Leptin Does Not Mediate Short-Term Fasting-Induced Changes in Growth Hormone Pulsatility but Increases IGF-I in Leptin Deficiency States

Chan, Jean L.; Williams, Catherine J.; Raciti, Patricia; Blakeman, Jennifer; Kelesidis, Theodore; Kelesidis, Iosif; Johnson, Michael L.; Thorner, Michael O.; Mantzoros, Christos S.

doi:10.1210/jc.2008-0056

Cited by 75Growth Hormone and Insulin-like Growth FactorsRegulation of Appetite and ObesityHypothalamic control of reproductive hormones

Leptin Does Not Mediate Short-Term Fasting-Induced Changes in Growth Hormone Pulsatility but Increases IGF-I in Leptin Deficiency States

Open access

Chan, Jean L., Williams, Catherine J., Raciti, Patricia, Blakeman, Jennifer, Kelesidis, Theodore, Kelesidis, Iosif, Johnson, Michael L., Thorner, Michael O. +1 more·2008·The Journal of Clinical Endocrinology & Metabolism

DOI 10.1210/jc.2008-0056PMC PMC2453057

Open this paper in CoChat — free account

Abstract

Context: States of acute and chronic energy deficit are characterized by increased GH secretion and decreased IGF-I levels. Objective: The objective of the study was to determine whether changes in levels of leptin, a key mediator of the adaptation to starvation, regulate the GH-IGF system during energy deficit. Design, Setting, Patients, and Intervention: We studied 14 healthy normal-weight men and women during three conditions: baseline fed and 72-h fasting (to induce hypoleptinemia) with administration of placebo or recombinant methionyl human leptin (r-metHuLeptin) (to reverse the fasting associated hypoleptinemia). We also studied eight normal-weight women with exercise-induced chronic energy deficit and hypothalamic amenorrhea at baseline and during 2–3 months of r-metHuLeptin treatment. Main Outcome Measures: GH pulsatility, IGF levels, IGF and GH binding protein (GHBP) levels were measured. Results: During short-term energy deficit, measures of GH pulsatility and disorderliness and levels of IGF binding protein (IGFBP)-1 increased, whereas leptin, insulin, IGF-I (total and free), IGFBP-4, IGFBP-6, and GHBP decreased; r-metHuLeptin administration blunted the starvation-associated decrease of IGF-I. In chronic energy deficit, total and free IGF-I, IGFBP-6, and GHBP levels were lower, compared with euleptinemic controls; r-metHuLeptin administration had no major effect on GH pulsatility after 2 wk but increased total IGF-I levels and tended to increase free IGF-I and IGFBP-3 after 1 month. Conclusions: The GH/IGF system changes associated with energy deficit are largely independent of leptin deficiency. During acute energy deficit, r-metHuLeptin administration in replacement doses blunts the starvation-induced decrease of IGF-I, but during chronic energy deficit, r-metHuLeptin administration increases IGF-I and tends to increase free IGF-I and IGFBP-3.

Integrity signals

Registry

Crossref · 10.1210/jc.2008-0056

Cites

43 of 43 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Short-term starvation of mice and humans results in hypoleptinemia and alterations in the reproductive, thyroid, and growth hormone axes.
“Studies have shown that short-term starvation of mice (11) and humans (12, 21, 22) results in hypoleptinemia and alterations in the reproductive, thyroid, and growth hormone axes, which are normalized with exogenous administration of leptin.”
From Leptin is an effective treatment for hypothalamic amenorrhea (2011) · cites this paper as [21]
Exogenous leptin administration normalizes the starvation-induced alterations in the reproductive, thyroid, and growth hormone axes.
“Studies have shown that short-term starvation of mice (11) and humans (12, 21, 22) results in hypoleptinemia and alterations in the reproductive, thyroid, and growth hormone axes, which are normalized with exogenous administration of leptin.”
From Leptin is an effective treatment for hypothalamic amenorrhea (2011) · cites this paper as [21]

