Leptin Regulation of Neuroendocrine Systems

Ahima, Rexford S.; Saper, Clifford B.; Flier, Jeffrey S.; Elmquist, Joel K.

doi:10.1006/frne.2000.0197

Cited by 767Regulation of Appetite and ObesityHypothalamic control of reproductive hormonesAdipokines, Inflammation, and Metabolic Diseases

Leptin Regulation of Neuroendocrine Systems

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Ahima, Rexford S., Saper, Clifford B., Flier, Jeffrey S., Elmquist, Joel K.·2000·Frontiers in Neuroendocrinology

DOI 10.1006/frne.2000.0197

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Abstract

The discovery of leptin has enhanced understanding of the interrelationship between adipose energy stores and neuronal circuits in the brain involved in energy balance and regulation of the neuroendocrine axis. Leptin levels are dependent on the status of fat stores as well as changes in energy balance as a result of fasting and overfeeding. Although leptin was initially thought to serve mainly as an anti-satiety hormone, recent studies have shown that it mediates the adaptation to fasting. Furthermore, leptin has been implicated in the regulation of the reproductive, thyroid, growth hormone, and adrenal axes, independent of its role in energy balance. Although it is widely known that leptin acts on hypothalamic neuronal targets to regulate energy balance and neuroendocrine function, the specific neuronal populations mediating leptin action on feeding behavior and autonomic and neuroendocrine function are not well understood. In this review, we have discussed how leptin engages arcuate hypothalamic neurons expressing putative orexigenic peptides, e.g., neuropeptide Y and agouti-regulated peptide, and anorexigenic peptides, e.g., pro-opiomelanocortin (precursor of alpha-melanocyte-stimulating hormone) and cocaine- and amphetamine-regulated transcript. We show that leptin's effects on energy balance and the neuroendocrine axis are mediated by projections to other hypothalamic nuclei, e.g., paraventricular, lateral, and perifornical areas, as well as other sites in the brainstem, spinal cord, and cortical and subcortical regions.

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Sleep modulates the 24-hour pattern of secretion of leptin and ghrelin.
“Sleep modulates the 24 h pattern of secretion of two key hormones involved in energy balance regulation, i.e., leptin and ghrelin [1, 193].”
From Sleep and metabolic function (2012) · cites this paper as [1]
Leptin inhibits hunger and food intake, increases energy expenditure, and promotes fat utilization.
“Leptin inhibits hunger and food intake, increases EE, and promotes fat utilization [1, 193].”
From Sleep and metabolic function (2012) · cites this paper as [1]
Leptin is an adipocyte-derived hormone, a satiety factor secreted in proportion to the amount of body energy stores, and was one of the first factors linking metabolism with the reproductive axis.
“Leptin, an adipocyte-derived hormone, is a satiety factor secreted in proportion to the amount of body energy stores, and was one of the first factors linking metabolism with the reproductive axis.93”
From Pubertal development and regulation (2016) · cites this paper as [93]

