Cited by 367Regulation of Appetite and ObesityAdipokines, Inflammation, and Metabolic DiseasesHypothalamic control of reproductive hormones

The DOI matches its Crossref record; 129 of the 129 references it cites were found in a registry or an index.

Sixteen years and counting: an update on leptin in energy balance

Open access

Gautron, Laurent, Elmquist, Joel K.·2011·Journal of Clinical Investigation

DOI 10.1172/jci45888PMC PMC3104762

Open this paper in CoChat — free account Open PDF

Abstract

Cloned in 1994, the ob gene encodes the protein hormone leptin, which is produced and secreted by white adipose tissue. Since its discovery, leptin has been found to have profound effects on behavior, metabolic rate, endocrine axes, and glucose fluxes. Leptin deficiency in mice and humans causes morbid obesity, diabetes, and various neuroendocrine anomalies, and replacement leads to decreased food intake, normalized glucose homeostasis, and increased energy expenditure. Here, we provide an update on the most current understanding of leptin-sensitive neural pathways in terms of both anatomical organization and physiological roles.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1172/jci45888

Cites

129 of 129 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

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?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Positional cloning of the mouse obese gene and its human homologue
Zhang, Y., Proenca, R., Maffei, M., Barone, M., Leopold, L., & Friedman, J. M. (1994) · Nature · doi:10.1038/372425a0 · Cited by 13,419
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
Weight-Reducing Effects of the Plasma Protein Encoded by the obese Gene
Halaas, J. L., Gajiwala, K. S., Maffei, M., Cohen, S. L., Chait, B. T., Rabinowitz, D., Lallone, R. L., Burley, S. K., & Friedman, J. M. (1995) · Science · doi:10.1126/science.7624777 · Cited by 4,451
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
Leptin levels in human and rodent: Measurement of plasma leptin and ob RNA in obese and weight-reduced subjects
Maffei, M., Halaas, J., Ravussin, E., Pratley, R. E., Lee, G. H., Zhang, Y., Fei, H., Kim, S., Lallone, R., Ranganathan, S., et al. (1995) · Nature Medicine · doi:10.1038/nm1195-1155 · Cited by 3,725
Identification and expression cloning of a leptin receptor, OB-R.
Tartaglia, L. A., Dembski, M., Weng, X., Deng, N., Culpepper, J., Devos, R., Richards, G. J., Campfield, L. A., Clark, F. T., Deeds, J., et al. (1995) · Cell · doi:10.1016/0092-8674(95)90151-5 · Cited by 3,496
Recombinant Mouse OB Protein: Evidence for a Peripheral Signal Linking Adiposity and Central Neural Networks
Campfield, L. A., Smith, F. J., Guisez, Y., Devos, R., & Burn, P. (1995) · Science · doi:10.1126/science.7624778 · Cited by 3,243
Positive reinforcement produced by electrical stimulation of septal area and other regions of rat brain.
Olds, J., & Milner, P. (1954) · Journal of Comparative and Physiological Psychology · doi:10.1037/h0058775 · Cited by 3,176
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
Congenital leptin deficiency is associated with severe early-onset obesity in humans
Montague, C. T., Farooqi, I. S., Whitehead, J. P., Soos, M. A., Rau, H., Wareham, N. J., Sewter, C. P., Digby, J. E., Mohammed, S. N., Hurst, J. A., et al. (1997) · Nature · doi:10.1038/43185 · Cited by 2,936
Leptin levels reflect body lipid content in mice: Evidence for diet-induced resistance to leptin action
Frederich, R. C., Hamann, A., Anderson, S., Löllmann, B., Lowell, B. B., & Flier, J. S. (1995) · Nature Medicine · doi:10.1038/nm1295-1311 · Cited by 1,660
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 1,374
Trophic Action of Leptin on Hypothalamic Neurons That Regulate Feeding
Bouret, S. G., Draper, S. J., & Simerly, R. B. (2004) · Science · doi:10.1126/science.1095004 · Cited by 1,247
Leptin-Replacement Therapy for Lipodystrophy
Oral, E. A., Simha, V., Ruiz, E., Andewelt, A., Premkumar, A., Snell, P., Wagner, A. J., DePaoli, A. M., Reitman, M. L., Taylor, S. I., et al. (2002) · New England Journal of Medicine · doi:10.1056/nejmoa012437 · Cited by 1,247 · cited 1×
“(25, 26) and completely reverses the obese phenotype of leptindeficient individuals (27, 28).”
Background
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
Agouti protein is an antagonist of the melanocyte-stimulating-hormone receptor
Lu, D., Willard, D. H., Patel, I. R., Kadwell, S. H., Overton, L. K., Kost, T., Luther, M., Chen, W., Woychik, R. P., Wilkison, W. O., et al. (1994) · Nature · doi:10.1038/371799a0 · Cited by 1,075