Approximate entropy as a measure of system complexity.
Pincus, S. M. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.6.2297 · Cited by 5,811 · see citing works
Role of leptin in the neuroendocrine response to fasting
Ahima, R. S., Prabakaran, D., Mantzoros, C., Qu, D., Lowell, B., Maratos-Flier, E., & Flier, J. S. (1996) · Nature · doi:10.1038/382250a0 · Cited by 3,117 · see citing works
Self-citation
A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction
Clément, K., Vaisse, C., Lahlou, N., Cabrol, S., Pelloux, V., Cassuto, D., Gourmelen, M., Dina, C., Chambaz, J., Lacorte, J.-M., et al. (1998) · Nature · doi:10.1038/32911 · Cited by 2,346 · see citing works
Nutritional Regulation of the Insulin-Like Growth Factors*
Thissen, J., Ketelslegers, J., & Underwood, L. E. (1994) · Endocrine Reviews · doi:10.1210/edrv-15-1-80 · Cited by 1,578 · see citing works
Recombinant human leptin in women with hypothalamic amenorrhea
Welt, C. K., Chan, J. L., Bullen, J., Murphy, R., Smith, P., DePaoli, A. M., Karalis, A., & Mantzoros, C. S. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa040388 · Cited by 908 · see citing works
Self-citation
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 Defects
Ozata, M., Ozdemir, I. C., & Licinio, J. (1999) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.84.10.5999 · Cited by 739 · see citing works
Clinical and molecular genetic spectrum of congenital deficiency of the leptin receptor.
Farooqi, I. S., Wangensteen, T., Collins, S., Kimber, W., Matarese, G., Keogh, J. M., Lank, E., Bottomley, B., Lopez-Fernandez, J., Ferraz-Amaro, I., et al. (2007) · New England Journal of Medicine · doi:10.1056/nejmoa063988 · Cited by 732 · see citing works
The role of falling leptin levels in the neuroendocrine and metabolic adaptation to short-term starvation in healthy men
Chan, J. L., Heist, K., DePaoli, A. M., Veldhuis, J. D., & Mantzoros, C. S. (2003) · Journal of Clinical Investigation · doi:10.1172/jci17490 · Cited by 697 · see citing works
Self-citation
The pituitary gland secretes in bursts: appraising the nature of glandular secretory impulses by simultaneous multiple-parameter deconvolution of plasma hormone concentrations.
Veldhuis, J. D., Carlson, M. L., & Johnson, M. L. (1987) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.84.21.7686 · Cited by 556 · see citing works
Self-citation
Phenotypic effects of leptin replacement on morbid obesity, diabetes mellitus, hypogonadism, and behavior in leptin-deficient adults
Licinio, J., Caglayan, S., Ozata, M., Yildiz, B. O., de Miranda, P. B., O'Kirwan, F., Whitby, R., Liang, L., Cohen, P., Bhasin, S., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0308767101 · Cited by 505 · see citing works
Fasting enhances growth hormone secretion and amplifies the complex rhythms of growth hormone secretion in man.
Ho, K. Y., Veldhuis, J. D., Johnson, M. L., Furlanetto, R., Evans, W. S., Alberti, K. G., & Thorner, M. O. (1988) · Journal of Clinical Investigation · doi:10.1172/jci113450 · Cited by 503 · see citing works
Self-citation
Hypoleptinemia in Women Athletes: Absence of a Diurnal Rhythm with Amenorrhea
Laughlin, G. A., & Yen, S. S. C. (1997) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.82.1.3840 · Cited by 348 · see citing works
The effect of anorexia nervosa and refeeding on growth hormone-binding protein, the insulin-like growth factors (IGFs), and the IGF-binding proteins
Counts, D. R., Gwirtsman, H., Carlsson, L. M., Lesem, M., & Cutler, G. B. (1992) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.75.3.1381372 · Cited by 344 · see citing works
Neuroendocrine Aberrations in Women With Functional Hypothalamic Amenorrhea*
BERGA, S. L., MORTOLA, J. F., GIRTON, L., SUH, B., LAUGHLIN, G., PHAM, P., & YEN, S. S. C. (1989) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-68-2-301 · Cited by 337 · see citing works
Alterations in Cortisol Secretory Dynamics in Adolescent Girls with Anorexia Nervosa and Effects on Bone Metabolism
Misra, M., Miller, K. K., Almazan, C., Ramaswamy, K., Lapcharoensap, W., Worley, M., Neubauer, G., Herzog, D. B., & Klibanski, A. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2004-0723 · Cited by 317 · see citing works
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 & Metabolism · doi:10.1210/jc.74.4.757 · Cited by 296 · see citing works
Insulin-Like Growth Factors in the Fed and Fasted States*
MERIMEE, T. J., ZAPF, J., & FROESCH, E. R. (1982) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-55-5-999 · Cited by 228 · see citing works
Long-Term Efficacy of Leptin Replacement in Patients With Generalized Lipodystrophy
Javor, E. D., Cochran, E. K., Musso, C., Young, J. R., DePaoli, A. M., & Gorden, P. (2005) · Diabetes · doi:10.2337/diabetes.54.7.1994 · Cited by 226 · cited 1× · see citing works
“... leptin deficiency led to an increase in IGFBP-1 and IGFBP-2 but not IGF-I, IGFBP3, IGFBP-6, or IGF-II (12); however, leptin replacement also led to dramatic weight loss and improved insulin sensitivity, which may have contributed to the increaseinIGFBP-1.Leptintreatmentinanothermodelofleptin deficiency (congenital…”
Background
Alterations in Growth Hormone Secretory Dynamics in Adolescent Girls with Anorexia Nervosa and Effects on Bone Metabolism
Misra, M., Miller, K. K., Bjornson, J., Hackman, A., Aggarwal, A., Chung, J., Ott, M., Herzog, D. B., Johnson, M. L., & Klibanski, A. (2003) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-030532 · Cited by 225 · see citing works
Self-citation
Nutritional and Endocrine-Metabolic Aberrations in Women with Functional Hypothalamic Amenorrhea1
Laughlin, G. A., Dominguez, C. E., & Yen, S. S. C. (1998) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.83.1.4502 · Cited by 216 · see citing works
Differential regulation of metabolic, neuroendocrine, and immune function by leptin in humans.
Chan, J. L., Matarese, G., Shetty, G. K., Raciti, P., Kelesidis, I., Aufiero, D., De Rosa, V., Perna, F., Fontana, S., & Mantzoros, C. S. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0505429103 · Cited by 213 · see citing works
Self-citation
Nutritional and endocrine-metabolic aberrations in amenorrheic athletes.
Laughlin, G. A., & YEN, S. S. C. (1996) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.81.12.8954031 · Cited by 212 · see citing works
Functional Hypothalamic Amenorrhea: Hypoleptinemia and Disordered Eating
