Leptin replacement alters brain response to food cues in genetically leptin-deficient adults.

Baicy, Kate; London, Edythe D.; Monterosso, John; Wong, Ma-Li; Delibasi, Tuncay; Sharma, Anil; Licinio, Julio

doi:10.1073/pnas.0706481104

Cited by 212Regulation of Appetite and ObesityAdipokines, Inflammation, and Metabolic DiseasesEating Disorders and Behaviors

Leptin replacement alters brain response to food cues in genetically leptin-deficient adults.

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Baicy, Kate, London, Edythe D., Monterosso, John, Wong, Ma-Li, Delibasi, Tuncay, Sharma, Anil, Licinio, Julio·2007·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.0706481104PMC PMC2084333

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Abstract

A missense mutation in the ob gene causes leptin deficiency and morbid obesity. Leptin replacement to three adults with this mutation normalized body weight and eating behavior. Because the neural circuits mediating these changes were unknown, we paired functional magnetic resonance imaging (fMRI) with presentation of food cues to these subjects. During viewing of food-related stimuli, leptin replacement reduced brain activation in regions linked to hunger (insula, parietal and temporal cortex) while enhancing activation in regions linked to inhibition and satiety (prefrontal cortex). Leptin appears to modulate feeding behavior through these circuits, suggesting therapeutic targets for human obesity.

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Normal individuals typically show this activity only in the starved state and do not show this response after eating.
“Normal individuals typically show this activity only in the starved state and do not show this response after eating.”
From Leptin at 14 y of age: an ongoing story (2009) · cites this paper as [53]
In leptin-deficient subjects, functional magnetic resonance imaging reveals a marked increase in activity in the nucleus accumbens in response to images of food even after eating.
“Consistent with this, functional magnetic resonance imaging of leptin-deficient subjects has revealed a marked increase in activity in the nucleus accumbens in response to images of food even after eating (52)(53)(54).”
From Leptin at 14 y of age: an ongoing story (2009) · cites this paper as [53]
Leptin-deficient patients show markedly different food preferences and perception of food than do normal individuals.
“In addition, leptin-deficient patients show markedly different food preferences and perception of food than do normal individuals (52)(53)(54).”
From Leptin at 14 y of age: an ongoing story (2009) · cites this paper as [53]
Leptin therapy normalizes the increased accumbens activity after eating in leptin-deficient patients.
“The activity that is seen in the accumbens in leptin-deficient patients after eating was normalized by the use of leptin therapy (52)(53)(54).”
From Leptin at 14 y of age: an ongoing story (2009) · cites this paper as [53]

An Integrative Theory of Prefrontal Cortex Function
Miller, E. K., & Cohen, J. D. (2001) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.24.1.167 · Cited by 12,803 · see citing works
Serum Immunoreactive-Leptin Concentrations in Normal-Weight and Obese Humans
Considine, R. V., Sinha, M. K., Heiman, M. L., Kriauciunas, A., Stephens, T. W., Nyce, M. R., Ohannesian, J. P., Marco, C. C., McKee, L. J., Bauer, T. L., et al. (1996) · New England Journal of Medicine · doi:10.1056/nejm199602013340503 · Cited by 6,326 · see citing works
Effects of the obese Gene Product on Body Weight Regulation in ob / ob Mice
Pelleymounter, M. A., Cullen, M. J., Baker, M. B., Hecht, R., Winters, D., Boone, T., & Collins, F. (1995) · Science · doi:10.1126/science.7624776 · Cited by 4,017 · see citing works
Neural systems supporting interoceptive awareness
Critchley, H. D., Wiens, S., Rotshtein, P., Öhman, A., & Dolan, R. J. (2004) · Nature Neuroscience · doi:10.1038/nn1176 · Cited by 3,406 · see citing works
The role of the medial frontal cortex in cognitive control
Ridderinkhof, K. R., Ullsperger, M., Crone, E. A., & Nieuwenhuis, S. (2004) · Science · doi:10.1126/science.1100301 · Cited by 2,974 · see citing works
The role of leptin and ghrelin in the regulation of food intake and body weight in humans: a review
Klok, M. D., Jakobsdottir, S., & Drent, M. L. (2007) · Obesity Reviews · doi:10.1111/j.1467-789x.2006.00270.x · Cited by 1,442 · see citing works
Recombinant Leptin for Weight Loss in Obese and Lean Adults: A Randomized, Controlled, Dose-Escalation Trial
Heymsfield, S. B., Greenberg, A. S., Fujioka, K., Dixon, R. M., Kushner, R., Hunt, T., Lubina, J. A., Patane, J., Self, B., Hunt, P., et al. (1999) · JAMA · doi:10.1001/jama.282.16.1568 · Cited by 1,422 · see citing works
Beneficial effects of leptin on obesity, T cell hyporesponsiveness, and neuroendocrine/metabolic dysfunction of human congenital leptin deficiency
Farooqi, I. S., Matarese, G., Lord, G. M., Keogh, J. M., Lawrence, E., Agwu, C., Sanna, V., Jebb, S. A., Perna, F., Fontana, S., et al. (2002) · Journal of Clinical Investigation · doi:10.1172/jci15693 · Cited by 1,359 · see citing works
Beneficial effects of leptin on obesity, T cell hyporesponsiveness, and neuroendocrine/metabolic dysfunction of human congenital leptin deficiency
Farooqi, I. S., Matarese, G., Lord, G. M., Keogh, J. M., Lawrence, E., Agwu, C., Sanna, V., Jebb, S. A., Perna, F., Fontana, S., et al. (2002) · Journal of Clinical Investigation · doi:10.1172/jci0215693 · Cited by 1,105 · see citing works
Activation of memory circuits during cue-elicited cocaine craving.