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Licinio, J., Negrão, A. B., Mantzoros, C., Kaklamani, V., Wong, M.-L., Bongiorno, P. B., Mulla, A., Cearnal, L., Veldhuis, J. D., Flier, J. S., et al. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.5.2541 · Cited by 287 · see citing works
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Augmented Placental Production of Leptin in Preeclampsia: Possible Involvement of Placental Hypoxia1
Mise, H., Sagawa, N., Matsumoto, T., Yura, S., Nanno, H., Itoh, H., Mori, T., Masuzaki, H., Hosoda, K., Ogawa, Y., et al. (1998) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.83.9.5117 · Cited by 282 · see citing works
The projections of the dorsomedial hypothalamic nucleus in the rat
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Neuroendocrine Responses to Starvation and Weight Loss
Schwartz, M. W., & Seeley, R. J. (1997) · New England Journal of Medicine · doi:10.1056/nejm199706193362507 · Cited by 265 · see citing works
Testosterone Substitution Normalizes Elevated Serum Leptin Levels in Hypogonadal Men
Jockenhövel, F., Blum, W. F., Vogel, E., Englaro, P., Müller-Wieland, D., Reinwein, D., Rascher, W., & Krone, W. (1997) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.82.8.4174 · Cited by 261 · see citing works
Further studies on the anatomical distribution of CART by in situ hybridization
Couceyro, P. R., Koylu, E. O., & Kuhar, M. J. (1997) · Journal of Chemical Neuroanatomy · doi:10.1016/s0891-0618(97)00212-3 · Cited by 260 · see citing works
Regulation of ob gene mRNA levels in cultured adipocytes
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Threading analysis suggests that the obese gene product may be a helical cytokine
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Distinct Physiologic and Neuronal Responses to Decreased Leptin and Mild Hyperleptinemia1
Ahima, R. S., Kelly, J. F., Elmquist, J. K., & Flier, J. S. (1999) · Endocrinology · doi:10.1210/endo.140.11.7105 · Cited by 253 · see citing works
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Functional properties of leptin receptor isoforms: internalization and degradation of leptin and ligand-induced receptor downregulation.
Uotani, S., Bjørbæk, C., Tornøe, J., & Flier, J. S. (1999) · Diabetes · doi:10.2337/diabetes.48.2.279 · Cited by 253 · see citing works
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Daily Melatonin Administration at Middle Age Suppresses Male Rate Visceral Fat, Plasma Leptin, and Plasma Insulin to Youthful Levels
Rasmussen, D. D., Boldt, B. M., Wilkinson, C. W., Yellon, S. M., & Matsumoto, A. M. (1999) · Endocrinology · doi:10.1210/endo.140.2.6674 · Cited by 250 · see citing works
Toward a new neurobiology of energy balance, appetite, and obesity: The anatomists weigh in
Sawchenko, P. E. (1998) · The Journal of Comparative Neurology · doi:10.1002/(sici)1096-9861(19981228)402:4 · Cited by 248 · see citing works
The perifornical area: the major focus of (a) patchily distributed hypothalamic neuropeptide Y-sensitive feeding system(s)
Stanley, B. G., Magdalin, W., Seirafi, A., Thomas, W. J., & LEIBOWITZ, S. F. (1993) · Brain Research · doi:10.1016/0006-8993(93)90382-w · Cited by 246 · see citing works
Evidence for Leptin Binding to Proteins in Serum of Rodents and Humans: Modulation With Obesity
Houseknecht, K. L., Mantzoros, C. S., Kuliawat, R., Hadro, E., Flier, J. S., & Kahn, B. B. (1996) · Diabetes · doi:10.2337/diab.45.11.1638 · Cited by 245 · see citing works
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Relatively low plasma leptin concentrations precede weight gain in Pima Indians