Warren, M. P., Voussoughian, F., Geer, E. B., Hyle, E. P., Adberg, C. L., & Ramos, R. H. (1999) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.84.3.5551 · Cited by 202 · see citing works
A low dose euglycemic infusion of recombinant human insulin-like growth factor I rapidly suppresses fasting-enhanced pulsatile growth hormone secretion in humans.
Hartman, M. L., Clayton, P., Johnson, M. L., Celniker, A. C., Perlman, A. J., Alberti, K. G. M. M., & Thorner, M. O. (1993) · Journal of Clinical Investigation · doi:10.1172/jci116480 · Cited by 192 · see citing works
Self-citation
Both oral and transdermal estrogen increase growth hormone release in postmenopausal women--a clinical research center study
Friend, K. E., Hartman, M. L., Pezzoli, S. S., Clasey, J. L., & Thorner, M. O. (1996) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.81.6.8964860 · Cited by 189 · see citing works
Self-citation
Nutritional and Endocrine-Metabolic Aberrations in Women with Functional Hypothalamic Amenorrhea
Laughlin, G. A. (1998) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.83.1.25 · Cited by 187 · see citing works
Multiple Endocrine Abnormalities of the Growth Hormone and Insulin-Like Growth Factor Axis in Patients with Anorexia Nervosa: Effect of Short- and Long-Term Weight Recuperation1
Argente, J., Caballo, N., Barrios, V., Muñoz, M. T., Pozo, J., Chowen, J. A., Morandé, G., & Hernández, M. (1997) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.82.7.4090 · Cited by 173 · see citing works
A review of endocrine changes in anorexia nervosa
Støving, R. K., Hangaard, J., Hansen‐Nord, M., & Hagen, C. (1999) · Journal of Psychiatric Research · doi:10.1016/s0022-3956(98)00049-1 · Cited by 151 · see citing works
The long-term effect of recombinant methionyl human leptin therapy on hyperandrogenism and menstrual function in female and pituitary function in male and female hypoleptinemic lipodystrophic patients
Musso, C., Cochran, E., Javor, E., Young, J., DePaoli, A. M., & Gorden, P. (2005) · Metabolism · doi:10.1016/j.metabol.2004.08.021 · Cited by 146 · see citing works
Serum Concentrations of Insulin-Like Growth Factor II Are Not Changed by Short Term Fasting And Refeeding*
Davenport, M. L., SVOBODA, M. E., Koerber, K. L., Wyk, J. J. V., Clemmons, D. R., & Underwood, L. E. (1988) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-67-6-1231 · Cited by 125 · see citing works
Multiple Endocrine Abnormalities of the Growth Hormone and Insulin-Like Growth Factor Axis in Patients with Anorexia Nervosa: Effect of Short- and Long-Term Weight Recuperation
Argente, J. (1997) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.82.7.2084 · Cited by 116 · see citing works
Functional hypothalamic amenorrhoea: a partial and reversible gonadotrophin deficiency of nutritional origin
Couzinet, B., Young, J., Brailly, S., Bouc, Y. L., Chanson, P., & SCHAISON, G. (1999) · Clinical Endocrinology · doi:10.1046/j.1365-2265.1999.00649.x · Cited by 106 · see citing works
Free and Total Insulin-Like Growth Factor (IGF)-I Levels Decline during Fasting: Relationships with Insulin and IGF-Binding Protein-1
Katz, L. E. L., León, D. D. D., Zhao, H., & Jawad, A. F. (2002) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.87.6.8601 · Cited by 88 · see citing works
Free Rather than Total Circulating Insulin-Like Growth Factor-I Determines the Feedback on Growth Hormone Release in Normal Subjects
Chen, J., Højlund, K., Beck‐Nielsen, H., Christiansen, J. S., Ørskov, H., & Frystyk, J. (2005) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2004-0039 · Cited by 72 · see citing works
Physiology and pathophysiology of growth hormone-binding protein: Methodological and clinical aspects
Fisker, S. (2005) · Growth Hormone & IGF Research · doi:10.1016/j.ghir.2005.11.001 · Cited by 64 · see citing works
Short-Term Fasting Suppresses Leptin and (Conversely) Activates Disorderly Growth Hormone Secretion in Midluteal Phase Women—A Clinical Research Center Study1
Bergendahl, M., Evans, W. S., Pastor, C. L., Patel, A. C., Iranmanesh, A., & Veldhuis, J. D. (1999) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.84.3.5536 · Cited by 56 · see citing works
Leptin levels and IgF-binding proteins in malnourished children: effect of weight gain
Palacio, A. C., Pérez‐Bravo, F., Santos, J. L., Liana Schlesinger, F., & Mönckeberg, F. (2002) · Nutrition · doi:10.1016/s0899-9007(01)00690-6 · Cited by 50 · see citing works
Short-term fasting abolishes the sex-related difference in GH and leptin secretion in humans
Maccario, M., Aimaretti, G., Corneli, G., Gauna, C., Grottoli, S., Bidlingmaier, M., Strasburger, C. J., Diéguez, C., Casanueva, F. F., & Ghigo, E. (2000) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.2000.279.2.e411 · Cited by 47 · see citing works
Short-Term Fasting Suppresses Leptin and (Conversely) Activates Disorderly Growth Hormone Secretion in Midluteal Phase Women--A Clinical Research Center Study
Bergendahl, M. (1999) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.84.3.883 · Cited by 28 · see citing works
Growth Hormone-Binding Protein Directly Depends on Serum Leptin Levels in Adults with Different Nutritional Status1
Llopis, M. A., Granada, M., Cuatrecasas, G., Formiguera, X., Planell, L. S., Sanmartı́, A., Alastrue, A., Rull, M., Corominas, A., & Foz, M. (1998) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.83.6.4894 · Cited by 26 · see citing works
The Impact of Short-Term Fasting on the Dynamics of 24-Hour Growth Hormone (GH) Secretion in Patients with Severe Radiation-Induced GH Deficiency
Darzy, K. H., Murray, R. D., Gleeson, H. K., Pezzoli, S. S., Thorner, M. O., & Shalet, S. M. (2006) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2005-2145 · Cited by 22 · see citing works
Self-citation
Growth Hormone-Binding Protein Directly Depends on Serum Leptin Levels in Adults with Different Nutritional Status
Llopis, M. A. (1998) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.83.6.2006 · Cited by 20 · see citing works
Dynamic changes of growth hormone—binding protein concentrations in normal men and patients with acromegaly: Effects of short-term fasting
Ho, P. J., Gesundheit, N., Wong, W. L., Huang, S. H., Friberg, R. D., & Barkan, A. L. (1995) · Metabolism · doi:10.1016/0026-0495(95)90126-4 · Cited by 8 · see citing works