Phenotypes of Mouse diabetes and Rat fatty Due to Mutations in the OB (Leptin) Receptor
Chua, S. C., Chung, W. K., Wu-Peng, X. S., Zhang, Y., Liu, S.-M., Tartaglia, L. A., & Leibel, R. L. (1996) · Science · doi:10.1126/science.271.5251.994 · Cited by 1,071
Hypothalamic lesions and adiposity in the rat
Hetherington, A. W., & Ranson, S. W. (1940) · The Anatomical Record · doi:10.1002/ar.1090780203 · Cited by 1,028
Rapid Rewiring of Arcuate Nucleus Feeding Circuits by Leptin
Pinto, S., Roseberry, A. G., Liu, H., Diano, S., Shanabrough, M., Cai, X., Friedman, J. M., & Horvath, T. L. (2004) · Science · doi:10.1126/science.1089459 · Cited by 987
Receptor-mediated regional sympathetic nerve activation by leptin.
Haynes, W. G., Morgan, D. A., Walsh, S. A., Mark, A. L., & Sivitz, W. I. (1997) · Journal of Clinical Investigation · doi:10.1172/jci119532 · Cited by 979
Obesity and leptin resistance: distinguishing cause from effect
Myers, M. G., Leibel, R. L., Seeley, R. J., & Schwartz, M. W. (2010) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2010.08.002 · Cited by 943
Leptin receptor signaling in POMC neurons is required for normal body weight homeostasis
Balthasar, N., Coppari, R., McMinn, J., Liu, S. M., Lee, C. E., Tang, V., Kenny, C. D., McGovern, R. A., Chua, S. C., Elmquist, J. K., et al. (2004) · Neuron · doi:10.1016/j.neuron.2004.06.004 · Cited by 935
Self-citation
Leptin Differentially Regulates NPY and POMC Neurons Projecting to the Lateral Hypothalamic Area
Elias, C. F., Aschkenasi, C., Lee, C., Kelly, J., Ahima, R. S., Bjorbæk, C., Flier, J. S., Saper, C. B., & Elmquist, J. K. (1999) · Neuron · doi:10.1016/s0896-6273(01)80035-0 · Cited by 924
Self-citation
Leptin Receptor Signaling in Midbrain Dopamine Neurons Regulates Feeding
Hommel, J. D., Trinko, R., Sears, R. M., Georgescu, D., Liu, Z.-W., Gao, X.-B., Thurmon, J. J., Marinelli, M., & DiLeone, R. J. (2006) · Neuron · doi:10.1016/j.neuron.2006.08.023 · Cited by 902
The full-length leptin receptor has signaling capabilities of interleukin 6-type cytokine receptors.
Baumann, H., Morella, K. K., White, D. W., Dembski, M., Bailon, P., Kim, H., Lai, C. F., & Tartaglia, L. A. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.16.8374 · Cited by 827
Leptin Activates Hypothalamic CART Neurons Projecting to the Spinal Cord
Elias, C. F., Lee, C., Kelly, J., Aschkenasi, C. J., Ahima, R. S., Couceyro, P. R., Kuhar, M. J., Saper, C. B., & Elmquist, J. K. (1998) · Neuron · doi:10.1016/s0896-6273(00)80656-x · Cited by 809
Self-citation
Leptin reverses insulin resistance and hepatic steatosis in patients with severe lipodystrophy
Petersen, K. F., Oral, E. A., Dufour, S., Befroy, D., Ariyan, C., Yu, C., Cline, G. W., DePaoli, A. M., Taylor, S. I., Gorden, P., et al. (2002) · Journal of Clinical Investigation · doi:10.1172/jci0215001 · Cited by 800 · cited 1×
“(25, 26) and completely reverses the obese phenotype of leptindeficient individuals (27, 28).”
Background
Leptin directly activates SF1 neurons in the VMH, and this action by leptin is required for normal body-weight homeostasis
Dhillon, H., Zigman, J. M., Ye, C., Lee, C. E., McGovern, R. A., Tang, V., Kenny, C. D., Christiansen, L. M., White, R. D., Edelstein, E. A., et al. (2006) · Neuron · doi:10.1016/j.neuron.2005.12.021 · Cited by 791
Self-citation
Proopiomelanocortin Neurons Are Direct Targets for Leptin in the Hypothalamus
Cheung, C. C., Clifton, D. K., & Steiner, R. A. (1997) · Endocrinology · doi:10.1210/endo.138.10.5570 · Cited by 769
OVERWEIGHT AND OBESITY
Wit, J. M., & Ranke, M. B. (2007) · Hormone Research · doi:10.1159/000112056 · Cited by 732
Acute stimulation of glucose metabolism in mice by leptin treatment
Kamohara, S., Burcelin, R., Halaas, J. L., Friedman, J. M., & Charron, M. J. (1997) · Nature · doi:10.1038/38717 · Cited by 708
Localization of a "Feeding Center" in the Hypothalamus of the Rat
Anand, B. K., & Brobeck, J. R. (1951) · Experimental Biology and Medicine · doi:10.3181/00379727-77-18766 · Cited by 670
Selective deletion of leptin receptor in neurons leads to obesity
Cohen, P., Zhao, C., Cai, X., Montez, J. M., Rohani, S., Feinstein, P. G., Mombaerts, P., & Friedman, J. M. (2001) · Journal of Clinical Investigation · doi:10.1172/jci13914 · Cited by 664
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
Handbook of obesity
Bray, G. A., & Bouchard, C. (1997) · CRC Press eBooks · Cited by 618
Studies on the Physiological Functions of the Melanocortin System
Cone, R. D. (2006) · Endocrine Reviews · doi:10.1210/er.2006-0034 · Cited by 615