Grant, S., London, E. D., Newlin, D. B., Villemagne, V. L., Liu, X., Contoreggi, C., Phillips, R. L., Kimes, A. S., & Margolin, A. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.21.12040 · Cited by 936 · 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
Self-citation
Neuroanatomical correlates of hunger and satiation in humans using positron emission tomography
Tataranni, P. A., Gautier, J., Chen, K., Uecker, A., Bandy, D. J., Salbe, A. D., Pratley, R. E., Lawson, M. A., Reiman, E. M., & Ravussin, É. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.8.4569 · Cited by 592 · see citing works
Cortical and limbic activation during viewing of high- versus low-calorie foods
Killgore, W. D. S., Young, A. D., Femia, L. A., Bogorodzki, P., Rogowska, J., & Yurgelun-Todd, D. A. (2003) · NeuroImage · doi:10.1016/s1053-8119(03)00191-5 · Cited by 581 · see citing works
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
Self-citation
Exposure to appetitive food stimuli markedly activates the human brain
Wang, G.-J., Volkow, N. D., Telang, F., Jayne, M., Ma, J., Rao, M., Zhu, W., Wong, C. T., Pappas, N. R., Geliebter, A., et al. (2004) · NeuroImage · doi:10.1016/j.neuroimage.2003.11.026 · Cited by 402 · see citing works
The neural mechanisms of gustation: A distributed processing code
Simon, S. A., de Araujo, I. E., Gutierrez, R., & Nicolelis, M. A. L. (2006) · Nature reviews. Neuroscience · doi:10.1038/nrn2006 · Cited by 305 · see citing works
Differential brain responses to satiation in obese and lean men.
Gautier, J., Chen, K., Salbe, A. D., Bandy, D. J., Pratley, R. E., Heiman, M. L., Ravussin, É., Reiman, E. M., & Tataranni, P. A. (2000) · Diabetes · doi:10.2337/diabetes.49.5.838 · Cited by 283 · see citing works
Congenital Leptin Deficiency Due to Homozygosity for the Δ133G Mutation: Report of Another Case and Evaluation of Response to Four Years of Leptin Therapy
Gibson, W. T., Farooqi, I. S., Moreau, M., DePaoli, A. M., Lawrence, E., O’Rahilly, S., & Trussell, R. A. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2004-0376 · Cited by 275 · see citing works
Successful dieters have increased neural activity in cortical areas involved in the control of behavior
DelParigi, A., Chen, K., Salbe, A. D., Hill, J. O., Wing, R. R., Reiman, E. M., & Tataranni, P. A. (2007) · International Journal of Obesity · doi:10.1038/sj.ijo.0803431 · Cited by 255 · see citing works
Effect of Satiation on Brain Activity in Obese and Lean Women
Gautier, J., Parigi, A. D., Chen, K., Salbe, A. D., Bandy, D. J., Pratley, R. E., Ravussin, É., Reiman, E. M., & Tataranni, P. A. (2001) · Obesity Research · doi:10.1038/oby.2001.92 · Cited by 207 · see citing works
Neuroimaging and obesity: mapping the brain responses to hunger and satiation in humans using positron emission tomography.