Flagged first, then by citations

Sorted by citations

Physiology of leptin: energy homeostasis, neuroendocrine function and metabolism
Park, H. K., & Ahima, R. S. (2014) · Metabolism · doi:10.1016/j.metabol.2014.08.004 · Cited by 675 · see citing works
Narrative Review: The Role of Leptin in Human Physiology: Emerging Clinical Applications
Kelesidis, T., Kelesidis, I., Chou, S. H.-H., & Mantzoros, C. S. (2010) · Annals of Internal Medicine · doi:10.7326/0003-4819-152-2-201001190-00008 · Cited by 667 · see citing works
Self-citation
Leptin in Human Physiology and Pathophysiology
Mantzoros, C. S., Magkos, F., Brinkoetter, M., Sienkiewicz, E., Dardeno, T. A., Kim, S.-Y., Hamnvik, O.-P. R., & Koniaris, A. (2011) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00315.2011 · Cited by 593 · see citing works
Self-citation
Leptin is an effective treatment for hypothalamic amenorrhea
Chou, S. H., Chamberland, J. P., Liu, X., Matarese, G., Gao, C., Stefanakis, R., Brinkoetter, M. T., Gong, H., Arampatzi, K., & Mantzoros, C. S. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1015674108 · Cited by 287 · see citing works
Self-citation
The role of leptin in regulating bone metabolism
Upadhyay, J., Farr, O. M., & Mantzoros, C. S. (2014) · Metabolism · doi:10.1016/j.metabol.2014.10.021 · Cited by 269 · see citing works
Self-citation
Leptin in Leanness and Obesity
Perakakis, N., Farr, O. M., & Mantzoros, C. S. (2021) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2020.11.069 · Cited by 218 · see citing works
Self-citation
Leptin in humans: lessons from translational research
Blüher, S., & Mantzoros, C. S. (2009) · The American Journal of Clinical Nutrition · doi:10.3945/ajcn.2008.26788e · Cited by 203 · see citing works
Self-citation
Adaptive reciprocity of lipid and glucose metabolism in human short-term starvation
Soeters, M. R., Soeters, P. B., Schooneman, M. G., Houten, S. M., & Romijn, J. A. (2012) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00397.2012 · Cited by 177 · see citing works
Determinants of GH resistance in malnutrition
Fazeli, P. K., & Klibanski, A. (2013) · Journal of Endocrinology · doi:10.1530/joe-13-0477 · Cited by 158 · see citing works
Central (ICV) leptin injection increases bone formation, bone mineral density, muscle mass, serum IGF-1, and the expression of osteogenic genes in leptin-deficient ob/ob mice
Bartell, S. M., Rayalam, S., Ambati, S., Gaddam, D. R., Hartzell, D. L., Hamrick, M. W., She, J., Della‐Fera, M. A., & Baile, C. A. (2011) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.406 · Cited by 156 · see citing works
Weight regain after Roux-en-Y: A significant 20% complication related to PYY
Meguid, M. M., Glade, M. J., & Middleton, F. A. (2008) · Nutrition · doi:10.1016/j.nut.2008.06.027 · Cited by 140 · see citing works
Neuroendocrine Regulation of Growth Hormone Secretion
Steyn, F. J., Tolle, V., Chen, C., & Epelbaum, J. (2016) · Comprehensive physiology · doi:10.1002/cphy.c150002 · Cited by 166 · see citing works
20 YEARS OF LEPTIN: Role of leptin in human reproductive disorders
Chou, S. H.-H., & Mantzoros, C. S. (2014) · Journal of Endocrinology · doi:10.1530/joe-14-0245 · Cited by 107 · see citing works
Self-citation
Leptin and Hormones
Triantafyllou, G. A., Paschou, S. Α., & Mantzoros, C. S. (2016) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2016.04.012 · Cited by 99 · see citing works
Self-citation
Relative Energy Deficiency in Sport (REDs): Endocrine Manifestations, Pathophysiology and Treatments
Angelidi, A. M., Stefanakis, K., Chou, S. H.-H., Valenzuela‐Vallejo, L., Δίπλα, Κ., Boutari, C., Ntoskas, K. T., Tokmakidis, P., Kokkinos, A. D., Goulis, D. G., et al. (2024) · Endocrine Reviews · doi:10.1210/endrev/bnae011 · Cited by 95 · see citing works
Self-citation
Leptin: A hormone linking activation of neuroendocrine axes with neuropathology
Stieg, M. R., Sievers, C., Farr, O. M., Stalla, G. K., & Mantzoros, C. S. (2014) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2014.09.004 · Cited by 75 · see citing works
Self-citation
Leptin as a Modulator of Neuroendocrine Function in Humans
Khan, S. M., Hamnvik, O. R., Brinkoetter, M. T., & Mantzoros, C. S. (2012) · Yonsei Medical Journal · doi:10.3349/ymj.2012.53.4.671 · Cited by 67 · see citing works
Self-citation
The role of obesity in inflammatory bowel disease
Kreuter, R., Wankell, M., Ahlenstiel, G., & Hebbard, L. (2018) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2018.10.020 · Cited by 60 · see citing works
Effect of Low-Intensity Aerobic Exercise on Insulin-Like Growth Factor-I and Insulin-Like Growth Factor-Binding Proteins in Healthy Men
Nishida, Y., Matsubara, T., Tobina, T., Shindo, M., Tokuyama, K., Tanaka, K., & Tanaka, H. (2010) · International Journal of Endocrinology · doi:10.1155/2010/452820 · Cited by 59 · see citing works
Neuroendocrine alterations in the exercising human: Implications for energy homeostasis
Fuqua, J. S., & Rogol, A. D. (2013) · Metabolism · doi:10.1016/j.metabol.2013.01.016 · Cited by 58 · see citing works
Leptin physiology and pathophysiology in energy homeostasis, immune function, neuroendocrine regulation and bone health
Stefanakis, K., Upadhyay, J., Ramirez-Cisneros, A., Patel, N., Sahai, A., & Mantzoros, C. S. (2024) · Metabolism · doi:10.1016/j.metabol.2024.156056 · Cited by 63 · see citing works
Self-citation
Leptin Deficiency: Clinical Implications and Opportunities for Therapeutic Interventions
Blüher, S., Shah, S., & Mantzoros, C. S. (2009) · Journal of Investigative Medicine · doi:10.2310/jim.0b013e3181b9163d · Cited by 55 · see citing works
Self-citation
Energy Deprivation Alters in a Leptin- and Cortisol-Independent Manner Circulating Levels of Activin A and Follistatin But Not Myostatin in Healthy Males
Vamvini, M. T., Aronis, K. N., Chamberland, J. P., & Mantzoros, C. S. (2011) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-1665 · Cited by 53 · see citing works
Self-citation
Changes of orexin A plasma levels in girls with anorexia nervosa during eight weeks of realimentation
Bronský, J., Nedvidkova, J., Krásnicanová, H., Veselá, M., Schmidtova, J., Koutek, J., Kellermayer, R., Chada, M., Kabelka, Z., Hrdlička, M., et al. (2010) · International Journal of Eating Disorders · doi:10.1002/eat.20857 · Cited by 53 · see citing works
Absence of Functional Leptin Receptor Isoforms in the POUND (Leprdb/lb) Mouse Is Associated with Muscle Atrophy and Altered Myoblast Proliferation and Differentiation