Ravussin, É., Pratley, R. E., Maffei, M., Wang, H., Friedman, J. M., Bennett, P. H., & Bogardus, C. (1997) · Nature Medicine · doi:10.1038/nm0297-238 · Cited by 240 · see citing works
Central Administration of Leptin to Ovariectomized Ewes Inhibits Food Intake without Affecting the Secretion of Hormones from the Pituitary Gland: Evidence for a Dissociation of Effects on Appetite and Neuroendocrine Function
Henry, B. A., Goding, J. W., Alexander, W. S., Tilbrook, A. J., Canny, B. J., Dunshea, F. R., Rao, A., Mansell, A. S., & Clarke, I. J. (1999) · Endocrinology · doi:10.1210/en.140.3.1175 · Cited by 238 · see citing works
Genomic Structure and Promoter Analysis of the Human obese Gene
Gong, D.-W., Bi, S., Pratley, R. E., & Weintraub, B. D. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.8.3971 · Cited by 238 · see citing works
The distribution of growth‐hormone‐releasing factor (GRF) immunoreactivity in the central nervous system of the rat: An immunohistochemical study using antisera directed against rat hypothalamic GRF
Sawchenko, P. E., Swanson, L. W., Rivier, J., & Vale, W. (1985) · The Journal of Comparative Neurology · doi:10.1002/cne.902370108 · Cited by 236 · see citing works
Nitric Oxide Mediates Leptin-Induced Luteinizing Hormone-Releasing Hormone (LHRH) and LHRH and Leptin-Induced LH Release from the Pituitary Gland
Yu, W. H., Walczewska, A., Karanth, S., & McCann, S. M. (1997) · Endocrinology · doi:10.1210/endo.138.11.5649 · Cited by 234 · see citing works
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 Men1
Casabiell, X. A., Piñeiro, V., Peino, R., Lage, M., Camiña, J. P., Gallego, R., Vallejo, L. G., Diéguez, C., & Casanueva, F. F. (1998) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.83.6.4849 · Cited by 229 · see citing works
Phenotype of the Obese Koletsky (f) Rat Due to Tyr763Stop Mutation in the Extracellular Domain of the Leptin Receptor (Lepr): Evidence for Deficient Plasma-to-CSF Transport of Leptin in Both the Zucker and Koletsky Obese Rat
Wu-Peng, X. S., Chua, S. C., Okada, N. A., Liu, S.-M., Nicolson, M. A., & Leibel, R. L. (1997) · Diabetes · doi:10.2337/diab.46.3.513 · Cited by 225 · see citing works
The Weight-Reducing Effect of an Intracerebroventricular Bolus Injection of Leptin in Genetically Obese fa/fa Rats: Reduced Sensitivity Compared With Lean Animals
Cusin, I., Rohner‐Jeanrenaud, F., Stricker‐Krongrad, A., & Jeanrenaud, B. (1996) · Diabetes · doi:10.2337/diab.45.10.1446 · Cited by 212 · see citing works
Effects of Starvation in Rats on Serum Levels of Follicle Stimulating Hormone, Luteinizing Hormone, Thyrotropin, Growth Hormone and Prolactin; Response to LH-Releasing Hormone and Thyrotropin-Releasing Hormone
Campbell, G. A., Kurcz, M., Marshall, S., & Meites, J. (1977) · Endocrinology · doi:10.1210/endo-100-2-580 · Cited by 211 · see citing works
Nonsense mutation of leptin receptor in the obese spontaneously hypertensive Koletsky rat
Takaya, K., Ogawa, Y., Hiraoka, J., Hosoda, K., Yamori, Y., Nakao, K., & Koletsky, R. J. (1996) · Nature Genetics · doi:10.1038/ng1096-130 · Cited by 207 · see citing works
Short-term dexamethasone treatment increases plasma leptin independently of changes in insulin sensitivity in healthy women
Larsson, H. E., & Åhrén, B. (1996) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.81.12.8954054 · Cited by 207 · see citing works
Leptin Inhibits Directly Glucocorticoid Secretion by Normal Human and Rat Adrenal Gland**This work was supported by a grant from the Swiss National Science Foundation (No. 3100–050748.97/1).
Pralong, F. P., Roduit, R., Waeber, G., Castillo, E., Mosimann, F., Thorens, B., & Gaillard, R. C. (1998) · Endocrinology · doi:10.1210/endo.139.10.6254 · Cited by 202 · see citing works
