Physiological response to long-term peripheral and central leptin infusion in lean and obese mice.

Halaas, Jeffrey L.; Boozer, Carol; Blair-West, John; Fidahusein, Naseem; Denton, Derek A.; Friedman, Jeffrey M.

doi:10.1073/pnas.94.16.8878

Cited by 1,033Regulation of Appetite and ObesityAdipokines, Inflammation, and Metabolic DiseasesHypothalamic control of reproductive hormones

Physiological response to long-term peripheral and central leptin infusion in lean and obese mice.

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Halaas, Jeffrey L., Boozer, Carol, Blair-West, John, Fidahusein, Naseem, Denton, Derek A., Friedman, Jeffrey M.·1997·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.94.16.8878PMC PMC23177

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Abstract

Recent data have identified leptin as an afferent signal in a negative-feedback loop regulating the mass of the adipose tissue. High leptin levels are observed in obese humans and rodents, suggesting that, in some cases, obesity is the result of leptin insensitivity. This hypothesis was tested by comparing the response to peripherally and centrally administered leptin among lean and three obese strains of mice: diet-induced obese AKR/J, New Zealand Obese (NZO), and Ay. Subcutaneous leptin infusion to lean mice resulted in a dose-dependent loss of body weight at physiologic plasma levels. Chronic infusions of leptin intracerebroventricularly (i.c.v.) at doses of 3 ng/hr or greater resulted in complete depletion of visible adipose tissue, which was maintained throughout 30 days of continuous i.c.v. infusion. Direct measurement of energy balance indicated that leptin treatment did not increase total energy expenditure but prevented the decrease that follows reduced food intake. Diet-induced obese mice lost weight in response to peripheral leptin but were less sensitive than lean mice. NZO mice were unresponsive to peripheral leptin but were responsive to i.c.v. leptin. Ay mice did not respond to subcutaneous leptin and were 1/100 as sensitive to i.c.v. leptin. The decreased response to leptin in diet-induced obese, NZO, and Ay mice suggests that obesity in these strains is the result of leptin resistance. In NZO mice, leptin resistance may be the result of decreased transport of leptin into the cerebrospinal fluid, whereas in Ay mice, leptin resistance probably results from defects downstream of the leptin receptor in the hypothalamus.

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Animals with diet-induced obesity produced by a cafeteria or highly palatable diet show a minimal response to leptin administration.
“Animals with diet-induced obesity produced by a cafeteria or highly palatable diet, often a reliable predictor of responses in humans, showed a minimal response to leptin administration.”
From Leptin at 14 y of age: an ongoing story (2009) · cites this paper as [23]
In rodents, leptin sensitivity varies among strains: leptin-deficient animals are extremely sensitive, and animals with leptin receptor mutations are most resistant.
“Leptin's efficacy was first shown to be variable in rodents in which there was a spectrum of leptin sensitivity among different strains; animals in leptin-deficient states had extreme leptin sensitivity and animals with leptin receptor mutations were the most resistant (23).”
From Leptin at 14 y of age: an ongoing story (2009) · cites this paper as [23]