Parigi, A. D., Gautier, J., Chen, K., Salbe, A. D., Ravussin, É., Reiman, E. M., & Tataranni, P. A. (2002) · PubMed · Cited by 206 · see citing works
Neuroimaging and Obesity
Parigi, A. D., Gautier, J., CHEN, K., Salbe, A. D., Ravussin, É., Reiman, E. M., & Tataranni, P. A. (2002) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2002.tb04294.x · Cited by 192 · see citing works
Effect of Leptin Replacement on Brain Structure in Genetically Leptin-Deficient Adults
Matochik, J. A., London, E. D., Yıldız, B. O., Özata, M., Çağlayan, S., DePaoli, A. M., Wong, M., & Licinio, J. (2005) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2004-1979 · Cited by 181 · see citing works
Self-citation
The Long Form of the Leptin Receptor (OB-Rb) Is Widely Expressed in the Human Brain
Burguera, B. G., Couce, M., Long, J., Lamsam, J. L., LAAKSO, K., Jensen, M. D., Parisi, J. E., & Lloyd, R. V. (2000) · Neuroendocrinology · doi:10.1159/000054536 · Cited by 161 · see citing works
Changes in brain activation associated with reward processing in smokers and nonsmokers
Martin-Söelch, C., Magyar‐Lehmann, S., Künig, G., Missimer, J. H., Schultz, W., & Leenders, K. L. (2001) · Experimental Brain Research · doi:10.1007/s002210100751 · Cited by 118 · see citing works
Microanalysis of eating behavior of three leptin deficient adults treated with leptin therapy
Williamson, D. A., Ravussin, É., Wong, M., Wagner, A., DiPaoli, A., Çağlayan, S., Özata, M., Martin, C. K., Walden, H. M., Arnett, C., et al. (2005) · Appetite · doi:10.1016/j.appet.2005.01.002 · Cited by 51 · see citing works
Self-citation
Hunger and the temporal lobe
Fisher, C. (1994) · Neurology · doi:10.1212/wnl.44.9.1577 · Cited by 10 · see citing works

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Reward, dopamine and the control of food intake: implications for obesity
Volkow, N. D., Wang, G.-J., & Baler, R. D. (2011) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2010.11.001 · Cited by 1,400 · see citing works
Obesity and addiction: Neurobiological overlaps
Volkow, N. D., Wang, G. ‐., Tomasi, D., & Baler, R. D. (2013) · Obesity Reviews · doi:10.1111/j.1467-789x.2012.01031.x · Cited by 800 · see citing works
Reward mechanisms in obesity: new insights and future directions
Kenny, P. J. (2011) · Neuron · doi:10.1016/j.neuron.2011.02.016 · Cited by 748 · see citing works
Low dopamine striatal D2 receptors are associated with prefrontal metabolism in obese subjects: Possible contributing factors
Volkow, N. D., Wang, G.-J., Telang, F., Fowler, J. S., Thanos, P. K., Logan, J., Alexoff, D., Ding, Y.-S., Wong, C., Ma, Y., et al. (2008) · NeuroImage · doi:10.1016/j.neuroimage.2008.06.002 · Cited by 573 · see citing works
Dopamine Signaling in reward-related behaviors
Baik, J. (2013) · Frontiers in Neural Circuits · doi:10.3389/fncir.2013.00152 · Cited by 534 · see citing works
Neuroimaging and obesity: current knowledge and future directions
Carnell, S., Gibson, C., Benson, L., Ochner, C. N., & Geliebter, A. (2012) · Obesity Reviews · doi:10.1111/j.1467-789x.2011.00927.x · Cited by 441 · 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
Sixteen years and counting: an update on leptin in energy balance
Gautron, L., & Elmquist, J. K. (2011) · Journal of Clinical Investigation · doi:10.1172/jci45888 · Cited by 367 · see citing works
Fasting biases brain reward systems towards high‐calorie foods
Goldstone, A. P., Prechtl de Hernandez, C. G., Beaver, J. D., Muhammed, K., Croese, C., Bell, G., Durighel, G., Hughes, E., Waldman, A. D., Frost, G., et al. (2009) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2009.06949.x · Cited by 356 · see citing works
The Gut Hormones PYY3-36 and GLP-17-36 amide Reduce Food Intake and Modulate Brain Activity in Appetite Centers in Humans
Silva, A. D., Salem, V., Long, C. J., Makwana, A., Newbould, R. D., Rabiner, E. A., Ghatei, M. A., Bloom, S. R., Matthews, P. M., Beaver, J. D., et al. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.09.010 · Cited by 351 · see citing works
The defence of body weight: a physiological basis for weight regain after weight loss
Sumithran, P., & Proietto, J. (2013) · Clinical Science · doi:10.1042/cs20120223 · Cited by 310 · see citing works
Leptin in human physiology and therapeutics
Dardeno, T. A., Chou, S. H.-H., Moon, H., Chamberland, J. P., Fiorenza, C. G., & Mantzoros, C. S. (2010) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2010.06.002 · Cited by 288 · see citing works
Sleep restriction leads to increased activation of brain regions sensitive to food stimuli
St-Onge, M.-P., McReynolds, A., Trivedi, Z. B., Roberts, A. L., Sy, M., & Hirsch, J. (2012) · The American Journal of Clinical Nutrition · doi:10.3945/ajcn.111.027383 · Cited by 277 · see citing works
Leptin at 14 y of age: an ongoing story
Friedman, J. M. (2009) · The American Journal of Clinical Nutrition · doi:10.3945/ajcn.2008.26788b · Cited by 272 · see citing works
Genetics of eating behavior: established and emerging concepts
Grimm, E. R., & Steinle, N. (2011) · Nutrition Reviews · doi:10.1111/j.1753-4887.2010.00361.x · Cited by 247 · see citing works
Leptin applications in 2015: what have we learned about leptin and obesity?