Key enzyme in leptin-induced anorexia
Niswender, K. D., Morton, G. J., Stearns, W. H., Rhodes, C. J., Myers, M. G., & Schwartz, M. W. (2001) · Nature · doi:10.1038/35101657 · Cited by 585
Low-dose leptin reverses skeletal muscle, autonomic, and neuroendocrine adaptations to maintenance of reduced weight
Rosenbaum, M. (2005) · Journal of Clinical Investigation · doi:10.1172/jci25977 · Cited by 575
Selective deletion of leptin receptor in neurons leads to obesity
Cohen, P., Zhao, C., Cai, X., et al. (2001) · Journal of Clinical Investigation · doi:10.1172/jci200113914 · Cited by 554
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
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
Self-citation
The hypothalamic arcuate nucleus: A key site for mediating leptin’s effects on glucose homeostasis and locomotor activity
Coppari, R., Ichinose, M., Lee, C. E., Pullen, A. E., Kenny, C. D., McGovern, R. A., Tang, V., Liu, S. M., Ludwig, T., Chua, S. C., et al. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2004.12.004 · Cited by 457
Self-citation
Synaptic input organization of the melanocortin system predicts diet-induced hypothalamic reactive gliosis and obesity
Horváth, T. L., Sármán, B., García‐Cáceres, C., Enriori, P. J., Sótonyi, P., Shanabrough, M., Borók, E., Argente, J., Chowen, J. A., Pérez–Tilve, D., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1004282107 · Cited by 446
Synergistic interaction between leptin and cholecystokinin to reduce short-term food intake in lean mice
Barrachina, M. D., Martínez, V., Wang, L., Wei, J. Y., & Taché, Y. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.19.10455 · Cited by 440
Gluttony, sloth and the metabolic syndrome: a roadmap to lipotoxicity
Unger, R. H., & Scherer, P. E. (2010) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2010.01.009 · Cited by 436
Modulation of Brain Reward Circuitry by Leptin
Fulton, S. E., Woodside, B. C., & Shizgal, P. (2000) · Science · doi:10.1126/science.287.5450.125 · Cited by 421
Leptin Acts via Leptin Receptor-Expressing Lateral Hypothalamic Neurons to Modulate the Mesolimbic Dopamine System and Suppress Feeding
Leinninger, G. M., Jo, Y.-H., Leshan, R. L., Louis, G. W., Yang, H., Barrera, J. G., Wilson, H., Opland, D. M., Faouzi, M. A., Gong, Y., et al. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2009.06.011 · Cited by 412
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
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
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
Serum Adiponectin and Leptin Levels in Patients with Lipodystrophies
Haque, W. A., Shimomura, I., Matsuzawa, Y., & Garg, A. (2002) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.87.5.8624 · Cited by 394
Complete rescue of obesity, diabetes, and infertility in db/db mice by neuron-specific LEPR-B transgenes
de Luca, C., Kowalski, T. J., Zhang, Y., Elmquist, J. K., Lee, C., Kilimann, M. W., Ludwig, T. E., Liu, S.-M., & Chua, S. C. (2005) · Journal of Clinical Investigation · doi:10.1172/jci24059 · Cited by 385
Self-citation
Leptin activates distinct projections from the dorsomedial and ventromedial hypothalamic nuclei
Elmquist, J. K., Ahima, R. S., Elias, C. F., Flier, J. S., & Saper, C. B. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.2.741 · Cited by 376
Self-citation
Acute effects of leptin require PI3K signaling in hypothalamic proopiomelanocortin neurons in mice
Hill, J. W., Williams, K. W., Ye, C., Luo, J., Balthasar, N., Coppari, R., Cowley, M. A., Cantley, L. C., Lowell, B. B., & Elmquist, J. K. (2008) · Journal of Clinical Investigation · doi:10.1172/jci32964 · Cited by 362
Self-citation
Ghrelin in the regulation of body weight and metabolism
Castañeda, T. R., Tong, J., Datta, R., Culler, M. D., & Tschöp, M. H. (2009) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2009.10.008 · Cited by 361
Leptin controls adipose tissue lipogenesis via central, STAT3–independent mechanisms
Buettner, C., Muse, E. D., Cheng, A. M., Chen, L., Scherer, T., Pocai, A., Su, K., Cheng, B., Li, X., Harvey-White, J. D., et al. (2008) · Nature Medicine · doi:10.1038/nm1775 · Cited by 352
Transcriptional regulation of the thyrotropin-releasing hormone gene by leptin and melanocortin signaling
Harris, M., Aschkenasi, C., Elias, C. F., Chandrankunnel, A., Nillni, E. A., Bjørbæk, C., Elmquist, J. K., Flier, J. S., & Hollenberg, A. N. (2001) · Journal of Clinical Investigation · doi:10.1172/jci10741 · Cited by 341
Self-citation
Collective and individual functions of leptin receptor modulated neurons controlling metabolism and ingestion