Insulin in the brain: a hormonal regulator of energy balance
Schwartz, M. W. (1992) · Endocrine Reviews · doi:10.1210/er.13.3.387 · Cited by 201 · see citing works
Leptin Concentrations in the Polycystic Ovary Syndrome
Mantzoros, C. S., Dunaif, A. E., & Flier, J. S. (1997) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.82.6.4017 · Cited by 200 · see citing works
Self-citation
Arcuate nucleus neurons that project to the hypothalamic paraventricular nucleus: Neuropeptidergic identity and consequences of adrenalectomy on mRNA levels in the rat
Baker, R. A., & Herkenham, M. A. (1995) · The Journal of Comparative Neurology · doi:10.1002/cne.903580405 · Cited by 200 · see citing works
Dexamethasone Regulates Obese Expression in Isolated Rat Adipocytes
Murakami, T., Iida, M., & Shima, K. (1995) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1995.2422 · Cited by 200 · see citing works
Recombinant Porcine Leptin Reduces Feed Intake and Stimulates Growth Hormone Secretion in Swine
Barb, C. R., Yan, X., Azain, M. J., Kraeling, R. R., Rampacek, G. B., & Ramsay, T. G. (1998) · Domestic Animal Endocrinology · doi:10.1016/s0739-7240(97)00064-7 · Cited by 197 · see citing works
Interleukin 1α Increases Serum Leptin Concentrations in Humans
Janik, J. E., Curti, B. D., Considine, R. V., Rager, H., Powers, G. C., Alvord, W. G., Smith, J. W., Gause, B. L., & Kopp, W. C. (1997) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.82.9.4214 · Cited by 197 · see citing works
Leptin alters metabolic rates before acquisition of its anorectic effect in developing neonatal mice
Mistry, A. M., Swick, A. G., & Romsos, D. R. (1999) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1999.277.3.r742 · Cited by 193 · see citing works
OBESE, A NEW MUTATION IN THE HOUSE MOUSE*
Ingalls, A. M., Dickie, M. M., & Snell, G. D. (1996) · Obesity Research · doi:10.1002/j.1550-8528.1996.tb00519.x · Cited by 191 · see citing works
Augmented Placental Production of Leptin in Preeclampsia: Possible Involvement of Placental Hypoxia
Mise, H. (1998) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.83.9.3225 · Cited by 190 · see citing works
Reversal of the Sex Difference in Serum Leptin Levels upon Cross-Sex Hormone Administration in Transsexuals
Elbers, J. M. H., Asscheman, H., Seidell, J. C., Frölich, M., Meinders, A. E., & Gooren, L. J. (1997) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.82.10.4284 · Cited by 189 · see citing works
Glucocorticoid Regulation of Leptin Synthesis and Secretion in Humans: Elevated Plasma Leptin Levels in Cushing’s Syndrome1
Masuzaki, H., Ogawa, Y., Hosoda, K., Miyawaki, T., Hanaoka, I., Hiraoka, J., Yasuno, A., Nishimura, H., Yoshimasa, Y., Nishi, S., et al. (1997) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.82.8.4128 · Cited by 188 · see citing works
Transcriptional activation of the mouse obese (ob) gene by CCAAT/enhancer binding protein alpha.
Hwang, C.-S., Mandrup, S., MacDougald, O. A., Geiman, D. E., & Lane, M. D. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.2.873 · Cited by 184 · see citing works
Central infusions of leptin and GLP-1-(7-36) amide differentially stimulate c-FLI in the rat brain
van Dijk, G., Thiele, T. E., Donahey, J. C. K., Campfield, L. A., Smith, F. J., Burn, P., Bernstein, I. L., Woods, S. C., & Seeley, R. J. (1996) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1996.271.4.r1096 · Cited by 179 · see citing works
Leptin Is a Potent Stimulator of Spontaneous Pulsatile Growth Hormone (GH) Secretion and the GH Response to GH-Releasing Hormone*
Tannenbaum, G. S., Gurd, W., & Lapointe, M. (1998) · Endocrinology · doi:10.1210/endo.139.9.6206 · Cited by 177 · see citing works