Farr, O. M., Gavrieli, A., & Mantzoros, C. S. (2015) · Current Opinion in Endocrinology, Diabetes & Obesity · doi:10.1097/med.0000000000000184 · Cited by 233 · see citing works
The role of leptin in the control of insulin-glucose axis
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Dorsal Striatum and Its Limbic Connectivity Mediate Abnormal Anticipatory Reward Processing in Obesity
Nummenmaa, L., Hirvonen, J., Hannukainen, J. C., Immonen, H., Lindroos, M. M., Salminen, P., & Nuutila, P. (2012) · PLoS ONE · doi:10.1371/journal.pone.0031089 · Cited by 220 · see citing works
Leptin treatment: Facts and expectations
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Leptin signaling in brain: A link between nutrition and cognition?
Morrison, C. D. (2008) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2008.12.004 · Cited by 218 · see citing works
Circulating glucose levels modulate neural control of desire for high-calorie foods in humans
Page, K. A., Seo, D., Belfort-DeAguiar, R., Lacadie, C., Dzuira, J., Naik, S., Amarnath, S., Constable, R. T., Sherwin, R. S., & Sinha, R. (2011) · Journal of Clinical Investigation · doi:10.1172/jci57873 · Cited by 212 · see citing works
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Ahima, R. S. (2008) · Journal of Clinical Investigation · doi:10.1172/jci36284 · Cited by 204 · see citing works
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Wang, C., Chan, J. S. Y., Ren, L., & Yan, J. H. (2016) · Neural Plasticity · doi:10.1155/2016/2473081 · Cited by 199 · see citing works
Sex-based differences in the behavioral and neuronal responses to food
Cornier, M.-A., Salzberg, A. K., Endly, D. C., Bessesen, D. H., & Tregellas, J. R. (2010) · Physiology & Behavior · doi:10.1016/j.physbeh.2010.01.008 · Cited by 196 · see citing works
Leptin at the Intersection of Neuroendocrinology and Metabolism: Current Evidence and Therapeutic Perspectives
Dalamaga, Μ., Chou, S. H.-H., Shields, K. S., Papageorgiou, P., Pοlyzos, S. A., & Mantzoros, C. S. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.05.010 · Cited by 191 · see citing works
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Schur, E. A., Kleinhans, N. M., Goldberg, J. H., Buchwald, D., Schwartz, M. W., & Maravilla, K. R. (2009) · International Journal of Obesity · doi:10.1038/ijo.2009.56 · Cited by 170 · see citing works
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Cornier, M., Salzberg, A. K., Endly, D. C., Bessesen, D. H., Rojas, D. C., & Tregellas, J. R. (2009) · PLoS ONE · doi:10.1371/journal.pone.0006310 · Cited by 154 · see citing works
Leptin Replacement Improves Cognitive Development
Paz-Filho, G., Babikian, T., Asarnow, R. F., Esposito, K. F., Erol, H. K., Wong, M., & Licinio, J. (2008) · PLoS ONE · doi:10.1371/journal.pone.0003098 · Cited by 152 · see citing works
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Evero, N., Hackett, L. C., Clark, R. D., Phelan, S., & Hagobian, T. A. (2012) · Journal of Applied Physiology · doi:10.1152/japplphysiol.01365.2011 · Cited by 150 · see citing works
Leptin and the brain: Influences on brain development, cognitive functioning and psychiatric disorders
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Selective deletion of the leptin receptor in dopamine neurons produces anxiogenic-like behavior and increases dopaminergic activity in amygdala
Liu, J., Perez, S. M., Zhang, W., Lodge, D. J., & Lu, X.-Y. (2011) · Molecular Psychiatry · doi:10.1038/mp.2011.36 · Cited by 118 · see citing works
Integrative Hedonic and Homeostatic Food Intake Regulation by the Central Nervous System: Insights from Neuroimaging
Campos, A., Port, J. D., & Acosta, A. J. (2022) · Brain Sciences · doi:10.3390/brainsci12040431 · Cited by 115 · see citing works
A functional neuroimaging review of obesity, appetitive hormones and ingestive behavior
Burger, K. S., & Berner, L. A. (2014) · Physiology & Behavior · doi:10.1016/j.physbeh.2014.04.025 · Cited by 110 · see citing works
The Use of Functional MRI to Study Appetite Control in the CNS
Silva, A. D., Salem, V., Matthews, P. M., & Dhillo, W. S. (2012) · Experimental Diabetes Research · doi:10.1155/2012/764017 · Cited by 105 · see citing works
Congenital leptin deficiency: diagnosis and effects of leptin replacement therapy
Paz-Filho, G., Mastronardi, C. A., Delibaşı, T., Wong, M., & Licinio, J. (2010) · Arquivos Brasileiros de Endocrinologia & Metabologia · doi:10.1590/s0004-27302010000800005 · Cited by 104 · see citing works
Self-citation