van de Wall, E., Leshan, R., Xu, A. W., Balthasar, N., Coppari, R., Liu, S. M., Jo, Y. H., MacKenzie, R. G., Allison, D. B., Dun, N. J., et al. (2008) · Endocrinology · doi:10.1210/en.2007-1132 · Cited by 338
Role of signal transducer and activator of transcription 3 in regulation of hypothalamic proopiomelanocortin gene expression by leptin
Münzberg, H., Huo, L., Nillni, E. A., Hollenberg, A. N., & Bjørbæk, C. (2003) · Endocrinology · doi:10.1210/en.2002-221037 · Cited by 328
Leptin therapy in insulin-deficient type I diabetes
Wang, M.-Y., Chen, L., Clark, G. O., Lee, Y., Stevens, R. D., Ilkayeva, O. R., Wenner, B. R., Bain, J. R., Charron, M. J., Newgard, C. B., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0909422107 · Cited by 327
Short Term Effects of Leptin on Hepatic Gluconeogenesis and in Vivo Insulin Action
Rossetti, L., Massillon, D., Barzilai, N., Vuguin, P., Chen, W., Hawkins, M., Wu, J., & Wang, J. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.44.27758 · Cited by 304
Microinjection of leptin into the ventromedial hypothalamus increases glucose uptake in peripheral tissues in rats.
Minokoshi, Y., Haque, M. S., & Shimazu, T. (1999) · Diabetes · doi:10.2337/diabetes.48.2.287 · Cited by 302
The Central Melanocortin System Can Directly Regulate Serum Insulin Levels*
Fan, W., Dinulescu, D. M., Butler, A. A., Zhou, J., Marks, D. L., & Cone, R. D. (2000) · Endocrinology · doi:10.1210/endo.141.9.7665 · Cited by 294
Leptin action in the forebrain regulates the hindbrain response to satiety signals
Morton, G. J., Blevins, J. E., Williams, D. L., Niswender, K. D., Gelling, R. W., Rhodes, C. J., Baskin, D. G., & Schwartz, M. W. (2005) · Journal of Clinical Investigation · doi:10.1172/jci22081 · Cited by 253
Enhanced leptin sensitivity and improved glucose homeostasis in mice lacking suppressor of cytokine signaling-3 in POMC-expressing cells
Kievit, P., Howard, J. K., Badman, M. K., Balthasar, N., Coppari, R., Mori, H., Lee, C. E., Elmquist, J. K., Yoshimura, A., & Flier, J. S. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.06.010 · Cited by 247
Self-citation
Endogenous Leptin Signaling in the Caudal Nucleus Tractus Solitarius and Area Postrema Is Required for Energy Balance Regulation
Hayes, M. R., Skibicka, K. P., Leichner, T. M., Guarnieri, D. J., Dileone, R., Bence, K. K., & Grill, H. J. (2010) · Cell Metabolism · doi:10.1016/j.cmet.2009.10.009 · Cited by 245
Leptin therapy improves insulin-deficient type 1 diabetes by CNS-dependent mechanisms in mice
Fujikawa, T., Chuang, J.-C., Sakata, I., Ramadori, G., & Coppari, R. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1008025107 · Cited by 225
Intracerebroventricular Leptin Regulates Hepatic but Not Peripheral Glucose Fluxes
Liu, L., Karkanias, G. B., Morales, J. C., Hawkins, M., Barzilai, N., Wang, J., & Rossetti, L. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.47.31160 · Cited by 222
Selective Loss of Leptin Receptors in the Ventromedial Hypothalamic Nucleus Results in Increased Adiposity and a Metabolic Syndrome
Bingham, N. C., Anderson, K. K., Reuter, A. L., Stallings, N. R., & Parker, K. L. (2008) · Endocrinology · doi:10.1210/en.2007-1200 · Cited by 221
Making insulin-deficient type 1 diabetic rodents thrive without insulin
Yu, X., Park, B.-H., Wang, M.-Y., Wang, Z. V., & Unger, R. H. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0806993105 · Cited by 219
Role of the sympathetic nervous system and insulin in enhancing glucose uptake in peripheral tissues after intrahypothalamic injection of leptin in rats
Haque, M. S., Minokoshi, Y., Hamai, M., Iwai, M., Horiuchi, M., & Shimazu, T. (1999) · Diabetes · doi:10.2337/diabetes.48.9.1706 · Cited by 215
The arcuate nucleus as a primary site of satiety effect of leptin in rats
Satoh, N., Ogawa, Y., Katsuura, G., Hayase, M., Tsuji, T., Imagawa, K., Yoshimasa, Y., Nishi, S., Hosoda, K., & Nakao, K. (1997) · Neuroscience Letters · doi:10.1016/s0304-3940(97)00163-8 · Cited by 213
Leptin replacement alters brain response to food cues in genetically leptin-deficient adults.
Baicy, K., London, E. D., Monterosso, J., Wong, M.-L., Delibasi, T., Sharma, A., & Licinio, J. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0706481104 · Cited by 212
Brain Stem Is a Direct Target for Leptin’s Action in the Central Nervous System
Hosoi, T., Kawagishi, T., Okuma, Y., Tanaka, J., & Nomura, Y. (2002) · Endocrinology · doi:10.1210/en.2002-220077 · Cited by 204
Leptin restores euglycemia and normalizes glucose turnover in insulin-deficient diabetes in the rat.