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Brief communication: Sleep curtailment in healthy young men is associated with decreased leptin levels, elevated ghrelin levels, and increased hunger and appetite
Spiegel, K., Tasali, E., Penev, P., & Cauter, E. V. (2004) · Annals of Internal Medicine · doi:10.7326/0003-4819-141-11-200412070-00008 · Cited by 2,459 · see citing works
The Distribution and Mechanism of Action of Ghrelin in the CNS Demonstrates a Novel Hypothalamic Circuit Regulating Energy Homeostasis
Cowley, M. A., Smith, R. G., Diano, S., Tschöp, M., Pronchuk, N., Grove, K. L., Strasburger, C. J., Bidlingmaier, M., Esterman, M., Heiman, M. L., et al. (2003) · Neuron · doi:10.1016/s0896-6273(03)00063-1 · Cited by 1,679 · see citing works
Physiological role of adipose tissue: white adipose tissue as an endocrine and secretory organ
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Trophic Action of Leptin on Hypothalamic Neurons That Regulate Feeding
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Sleep loss: a novel risk factor for insulin resistance and type 2 diabetes
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The Need to Feed
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Obesity and leptin resistance: distinguishing cause from effect
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The endocrine function of adipose tissue: an update
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Leptin directly activates SF1 neurons in the VMH, and this action by leptin is required for normal body-weight homeostasis
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Mouse models in non‐alcoholic fatty liver disease and steatohepatitis research
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Targeting adipose tissue in the treatment of obesity-associated diabetes
Kusminski, C. M., Bickel, P. E., & Scherer, P. E. (2016) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.75 · Cited by 678 · see citing works
Pubertal development and regulation
Abreu, A. P., & Kaiser, U. B. (2016) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(15)00418-0 · Cited by 611 · see citing works
Control of energy homeostasis and insulin action by adipocyte hormones: leptin, acylation stimulating protein, and adiponectin
Havel, P. J. (2002) · Current Opinion in Lipidology · doi:10.1097/00041433-200202000-00008 · Cited by 575 · see citing works
Puberty : ontogeny, neuroendocrinology, physiology, and disorders
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Leptin targets in the mouse brain
Scott, M. M., Lachey, J. L., Sternson, S. M., Lee, C. E., Elias, C. F., Friedman, J. M., & Elmquist, J. K. (2009) · Journal of Comparative Neurology · doi:10.1002/cne.22025 · Cited by 484 · see citing works
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Central Control of Body Weight and Appetite
Woods, S. C., & D’Alessio, D. A. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-1630 · Cited by 460 · see citing works
Obesity in Adult Survivors of Childhood Acute Lymphoblastic Leukemia: A Report from the Childhood Cancer Survivor Study
Oeffinger, K. C., Mertens, A. C., Sklar, C. A., Yasui, Y., Fears, T. R., Stovall, M., Vik, T. A., Inskip, P. D., & Robison, L. L. (2003) · Journal of Clinical Oncology · doi:10.1200/jco.2003.06.131 · Cited by 451 · see citing works
Association of Plasma Leptin Levels With Incident Alzheimer Disease and MRI Measures of Brain Aging
Lieb, W. (2009) · JAMA · doi:10.1001/jama.2009.1836 · Cited by 428 · see citing works
Convergence between bone and energy homeostases: Leptin regulation of bone mass
Karsenty, G. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.10.008 · Cited by 415 · see citing works
Evidence That the Caudal Brainstem Is a Target for the Inhibitory Effect of Leptin on Food Intake
Grill, H. J., Schwartz, M. W., Kaplan, J. M., Foxhall, J. S., Breininger, J., & Baskin, D. G. (2002) · Endocrinology · doi:10.1210/endo.143.1.8589 · Cited by 395 · see citing works
The Neuroanatomical Axis for Control of Energy Balance