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Paz-Filho, G., Wong, M., & Licinio, J. (2010) · International Journal of Clinical Practice · doi:10.1111/j.1742-1241.2010.02536.x · Cited by 103 · see citing works
Self-citation
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Higgs, S., Spetter, M. S., Thomas, J. M., Rotshtein, P., Lee, M. D., Hallschmid, M., & Dourish, C. T. (2017) · Journal of Psychopharmacology · doi:10.1177/0269881117736917 · Cited by 103 · see citing works
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Jastreboff, A. M., Sinha, R., Arora, J., Giannini, C., Kubat, J., Malik, S., Van Name, M. A., Santoro, N., Savoye, M., Duran, E. J., et al. (2016) · Diabetes · doi:10.2337/db15-1216 · Cited by 97 · see citing works
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Valerio, A., Dossena, M., Bertolotti, P., Boroni, F., Sarnico, I., Faraco, G., Chiarugi, A., Frontini, A., Giordano, A., Liou, H., et al. (2008) · Stroke · doi:10.1161/strokeaha.108.528588 · Cited by 92 · see citing works
Sleep and food intake: A multisystem review of mechanisms in children and adults
Lundahl, A., & Nelson, T. D. (2015) · Journal of Health Psychology · doi:10.1177/1359105315573427 · Cited by 88 · see citing works
The neuropathology of obesity: insights from human disease
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Ribeiro, A. C. D. M., Ceccarini, G., Dupré, C., Friedman, J. M., Pfaff, D. W., & Mark, A. L. (2011) · PLoS ONE · doi:10.1371/journal.pone.0023364 · Cited by 81 · see citing works
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An atlas of G-protein coupled receptor expression and function in human subcutaneous adipose tissue
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The impact of obesity-related SNP on appetite and energy intake
Dougkas, A., Yaqoob, P., Givens, D. I., Reynolds, C. K., & Minihane, A. M. (2013) · British Journal Of Nutrition · doi:10.1017/s0007114513000147 · Cited by 79 · see citing works
The role of leptin and ghrelin in the regulation of appetite in obesity
Skoracka, K., Hryhorowicz, S., Schulz, P., Zawada, A. E., Ratajczak, A. E., Rychter, A. M., Słomski, R., Dobrowolska, A., & Krela‐Kaźmierczak, I. (2025) · Peptides · doi:10.1016/j.peptides.2025.171367 · Cited by 74 · see citing works
Association of dopamine D2 receptor and leptin receptor genes with clinically severe obesity
Carpenter, C. L., Wong, A., Li, Z., Noble, E. P., & Heber, D. (2013) · Obesity · doi:10.1002/oby.20202 · Cited by 74 · see citing works
Peptide hormones regulating appetite—focus on neuroimaging studies in humans
Schloegl, H., Percik, R., Horstmann, A., Villringer, A., & Stumvoll, M. (2011) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.1154 · Cited by 70 · see citing works
Clinical Trials Required to Assess Potential Benefits and Side Effects of Treatment of Patients With Anorexia Nervosa With Recombinant Human Leptin
Hebebrand, J., Milos, G. F., Wabitsch, M., Teufel, M., Führer, D., Bühlmeier, J., Libuda, L., Ludwig, C., & Antel, J. (2019) · Frontiers in Psychology · doi:10.3389/fpsyg.2019.00769 · Cited by 68 · see citing works
Insights into amylin–leptin synergy
Trevaskis, J. L., Parkes, D. G., & Roth, J. D. (2010) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2010.03.006 · Cited by 68 · see citing works
Brain imaging studies of appetite in the context of obesity and the menstrual cycle
Vugt, D. A. V. (2009) · Human Reproduction Update · doi:10.1093/humupd/dmp051 · Cited by 68 · see citing works
Dopamine-related frontostriatal abnormalities in obesity and binge-eating disorder: Emerging evidence for developmental psychopathology
Michaelides, M., Thanos, P. K., Volkow, N. D., & Wang, G. (2012) · International Review of Psychiatry · doi:10.3109/09540261.2012.679918 · Cited by 65 · see citing works
Association of Body Mass and Brain Activation during Gastric Distention: Implications for Obesity
Tomasi, D., Wang, G.-J., Wang, R., Backus, W., Geliebter, A., Telang, F., Jayne, M. C., Wong, C., Fowler, J. S., & Volkow, N. D. (2009) · PLoS ONE · doi:10.1371/journal.pone.0006847 · Cited by 64 · 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
Leptin Therapy in a Congenital Leptin-Deficient Patient Leads to Acute and Long-Term Changes in Homeostatic, Reward, and Food-Related Brain Areas
Frank, S., Heni, M., Moß, A., von Schnurbein, J., Fritsche, A., Häring, H., Farooqi, I. S., Preissl, H. T., & Wabitsch, M. (2011) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2010-2713 · Cited by 62 · see citing works
The role of hypoleptinemia in the psychological and behavioral adaptation to starvation: Implications for anorexia nervosa
