkner,et al.  Relationship of leptin concentration to gender, menopause, age, diabetes, and fat mass in African Americans. , 1998, Obesity research.

[174]  C. Gravholt,et al.  Increased levels but preserved diurnal variation of serum leptin in GH-deficient patients: lack of impact of different modes of GH administration. , 1998, European journal of endocrinology.

[175]  J. Zierath,et al.  Evidence Against a Direct Effect of Leptin on Glucose Transport in Skeletal Muscle and Adipocytes , 1998, Diabetes.

[176]  F. Cella,et al.  Serum leptin concentrations during the menstrual cycle in normal-weight women: effects of an oral triphasic estrogen-progestin medication. , 2000, European journal of endocrinology.

[177]  L. Hardie,et al.  Circulating leptin levels are modulated by fasting, cold exposure and insulin administration in lean but not Zucker (fa/fa) rats as measured by ELISA. , 1996, Biochemical and biophysical research communications.

[178]  K. Clément,et al.  Leptin receptor gene in a large cohort of massively obese subjects: no indication of the fa/fa rat mutation. Detection of an intronic variant with no association with obesity. , 1998, Obesity research.

[179]  R. Harris,et al.  Acute and chronic effects of leptin on glucose utilization in lean mice. , 1998, Biochemical and biophysical research communications.

[180]  D. Apter,et al.  Gonadotropin-releasing hormone pulse generator activity during pubertal transition in girls: pulsatile and diurnal patterns of circulating gonadotropins. , 1993, The Journal of clinical endocrinology and metabolism.

[181]  S. Roh,et al.  The in vitro Effect of Leptin onBasal and Growth Hormone-Releasing Hormone-StimulatedGrowth Hormone Secretion from theOvine Pituitary Gland , 1998, Neuroendocrinology.

[182]  R. Devos,et al.  Recombinant mouse OB protein: evidence for a peripheral signal linking adiposity and central neural networks. , 1995, Science.

[183]  C. Fanelli,et al.  Plasma Leptin and Insulin Relationships in Obese and Nonobese Humans , 1996, Diabetes.

[184]  R. Burcelin,et al.  Acute stimulation of glucose metabolism in mice by leptin treatment , 1997, Nature.

[185]  R. Curi,et al.  Comparing effects of leptin and insulin on glucose metabolism in skeletal muscle: evidence for an effect of leptin on glucose uptake and decarboxylation , 1999, International Journal of Obesity.

[186]  S. Phinney,et al.  Gender differences in plasma leptin concentrations , 1996, Nature Medicine.

[187]  F. Lönnqvist,et al.  Overexpression of the obese (ob) gene in adipose tissue of human obese subjects , 1995, Nature Medicine.

[188]  U. Feldt-Rasmussen,et al.  The relationship between the serum leptin concentrations of thyrotoxic patients during treatment and their total fat mass is different from that of normal subjects , 1998, Clinical endocrinology.

[189]  S. B. Pedersen,et al.  Regulation of leptin by steroid hormones in rat adipose tissue. , 1999, Biochemical and biophysical research communications.

[190]  P. Björntorp,et al.  Effects of growth hormone treatment on the leptin system and on energy expenditure in abdominally obese men. , 1998, European journal of endocrinology.

[191]  H. Snodgrass,et al.  The expression of leptin and its receptors in pre-ovulatory human follicles. , 1997, Molecular human reproduction.

[192]  J. Jørgensen,et al.  Serum leptin levels and leptin expression in growth hormone (GH)-deficient and healthy adults: influence of GH treatment, gender, and fasting. , 1998, Metabolism: clinical and experimental.

[193]  W. Rascher,et al.  High leptin concentrations in serum of very obese children are further stimulated by dexamethasone. , 1996, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.

[194]  T. Stein,et al.  Plasma leptin influences gestational weight gain and postpartum weight retention. , 1998, The American journal of clinical nutrition.

[195]  Steven L. Cohen,et al.  Weight-reducing effects of the plasma protein encoded by the obese gene. , 1995, Science.

[196]  N. Guilhot,et al.  Regulation of Leptin Production in Cultured Mature White Adipocytes , 1996, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.

[197]  Støving,et al.  Diurnal variation of the serum leptin concen_tration in patients with anorexia nervosa , 1998, Clinical endocrinology.

[198]  C. Christoffersen,et al.  Insulin and Cortisol Promote Leptin Production in Cultured Human Fat Cells , 1996, Diabetes.

[199]  B. Cohen,et al.  Modulation of Insulin Activities by Leptin , 1996, Science.