Grill, H. J., & Kaplan, J. M. (2002) · Frontiers in Neuroendocrinology · doi:10.1006/frne.2001.0224 · Cited by 395 · see citing works
Brain Regulation of Appetite and Satiety
Ahima, R. S., & Antwi, D. A. (2008) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2008.08.005 · Cited by 387 · see citing works
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Novel signals for the integration of energy balance and reproduction
Fernandez-Fernandez, R., Martini, A. C., Navarro, V. M., Castellano, J. M., Diéguez, C., Aguilar, E., Pinilla, L., & Tena‐Sempere, M. (2006) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2006.04.026 · Cited by 385 · see citing works
Biological Rhythm and Chronotype: New Perspectives in Health
Montaruli, A., Castelli, L., Mulè, A., Scurati, R., Esposito, F., Galasso, L., & Roveda, E. (2021) · Biomolecules · doi:10.3390/biom11040487 · Cited by 366 · see citing works
The Neuroendocrinology of Human Puberty Revisited
Grumbach, M. M. (2002) · Hormone Research in Paediatrics · doi:10.1159/000058094 · Cited by 362 · see citing works
The TRH neuron: a hypothalamic integrator of energy metabolism
Lechan, R. M., & Fekete, C. (2006) · Progress in brain research · doi:10.1016/s0079-6123(06)53012-2 · Cited by 338 · see citing works
Nicotinic receptor‐mediated effects on appetite and food intake
Jo, Y., Talmage, D. A., & Role, L. W. (2002) · Journal of Neurobiology · doi:10.1002/neu.10147 · Cited by 323 · see citing works
Interactions between sleep, circadian function, and glucose metabolism: implications for risk and severity of diabetes
Reutrakul, S., & Van Cauter, E. (2014) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.12355 · Cited by 321 · see citing works
Leptin signaling
Ahima, R. S., & Osei, S. Y. (2004) · Physiology & Behavior · doi:10.1016/j.physbeh.2004.02.014 · Cited by 315 · see citing works
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Adipokines and the Peripheral and Neural Control of Energy Balance
Ahima, R. S., & Lazar, M. A. (2008) · Molecular Endocrinology · doi:10.1210/me.2007-0529 · Cited by 314 · see citing works
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Gastrointestinal Satiety Signals I. An overview of gastrointestinal signals that influence food intake
Woods, S. C. (2004) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00448.2003 · Cited by 311 · see citing works
Neuroendocrinology of nutritional infertility
Wade, G. N., & Jones, J. E. (2004) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00475.2004 · Cited by 296 · see citing works
Profiling Gene Transcription In Vivo Reveals Adipose Tissue as an Immediate Target of Tumor Necrosis Factor-α
Ruan, H., Miles, P. D. G., Ladd, C. M., Ross, K. N., Golub, T. R., Olefsky, J. M., & Lodish, H. F. (2002) · Diabetes · doi:10.2337/diabetes.51.11.3176 · Cited by 297 · see citing works
The Geometry of Leptin Action in the Brain: More Complicated Than a Simple ARC
Myers, M. G., Münzberg, H., Leinninger, G. M., & Leshan, R. L. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2008.12.001 · Cited by 294 · see citing works
Role of sleep duration in the regulation of glucose metabolism and appetite
Morselli, L., Leproult, R., Balbo, M., & Spiegel, K. (2010) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2010.07.005 · Cited by 283 · see citing works
Metabolic liver disease of obesity and role of adipose tissue in the pathogenesis of nonalcoholic fatty liver disease
Qureshi, K. (2007) · World Journal of Gastroenterology · doi:10.3748/wjg.v13.i26.3540 · Cited by 282 · see citing works
Pancreatic signals controlling food intake; insulin, glucagon and amylin
Woods, S. C., Lutz, T. A., Geary, N., & Langhans, W. (2006) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2006.1858 · Cited by 286 · see citing works
Role of leptin in the control of feeding of goldfish Carassius auratus: interactions with cholecystokinin, neuropeptide Y and orexin A, and modulation by fasting
Volkoff, H., Eykelbosh, A., & Peter, R. E. (2003) · Brain Research · doi:10.1016/s0006-8993(03)02507-1 · Cited by 271 · see citing works