Hebebrand, J., Hildebrandt, T., Schlögl, H., Seitz, J., Denecke, S., Vieira, D. B., Gradl-Dietsch, G., Peters, T., Antel, J., Lau, D., et al. (2022) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2022.104807 · Cited by 61 · see citing works
Neuroimaging, Gut Peptides and Obesity: Novel Studies of the Neurobiology of Appetite
Gibson, C. D., Carnell, S., Ochner, C. N., & Geliebter, A. (2010) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2010.02025.x · Cited by 61 · see citing works
Eight weeks of supplementation with a multi-ingredient weight loss product enhances body composition, reduces hip and waist girth, and increases energy levels in overweight men and women
Lopez, H. L., Ziegenfuss, T. N., Hofheins, J. E., Habowski, S. M., Arent, S. M., Weir, J. P., & Ferrando, A. A. (2013) · Journal of the International Society of Sports Nutrition · doi:10.1186/1550-2783-10-22 · Cited by 59 · see citing works
Brain structure predicts risk for obesity
Smucny, J., Cornier, M., Eichman, L. C., Thomas, E. A., Bechtell, J. L., & Tregellas, J. R. (2012) · Appetite · doi:10.1016/j.appet.2012.08.027 · Cited by 57 · see citing works
Impact of the neural correlates of stress and cue reactivity on stress related binge eating in the natural environment
Fischer, S. F., Breithaupt, L. E., Wonderlich, J. A., Westwater, M. L., Crosby, R. D., Engel, S. G., Thompson, J., Lavender, J. M., & Wonderlich, S. A. (2017) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2017.03.017 · Cited by 55 · see citing works
Neuroimaging in Eating Disorders and Obesity: Implications for Research
den Eynde, F. V., & Treasure, J. L. (2008) · Child and Adolescent Psychiatric Clinics of North America · doi:10.1016/j.chc.2008.07.016 · Cited by 51 · see citing works
Changes in insulin sensitivity during leptin replacement therapy in leptin-deficient patients
Paz-Filho, G., Esposito, K. F., Hurwitz, B. E., Sharma, A. M., Dong, C., Andreev, V., Delibaşı, T., Erol, H. K., Ayala, A. R., Wong, M., et al. (2008) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90450.2008 · Cited by 50 · see citing works
Self-citation
The Adipokines in Cancer Cachexia
Mannelli, M., Gamberi, T., Magherini, F., & Fiaschi, T. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21144860 · Cited by 50 · see citing works
Fat Mass and Obesity-Associated Gene (FTO) Is Linked to Higher Plasma Levels of the Hunger Hormone Ghrelin and Lower Serum Levels of the Satiety Hormone Leptin in Older Adults
Benedict, C., Axelsson, T., Söderberg, S., Larsson, A. O., Ingelsson, E., Lind, L., & Schiöth, H. B. (2014) · Diabetes · doi:10.2337/db14-0470 · Cited by 50 · see citing works
Functional Magnetic Resonance Imaging Analysis of Food-Related Brain Activity in Patients with Lipodystrophy Undergoing Leptin Replacement Therapy
Aotani, D., Ebihara, K., Sawamoto, N., Kusakabe, T., Aizawa‐Abe, M., Yamamoto‐Kataoka, S., Sakai, T., Iogawa, H., Ebihara, C., Fujikura, J., et al. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2012-1872 · Cited by 49 · see citing works
Leptin resistance and the response to positive energy balance
Morrison, C. D. (2008) · Physiology & Behavior · doi:10.1016/j.physbeh.2008.04.009 · Cited by 49 · see citing works
Evidence from clinical studies of leptin: current and future clinical applications in humans
Perakakis, N., & Mantzoros, C. S. (2024) · Metabolism · doi:10.1016/j.metabol.2024.156053 · Cited by 48 · see citing works
Food Addiction and Neuroimaging
Zhang, Y., von Deneen, K. M., Tian, J., Gold, M. S., & Liu, Y. (2011) · Current Pharmaceutical Design · doi:10.2174/138161211795656855 · Cited by 46 · see citing works
Neuroendocrinological mechanisms underlying impulsive and compulsive behaviors in obesity: a narrative review of fMRI studies
Steward, T., Miranda‐Olivos, R., Soriano‐Mas, C., & Fernández‐Aranda, F. (2019) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-019-09515-x · Cited by 46 · see citing works
Nutritional modulation of leptin expression and leptin action in obesity and obesity-associated complications
la Paz, S. M., Pérez‐Pérez, A., Vilariño‐García, T., Jiménez‐Cortegana, C., Muriana, F. J. G., Millán-Linares, M. C., & Sánchez‐Margalet, V. (2020) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2020.108561 · Cited by 46 · see citing works
Differences in response to food stimuli in a rat model of obesity: in-vivo assessment of brain glucose metabolism
Thanos, P. K., Michaelides, M., Gispert, J. D., Pascau, J., Soto‐Montenegro, M. L., Desco, M., Wang, R., Wang, G.-J., & Volkow, N. D. (2008) · International Journal of Obesity · doi:10.1038/ijo.2008.50 · Cited by 46 · see citing works