Chinookoswong, N., Wang, J. L., & Shi, Z. Q. (1999) · Diabetes · doi:10.2337/diabetes.48.7.1487 · Cited by 197
Satiety effect and sympathetic activation of leptin are mediated by hypothalamic melanocortin system
Satoh, N., Ogawa, Y., Katsuura, G., Numata, Y., Masuzaki, H., Yoshimasa, Y., & Nakao, K. (1998) · Neuroscience Letters · doi:10.1016/s0304-3940(98)00401-7 · Cited by 188
Functional Role of Suppressor of Cytokine Signaling 3 Upregulation in Hypothalamic Leptin Resistance and Long-Term Energy Homeostasis
Reed, A. S., Unger, E. K., Olofsson, L. E., Piper, M. L., Myers, M. G., & Xu, A. W. (2010) · Diabetes · doi:10.2337/db09-1024 · Cited by 176
The development of obesity, hyperinsulinemia, and hyperglycemia in ob/ob mice
Dubuc, P. U. (1976) · Metabolism · doi:10.1016/0026-0495(76)90109-8 · Cited by 175
Intraventricular insulin and leptin decrease sucrose self-administration in rats
Figlewicz, D. P., Bennett, J. L., Naleid, A. M., Davis, C. D., & Grimm, J. W. (2006) · Physiology & Behavior · doi:10.1016/j.physbeh.2006.07.023 · Cited by 170
Inactivation of Signal Transducer and Activator of Transcription 3 in Proopiomelanocortin (Pomc) Neurons Causes Decreased Pomc Expression, Mild Obesity, and Defects in Compensatory Refeeding
Xu, A. W., Marie, L. S., Kaelin, C. B., & Barsh, G. S. (2006) · Endocrinology · doi:10.1210/en.2006-1119 · Cited by 169
Dominant Role of the p110β Isoform of PI3K over p110α in Energy Homeostasis Regulation by POMC and AgRP Neurons
Al‐Qassab, H., Smith, M. A., Irvine, E. E., Guillermet‐Guibert, J., Claret, M., Choudhury, A. I., Selman, C., Piipari, K., Clements, M., Lingard, S. J., et al. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2009.09.008 · Cited by 165
Hypothalamic Leptin Signaling Regulates Hepatic Insulin Sensitivity via a Neurocircuit Involving the Vagus Nerve
German, J., Kim, F., Schwartz, G. J., Havel, P. J., Rhodes, C. J., Schwartz, M. W., & Morton, G. J. (2009) · Endocrinology · doi:10.1210/en.2009-0445 · Cited by 164
Direct Innervation of GnRH Neurons by Metabolic- and Sexual Odorant-Sensing Leptin Receptor Neurons in the Hypothalamic Ventral Premammillary Nucleus
Leshan, R. L., Louis, G. W., Jo, Y., Rhodes, C. J., Münzberg, H., & Myers, M. G. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.0155-09.2009 · Cited by 162
Arcuate Nucleus-Specific Leptin Receptor Gene Therapy Attenuates the Obesity Phenotype of Koletsky (fak/fak) Rats
Morton, G. J., Niswender, K. D., Rhodes, C. J., Myers, M. G., Blevins, J. E., Baskin, D. G., & Schwartz, M. W. (2003) · Endocrinology · doi:10.1210/en.2002-0115 · Cited by 158
Chronic administration of OB protein decreases food intake by selectively reducing meal size in female rats
Eckel, L. A., Langhans, W., Kahler, A., Campfield, L. A., Smith, F. J., & Geary, N. (1998) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1998.275.1.r186 · Cited by 158
HF diets increase hypothalamic PTP1B and induce leptin resistance through both leptin-dependent and -independent mechanisms
White, C. L., Whittington, A., Barnes, M. J., Wang, Z., Bray, G. A., & Morrison, C. D. (2008) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90513.2008 · Cited by 150
Transgenic Complementation of Leptin-Receptor Deficiency
Kowalski, T. J., Liu, S.-M., Leibel, R. L., & Chua, S. C. (2001) · Diabetes · doi:10.2337/diabetes.50.2.425 · Cited by 150
Leptin and the Control of Food Intake: Neurons in the Nucleus of the Solitary Tract Are Activated by Both Gastric Distension and Leptin
Huo, L., Maeng, L. Y., Bjørbæk, C., & Grill, H. J. (2007) · Endocrinology · doi:10.1210/en.2006-1572 · Cited by 147
THE CRITICAL ROLE OF THE MELANOCORTIN SYSTEM IN THE CONTROL OF ENERGY BALANCE
Seeley, R. J., Drazen, D. L., & Clegg, D. J. (2004) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.24.012003.132428 · Cited by 145
The Effect of Leptin Is Enhanced by Microinjection Into the Ventromedial Hypothalamus
Jacob, R. J., Dziura, J. D., Medwick, M. B., Leone, P., Caprio, S., During, M. J., Shulman, G. I., & Sherwin, R. (1997) · Diabetes · doi:10.2337/diab.46.1.150 · Cited by 134
The structure of meals in humans: Eating and drinking patterns in lean and obese subjects
Bellisle, F., & Magnen, J. L. (1981) · Physiology & Behavior · doi:10.1016/0031-9384(81)90237-7 · Cited by 133
Characterization of Leptin-Responsive Neurons in the Caudal Brainstem
Ellacott, K. L. J., Halatchev, I. G., & Cone, R. D. (2006) · Endocrinology · doi:10.1210/en.2005-0877 · Cited by 132
Activation of Stat3 Signaling in AgRP Neurons Promotes Locomotor Activity