Arounleut, P., Bowser, M., Upadhyay, S. K., Shi, X., Fulzele, S., Johnson, M. H., Stranahan, A. M., Hill, W., Isales, C. M., & Hamrick, M. W. (2013) · PLoS ONE · doi:10.1371/journal.pone.0072330 · Cited by 49 · see citing works
Self-citation
Control of leptin by metabolic state and its regulatory interactions with pituitary growth hormone and hepatic growth hormone receptors and insulin like growth factors in the tilapia ( Oreochromis mossambicus )
Douros, J. D., Baltzegar, D. A., Mankiewicz, J. L., Taylor, J., Yamaguchi, Y., Lerner, D. T., Seale, A. P., Grau, E. G., Breves, J. P., & Borski, R. J. (2016) · General and Comparative Endocrinology · doi:10.1016/j.ygcen.2016.07.017 · Cited by 46 · see citing works
Body composition and reproductive function exert unique influences on indices of bone health in exercising women
Mallinson, R. J., Williams, N. I., Hill, B. R., & Souza, M. J. D. (2013) · Bone · doi:10.1016/j.bone.2013.05.008 · Cited by 44 · see citing works
Leptin stimulates hepatic growth hormone receptor and insulin-like growth factor gene expression in a teleost fish, the hybrid striped bass
Won, E., Douros, J. D., Hurt, D. A., & Borski, R. J. (2016) · General and Comparative Endocrinology · doi:10.1016/j.ygcen.2016.02.003 · Cited by 39 · see citing works
2D-electrophoresis and multiplex immunoassay proteomic analysis of different body fluids and cellular components reveal known and novel markers for extended fasting
Bouwman, F. G., de Roos, B., Rubio‐Aliaga, I., Crosley, L. K., Duthie, S. J., Mayer, C., Horgan, G. W., Polley, A. C. J., Heim, C., Coort, S. L., et al. (2011) · BMC Medical Genomics · doi:10.1186/1755-8794-4-24 · Cited by 34 · see citing works
r-metHuLeptin improves highly active antiretroviral therapy-induced lipoatrophy and the metabolic syndrome, but not through altering circulating IGF and IGF-binding protein levels: observational and interventional studies in humans
Brennan, A. M., Lee, J. H., Tsiodras, S., Chan, J. L., Doweiko, J. P., Chimienti, S. N., Wadhwa, S. G., Karchmer, A. W., & Mantzoros, C. S. (2008) · European Journal of Endocrinology · doi:10.1530/eje-08-0597 · Cited by 34 · see citing works
Self-citation
The adipokine leptin mediates muscle- and liver-derived IGF-1 in aged mice
Hamrick, M. W., Dukes, A., Arounleut, P., Davis, C. L., Periyasamy‐Thandavan, S., Mork, S., Herberg, S., Johnson, M. H., Isales, C. M., Hill, W., et al. (2015) · Experimental Gerontology · doi:10.1016/j.exger.2015.07.014 · Cited by 29 · see citing works
Self-citation
Bone metabolism in anorexia nervosa and hypothalamic amenorrhea
Chou, S. H.-H., & Mantzoros, C. S. (2017) · Metabolism · doi:10.1016/j.metabol.2017.10.009 · Cited by 28 · see citing works
Self-citation
Neuroendocrine adaptations to starvation
Amorim, T., Khiyami, A. M., Latif, T., & Fazeli, P. K. (2023) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2023.106365 · Cited by 26 · see citing works
Neuroendocrine Regulation of Growth Hormone Secretion
Steyn, F. J., Tolle, V., Chen, C., & Epelbaum, J. (2016) · Comprehensive physiology · doi:10.1002/j.2040-4603.2016.tb00692.x · Cited by 26 · see citing works
Trajectories of IGF-I Predict Mortality in Older Adults: The Cardiovascular Health Study
Sanders, J. L., Guo, W., O’Meara, E. S., Kaplan, R. C., Pollak, M., Bartz, T. M., Newman, A. B., Fried, L. P., & Cappola, A. R. (2017) · The Journals of Gerontology Series A · doi:10.1093/gerona/glx143 · Cited by 25 · see citing works
Transcriptomics provides mechanistic indicators of fluoride toxicology on endochondral ossification in the hind limb of Bufo gargarizans
Chao, W., Zhang, Y., Chai, L., & Wang, H. (2018) · Aquatic Toxicology · doi:10.1016/j.aquatox.2018.06.006 · Cited by 22 · see citing works
Serum IGF1 and linear growth in children with congenital leptin deficiency before and after leptin substitution
Beghini, M., Brandt, S., Körber, I., Kohlsdorf, K., Vollbach, H., Lennerz, B. S., Denzer, C., Shalitin, S., Santini, F., Blum, W. F., et al. (2021) · International Journal of Obesity · doi:10.1038/s41366-021-00809-2 · Cited by 20 · see citing works
GEOFFREY HARRIS PRIZE LECTURE 2018: Novel pathways regulating neuroendocrine function, energy homeostasis and metabolism in humans
Papathanasiou, A. E., Nolen-Doerr, E., Farr, O. M., & Mantzoros, C. S. (2019) · European Journal of Endocrinology · doi:10.1530/eje-18-0847 · Cited by 20 · see citing works
The Impact of Obstructive Sleep Apnea and Positive Airway Pressure Therapy on Metabolic Peptides Regulating Appetite, Food Intake, Energy Homeostasis, and Systemic Inflammation: A Literature Review
Mashaqi, S., & Badr, M. S. (2019) · Journal of Clinical Sleep Medicine · doi:10.5664/jcsm.7890 · Cited by 20 · see citing works
Alterations in Mouse Hypothalamic Adipokine Gene Expression and Leptin Signaling following Chronic Spinal Cord Injury and with Advanced Age
Bigford, G. E., Bracchi-Ricard, V. C., Nash, M. S., & Bethea, J. R. (2012) · PLoS ONE · doi:10.1371/journal.pone.0041073 · Cited by 20 · see citing works
Testicular Disorders
Matsumoto, A. M., & Bremner, W. J. (2016) · Elsevier eBooks · doi:10.1016/b978-0-323-29738-7.00019-8 · Cited by 18 · see citing works
Testicular disorders.
Matsumoto, A. M., & Bremner, W. J. (2011) · Williams Textbook of Endocrinology · doi:10.1016/b978-1-4377-0324-5.00019-5 · Cited by 18 · see citing works
Total and H-specific GDF-15 levels increase in caloric deprivation independently of leptin in humans
Chrysafi, P., Valenzuela‐Vallejo, L., Stefanakis, K., Kelesidis, T., Connelly, M. A., & Mantzoros, C. S. (2024) · Nature Communications · doi:10.1038/s41467-024-49366-y · Cited by 17 · see citing works
Self-citation
A Critical Assessment of Fasting to Promote Metabolic Health and Longevity
Fazeli, P. K., & Steinhauser, M. L. (2025) · Endocrine Reviews · doi:10.1210/endrev/bnaf021 · Cited by 19 · see citing works
Serum leptin level as a diagnostic and prognostic marker in infectious diseases and sepsis
Bîrluțiu, V., & Boicean, L. C. (2021) · Medicine · doi:10.1097/md.0000000000025720 · Cited by 16 · see citing works
Metabolic surgery-induced changes of the growth hormone system relate to improved adipose tissue function
Gancheva, S., KAHL, S., Herder, C., Straßburger, K., Sarabhai, T., Pafili, K., Szendroedi, J., Schlensak, M., & Roden, M. (2023) · International Journal of Obesity · doi:10.1038/s41366-023-01292-7 · Cited by 15 · see citing works
Pre- and postnatal nutrition in sheep affects β-cell secretion and hypothalamic control