Short-Term Plasticity of Gray Matter Associated with Leptin Deficiency and Replacement
London, E. D., Berman, S. M., Chakrapani, S., Delibaşı, T., Monterosso, J. R., Erol, H. K., Paz-Filho, G., Wong, M., & Licinio, J. (2011) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-0314 · Cited by 45 · see citing works
Self-citation
Leptin reduces food intake via a dopamine D2 receptor-dependent mechanism
Billes, S. K., Simonds, S. E., & Cowley, M. A. (2012) · Molecular Metabolism · doi:10.1016/j.molmet.2012.07.003 · Cited by 45 · see citing works
The neurohormonal regulation of energy intake in relation to bariatric surgery for obesity
Ochner, C. N., Gibson, C. D., Carnell, S., Dambkowski, C. L., & Geliebter, A. (2010) · Physiology & Behavior · doi:10.1016/j.physbeh.2010.04.032 · Cited by 45 · see citing works
Sensitivity to sweetness correlates to elevated reward brain responses to sweet and high-fat food odors in young healthy volunteers
Han, P., Mohebbi, M., Seo, H., & Hummel, T. R. (2019) · NeuroImage · doi:10.1016/j.neuroimage.2019.116413 · Cited by 42 · see citing works
Functional neuroimaging in obesity and the potential for development of novel treatments
Schlögl, H., Horstmann, A., Villringer, A., & Stümvoll, M. (2016) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(15)00475-1 · Cited by 41 · see citing works
A focus on reward in anorexia nervosa through the lens of the activity‐based anorexia rodent model
Foldi, C. J., Milton, L. K., & Oldfield, B. J. (2017) · Journal of Neuroendocrinology · doi:10.1111/jne.12479 · Cited by 40 · see citing works
Effects of leptin and ghrelin on neural cue-reactivity in alcohol addiction: Two streams merge to one river?
Bach, P., Bumb, J. M., Schuster, R., Vollstädt‐Klein, S., Reinhard, I., Rietschel, M., Witt, S. H., Wiedemann, K., Kiefer, F., & Koopmann, A. (2018) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2018.09.026 · Cited by 40 · see citing works
Functional Neuroimaging in Craniopharyngioma: A Useful Tool to Better Understand Hypothalamic Obesity?
Roth, C. L., Aylward, E., Liang, O., Kleinhans, N. M., Pauley, G., & Schur, E. A. (2012) · Obesity Facts · doi:10.1159/000338695 · Cited by 40 · see citing works
Differences in brain responses between lean and obese women to a sweetened drink
Connolly, L., Coveleskie, K., Kilpatrick, L. A., Labus, J. S., Ebrat, B., Stains, J., Jiang, Z., Tillisch, K., Raybould, H. E., & Mayer, E. A. (2013) · Neurogastroenterology & Motility · doi:10.1111/nmo.12125 · Cited by 38 · see citing works
When Leptin Is Not There: A Review of What Nonsyndromic Monogenic Obesity Cases Tell Us and the Benefits of Exogenous Leptin
Salum, K. C. R., Rolando, J. D. M., Zembrzuski, V. M., Carneiro, J. R. I., Neto, C. B. D. M., Maya‐Monteiro, C. M., Bozza, P. T., Kohlrausch, F. B., & da Fonseca, A. C. P. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.722441 · Cited by 38 · see citing works
Gaining New Insights into Food Reward with Functional Neuroimaging
Neary, M. T., & Batterham, R. L. (2009) · Forum of nutrition/Bibliotheca Nutritio et dieta · doi:10.1159/000264403 · Cited by 38 · see citing works
Abdominal fat distribution and its relationship to brain changes: the differential effects of age on cerebellar structure and function: a cross-sectional, exploratory study
Raschpichler, M., Straatman, K. R., Schroeter, M. L., Arélin, K., Schlögl, H., Fritzsch, D., Mende, M., Pampel, A., Böttcher, Y., Stümvoll, M., et al. (2013) · BMJ Open · doi:10.1136/bmjopen-2012-001915 · Cited by 38 · see citing works
Leptin in Early Life: A Key Factor for the Development of the Adult Metabolic Profile
Granado, M., Fuente-Martín, E., García‐Cáceres, C., Argente, J., & Chowen, J. A. (2012) · Obesity Facts · doi:10.1159/000336967 · Cited by 38 · see citing works
A Longitudinal Study on the Impact of Antipsychotic Treatment on Serum Leptin in Schizophrenia
Venkatasubramanian, G., Chittiprol, S., Neelakantachar, N., Shetty, T. K., & Gangadhar, B. N. (2010) · Clinical Neuropharmacology · doi:10.1097/wnf.0b013e3181fa2a6f · Cited by 38 · see citing works
The neural basis of emotions varies over time: different regions go with onset- and offset-bound processes underlying emotion intensity
Résibois, M., Verduyn, P., Delaveau, P., Rotgé, J., Kuppens, P., Mechelen, I. V., & Fossati, P. (2017) · Social Cognitive and Affective Neuroscience · doi:10.1093/scan/nsx051 · Cited by 38 · see citing works
Long-Term Stabilization Effects of Leptin on Brain Functions in a Leptin-Deficient Patient