Mesaros, A., Koralov, S. B., Rother, E., Wunderlich, F. T., Ernst, M. B., Barsh, G. S., Rajewsky, K., & Brüning, J. C. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2008.01.007 · Cited by 128
Ventral Tegmental Area Leptin Receptor Neurons Specifically Project to and Regulate Cocaine- and Amphetamine-Regulated Transcript Neurons of the Extended Central Amygdala
Leshan, R. L., Opland, D. M., Louis, G. W., Leinninger, G. M., Patterson, C. M., Rhodes, C. J., Münzberg, H., & Myers, M. G. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.1001-10.2010 · Cited by 127
Divergent Regulation of Proopiomelanocortin Neurons by Leptin in the Nucleus of the Solitary Tract and in the Arcuate Hypothalamic Nucleus
Huo, L., Grill, H. J., & Bjørbæk, C. (2006) · Diabetes · doi:10.2337/diabetes.55.03.06.db05-1143 · Cited by 127
Synergistic interaction between CCK and leptin to regulate food intake
Wang, L., Barachina, M. D., Martı́nez, V., Wei, J. Y., & Taché, Y. (2000) · Regulatory Peptides · doi:10.1016/s0167-0115(00)00153-1 · Cited by 125
Distinct Effects of Leptin and a Melanocortin Receptor Agonist Injected Into Medial Hypothalamic Nuclei on Glucose Uptake in Peripheral Tissues
Toda, C., Shiuchi, T., Lee, S. P., Yamato-Esaki, M., Fujino, Y., Suzuki, A., Okamoto, S., & Minokoshi, Y. (2009) · Diabetes · doi:10.2337/db09-0638 · Cited by 120
Mode of action of OB protein (leptin) on feeding
Flynn, M. C., Scott, T. R., Pritchard, T. C., & Plata‐Saláman, C. R. (1998) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1998.275.1.r174 · Cited by 119
Role of hypothalamic melanocortin 3/4-receptors in mediating chronic cardiovascular, renal, and metabolic actions of leptin
da Silva, A. A., Kuo, J. J., & Hall, J. E. (2004) · Hypertension · doi:10.1161/01.hyp.0000128421.23499.b9 · Cited by 117
Melanocortin-independent Effects of Leptin on Hepatic Glucose Fluxes
Gutiérrez-Juárez, R., Obici, S., & Rossetti, L. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m408665200 · Cited by 115
Selective Inactivation of Socs3 in SF1 Neurons Improves Glucose Homeostasis without Affecting Body Weight
Zhang, R., Dhillon, H., Yin, H., Yoshimura, A., Lowell, B. B., Maratos–Flier, E., & Flier, J. S. (2008) · Endocrinology · doi:10.1210/en.2008-0805 · Cited by 113
Direct Innervation and Modulation of Orexin Neurons by Lateral Hypothalamic LepRb Neurons
Louis, G. W., Leinninger, G. M., Rhodes, C. J., & Myers, M. G. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.1340-10.2010 · Cited by 113
From observation to experimentation: leptin action in the mediobasal hypothalamus
Williams, K. W., Scott, M. M., & Elmquist, J. K. (2009) · American Journal of Clinical Nutrition · doi:10.3945/ajcn.2008.26788d · Cited by 104
Self-citation
Presynaptic NMDA receptor subunit immunoreactivity in GABAergic terminals in rat brain
Paquet, M., & Smith, Y. (2000) · The Journal of Comparative Neurology · doi:10.1002/1096-9861(20000724)423:2 · Cited by 95
Self-citation
A potential role for hypothalamomedullary POMC projections in leptin-induced suppression of food intake
Zheng, H., Patterson, L. M., Rhodes, C. J., Louis, G. W., Skibicka, K. P., Grill, H. J., Myers, M. G., & Berthoud, H. (2010) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00619.2009 · Cited by 84
Identifying the efferent projections of leptin‐responsive neurons in the dorsomedial hypothalamus using a novel conditional tracing approach
Gautron, L., Lazarus, M., Scott, M. M., Saper, C. B., & Elmquist, J. K. (2010) · The Journal of Comparative Neurology · doi:10.1002/cne.22323 · Cited by 81
Self-citation
Leptin amplifies the feeding inhibition and neural activation arising from a gastric nutrient preload
Emond, M. H., Ladenheim, E. E., Schwartz, G. J., & Moran, T. H. (2001) · Physiology & Behavior · doi:10.1016/s0031-9384(00)00393-0 · Cited by 81
Divergent Leptin Signaling in Proglucagon Neurons of the Nucleus of the Solitary Tract in Mice and Rats
Huo, L., Gamber, K. M., Grill, H. J., & Bjørbæk, C. (2007) · Endocrinology · doi:10.1210/en.2007-0633 · Cited by 80
Signal Transducer and Activator of Transcription-3 Is Required in Hypothalamic Agouti-Related Protein/Neuropeptide Y Neurons for Normal Energy Homeostasis
Gong, L., Yao, F., Hockman, K., Heng, H. H., Morton, G. J., Takeda, K., Akira, S., Low, M. J., Rubinstein, M., & MacKenzie, R. G. (2008) · Endocrinology · doi:10.1210/en.2007-0945 · Cited by 80
Hindbrain Leptin Stimulation Induces Anorexia and Hyperthermia Mediated by Hindbrain Melanocortin Receptors
Skibicka, K. P., & Grill, H. J. (2008) · Endocrinology · doi:10.1210/en.2008-1316 · Cited by 80