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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 · see citing works
Self-citation
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
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 · see citing works
Self-citation
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
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 · see citing works
Self-citation
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 · see citing works
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 · see citing works
Role of leptin in the neuroendocrine response to fasting
Ahima, R. S., Prabakaran, D., Mantzoros, C., Qu, D., Lowell, B., Maratos-Flier, E., & Flier, J. S. (1996) · Nature · doi:10.1038/382250a0 · Cited by 3,117 · see citing works
Targeted disruption of the melanocortin-4 receptor results in obesity in mice
Huszar, D., Lynch, C. A., Fairchild-Huntress, V., Dunmore, J. H., Fang, Q., Berkemeier, L. R., Gu, W., Kesterson, R. A., Boston, B. A., Cone, R. D., et al. (1997) · Cell · doi:10.1016/s0092-8674(00)81865-6 · Cited by 3,030 · see citing works
Abnormal splicing of the leptin receptor in diabetic mice
Lee, G.-H., Proenca, R., Montez, J. M., Carroll, K. M., Darvishzadeh, J. G., Lee, J. I., & Friedman, J. M. (1996) · Nature · doi:10.1038/379632a0 · Cited by 2,327 · see citing works
Self-citation
Changes in Energy Expenditure Resulting from Altered Body Weight
Leibel, R. L., Rosenbaum, M., & Hirsch, J. (1995) · New England Journal of Medicine · doi:10.1056/nejm199503093321001 · Cited by 2,012 · see citing works
Role of melanocortinergic neurons in feeding and the agouti obesity syndrome
Fan, W., Boston, B. A., Kesterson, R. A., Hruby, V. J., & Cone, R. D. (1997) · Nature · doi:10.1038/385165a0 · Cited by 1,902 · see citing works
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 · see citing works
The role of neuropeptide Y in the antiobesity action of the obese gene product
Stephens, T. W., Basinski, M., Bristow, P. K., Bue-Valleskey, J. M., Burgett, S. G., Craft, L., Hale, J., Hoffmann, J., Hsiung, H. M., Kriauciunas, A., et al. (1995) · Nature · doi:10.1038/377530a0 · Cited by 1,498 · see citing works
Adipogenesis and Obesity: Rounding Out the Big Picture
Spiegelman, B. M., & Flier, J. S. (1996) · Cell · doi:10.1016/s0092-8674(00)81359-8 · Cited by 1,254 · see citing works
Leptin enters the brain by a saturable system independent of insulin
Banks, W. A., Kastin, A. J., Huang, W., Jaspan, J. B., & Maness, L. M. (1996) · Peptides · doi:10.1016/0196-9781(96)00025-3 · Cited by 1,222 · see citing works
Localization of the melanocortin-4 receptor (MC4-R) in neuroendocrine and autonomic control circuits in the brain
Mountjoy, K. G., Mortrud, M. T., Low, M. J., Simerly, R. B., & Cone, R. D. (1994) · Molecular Endocrinology · doi:10.1210/mend.8.10.7854347 · Cited by 1,157 · see citing works
Leptin activation of Stat3 in the hypothalamus of wild-type and ob/ob mice but not db/db mice.
Vaisse, C., Halaas, J. L., Horvath, C. M., Darnell, J. E., Stoffel, M., & Friedman, J. M. (1996) · Nature Genetics · doi:10.1038/ng0996-95 · Cited by 1,086 · see citing works
Self-citation
Cerebrospinal fluid leptin levels: Relationship to plasma levels and to adiposity in humans
Schwartz, M. W., Peskind, E., Raskind, M., Boyko, E. J., & Porte, D. (1996) · Nature Medicine · doi:10.1038/nm0596-589 · Cited by 1,014 · see citing works
Specificity of Leptin Action on Elevated Blood Glucose Levels and Hypothalamic Neuropeptide Y Gene Expression in ob/ob Mice
Schwartz, M. W., Baskin, D. G., Bukowski, T. R., Kuijper, J. L., Foster, D., Lasser, G., Prunkard, D. E., Porte, D., Woods, S. C., Seeley, R. J., et al. (1996) · Diabetes · doi:10.2337/diab.45.4.531 · Cited by 904 · see citing works
Diet-induced obese mice develop peripheral, but not central, resistance to leptin.
van Heek, M., Compton, D. S., France, C. F., Tedesco, R. P., Fawzi, A. B., Graziano, M. P., Sybertz, E. J., Strader, C. D., & Davis, H. (1997) · Journal of Clinical Investigation · doi:10.1172/jci119171 · Cited by 752 · see citing works