Obesity and dyslipidemia
Franssen, R., Monajemi, H., Stroes, E. S. G., & Kastelein, J. J. P. (2011) · Medical Clinics of North America · doi:10.1016/j.mcna.2011.06.003 · Cited by 270 · see citing works
Insulin and Leptin as Adiposity Signals
Benoit, S. C. (2004) · Recent Progress in Hormone Research · doi:10.1210/rp.59.1.267 · Cited by 266 · see citing works
Characterizaton of Short Isoforms of the Leptin Receptor in Rat Cerebral Microvessels and of Brain Uptake of Leptin in Mouse Models of Obesity
Hileman, S. M., Pierroz, D. D., Masuzaki, H., Bjørbæk, C., El-Haschimi, K., Banks, W. A., & Flier, J. S. (2002) · Endocrinology · doi:10.1210/endo.143.3.8669 · Cited by 267 · see citing works
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The Regulation of Glucose-Excited Neurons in the Hypothalamic Arcuate Nucleus by Glucose and Feeding-Relevant Peptides
Wang, R., Liu, X., Hentges, S. T., Dunn-Meynell, A. A., Levin, B. E., Wang, W., & Routh, V. H. (2004) · Diabetes · doi:10.2337/diabetes.53.8.1959 · Cited by 267 · see citing works
Maternal and Postnatal Overnutrition Differentially Impact Appetite Regulators and Fuel Metabolism
Chen, H., Simar, D., Lambert, K., Mercier, J. G., & Morris, M. J. (2008) · Endocrinology · doi:10.1210/en.2008-0582 · Cited by 263 · see citing works
Adipokines: New potential therapeutic target for obesity and metabolic, rheumatic, and cardiovascular diseases
Recinella, L., Orlando, G., Ferrante, C., Chiavaroli, A., Brunetti, L., & Leone, S. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2020.578966 · Cited by 261 · see citing works
Cephalic phase responses and appetite
Smeets, P. A. M., Erkner, A., & de Graaf, C. (2010) · Nutrition Reviews · doi:10.1111/j.1753-4887.2010.00334.x · Cited by 263 · see citing works
Analysis of paradoxical observations on the association between leptin and insulin resistance
Ceddia, R. B., Koistinen, H. A., Zierath, J. R., & Sweeney, G. (2002) · The FASEB Journal · doi:10.1096/fj.02-0158rev · Cited by 256 · see citing works
Longitudinal Changes in Obesity and Body Mass Index Among Adult Survivors of Childhood Acute Lymphoblastic Leukemia: A Report From the Childhood Cancer Survivor Study
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Authors: Ahima, R. S., Saper, C. B., Flier, J. S., & Elmquist, J. K.
Affiliations: University of Pennsylvania (US)
Beth Israel Deaconess Medical Center (US)
ORCID: Ahima, Rexford S.
Saper, Clifford B.
Flier, Jeffrey S.
Elmquist, Joel K.
Venue: Frontiers in Neuroendocrinology
Publisher: Elsevier BV
Published: 2000-07
Volume: 21
Issue: 3
Pages: 263-307
ISSN: 0091-3022 (ISSN-L)
DOI: 10.1006/frne.2000.0197
OpenAlex: W2039347019
Cited by: 767
References: 310
Citations by year: 2026: 9 · 2025: 6 · 2024: 6 · 2023: 20 · 2022: 19 · 2021: 11 · 2020: 25 · 2019: 26 · 2018: 22 · 2017: 15 · 2016: 28 · 2015: 22 · 2014: 42 · 2013: 27 · 2012: 36
FWCI: 16.04
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc-nd
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
creativecommons.org/licenses/by-nc-nd/4.0/ (vor, 1058 d)
Locations: Frontiers in Neuroendocrinology (publishedVersion, cc-by-nc-nd)
PubMed (publishedVersion)
Funders: National Institute of Diabetes and Digestive and Kidney Diseases (DK-48506, DK53301, R01DK048506)
National Institute of Neurological Disorders and Stroke (NS 33987, R01NS033987)
Topics: Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
Keywords: leptin, neuroendocrine regulation, energy balance, hypothalamus, arcuate nucleus, neuropeptide Y, agouti-related protein, proopiomelanocortin, cocaine- and amphetamine-regulated transcript, feeding behavior, fasting adaptation, reproductive axis, hypothalamic-pituitary-thyroid axis, growth hormone axis, adrenal axis, hypothalamic projections
MeSH terms: Animals, Biological Transport, Brain, Energy Metabolism, Homeostasis, Humans, Neurosecretory Systems, Leptin

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Leptin Regulation of Neuroendocrine Systems

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