Kongsted, A. H., Husted, S. V., Thygesen, M. P., Christensen, V. G., Blache, D., Tolver, A., Larsen, T., Quistorff, B., & Nielsen, M. O. (2013) · Journal of Endocrinology · doi:10.1530/joe-13-0099 · Cited by 14 · see citing works
Weight Regain after Metabolic Surgery: Beyond the Surgical Failure
Salazar, J. J., Durán, P., Garrido, B., Parra, H., Hernández, M., Cano, C., Áñez, R., García-Pacheco, H., Cubillos-Valencia, G., Vasquez, N., et al. (2024) · Journal of Clinical Medicine · doi:10.3390/jcm13041143 · Cited by 13 · see citing works
Growth Hormone
Bonert, V. S., & Melmed, S. K. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-804169-7.00004-0 · Cited by 14 · see citing works
Adaptive Responses in Severe Acute Malnutrition: Endocrinology, Metabolomics, Mortality, and Growth
PAGE, L. C., McCain, E., & Freemark, M. (2025) · Nutrients · doi:10.3390/nu17172864 · Cited by 15 · see citing works
Circulating levels of the components of the GH/IGF-1/IGFBPs axis total and intact IGF-binding proteins (IGFBP) 3 and IGFBP 4 and total IGFBP 5, as well as PAPPA, PAPPA2 and Stanniocalcin-2 levels are not altered in response to energy deprivation and/or metreleptin administration in humans
Pilitsi, E., Peradze, N., Perakakis, N., & Mantzoros, C. S. (2019) · Metabolism · doi:10.1016/j.metabol.2019.05.004 · Cited by 12 · see citing works
Self-citation
Longitudinal proteomics of leptin treatment in humans with acute and chronic energy deficiency-induced hypoleptinemia reveal novel, mainly immune-related, pleiotropic effects
Stefanakis, K., Samiotaki, M. K., Papaevangelou, V., Valenzuela‐Vallejo, L., Giannoukakis, N., & Mantzoros, C. S. (2024) · Metabolism · doi:10.1016/j.metabol.2024.155984 · Cited by 11 · see citing works
Self-citation
Body Fat as a Regulator of Bone Mass: Experimental Evidence from Animal Models
Hamrick, M. W., Della‐Fera, M. A., Baile, C. A., Pollock, N. K., & Lewis, R. D. (2009) · Clinical Reviews in Bone and Mineral Metabolism · doi:10.1007/s12018-009-9046-6 · Cited by 8 · see citing works
Metabolism updates: new directions, techniques, and exciting research that is broadening the horizons
Boutari, C., Bouzoni, E., Joshi, A., Stefanakis, K., Farr, O. M., & Mantzoros, C. S. (2019) · Metabolism · doi:10.1016/j.metabol.2019.154009 · Cited by 6 · see citing works
Self-citation
Adipokines and Metabolism
Ahima, R. S., Scolaro, L. M., & Park, H.-K. (2016) · Springer eBooks · doi:10.1007/978-3-319-11251-0_24 · Cited by 5 · see citing works
Effect of exercise on hormonal responses in adolescents with obesity and leptin resistance: a randomized trial
Jeong, D., Valentine, R. J., Park, K. O., Jeong, H., Hong, J., & Kang, S. (2026) · Scientific Reports · doi:10.1038/s41598-026-36045-9 · Cited by 4 · see citing works
Old and new tools to study human brain physiology: Current state, future directions and implications for metabolic regulation
Farr, O. M., & Mantzoros, C. S. (2019) · Metabolism · doi:10.1016/j.metabol.2019.153957 · Cited by 4 · see citing works
Self-citation
Growth Hormone
Herman-Bonert, V. S., & Melmed, S. K. (2010) · Elsevier eBooks · doi:10.1016/b978-0-12-380926-1.10004-5 · Cited by 4 · see citing works
Of mice and men: incretin actions in the central nervous system
Farr, O. M., Pilitsi, E., & Mantzoros, C. S. (2019) · Metabolism · doi:10.1016/j.metabol.2019.05.013 · Cited by 3 · see citing works
Self-citation
Early Growth and Development of Later Life Metabolic Disorders
Foo, J., & Mantzoros, C. S. (2013) · Nestlé Nutrition Institute Workshop series · doi:10.1159/000342570 · Cited by 3 · see citing works
Self-citation
Growth Hormone
Herman-Bonert, V. S., & Melmed, S. K. (2022) · Elsevier eBooks · doi:10.1016/b978-0-323-99899-4.00023-8 · Cited by 2 · see citing works
Adipokines and Metabolism
Ahima, R. S., Scolaro, L. M., & Park, H.-K. (2015) · Springer eBooks · doi:10.1007/978-3-319-12125-3_24-1 · Cited by 2 · see citing works
THE CENTRAL ROLE OF GLUCOSE IN METABOLISM AND NUTRITION OF CRITICALLY ILL PATIENTS
Skořepa, P., Sobotka, O., Fortunato, J., Blaha, V., & Horáček, J. M. (2017) · Military Medical Science Letters · doi:10.31482/mmsl.2017.026 · Cited by 2 · see citing works
Duration-Dependent Changes in Body Composition During Prolonged Fasting: A Systematic Review and Meta-Analysis
Ulupınar, S., Terzi, M., Çamli, A., Asan, S., Şeran, B., İnce, İ., Gençoglu, C., Çabuk, S., Yağan, E., & Özbay, S. (2026) · Nutrition Reviews · doi:10.1093/nutrit/nuag092 · Cited by 1 · see citing works
Secretion Patterns of Circulating Osteoprotegerin and Response to Acute and Chronic Energy Deprivation in Young Healthy Adults
Aronis, K. N., Foo, J., Chamberland, J. P., & Mantzoros, C. S. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2012-1618 · Cited by 1 · see citing works
Self-citation
Leptin Therapy in Women with Hypothalamic Amenorrhea
Chou, S. H.-H., & Mantzoros, C. S. (2014) · Springer eBooks · doi:10.1007/978-3-319-09915-6_19
Self-citation
4. Bone responses to weight and exercise in obese animal models
Tou, J. C. L., Baer, L. A., Wade, C. E., & Seem, M. (2016) · Wageningen Academic Publishers eBooks · doi:10.3920/978-90-8686-823-0_4
Leptin Hormone in Health and Disease: Overview
M, R. A., I, S. A., & Odeh, S. O. (2015)
Adipokines and Metabolism
Ahima, R. S., Scolaro, L. M., & Park, H.-K. (2017) · Springer eBooks · doi:10.1007/978-3-319-12125-3_24-2
Pituitary
Seejore, K., & Murray, R. D. (2020) · Encyclopedia of Life Sciences · doi:10.1002/9780470015902.a0029139
The Growth Hormone-IGF-1 Axis in Anorexia Nervosa
Khiyami, A. M., & Fazeli, P. K. (2022) · Springer eBooks · doi:10.1007/978-3-030-67929-3_39-1
The Growth Hormone-IGF-1 Axis in Anorexia Nervosa
Khiyami, A. M., & Fazeli, P. K. (2023) · Springer eBooks · doi:10.1007/978-3-031-16691-4_39
Effect of Ramadan Fasting on Circulating Leptin and Adiponectin Levels and Metabolic Profiles in Healthy Men Thai Muslim Population
Prasetya, G. (2016) · doi:10.58837/chula.the.2016.1592
Investigating the role of melanocortin system in regulating linear growth and growth hormone secretion
Tan, H. Y. (2014) · The University of Queensland · doi:10.14264/uql.2015.99
Association between IGF-1 levels and markers of nutritional status and inflammation in long-livers
Matchekhina, L. V., Shelley, E. M., Мамчур, А. А., Kashtanova, D. A., Rumyantseva, A. M., Yudin, V. S., Makarov, V. V., Keskinov, A. A., Александрович, К. С., Yudin, S. M., et al. (2026) · Russian Journal of Geriatric Medicine · doi:10.37586/2686-8636-2-2026-148-156

Growth hormone/insulin-like growth factor I axis, glucose metabolism, and lypolisis but not leptin show some degree of refractoriness to snort-term fasting in acromegaly
Grottoli, S., Gasco, V., Mainolfi, A., Beccuti, G., Corneli, G., Aimaretti, G., Diéguez, C., Casanueva, F. F., & Ghigo, E. (2008) · Journal of Endocrinological Investigation · doi:10.1007/bf03345660 · Cited by 11 · see citing works
Increased levels but preserved diurnal variation of serum leptin in GH-deficient patients: lack of impact of different modes of GH administration
Nørrelund, H., Gravholt, C. H., Englaro, P., Blum, W., Rascher, W., Chistiansen, J., & Jørgensen, J. O. L. (1998) · European Journal of Endocrinology · doi:10.1530/eje.0.1380644 · Cited by 23 · see citing works
Serum Leptin Response to the Acute and Chronic Administration of Growth Hormone (GH) to Elderly Subjects with GH Deficiency
Gill, M. S., Toogood, A. A., Jones, J., Clayton, P., & Shalet, S. M. (1999) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.84.4.5608 · Cited by 57 · see citing works
Short-Term Fasting Suppresses Leptin and (Conversely) Activates Disorderly Growth Hormone Secretion in Midluteal Phase Women—A Clinical Research Center Study1
Bergendahl, M., Evans, W. S., Pastor, C. L., Patel, A. C., Iranmanesh, A., & Veldhuis, J. D. (1999) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.84.3.5536 · Cited by 56 · see citing works
The Effect of Growth Hormone on the Insulin-Like Growth Factor System during Fasting
Nørrelund, H., Frystyk, J., Jørgensen, J. O. L., Møller, N., Christiansen, J. S., Ørskov, H., & Flyvbjerg, A. (2003) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2002-021983 · Cited by 35 · see citing works