Role of Signal Transducer and Activator of Transcription 3 in Regulation of Hypothalamic trh Gene Expression by Leptin
Huo, L., Münzberg, H., Nillni, E. A., & Bjørbæk, C. (2004) · Endocrinology · doi:10.1210/en.2003-1242 · Cited by 78
Forebrain melanocortin signaling enhances the hindbrain satiety response to CCK-8
Blevins, J. E., Morton, G. J., Williams, D. L., Caldwell, D. W., Bastian, L. S., Wisse, B. E., Schwartz, M. W., & Baskin, D. G. (2008) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.90544.2008 · Cited by 73
Melanocortin‐4 receptor expression in a vago‐vagal circuitry involved in postprandial functions
Gautron, L., Lee, C., Funahashi, H., Friedman, J. M., Lee, S., & Elmquist, J. K. (2009) · The Journal of Comparative Neurology · doi:10.1002/cne.22221 · Cited by 72
Self-citation
Important role of the hepatic vagus nerve in glucose uptake and production by the liver
Matsuhisa, M., Yamasaki, Y., Shiba, Y., Nakahara, I., Kuroda, A., Tomita, T., Iida, M., Ikeda, M., Kajimoto, Y., Kubota, M., et al. (2000) · Metabolism · doi:10.1016/s0026-0495(00)90538-9 · Cited by 70
High-fat diet-induced changes in body mass and hypothalamic gene expression in wild-type and leptin-deficient mice
Townsend, K. L., Lorenzi, M. M., & Widmaier, E. P. (2008) · Endocrine · doi:10.1007/s12020-008-9070-1 · Cited by 61
Female odors stimulate CART neurons in the ventral premammillary nucleus of male rats
Cavalcante, J. C., Bittencourt, J. C., & Elias, C. F. (2006) · Physiology & Behavior · doi:10.1016/j.physbeh.2006.03.032 · Cited by 58
The roles of leptin receptors on POMC neurons in the regulation of sex-specific energy homeostasis
Shi, H., Sorrell, J. E., Clegg, D. J., Woods, S. C., & Seeley, R. J. (2010) · Physiology & Behavior · doi:10.1016/j.physbeh.2010.02.018 · Cited by 55
Leptin transgene expression in the hypothalamus enforces euglycemia in diabetic, insulin-deficient nonobese Akita mice and leptin-deficient obese ob/ob mice
Ueno, N., Inui, A., Kalra, P. S., & Kalra, S. P. (2006) · Peptides · doi:10.1016/j.peptides.2006.03.006 · Cited by 53
Hindbrain leptin receptor stimulation enhances the anorexic response to cholecystokinin
Williams, D. L., Baskin, D. G., & Schwartz, M. W. (2009) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00182.2009 · Cited by 52
Central Leptin Infusion Attenuates the Cardiovascular and Metabolic Effects of Fasting in Rats
Overton, J. M., Williams, T. D., Chambers, J. B., & Rashotte, M. E. (2001) · Hypertension · doi:10.1161/01.hyp.37.2.663 · Cited by 51
Hyperleptinemia Precipitates Diet-Induced Obesity in Transgenic Mice Overexpressing Leptin
Ogus, S., Ke, Y., Qiu, J., Wang, B., & Chehab, F. (2003) · Endocrinology · doi:10.1210/en.2002-0178 · Cited by 49
Leptin Potentiates Thermogenic Sympathetic Responses to Hypothermia
Hausberg, M., Morgan, D. A., Mitchell, J., Sivitz, W. I., Mark, A. L., & Haynes, W. G. (2002) · Diabetes · doi:10.2337/diabetes.51.8.2434 · Cited by 48
Central leptin gene therapy, a substitute for insulin therapy to ameliorate hyperglycemia and hyperphagia, and promote survival in insulin-deficient diabetic mice
Kojima, S., Asakawa, A., Amitani, H., Sakoguchi, T., Ueno, N., Inui, A., & Kalra, S. P. (2009) · Peptides · doi:10.1016/j.peptides.2009.01.007 · Cited by 47
Historical Framework for the Development of Ideas About Obesity
Bray, G. A. (2003) · CRC Press eBooks · doi:10.3109/9780203913376-5 · Cited by 35
Involvement of the vagus nerves in the regulation of basal hepatic glucose production in conscious dogs
Cardin, S., Walmsley, K., Neal, D. W., Williams, P. E., & Cherrington, A. D. (2002) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00566.2001 · Cited by 30
The effect of leptin is enhanced by microinjection into the ventromedial hypothalamus
Jacob, R. J., Dziura, J., Medwick, M. B., et al. (1997) · Diabetes · doi:10.2337/diabetes.46.1.150 · Cited by 24
Effects of leptin replacement on macro- and micronutrient preferences
Licinio, J., Ribeiro, L., Busnello, J. V., Delibaşı, T., Thakur, S., Elashoff, R. M., Sharma, A. M., Jardack, P. M., DePaoli, A. M., & Wong, M. (2007) · International Journal of Obesity · doi:10.1038/sj.ijo.0803703 · Cited by 19
Acute third ventricular administration of leptin decreases protein and fat in self-selecting rats
Wetzler, S., Jean-Joseph, G., Even, P. C., Tomé, D., & Larue‐Achagiotis, C. (2004) · Behavioural Brain Research · doi:10.1016/j.bbr.2004.10.008 · Cited by 11
Untitled work
Elmquist (1998) · doi:10.1002/(sici)1096-9861(19980615)395:4
Self-citation