[200]  B. Cobanov,et al.  Serum insulin but not leptin is associated with spontaneous and growth hormone (GH)-releasing hormone-stimulated GH secretion in normal volunteers with and without weight loss. , 1998, Metabolism: clinical and experimental.

[201]  M. Shigemoto,et al.  Molecular screening of both the promoter and the protein coding regions in the human ob gene in Japanese obese subjects with non-insulin-dependent diabetes mellitus. , 1997, European journal of endocrinology.

[202]  M. Deitel,et al.  Increased obese mRNA expression in omental fat cells from massively obese humans , 1995, Nature Medicine.

[203]  G. Reach,et al.  Inhibition of Insulin Secretion by Leptin in Normal Rodent Islets of Langerhans. , 1998, Endocrinology.

[204]  B. Ahrén,et al.  Short-term dexamethasone treatment increases plasma leptin independently of changes in insulin sensitivity in healthy women. , 1996, The Journal of clinical endocrinology and metabolism.

[205]  S. Bahouth,et al.  Expression of leptin and beta 3-adrenergic receptors in rat adipose tissue in altered thyroid states. , 1997, The Biochemical journal.

[206]  A. Blakemore,et al.  Leptin binding activity changes with age: the link between leptin and puberty. , 1999, The Journal of clinical endocrinology and metabolism.

[207]  J. Flier,et al.  Leptin accelerates the onset of puberty in normal female mice. , 1997, The Journal of clinical investigation.

[208]  A. Ryan,et al.  The effects of acute hyperglycemia and hyperinsulinemia on plasma leptin levels: its relationships with body fat, visceral adiposity, and age in women. , 1996, The Journal of clinical endocrinology and metabolism.

[209]  E. Reece,et al.  Leptin in human pregnancy: the relationship with gestational hormones. , 1998, American journal of obstetrics and gynecology.

[210]  E. Ravussin,et al.  Absence of Mutations in the Human OB Gene in Obese/Diabetic Subjects , 1996, Diabetes.

[211]  J. Auwerx,et al.  The expression of ob gene is not acutely regulated by insulin and fasting in human abdominal subcutaneous adipose tissue. , 1996, The Journal of clinical investigation.

[212]  N. Barzilai,et al.  Short Term Effects of Leptin on Hepatic Gluconeogenesis and in Vivo Insulin Action* , 1997, The Journal of Biological Chemistry.

[213]  H. Häring,et al.  Leptin stimulates glucose transport and glycogen synthesis in C2C12 myotubes: evidence for a PI3-kinase mediated effect , 1997, Diabetologia.

[214]  A. Sainsbury,et al.  Glucocorticoids as Counterregulatory Hormones of Leptin: Toward an Understanding of Leptin Resistance , 1997, Diabetes.

[215]  P. Donohoue,et al.  Plasma leptin in diabetic and insulin-treated diabetic and normal rats. , 1998, Metabolism: clinical and experimental.

[216]  B. Göke,et al.  Leptin: A Potent Inhibitor of Insulin Secretion , 1997, Peptides.

[217]  R. Considine,et al.  Pleiotropic cellular effects of leptin , 1999 .

[218]  H. de Boer,et al.  Clinical aspects of growth hormone deficiency in adults. , 1995, Endocrine reviews.

[219]  H. Arnqvist,et al.  Serum leptin concentrations in a normal population and in GH deficiency: negative correlation with testosterone in men and effects of GH treatment , 1997, Clinical endocrinology.

[220]  S. Schneider,et al.  Dexamethasone increases leptin expression in humans in vivo. , 1997, The Journal of clinical endocrinology and metabolism.

[221]  A. Prentice,et al.  Effects of recombinant leptin therapy in a child with congenital leptin deficiency. , 1999, The New England journal of medicine.

[222]  C. Strader,et al.  Diet-induced obese mice develop peripheral, but not central, resistance to leptin. , 1997, The Journal of clinical investigation.

[223]  N. Emanuele,et al.  Leptin alters the response of the growth hormone releasing factor- growth hormone--insulin-like growth factor-I axis to fasting. , 1998, The Journal of endocrinology.

[224]  J. Dötsch,et al.  Journal of Clinical Endocrinology and Metabolism Printed in U.S.A. Copyright © 1997 by The Endocrine Society Levels of Leptin in Maternal Serum, Amniotic Fluid, and Arterial and Venous Cord Blood: Relation to Neonatal and Placental Weight , 2022 .

[225]  Y. Yoshimasa,et al.  Journal of Clinical Endocrinology and Metabolism Printed in U.S.A. Copyright © 1997 by The Endocrine Society Glucocorticoid Regulation of Leptin Synthesis and Secretion in Humans: Elevated Plasma Leptin Levels in Cushing’s Syndrome* , 2022 .

[226]  J. Ohannesian,et al.  Evidence of free and bound leptin in human circulation. Studies in lean and obese subjects and during short-term fasting. , 1996, The Journal of clinical investigation.

[227]  J. Flier,et al.  Leptin prevents fasting-induced suppression of prothyrotropin-releasing hormone messenger ribonucleic acid in neurons of the hypothalamic paraventricular nucleus. , 1997, Endocrinology.

[228]  M. Kasuga,et al.  Human Obese Gene: Molecular Screening in Japanese and Asian Indian NIDDM Patients Associated With Obesity , 1996, Diabetes.

[229]  W. Banks,et al.  Leptin enters the brain by a saturable system independent of insulin , 1996, Peptides.

[230]  W. Scherbaum,et al.  Expression of Ob receptor in normal human adrenals: differential regulation of adrenocortical and adrenomedullary function by leptin. , 1998, The Journal of clinical endocrinology and metabolism.

[231]  D. Romsos,et al.  Persistently enhanced sensitivity of pancreatic islets from ob/ob mice to PKC-stimulated insulin secretion. , 1997, The American journal of physiology.

[232]  J. Auwerx,et al.  Induction of ob Gene Expression by Corticosteroids Is Accompanied by Body Weight Loss and Reduced Food Intake (*) , 1995, The Journal of Biological Chemistry.

[233]  K. Nakao,et al.  Human Obese Gene Expression: Adipocyte-Specific Expression and Regional Differences in the Adipose Tissue , 1995, Diabetes.

[234]  R. Kraemer,et al.  Serum leptin concentration in women: effect of age, obesity, and estrogen administration. , 1998, Fertility and sterility.

[235]  D. Cocchi,et al.  Leptin regulates GH secretion in the rat by acting on GHRH and somatostatinergic functions. , 1999, Journal of Endocrinology.

[236]  M. Palkovits,et al.  Decreased central and peripheral catecholaminergic activation in obese Zucker rats. , 1995, Endocrinology.

[237]  S. O’Rahilly,et al.  Depot- and Sex-Specific Differences in Human Leptin mRNA Expression: Implications for the Control of Regional Fat Distribution , 1997, Diabetes.

[238]  D. Magoffin,et al.  Direct Intraovarian Effects of Leptin: Impairment of the Synergistic Action of Insulin-Like Growth Factor-I on Follicle-Stimulating Hormone-Dependent Estradiol-17β Production by Rat Ovarian Granulosa Cells. , 1997, Endocrinology.

[239]  P. B. Jensen,et al.  Difference in leptin mRNA levels between omental and subcutaneous abdominal adipose tissue from obese humans. , 1996, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.

[240]  K. Abromeit Music Received , 2023, Notes.

[241]  R. Goldenberg,et al.  Serum Leptin Concentrations During Pregnancy and Their Relationship to Fetal Growth , 1998, Obstetrics and gynecology.

[242]  J. Habener,et al.  Leptin inhibits insulin gene transcription and reverses hyperinsulinemia in leptin-deficient ob/ob mice. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[243]  T. Murakami,et al.  Dexamethasone regulates obese expression in isolated rat adipocytes. , 1995, Biochemical and biophysical research communications.

[244]  H. Harris,et al.  The Rat , 1958, Nature.

[245]  A. Sainsbury,et al.  The ob Gene and Insulin: A Relationship Leading to Clues to the Understanding of Obesity , 1995, Diabetes.

[246]  H. Mahfouz,et al.  Serum leptin as an additional possible pathogenic factor in polycystic ovary syndrome. , 1999, Clinical biochemistry.

[247]  N. Barzilai,et al.  Decreased visceral adiposity accounts for leptin effect on hepatic but not peripheral insulin action , 1999 .

[248]  R. Leibel,et al.  Linkages and associations between the leptin receptor (LEPR) gene and human body composition in the Québec Family Study , 1999, International Journal of Obesity.

[249]  R. Considine,et al.  Leptin: The Tale of an Obesity Gene , 1996, Diabetes.

[250]  M. Chiesi,et al.  Regulation of ob gene mRNA levels in cultured adipocytes , 1996, FEBS letters.

[251]  R. Frisch,et al.  Menstrual Cycles: Fatness as a Determinant of Minimum Weight for Height Necessary for Their Maintenance or Onset , 1974, Science.

[252]  V. Bini,et al.  Leptin serum levels in normal weight and obese children and adolescents: relationship with age, sex, pubertal development, body mass index and insulin , 1997, International Journal of Obesity.

[253]  M. Kimura,et al.  Hypothalamic Control of FSH and LH by FSH-RF, LHRH, Cytokines, Leptin and Nitric Oxide , 1998, Neuroimmunomodulation.

[254]  S. Agarwal,et al.  The Journal of Clinical Endocrinology & Metabolism Printed in U.S.A. Copyright © 1999 by The Endocrine Society Leptin Antagonizes the Insulin-Like Growth Factor-I Augmentation of Steroidogenesis in Granulosa and , 2022 .

[255]  C. Bouvattier,et al.  Circulating leptin level and growth hormone response to stimulation tests in obese and normal children. , 1998, European journal of endocrinology.

[256]  K. Takekoshi,et al.  Leptin directly stimulates catecholamine secretion and synthesis in cultured porcine adrenal medullary chromaffin cells. , 1999, Biochemical and biophysical research communications.

[257]  S. Yen,et al.  Journal of Clinical Endocrinology and Metabolism Printed in U.S.A. Copyright © 1997 by The Endocrine Society Serum Leptin Levels in Women with Polycystic Ovary Syndrome: The Role of Insulin Resistance/ , 2022 .

[258]  A. Marais,et al.  Effects of anabolic-androgenic steroid use or gonadal testosterone suppression on serum leptin concentration in men. , 1999, European journal of endocrinology.

[259]  D. Abramovich,et al.  CIRCULATING LEPTIN IN WOMEN : A LONGITUDINAL STUDY IN THE MENSTRUAL CYCLE AND DURING PREGNANCY , 1998 .

[260]  J. Livesey,et al.  Low‐dose growth hormone replacement lowers plasma leptin and fat stores without affecting body mass index in adults with growth hormone deficiency , 1996, Clinical endocrinology.

[261]  D. Romsos,et al.  Leptin constrains acetylcholine-induced insulin secretion from pancreatic islets of ob/ob mice. , 1997, The Journal of clinical investigation.

[262]  D. Johnston,et al.  Elevated leptin concentrations in growth hormone‐deficient hypopituitary adults , 1997, Clinical endocrinology.

[263]  L. Ross,et al.  Morphologic and molecular changes induced by recombinant human leptin in the white and brown adipose tissues of C57BL/6 mice. , 1997, Laboratory investigation; a journal of technical methods and pathology.

[264]  R. Baumgartner,et al.  Age-related changes in sex hormones affect the sex difference in serum leptin independently of changes in body fat. , 1999, Metabolism: clinical and experimental.

[265]  V. Emilsson,et al.  Leptin inhibits insulin secretion and reduces insulin mRNA levels in rat isolated pancreatic islets. , 1997, Biochemical and biophysical research communications.

[266]  A. Mikhail,et al.  Novel B219/OB receptor isoforms: Possible role of leptin in hematopoiesis and reproduction , 1996, Nature Medicine.

[267]  R. Considine,et al.  Decreased cerebrospinal-fluid/serum leptin ratio in obesity: a possible mechanism for leptin resistance , 1996, The Lancet.

[268]  R. Considine,et al.  Evidence against either a premature stop codon or the absence of obese gene mRNA in human obesity. , 1995, The Journal of clinical investigation.

[269]  W. Rascher,et al.  Testosterone substitution normalizes elevated serum leptin levels in hypogonadal men. , 1997, The Journal of clinical endocrinology and metabolism.

[270]  A. Çorakçı,et al.  The effects of thyroid status on plasma leptin levels in women , 1998, Journal of endocrinological investigation.

[271]  Marais Ad,et al.  Effects of anabolic-androgenic steroid use or gonadal testosterone suppression on serum leptin concentration in men , 1999 .

[272]  N. Chinookoswong,et al.  Leptin restores euglycemia and normalizes glucose turnover in insulin-deficient diabetes in the rat. , 1999, Diabetes.

[273]  H. Yki-Järvinen,et al.  Supraphysiological Hyperinsulinemia Increases Plasma Leptin Concentrations After 4 h in Normal Subjects , 1996, Diabetes.

[274]  L. Vignati,et al.  Serum leptin levels in women with anorexia nervosa. , 1996, The Journal of clinical endocrinology and metabolism.

[275]  J. Hebebrand,et al.  Plasma concentrations of obese protein in anorexia nervosa , 1995, The Lancet.

[276]  H. Fukuda,et al.  Transcriptional regulation of fatty acid synthase gene by insulin/glucose, polyunsaturated fatty acid and leptin in hepatocytes and adipocytes in normal and genetically obese rats. , 2001, European journal of biochemistry.