Expression of the Functional Leptin Receptor mRNA in Pancreatic Islets and Direct Inhibitory Action of Leptin on Insulin Secretion
Emilsson, V., Liu, Y.-L., Cawthorne, M. A., Morton, N. M., & Davenport, M. (1997) · Diabetes · doi:10.2337/diab.46.2.313 · Cited by 532 · see citing works
Role of leptin in fat regulation
Collins, S., Kuhn, C. M., Petro, A. E., Swick, A. G., Chrunyk, B. A., & Surwit, R. S. (1996) · Nature · doi:10.1038/380677a0 · Cited by 520 · see citing works
Increased expression in adipocytes of ob RNA in mice with lesions of the hypothalamus and with mutations at the db locus.
Maffei, M., Fei, H., Lee, G., Dani, C., Leroy, P., Zhang, Y., Proenca, R., Négrel, R., Ailhaud, G. P., & Friedman, J. M. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.15.6957 · Cited by 465 · see citing works
Self-citation
Urges to eat and drink in rats.
Adolph, E. F. (1947) · American Journal of Physiology-Legacy Content · doi:10.1152/ajplegacy.1947.151.1.110 · Cited by 449 · see citing works
Cloning of the mouse agouti gene predicts a secreted protein ubiquitously expressed in mice carrying the lethal yellow mutation.Preprint
Miller, M. W., Duhl, D. M. J., Vrieling, H., Cordes, S. P., Ollmann, M. M., Winkes, B. M., & Barsh, G. S. (1993) · Genes & Development · doi:10.1101/gad.7.3.454 · Cited by 430 · see citing works
Decreased food intake does not completely account for adiposity reduction after ob protein infusion.
Levin, N. W., Nelson, C., Gurney, A., VANDLEN, R. L., & de Sauvage, F. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.4.1726 · Cited by 372 · see citing works
Human blood-brain barrier leptin receptor. Binding and endocytosis in isolated human brain microvessels.
Golden, P. L., Maccagnan, T. J., & Pardridge, W. M. (1997) · Journal of Clinical Investigation · doi:10.1172/jci119125 · Cited by 369 · see citing works
Direct Intraovarian Effects of Leptin: Impairment of the Synergistic Action of Insulin-Like Growth Factor-I on Follicle-Stimulating Hormone-Dependent Estradiol-17β Production by Rat Ovarian Granulosa Cells*
Zachow, R. J., & Magoffin, D. A. (1997) · Endocrinology · doi:10.1210/endo.138.2.5035 · Cited by 310 · see citing works
Animal and Human Calorimetry
Moe, P. W. (1988) · Journal of Nutrition · doi:10.1093/jn/118.10.1254 · Cited by 258 · see citing works
Regulation of Energy Balance
Hervey, G. R. (1969) · Nature · doi:10.1038/222629a0 · Cited by 221 · see citing works
A R59W mutation in human protoporphyrinogen oxidase results in decreased enzyme activity and is prevalent in South Africans with variegate porphyria
Meissner, P. N., Dailey, T. A., Hift, R., Ziman, M. R., Corrigall, A. V., Roberts, A. G., Meissner, D. M., Kirsch, R. E., & Dailey, H. A. (1996) · Nature Genetics · doi:10.1038/ng0596-95 · Cited by 211 · see citing works
The alphabet of weight control.
Friedman, J. M. (1997) · Nature · doi:10.1038/385119a0 · Cited by 180 · see citing works
Self-citation
Leptin activation in hypothalamus
Woods, A. J., & Stock, M. J. (1996) · Nature · doi:10.1038/381745a0 · Cited by 176 · see citing works
Genetics of dietary obesity in AKR/JxSWR/J mice: segregation of the trait and identification of a linked locus on Chromosome 4
West, D. B., Waguespack, J., York, B., Goudey-Lefevre, J., & Price, R. A. (1994) · Mammalian Genome · doi:10.1007/bf00354928 · Cited by 108 · see citing works
Metabolic and health complications of obesity.
Grundy, S. M., & Barnett, J. (1990) · PubMed · Cited by 106 · see citing works
Metabolic and health complications of obesity
(1990) · Disease-a-Month · doi:10.1016/0011-5029(90)90015-j · Cited by 74 · see citing works
Angiotensin and salt appetite of BALB/c mice
Denton, D. A., Blair-West, J. R., McBurnie, M. I., et al. (1990) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1990.259.4.r729 · Cited by 42 · see citing works
Self-citation
Energetic pursuit of leptin function
Flier, J. S., & Elmquist, J. K. (1997) · Nature Biotechnology · doi:10.1038/nbt0197-20 · Cited by 21 · see citing works
The Interaction of Genes in Development.
Danforth, C. H. (1926) · Experimental Biology and Medicine · doi:10.3181/00379727-24-3232 · Cited by 10 · see citing works

Flagged first, then by citations

Research works printed but not linked: 4

[23]Bielschowsky M, Bielschowsky F. Proc Univ Otago Med Sch. 1953;31:29–31. [Google Scholar]
[24]Bateson W. Proc Zool Soc London. 1903;2:71–99. [Google Scholar]
[25]Danforth C. Proc Soc Exp Biol Med. 1926;24:69–71. [Google Scholar]
[29]Grundy S M, Barnett J P. DM, Dis-Mon. 1990;36:645–696. [PubMed] [Google Scholar]

Sorted by citations

Leptin and the regulation of body weight in mammals
Friedman, J. M., & Halaas, J. L. (1998) · Nature · doi:10.1038/27376 · Cited by 5,405 · see citing works
Self-citation
Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus
Cowley, M. A., Smart, J. L., Rubinstein, M., Cerdán, M. G., Diano, S., Horvath, T. L., Cone, R. D., & Low, M. J. (2001) · Nature · doi:10.1038/35078085 · Cited by 2,356 · see citing works
Leptin Inhibits Bone Formation through a Hypothalamic Relay
Ducy, P., Amling, M., Takeda, S., Priemel, M., Schilling, A. F., Beil, F. T., Shen, J., Vinson, C., Rueger, J. M., & Karsenty, G. (2000) · Cell · doi:10.1016/s0092-8674(00)81558-5 · Cited by 2,077 · see citing works
Leptin Regulates Bone Formation via the Sympathetic Nervous System
Takeda, S., Elefteriou, F., Levasseur, R., Liu, X., Zhao, L., Parker, K. L., Armstrong, D., Ducy, P., & Karsenty, G. (2002) · Cell · doi:10.1016/s0092-8674(02)01049-8 · Cited by 1,735 · see citing works
Adipose Tissue as an Endocrine Organ
Ahima, R. S., & Flier, J. S. (2000) · Trends in Endocrinology & Metabolism · doi:10.1016/s1043-2760(00)00301-5 · Cited by 1,608 · see citing works
Leptin
Ahima, R. S., & Flier, J. S. (2000) · Annual Review of Physiology · doi:10.1146/annurev.physiol.62.1.413 · Cited by 1,428 · see citing works
The metabolic consequences of sleep deprivation
Knutson, K. L., Spiegel, K., Penev, P., & Van Cauter, E. (2007) · Sleep Medicine Reviews · doi:10.1016/j.smrv.2007.01.002 · Cited by 1,365 · see citing works
The use of animal models in diabetes research
King, A. J. (2012) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2012.01911.x · Cited by 1,303 · see citing works
Adiponectin, Leptin, and Fatty Acids in the Maintenance of Metabolic Homeostasis through Adipose Tissue Crosstalk
Stern, J. H., Rutkowski, J. M., & Scherer, P. E. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.04.011 · Cited by 1,031 · see citing works
Identification of SOCS-3 as a Potential Mediator of Central Leptin Resistance
Bjørbæk, C., Elmquist, J. K., Frantz, J. D., Shoelson, S. E., & Flier, J. S. (1998) · Molecular Cell · doi:10.1016/s1097-2765(00)80062-3 · Cited by 1,014 · see citing works
Leptin Increases Hypothalamic Pro-opiomelanocortin mRNA Expression in the Rostral Arcuate Nucleus
Schwartz, M. W., Seeley, R. J., Woods, S. C., Weigle, D. S., Campfield, L. A., Burn, P., & Baskin, D. G. (1997) · Diabetes · doi:10.2337/diab.46.12.2119 · Cited by 879 · see citing works
Adipose tissue mass can be regulated through the vasculature
Rupnick, M. A., Panigrahy, D., Zhang, C.-Y., Dallabrida, S. M., Lowell, B. B., Langer, R., & Folkman, M. J. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.162349799 · Cited by 845 · see citing works
Associations between Sleep Loss and Increased Risk of Obesity and Diabetes
Knutson, K. L., & Van Cauter, E. (2008) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1417.033 · Cited by 810 · see citing works
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 · see citing works
Leptin Regulation of Neuroendocrine Systems
Ahima, R. S., Saper, C. B., Flier, J. S., & Elmquist, J. K. (2000) · Frontiers in Neuroendocrinology · doi:10.1006/frne.2000.0197 · Cited by 767 · see citing works
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 · see citing works
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 · see citing works
Self-citation
Leptin and the endocrine control of energy balance
Friedman, J. M. (2019) · Nature Metabolism · doi:10.1038/s42255-019-0095-y · Cited by 661 · see citing works
Self-citation
Leptin Regulation of the Mesoaccumbens Dopamine Pathway
Fulton, S., Pissios, P., Manchon, R. P., Stiles, L., Frank, L., Pothos, E. N., Maratos-Flier, E., & Flier, J. S. (2006) · Neuron · doi:10.1016/j.neuron.2006.09.006 · Cited by 644 · see citing works
Leptin, Obesity, and Leptin Resistance: Where Are We 25 Years Later
Izquierdo, A. G., Crujeiras, A. B., Casanueva, F. F., & Carreira, M. C. (2019) · Nutrients · doi:10.3390/nu11112704 · Cited by 525 · see citing works
Sex differences in the physiology of eating
Asarian, L., & Geary, N. (2013) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00446.2012 · Cited by 513 · see citing works
Enhanced leptin sensitivity and attenuation of diet-induced obesity in mice with haploinsufficiency of Socs3
Howard, J. K., Cave, B. J., Oksanen, L. J., Tzameli, I., Bjørbæk, C., & Flier, J. S. (2004) · Nature Medicine · doi:10.1038/nm1072 · Cited by 490 · see citing works
Sympathetic Neuro-adipose Connections Mediate Leptin-Driven Lipolysis
Zeng, W., Pirzgalska, R. M., Pereira, M. M. A., Kubasova, N., Barateiro, A., Seixas, E., Lu, Y.-H., Kozlova, A., Voss, H., Martins, G. G., et al. (2015) · Cell · doi:10.1016/j.cell.2015.08.055 · Cited by 490 · see citing works
Self-citation
Hypothalamic sensing of fatty acids
Lam, T. K. T., Schwartz, G. J., & Rossetti, L. (2005) · Nature Neuroscience · doi:10.1038/nn1456 · Cited by 478 · see citing works
Pathophysiological role of leptin in obesity-related hypertension
Aizawa-Abe, M., Ogawa, Y., Masuzaki, H., Ebihara, K., Satoh, N., Iwai, H., Matsuoka, N., Hayashi, T., Hosoda, K., Inoue, G., et al. (2000) · Journal of Clinical Investigation · doi:10.1172/jci8341 · Cited by 477 · see citing works
Leptin responsiveness restored by amylin agonism in diet-induced obesity: Evidence from nonclinical and clinical studies
Roth, J. D., Roland, B. L., Cole, R. L., Trevaskis, J. L., Weyer, C., Koda, J. E., Anderson, C. M., Parkes, D. G., & Baron, A. D. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0706473105 · Cited by 436 · see citing works
Modern science versus the stigma of obesity
Friedman, J. M. (2004) · Nature Medicine · doi:10.1038/nm0604-563 · Cited by 368 · see citing works
Self-citation
A metabolic defect promotes obesity in mice lacking melanocortin-4 receptors
Ste. Marie, L., Miura, G. I., Marsh, D. J., Yagaloff, K., & Palmiter, R. D. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.220409497 · Cited by 366 · see citing works
Interactions between the melanocortin system and leptin in control of sympathetic nerve traffic
Haynes, W. G., Morgan, D. A., Djalali, A., Sivitz, W. I., & Mark, A. L. (1999) · Hypertension · doi:10.1161/01.hyp.33.1.542 · Cited by 358 · see citing works
A leptin–BDNF pathway regulating sympathetic innervation of adipose tissue
Wang, P., Loh, K. H., Wu, M., Morgan, D. A., Schneeberger, M., Yu, X., Chi, J., Kosse, C., Kim, D., Rahmouni, K., et al. (2020) · Nature · doi:10.1038/s41586-020-2527-y · Cited by 332 · see citing works
Self-citation
Hyperleptinemia Is Required for the Development of Leptin Resistance
Knight, Z. A., Hannan, K. S., Greenberg, M. L., & Friedman, J. M. (2010) · PLoS ONE · doi:10.1371/journal.pone.0011376 · Cited by 311 · see citing works
Self-citation
Intranasal Treatment of Central Nervous System Dysfunction in Humans
Chapman, C. D., Frey, W. H., Craft, S., Danielyan, L., Hallschmid, M., Schiöth, H. B., & Benedict, C. (2013) · Pharmaceutical Research · doi:10.1007/s11095-012-0915-1 · Cited by 310 · 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
Self-citation
Contrasting blood pressure effects of obesity in leptin-deficient ob/ob mice and agouti yellow obese mice
Mark, A. L., Shaffer, R. A., Correia, M. L. G., Morgan, D. A., Sigmund, C. D., & Haynes, W. G. (1999) · Journal of Hypertension · doi:10.1097/00004872-199917121-00026 · Cited by 254 · see citing works
Cytokine Signaling Modulates Blood-Brain Barrier Function
Pan, W., P. Stone, K., Hsuchou, H., K. Manda, V., Zhang, Y., & J. Kastin, A. (2011) · Current Pharmaceutical Design · doi:10.2174/138161211798220918 · Cited by 241 · see citing works
The Concept of Selective Leptin Resistance
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The Gut Microbiota Reduces Leptin Sensitivity and the Expression of the Obesity-Suppressing Neuropeptides Proglucagon (Gcg) and Brain-Derived Neurotrophic Factor (Bdnf) in the Central Nervous System
Schéle, E., Grahnemo, L., Anesten, F., Hallén, A., Bäckhed, F., & Jansson, J.-O. (2013) · Endocrinology · doi:10.1210/en.2012-2151 · Cited by 209 · see citing works
Site and mechanism of leptin action in a rodent form of congenital lipodystrophy
Asilmaz, E., Cohen, P., Miyazaki, M., Dobrzyn, P., Ueki, K., Fayzikhodjaeva, G., Soukas, A. A., Kahn, C. R., Ntambi, J. M., Socci, N. D., et al. (2004) · Journal of Clinical Investigation · doi:10.1172/jci200419511 · Cited by 210 · see citing works
Self-citation
Lipoatrophy Revisited
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Porte Jr., D., Seeley, R. J., Woods, S. C., Baskin, D. G., Figlewicz, D. P., & Schwartz, M. W. (1998) · Diabetologia · doi:10.1007/s001250051002 · Cited by 186 · see citing works
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Prior, L. J., Eikelis, N., Armitage, J. A., Davern, P. J., Burke, S. L., Montani, J.-P., Barzel, B., & Head, G. A. (2010) · Hypertension · doi:10.1161/hypertensionaha.109.141119 · Cited by 157 · see citing works
Gene-Environment Interactions Controlling Energy and Glucose Homeostasis and the Developmental Origins of Obesity
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Müller, T. D., Sullivan, L. M., Habegger, K., Yi, C., Kabra, D., Grant, E., Ottaway, N., Krishna, R., Holland, J., Hembree, J., et al. (2012) · Journal of Peptide Science · doi:10.1002/psc.2408 · Cited by 156 · see citing works
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Synaptic plasticity in neuronal circuits regulating energy balance
Zeltser, L. M., Seeley, R. J., & Tschöp, M. H. (2012) · Nature Neuroscience · doi:10.1038/nn.3219 · Cited by 147 · see citing works
Latest approaches for the treatment of obesity
Jackson, V. M., Breen, D. M., Fortin, J.-P., Liou, A., Kuzmiski, J. B., Loomis, A. K., Rives, M.-L., Shah, B., & Carpino, P. A. (2015) · Expert Opinion on Drug Discovery · doi:10.1517/17460441.2015.1044966 · Cited by 132 · see citing works
Selective Resistance to Central Neural Administration of Leptin in Agouti Obese Mice
Rahmouni, K., Haynes, W. G., Morgan, D. A., & Mark, A. L. (2002) · Hypertension · doi:10.1161/hy0202.102836 · Cited by 126 · see citing works
Abnormal regulation of the leptin gene in the pathogenesis of obesity.
Ioffe, E., Moon, B., Connolly, E., & Friedman, J. M. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.20.11852 · Cited by 117 · see citing works
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Dysregulation of a long noncoding RNA reduces leptin leading to a leptin-responsive form of obesity
Dallner, O. S., Marinis, J. M., Lu, Y.-H., Birsoy, K., Werner, E., Fayzikhodjaeva, G., Dill, B. D., Molina, H., Moscati, A., Kutalik, Z., et al. (2019) · Nature Medicine · doi:10.1038/s41591-019-0370-1 · Cited by 106 · see citing works
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Hypothalamic, Metabolic, and Behavioral Responses to Pharmacological Inhibition of CNS Melanocortin Signaling in Rats
Adage, T., Scheurink, A. J. W., de Boer, S. F., de Vries, K., Konsman, J. P., Kuipers, F., Adan, R. A. H., Baskin, D. G., Schwartz, M. W., & van Dijk, G. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-10-03639.2001 · Cited by 106 · see citing works
The discovery of drugs for obesity, the metabolic effects of leptin and variable receptor pharmacology: perspectives from β3-adrenoceptor agonists
Arch, J. R. S. (2008) · Naunyn-Schmiedeberg's Archives of Pharmacology · doi:10.1007/s00210-008-0271-1 · Cited by 96 · see citing works
Acute intravenous leptin infusion increases glucose turnover but not skeletal muscle glucose uptake in ob/ob mice.
Burcelin, R., Kamohara, S., Li, J., Tannenbaum, G. S., Charron, M. J., & Friedman, J. M. (1999) · Diabetes · doi:10.2337/diabetes.48.6.1264 · Cited by 92 · see citing works
Self-citation
Leptin stimulates bone formation in ob/ob mice at doses having minimal impact on energy metabolism
Philbrick, K. A., Wong, C. P., Branscum, A. J., Turner, R. T., & Iwaniec, U. T. (2017) · Journal of Endocrinology · doi:10.1530/joe-16-0484 · Cited by 80 · see citing works
Mathematical models of energy homeostasis
Pattaranit, R., & van den Berg, H. A. (2008) · Journal of The Royal Society Interface · doi:10.1098/rsif.2008.0216 · Cited by 61 · see citing works
Obesity-related hypertension: Is there a role for selective leptin resistance?
Correia, M. L. G., & Haynes, W. G. (2004) · Current Hypertension Reports · doi:10.1007/s11906-004-0074-9 · Cited by 46 · see citing works
Loss of Leptin Actions in Obesity: Two Concepts with Cardiovascular Implications
Mark, A. L., Correia, M. L. G., Rahmouni, K., & Haynes, W. G. (2004) · Clinical and Experimental Hypertension · doi:10.1081/ceh-200031948 · Cited by 32 · see citing works

Authors: Halaas, J. L., Boozer, C., Blair-West, J., Fidahusein, N., Denton, D. A., & Friedman, J. M.
Affiliations: St. Luke's-Roosevelt Hospital Center (US)
ORCID: Denton, Derek A.
Friedman, Jeffrey M.
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 1997-08-05
Volume: 94
Issue: 16
Pages: 8878-8883
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.94.16.8878
PMC: PMC23177
OpenAlex: W2032777955
Cited by: 1,033
References: 40
Citations by year: 2026: 6 · 2025: 18 · 2024: 15 · 2023: 6 · 2022: 20 · 2021: 38 · 2020: 17 · 2019: 22 · 2018: 21 · 2017: 28 · 2016: 26 · 2015: 26 · 2014: 40 · 2013: 29 · 2012: 37
FWCI: 19.21
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: Amgen
National Institutes of Health (5r29dk049853-05)
National Institute of Diabetes and Digestive and Kidney Diseases (DK-41096, DK49853, R01DK041096)
Topics: Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
Keywords: leptin, leptin resistance, obesity, diet-induced obesity, energy balance, energy expenditure, dietary intake, adipose tissue, leptin receptor, hypothalamus, AKR/J mice
MeSH terms: Administration, Cutaneous, Animals, Body Weight, Diet, Dose-Response Relationship, Drug, Injections, Intraventricular, Mice, Inbred C57BL, Obesity, Proteins, Leptin, Mice

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Physiological response to long-term peripheral and central leptin infusion in lean and obese mice.

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