Authors: Chan, J. L., Williams, C. J., Raciti, P., Blakeman, J., Kelesidis, T., Kelesidis, I., Johnson, M. L., Thorner, M. O., & Mantzoros, C. S.
Affiliations: Beth Israel Deaconess Medical Center (US)
Division of Endocrinology, Diabetes, and Metabolism (J.L.C., C.J.W., P.R., J.B., T.K., I.K., C.S.M.), Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215
University of Virginia Health System (US)
Corresponding author: Mantzoros, Christos S.
ORCID: Raciti, Patricia
Johnson, Michael L.
Thorner, Michael O.
Mantzoros, Christos S.
Venue: The Journal of Clinical Endocrinology & Metabolism
Publisher: The Endocrine Society
Published: 2008-07-01
Volume: 93
Issue: 7
Pages: 2819-2827
ISSN: 0021-972X (ISSN-L)
1945-7197
DOI: 10.1210/jc.2008-0056
PMC: PMC2453057
OpenAlex: W2118769775
Cited by: 75
References: 43
Citations by year: 2026: 3 · 2025: 2 · 2024: 5 · 2023: 3 · 2022: 2 · 2021: 3 · 2020: 1 · 2019: 5 · 2018: 3 · 2017: 5 · 2016: 9 · 2015: 3 · 2014: 6 · 2013: 6 · 2012: 4
FWCI: 3.62
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Beth Israel Deaconess Medical Center
Deutsches Krebsforschungszentrum
U.S. Public Health Service (R0-158785)
National Institute of Diabetes and Digestive and Kidney Diseases (R25DK064122)
National Center for Research Resources (M01-RR-01032, M01RR001032, R01RR019991, K23RR018860)
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
Keywords: leptin, growth hormone pulsatility, insulin-like growth factor I, negative energy balance, fasting, hypoleptinemia, recombinant human leptin, hypothalamic amenorrhea, IGF binding proteins, GH-binding protein, starvation adaptation
MeSH terms: Adult, Fasting, Female, Humans, Insulin-Like Growth Factor I, Male, Insulin-Like Growth Factor Binding Proteins, Human Growth Hormone, Leptin

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Leptin Does Not Mediate Short-Term Fasting-Induced Changes in Growth Hormone Pulsatility but Increases IGF-I in Leptin Deficiency States

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Cites

Cited by

Related

Record

About these checks