Frank, S., Heni, M., Moß, A., von Schnurbein, J., Farooqi, I. S., Häring, H., Fritsche, A., Preissl, H. T., & Wabitsch, M. (2013) · PLoS ONE · doi:10.1371/journal.pone.0065893 · Cited by 37 · see citing works
Association between antipsychotic-induced metabolic side-effects and clinical improvement: A review on the Evidence for “metabolic threshold”
Sharma, E., Rao, N. P., & Venkatasubramanian, G. (2013) · Asian Journal of Psychiatry · doi:10.1016/j.ajp.2013.11.017 · Cited by 37 · see citing works
Leptin Substitution in Patients With Lipodystrophy: Neural Correlates for Long-term Success in the Normalization of Eating Behavior
Schlögl, H., Müller, K., Horstmann, A., Miehle, K., Püschel, J., Villringer, A., Pleger, B., Stümvoll, M., & Faßhauer, M. (2016) · Diabetes · doi:10.2337/db15-1550 · Cited by 36 · see citing works
Ghrelin and anorexia nervosa: A psychosomatic perspective
Ogiso, K., Asakawa, A., Amitani, H., & Inui, A. (2011) · Nutrition · doi:10.1016/j.nut.2011.05.005 · Cited by 35 · see citing works
Intranasal Neuropeptide Administration To Target the Human Brain in Health and Disease
Spetter, M. S., & Hallschmid, M. (2015) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.5b00047 · Cited by 35 · see citing works

Effects of Leptin Deficiency and Replacement on Cerebellar Response to Food-Related Cues
Berman, S. M., Paz-Filho, G., Wong, M., Kohno, M., Licinio, J., & London, E. D. (2012) · The Cerebellum · doi:10.1007/s12311-012-0360-z · Cited by 32 · see citing works
Self-citation
Leptin Regulates Striatal Regions and Human Eating Behavior
Farooqi, I. S., Bullmore, E., Keogh, J., Gillard, J., O'Rahilly, S., & Fletcher, P. C. (2007) · Science · doi:10.1126/science.1144599 · Cited by 622 · see citing works
Reward Processing During Monetary Incentive Delay Task After Leptin Substitution in Lipodystrophy—an fMRI Case Series
Schlögl, H., Janssen, L. K., Faßhauer, M., Miehle, K., Villringer, A., Stümvoll, M., & Mueller, K. (2023) · Journal of the Endocrine Society · doi:10.1210/jendso/bvad052 · Cited by 2 · see citing works
Leptin reverses weight loss–induced changes in regional neural activity responses to visual food stimuli
ROSENBAUM, M. S., Sy, M., Pavlovich, K. H., Leibel, R. L., & Joy Hirsch, C. (2008) · Journal of Clinical Investigation · doi:10.1172/jci35055 · Cited by 408 · see citing works
Leptin Therapy Alters Appetite and Neural Responses to Food Stimuli in Brain Areas of Leptin-Sensitive Subjects Without Altering Brain Structure
Farr, O. M., Fiorenza, C. G., Papageorgiou, P., Brinkoetter, M. T., Ziemke, F., Koo, B., Rojas, R., & Mantzoros, C. S. (2014) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2014-2774 · Cited by 46 · see citing works

Authors: Baicy, K., London, E. D., Monterosso, J., Wong, M.-L., Delibasi, T., Sharma, A., & Licinio, J.
Affiliations: University of California, Los Angeles (US)
Department of Psychiatry and Biobehavioral Sciences and Semel Institute, and
University of Miami (US)
Center for Pharmacogenomics, Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami, FL 33136; and
ORCID: London, Edythe D.
Monterosso, John
Wong, Ma-Li
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 2007-11-13
Volume: 104
Issue: 46
Pages: 18276-18279
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.0706481104
PMC: PMC2084333
OpenAlex: W2094808974
Cited by: 212
References: 27
Citations by year: 2026: 1 · 2025: 3 · 2024: 6 · 2023: 5 · 2022: 7 · 2021: 10 · 2020: 5 · 2019: 9 · 2018: 9 · 2017: 13 · 2016: 11 · 2015: 10 · 2014: 10 · 2013: 20 · 2012: 25
FWCI: 5.85
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute on Drug Abuse (DA021961, P20DA022539, DA 022539, R01DA020726, DA 020726, F30DA021961)
National Institute of General Medical Sciences (U01GM061394, GM-08042, GM061394, T32GM008042)
National Institute of Diabetes and Digestive and Kidney Diseases (DK 058851, R01DK063240, DK-063240, R01DK058851)
National Center for Research Resources (RR 016996, RR00865, K24RR017365, M01RR000865, K24RR016996, RR017365)
Topics: Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
Social Sciences › Psychology › Clinical Psychology › Eating Disorders and Behaviors
Keywords: leptin replacement, leptin deficiency, food cues, hunger, satiety, feeding behavior, insula, prefrontal cortex, obesity, brain activation, dietary habits
MeSH terms: Brain, Feeding Behavior, Humans, Magnetic Resonance Imaging, Leptin

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Leptin replacement alters brain response to food cues in genetically leptin-deficient adults.

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