Flagged first, then by citations

Research works printed but not linked: 8

10.1210/jc.87.5.2395 · DOI
10.1210/en.141.9.3072 · DOI · Paper page
Flynn, 1998, Am J Physiol., 275, R174
Kahler, 1998, Am J Physiol., 275, R180
10.1210/en.143.1.239 · DOI · Paper page
Morton, 2005, J Clin Invest., 115, 703, 10.1172/JCI200522081 · DOI
Rosenbaum, 2008, J Clin Invest., 118, 2583
10.1210/en.138.10.4489 · DOI · Paper page

Sorted by citations

Neurobiology of food intake in health and disease
Morton, G. J., Meek, T. H., & Schwartz, M. W. (2014) · Nature Reviews Neuroscience · doi:10.1038/nrn3745 · Cited by 748
The Role of Endoplasmic Reticulum in Hepatic Lipid Homeostasis and Stress Signaling
Fu, S., Watkins, S. M., & Hotamışlıgil, G. S. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.03.007 · Cited by 554
Leptin- and Leptin Receptor-Deficient Rodent Models: Relevance for Human Type 2 Diabetes
Wang, B., Chandrasekera, P. C., & Pippin, J. J. (2014) · Current Diabetes Reviews · doi:10.2174/1573399810666140508121012 · Cited by 527
Leptin signaling and leptin resistance
Zhou, Y., & Rui, L. (2013) · Frontiers of Medicine · doi:10.1007/s11684-013-0263-5 · Cited by 358
Rapid depot-specific activation of adipocyte precursor cells at the onset of obesity
Jeffery, E., Church, C. D., Holtrup, B., Colman, L., & Rodeheffer, M. S. (2015) · Nature Cell Biology · doi:10.1038/ncb3122 · Cited by 404

See all 367

Authors: Gautron, L., & Elmquist, J. K.
Affiliations: The University of Texas Southwestern Medical Center (US)
Corresponding author: Elmquist, Joel K.
ORCID: Elmquist, Joel K.
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 2011-06-01
Volume: 121
Issue: 6
Pages: 2087-2093
ISSN: 0021-9738 (ISSN-L)
DOI: 10.1172/jci45888
PMC: PMC3104762
OpenAlex: W2068769790
Cited by: 367
References: 128
Citations by year: 2026: 6 · 2025: 6 · 2024: 4 · 2023: 11 · 2022: 8 · 2021: 10 · 2020: 18 · 2019: 17 · 2018: 17 · 2017: 26 · 2016: 28 · 2015: 33 · 2014: 52 · 2013: 52 · 2012: 66
FWCI: 5.92
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Clinical Investigation (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: University of Michigan
Topics: Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
Keywords: leptin, ob gene, energy balance, white adipose tissue, leptin deficiency, morbid obesity, diabetes mellitus, glucose homeostasis, dietary intake, energy expenditure, neuroendocrine regulation, metabolic rate
MeSH terms: Adaptation, Physiological, Animals, Body Weight, Brain, Disease Models, Animal, Energy Metabolism, Feeding Behavior, Glucose, Humans, Hypothalamus, Mice, Obese, Models, Biological, Pro-Opiomelanocortin, Starvation, Sympathetic Nervous System, Leptin, Receptor, Melanocortin, Type 4, Overnutrition, Mice, Adipose Tissue, White, Receptors, 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

Sixteen years and counting: an update on leptin in energy balance

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks