The DOI matches its Crossref record.
Specificity of Leptin Action on Elevated Blood Glucose Levels and Hypothalamic Neuropeptide Y Gene Expression in ob/ob Mice
Abstract
Correction of the obese state induced by genetic leptin deficiency reduces elevated levels of both blood glucose and hypothalamic neuropeptide Y (NPY) mRNA in ob/ob mice. To determine whether these responses are due to a specific action of leptin or to the reversal of the obese state, we investigated the specificity of the effect of systemic leptin administration to ob/ob mice (n = 8) on levels of plasma glucose and insulin and on hypothalamic expression of NPY mRNA. Saline-treated controls were either fed ad libitum (n = 8) or pair-fed to the intake of the leptin-treated group (n = 8) to control for changes of food intake induced by leptin. The specificity of the effect of leptin was further assessed by 1) measuring NPY gene expression in db/db mice (n = 6) that are resistant to leptin, 2) measuring NPY gene expression in brain areas outside the hypothalamus, and 3) measuring the effect of leptin administration on hypothalamic expression of corticotropin-releasing hormone (CRH) mRNA. Five daily intraperitoneal injections of recombinant mouse leptin (150 micrograms) in ob/ob mice lowered food intake by 56% (P < 0.05), body weight by 4.1% (P < 0.05), and levels of NPY mRNA in the hypothalamic arcuate nucleus by 42.3% (P < 0.05) as compared with saline-treated controls. Pair-feeding of ob/ob mice to the intake of leptin-treated animals produced equivalent weight loss, but did not alter expression of NPY mRNA in the arcuate nucleus. Leptin administration was also without effect on food intake, body weight, or NPY mRNA levels in the arcuate nucleus of db/db mice. In ob/ob mice, leptin did not alter NPY mRNA levels in cerebral cortex or hippocampus or the expression of CRH mRNA in the hypothalamic paraventricular nucleus (PVN). Leptin administration to ob/ob mice also markedly reduced serum glucose (8.3 +/- 1.2 vs. 24.5 +/- 3.8 mmol/l; P < 0.01) and insulin levels (7,263 +/- 1,309 vs. 3,150 +/- 780 pmol/l), but was ineffective in db/db mice. Pair-fed mice experienced reductions of glucose and insulin levels that were < 60% of the reduction induced by leptin. The results suggest that in ob/ob mice, systemic administration of leptin inhibits NPY gene overexpression through a specific action in the arcuate nucleus and exerts a hypoglycemic action that is partly independent of its weight-reducing effects. Furthermore, both effects occur before reversal of the obesity syndrome. Defective leptin signaling due to either leptin deficiency (in ob/ob mice) or leptin resistance (in db/db mice) therefore leads directly to hyperglycemia and the overexpression of hypothalamic NPY that is implicated in the pathogenesis of the obesity syndrome.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
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?
In the citing paper
“Glucocorticoids increase plasma leptin and ghrelin levels, while ghrelin which also increases with stress, appears to contribute to regulating anxiety and mood”
From Role of addiction and stress neurobiology on food intake and obesity (2018) · cites this paper as Schwartz et al., 1996
In the citing paper
“leptin administration to leptin-deficient mice or humans ameliorates hyperglycemia and hyperinsulinemia (60, 141) even when differences of food intake are controlled by pair-feeding (80, 158).”
From Leptin and the Central Nervous System Control of Glucose Metabolism (2011) · cites this paper as [158]
Citations
Cited by
Sorted by citations
Items 301–400 of 870
The effect of leptin on Lep expression is tissue-specific and nutritionally regulated
Wang, J., Liu, R., Liu, L., Chowdhury, R., Barzilai, N., Tan, J., & Rossetti, L. (1999) · Nature Medicine · doi:10.1038/11335 · Cited by 75
“However, factors other than fat mass are important in regulating leptin biosynthesis and function during the early response to changes in the nutritional statu”
BackgroundLeptin is a negative acute phase protein in chronic hemodialysis patients
Don, B. R., Rosales, L. M., Levine, N. W., Mitch, W. E., & Kaysen, G. A. (2001) · Kidney International · doi:10.1046/j.1523-1755.2001.0590031114.x · Cited by 79
Evidence for Leptin Regulation of Food Intake in Humans1
Larsson, H., Elmståhl, S., Berglund, G. L., & Åhrén, B. (1998) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.83.12.5342 · Cited by 83
“hypothalamus (4, 21, 22), it is conceivable that leptin, in”
Scacchi, M., Pincelli, A. I., & Cavagnini, F. (2003) · Frontiers in Neuroendocrinology · doi:10.1016/s0091-3022(03)00014-1 · Cited by 79
da Silva, B. A., Bjørbæk, C., Uotani, S., & Flier, J. S. (1998) · Endocrinology · doi:10.1210/endo.139.9.6168 · Cited by 78
Overeating of palatable food is associated with blunted leptin and ghrelin responses
Lindqvist, A., de la Cour, C. D., Stegmark, A., Håkanson, R., & Erlanson‐Albertsson, C. (2005) · Regulatory Peptides · doi:10.1016/j.regpep.2005.05.002 · Cited by 83
“Serum leptin increases after feeding and is thought to induce satiety by interfering with the release of neuropeptides, such as NPY [27,28] and proopiomelanocortin-derived peptides [29,30], from neurons in the hypothalamus.”
BackgroundDiabesity and mood disorders: Multiple links through the microbiota-gut-brain axis
Farzi, A., Hassan, A. M., Zenz, G., & Holzer, P. D. (2018) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2018.11.003 · Cited by 83
Masaki, T., Yoshimichi, G., Chiba, S., Yasuda, T., Noguchi, H., Kakuma, T., Sakata, T., & Yoshimatsu, H. (2003) · Endocrinology · doi:10.1210/en.2003-0301 · Cited by 77
“These peptides include neuropeptide Y (12), agouti-related protein (13), proopiomelanocortinderived peptide (14, 15), and CRH (16–19).”
Shimizu‐Albergine, M., Ippolito, D. L., & Beavo, J. A. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-04-01238.2001 · Cited by 76
Attenuation of Diabetic Hyperphagia in Neuropeptide Y–Deficient Mice
Sindelar, D. K., Mystkowski, P., Marsh, D. J., Palmiter, R. D., & Schwartz, M. W. (2002) · Diabetes · doi:10.2337/diabetes.51.3.778 · Cited by 76
“In contrast to the effect of NPY, leptin administration increases ARC POMC gene expression in vivo (16) and increases electrical activity of these neurons in vitro (26).”
Self-citationAging and fasting regulation of leptin and hypothalamic neuropeptide Y gene expression
Li, H., Matheny, M. E., Tümer, N., & Scarpace, P. J. (1998) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1998.275.3.e405 · Cited by 75
Foster, D. L., & Hileman, S. M. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-397175-3.00031-4 · Cited by 76
Self-citationIntranasal Leptin Reduces Appetite and Induces Weight Loss in Rats with Diet-Induced Obesity (DIO)
Schulz, C., Paulus, K., Jöhren, O., & Lehnert, H. (2011) · Endocrinology · doi:10.1210/en.2011-1586 · Cited by 74
Leptin inhibits insulin secretion induced by cellular cAMP in a pancreatic B cell line (INS-1 cells)
Åhrén, B., & Havel, P. J. (1999) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1999.277.4.r959 · Cited by 74
Perello, M., Stuart, R. C., & Nillni, E. A. (2006) · Endocrinology · doi:10.1210/en.2005-1533 · Cited by 74
Lee, S. J., Verma, S., Simonds, S. E., Kirigiti, M. A., Kievit, P., Lindsley, S. R., Loche, A., Smith, M. S., Cowley, M. A., & Grove, K. L. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.0837-13.2013 · Cited by 76
“In the arcuate nucleus of hypothalamus (ARH), neuropeptide Y (NPY)/agouti related peptide (AgRP) neurons promote feeding and are directly inhibited by leptin (Stephens et al., 1995; Ahima et al., 1996; Schwartz et al., 1996).”
BackgroundKiess, W., Anil, M., Blum, W., Englaro, P., Juul, A., Attanasio, A. M., Dötsch, J., & Rascher, W. (1998) · European Journal of Endocrinology · doi:10.1530/eje.0.1380501 · Cited by 72
“Since these patients develop obesity despite relatively high leptin levels, the question remains whether insulin could also cause some kind of leptin insensitivity, possibly by directly stimulating neuropeptide Y expression in the hypothalamus (41, 42 ).”
BackgroundArvaniti, K., Huang, Q., & Richard, D. (2001) · Neuroendocrinology · doi:10.1159/000054639 · Cited by 77
Mobbs, C. V., Isoda, F., Makimura, H., Mastaitis, J. W., Mizuno, T. M., Shu, I.-W., Yen, K., & Yang, X.-J. (2005) · Physiology & Behavior · doi:10.1016/j.physbeh.2005.04.005 · Cited by 73
The Agouti-related protein and its role in energy homeostasis
Stütz, A. M., Morrison, C. D., & Argyropoulos, G. A. (2005) · Peptides · doi:10.1016/j.peptides.2004.12.024 · Cited by 75
Enhanced Food-Anticipatory Circadian Rhythms in the Genetically Obese Zucker Rat
Mistlberger, R. E., & Marchant, E. G. (1999) · Physiology & Behavior · doi:10.1016/s0031-9384(98)00311-4 · Cited by 73
Hypothalamic ER stress: A bridge between leptin resistance and obesity
Ramírez, S., & Claret, M. (2015) · FEBS Letters · doi:10.1016/j.febslet.2015.04.025 · Cited by 75
“In contrast, leptin hinders Npy and AgRP gene transcription [32-34] while reduces the direct GABAergic tone onto POMC neurons thereby disinhibiting POMC neuronal activity [7].”
Modulation of central leptin sensitivity and energy balance in a rat model of diet‐induced obesity
Fam, B. C., Morris, M. J., Hansen, M. J., Kebede, M. A., Andrikopoulos, S., Proietto, J., & Thorburn, A. W. (2006) · Diabetes Obesity and Metabolism · doi:10.1111/j.1463-1326.2006.00653.x · Cited by 72
Mansoub, S., Chan, M. K., & Adeli, K. (2006) · Clinical Biochemistry · doi:10.1016/j.clinbiochem.2006.02.013 · Cited by 70
Expression of leptin and its receptors in various tissues of ruminants
Bartha, T., Sayed-Ahmed, A., & Rudas, P. (2005) · Domestic Animal Endocrinology · doi:10.1016/j.domaniend.2005.03.010 · Cited by 71
Vagotomy in young obese hyperglycemic mice: effects on syndrome development and islet proliferation
Edvell, A., & Lindström, P. (1998) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1998.274.6.e1034 · Cited by 71
“Leptin is believed to regulate satiety and energy metabolism via central neural networks, such as the hypothalamus (4, 25), and the central nervous system probably plays an important role for the development of the syndrome (2).”
BackgroundSebert, S. P., Hyatt, M. A., Chan, L. L. Y., Patel, N. N., Bell, R. C., Keisler, D. H., Stephenson, T. J., Budge, H., Symonds, M. E., & Gardner, D. S. (2008) · Endocrinology · doi:10.1210/en.2008-0542 · Cited by 70
Zinc and Health: Current Status and Future Directions
Hambidge, M. (2000) · Cited by 70
Warnes, K. E., Morris, M. J., Symonds, M. E., Phillips, I., Clarke, I. J., Owens, J. A., & McMillen, I. C. (1998) · Journal of Neuroendocrinology · doi:10.1046/j.1365-2826.1998.00172.x · Cited by 67
The role of agouti-related protein in regulating body weight
Wilson, B. D., Ollmann, M. M., & Barsh, G. S. (1999) · Molecular Medicine Today · doi:10.1016/s1357-4310(99)01471-9 · Cited by 70
Nillni, E. A. (2007) · Endocrinology · doi:10.1210/en.2007-0173 · Cited by 70
Hypothalamic neuronal networks and feeding-related peptides involved in the regulation of feeding
Funahashi, H., Takenoya, F., Guan, J., Kageyama, H., Yada, T., & Shioda, S. (2003) · Anatomical Science International · doi:10.1046/j.0022-7722.2003.00055.x · Cited by 68
Food intake regulation in rodents: Y5 or Y1 NPY receptors or both?
Duhault, J., Boulanger, M., Chamorro, S., Boutin, J. A., Della‐Zuana, O., Douillet, E., Fauchère, J., Félétou, M., Germain, M., Husson, B., et al. (2000) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/cjpp-78-2-173 · Cited by 67
Feeding inhibition by neuropeptide Y
Smith, F. J., Campfield, L. A., Moschera, J. A., Bailon, P., & Burn, P. (1996) · Nature · doi:10.1038/382307a0 · Cited by 64
Wang, J.-H., Wang, F., Yang, M., Yu, D., Wu, W., Liu, J., Ma, L., Cai, F., & Chen, J. (2008) · Neuroscience · doi:10.1016/j.neuroscience.2008.04.079 · Cited by 66
Leptin in Anorexia and Cachexia Syndrome
Engineer, D. R., & Garcia, J. M. (2012) · International Journal of Peptides · doi:10.1155/2012/287457 · Cited by 70
“In leptin-deficient (ob/ob) mice, leptin injections led to dose-dependent reductions in serum glucose levels compared to fed ob/ob controls, before any significant change in body weight occurred [1, 18, 19].”
BackgroundAt the crossroads of physiology and ecology: Food supply and the timing of avian reproduction
Davies, S., & Deviche, P. (2014) · Hormones and Behavior · doi:10.1016/j.yhbeh.2014.04.003 · Cited by 66
Effects of excitatory amino acids on neuromuscular development in the chick embryo
Calderó, J., Ciutat, D., Lladó, J., Castán, E., Oppenheim, R. W., & Esquerda, J. E. (1997) · The Journal of Comparative Neurology · doi:10.1002/(sici)1096-9861(19971013)387:1 · Cited by 35
Hypothalamic CART and serum leptin levels are reduced in the anorectic (anx/anx) mouse
Johansen, J. E., Broberger, C., Lavebratt, C., Johansson, C. H., Kuhar, M. J., Hökfelt, T. G. M., & Schalling, M. (2000) · Molecular Brain Research · doi:10.1016/s0169-328x(00)00228-x · Cited by 66
Appetite- and Weight-Regulating Neuroendocrine Circuitry in Hypothalamic Obesity
Gan, H., Cerbone, M., & Dattani, M. (2023) · Endocrine Reviews · doi:10.1210/endrev/bnad033 · Cited by 75
Yamamoto, Y., Ueta, Y., Serino, R., Nomura, M. J., Shibuya, I., & Yamashita, H. (2000) · Brain Research Bulletin · doi:10.1016/s0361-9230(99)00271-3 · Cited by 64
Milewicz, A., Bidzinska, B., Mikulski, E., Demissie, M., & Tworowska, U. (2000) · Gynecological Endocrinology · doi:10.3109/09513590009167682 · Cited by 66
Update on Endocrine Disturbances in Anorexia Nervosa
Støving, R. K., Hangaard, J., & Hagen, C. (2001) · Journal of Pediatric Endocrinology and Metabolism · doi:10.1515/jpem.2001.14.5.459 · Cited by 65
Niskanen, L., Haffner, S. M., Karhunen, L., Turpeinen, A., Miettinen, H. M., & Uusitupa, M. (1997) · European Journal of Endocrinology · doi:10.1530/eje.0.1370061 · Cited by 64
Perelló, M., Stuart, R. C., & Nillni, E. A. (2007) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00466.2006 · Cited by 64
“The anorectic role of -MSH mediated by leptin has been extensively studied in the ARC of the hypothalamus (5, 43, 48) by examining pomc expression; however, limited information is available regarding regulation at the posttranslational processing and the secretion of POMCderived peptides by leptin (11, 40).”
BackgroundResultChapter 15 Food intake and leptin during pregnancy and lactation
Johnstone, L. E., & Higuchi, T. (2001) · Progress in brain research · doi:10.1016/s0079-6123(01)33016-9 · Cited by 63
Leptin binding in the arcuate nucleus is increased during fasting
Baskin, D. G., Breininger, J. F., Bonigut, S., & MILLER, M. A. (1999) · Brain Research · doi:10.1016/s0006-8993(99)01252-4 · Cited by 62
Self-citationDecreased visceral adiposity accounts for leptin effect on hepatic but not peripheral insulin action
Barzilai, N., She, L., Liu, L., Wang, J., Hu, M., Vuguin, P. M., & Rossetti, L. (1999) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1999.277.2.e291 · Cited by 63
“However, whereas some reports suggested that the improvement in glucose tolerance may precede the decline in body weight and total fat mass (34, 41), it has been difficult to discern the relative contribution of the associated changes in body composition to the improved glucose tolerance observed with leptin treatment…”
BackgroundBalaskó, M., Soós, S., Székely, M., & Pétervári, E. (2014) · Journal of Chemical Neuroanatomy · doi:10.1016/j.jchemneu.2014.08.006 · Cited by 64
Gunapala, K. M., Gallardo, C. M., Hsu, C. T., & Steele, A. D. (2011) · PLoS ONE · doi:10.1371/journal.pone.0018377 · Cited by 66
“Given its expression in the arcuate nucleus of the hypothalamus, NPY is poised to control FAA, leading us to investigate the phenotype of NPY KO mice on CR [20,43,44,45,46,47,48,49].”
BackgroundCircadian Rhythm of Serum Vaspin in Healthy Male Volunteers: Relation to Meals
Jeong, E., Youn, B., Kim, D. W., Kim, E. H., Park, J. W., NamKoong, C., Jeong, J. Y., Yoon, S. Y., Park, J. Y., Lee, K., et al. (2010) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2009-1088 · Cited by 63
The Possible Role of Prolactin in the Circadian Rhythm of Leptin Secretion in Male Rats
Mastronardi, C. A., Walczewska, A., Yu, W. H., Karanth, S., Parlow, A. F., & McCann, S. M. (2000) · Proceedings of The Society for Experimental Biology and Medicine · doi:10.1046/j.1525-1373.2000.22414.x · Cited by 67
Chavez, M., Seeley, R. J., Havel, P. J., Friedman, M. I., Cannon, C. M., Woods, S. C., & Schwartz, M. W. (1998) · Journal of Clinical Investigation · doi:10.1172/jci603 · Cited by 62
Self-citationCentral Regulation of Glucose Homeostasis
Tups, A., Benzler, J., Sergi, D., Ladyman, S. R., & Williams, L. M. (2017) · Comprehensive physiology · doi:10.1002/cphy.c160015 · Cited by 74
“energy homeostasis, it also has an important role in regulation of glucose homeostasis (3, 91, 209, 250, 313).”
Obesity pharmacotherapy: What is next?
Colón‐González, F., Kim, G. W., Lin, J. E., Valentino, M. A., & Waldman, S. A. (2012) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2012.10.005 · Cited by 61
“Modulation of central neuropeptide signaling The primary neural site for appetite regulation by peripheral signaling hormones is the arcuate nucleus (ARC) of the hypothalamus.”
BackgroundInfluentialIqbal, J., Li, X., Chang, B. H.-J., Chan, L., Schwartz, G. J., Chua, S. C., & Hussain, M. M. (2010) · Journal of Lipid Research · doi:10.1194/jlr.m005744 · Cited by 65
Chicken leptin: properties and actions
Taouis, M., Dridi, S., Cassy, S., et al. (2001) · Domestic Animal Endocrinology · doi:10.1016/s0739-7240(01)00122-9 · Cited by 62
Interoceptive and integrative contributions of forebrain and brainstem to energy balance control
GRILL, H. J., & Kaplan, J. (2001) · International Journal of Obesity · doi:10.1038/sj.ijo.0801917 · Cited by 64
Does Leptin Stimulate Nitric Oxide to Oppose the Effects of Sympathetic Activation?
Mitchell, J., Morgan, D. A., Correia, M., Mark, A. L., Sivitz, W. I., & Haynes, W. G. (2001) · Hypertension · doi:10.1161/hy1101.096053 · Cited by 62
Chen, Y., & Heiman, M. L. (2000) · Regulatory Peptides · doi:10.1016/s0167-0115(00)00157-9 · Cited by 65
The effect of leptin on feeding-regulating neurons in the rat hypothalamus
Funahashi, H., Yada, T., Muroya, S., Takigawa, M., Ryushi, T., Horie, S., Nakai, Y., & Shioda, S. (1999) · Neuroscience Letters · doi:10.1016/s0304-3940(99)00186-x · Cited by 64
Gonçalves, G. H. M., Li, W., Garcia, A. V. C.-G., Figueiredo, M. S., & Bjørbæk, C. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.04.010 · Cited by 64
Physiological glucose is critical for optimized neuronal viability and AMPK responsiveness in vitro
Kleman, A. M., Yuan, J., Aja, S. M., Ronnett, G. V., & Landree, L. E. (2007) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2007.08.028 · Cited by 58
Central Nervous and Metabolic Effects of Intranasally Applied Leptin
Schulz, C., Paulus, K., & Lehnert, H. (2004) · Endocrinology · doi:10.1210/en.2003-1431 · Cited by 60
Metabolic, gastrointestinal, and CNS neuropeptide effects of brain leptin administration in the rat
van Dijk, G., Seeley, R. J., Thiele, T. E., Friedman, M. I., Ji, H. L., Wilkinson, C. W., Burn, P., Campfield, L. A., Tenenbaum, R., Baskin, D. G., et al. (1999) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1999.276.5.r1425 · Cited by 60
“Hence, central leptin administration influences the synthesis and/or release of CNS peptides, such as neuropeptide Y (NPY) and corticotropinreleasing hormone (CRH) (4, 23, 24, 37, 43, 45), that regulate autonomic outflow.”
BackgroundResultSelf-citationPeptides and proteins regulating food intake: a comparative view
Gorissen, M., Flik, G., & Huising, M. O. (2006) · Animal Biology · doi:10.1163/157075606778967829 · Cited by 61
“Indeed, peripheral adiposity signals (leptin; insulin) decrease NPY mRNA expression (Stephens et al., 1995; Schwartz et al., 1996) and an absence of peripheral signals like leptin and insulin increases NPY mRNA expression and secretion (Kalra et al., 1991).”
BackgroundNeuropeptide Y, leptin, galanin and insulin in women with polycystic ovary syndrome
Baranowska, B., Radzikowska, M., Wasilewska-Dziubińska, E., Kapliński, A., Roguski, K., & Plonowski, A. (1999) · Gynecological Endocrinology · doi:10.3109/09513599909167578 · Cited by 58
Correia, M., Morgan, D. A., Mitchell, J., Sivitz, W. I., Mark, A. L., & Haynes, W. G. (2001) · Hypertension · doi:10.1161/01.hyp.38.3.384 · Cited by 58
13 C NMR study of the effects of leptin treatment on kinetics of hepatic intermediary metabolism
Cohen, S. M., Werrmann, J. G., & Tota, M. R. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.13.7385 · Cited by 62
Metabolic Abnormalities and the Role of Leptin in Human Obesity
Pi‐Sunyer, F. X., & Laferrère, B. (1999) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.84.1.5392-1 · Cited by 62
Nogueiras, R., López, M., Lage, R., Pérez–Tilve, D., Pfluger, P. T., Zerón, H. M., Σάκκου, Μ., Wiedmer, P., Benoit, S. C., Datta, R., et al. (2008) · Endocrinology · doi:10.1210/en.2007-1684 · Cited by 59
Impaired Glucose Homeostasis in Mice Lacking the α1b-Adrenergic Receptor Subtype
Burcelin, R., Uldry, M., Foretz, M., Perrin, C., Dacosta, A., Nenniger-Tosato, M., Seydoux, J., Cotecchia, S., & Thorens, B. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m307788200 · Cited by 59
Morphological evidence for neural interactions between leptin and orexin in the hypothalamus
Funahashi, H., Hori, T., Shimoda, Y., et al. (2000) · Regulatory Peptides · doi:10.1016/s0167-0115(00)00146-4 · Cited by 59
Evidence for Central Regulation of Glucose Metabolism
Carey, M., Kehlenbrink, S., & Hawkins, M. A. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.r113.506782 · Cited by 65
“Initial studies suggested that leptin mediates its effects on food intake and body weight at least partly via its ability to suppress expression of hypothalamic neuropeptide Y, an orexigenic molecule (62, 63).”
BackgroundRethinking leptin and insulin action: Therapeutic opportunities for diabetes
Yıldız, B. O., & Haznedaroğlu, İ. C. (2005) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2005.09.013 · Cited by 58
Schwartz, M. W., Strack, A. M., & Dallman, M. F. (1997) · Regulatory Peptides · doi:10.1016/s0167-0115(97)01043-4 · Cited by 57
Self-citationCellular, molecular and physiological aspects of leptin: Potential application in animal production
HOSSNER, K. L. (1998) · Canadian Journal of Animal Science · doi:10.4141/a98-061 · Cited by 56
Bergonzelli, G. E., Pralong, F. P., Glauser, M., Cavadas, C., Grouzmann, E., & Gaillard, R. C. (2001) · Diabetes · doi:10.2337/diabetes.50.12.2666 · Cited by 60
Neuromodulation in Polycystic Ovary Syndrome
Kalro, B. N., Loucks, T. L., & Berga, S. L. (2001) · Obstetrics and Gynecology Clinics of North America · doi:10.1016/s0889-8545(05)70184-4 · Cited by 60
Liu, X., SHI, J.-H., Du, W.-H., Fan, Y., Hu, X., Zhang, C., Xu, H., Miao, Y.-J., Zhou, H., Xiang, P., et al. (2011) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2011.292 · Cited by 58
“Systemic administration of leptin inhibits NPY gene overexpression through a specific action in the arcuate nucleus and exerts a hypoglycemic action that is partly independent of its weight-reducing effects (47).”
BackgroundSinha, R., Gu, P., Hart, R. L. D., & Guarnaccia, J. B. (2019) · Physiology & Behavior · doi:10.1016/j.physbeh.2019.112563 · Cited by 61
Regulation of ob gene and overexpression in obesity
Guerre-Millo, M. (1997) · Biomedicine & Pharmacotherapy · doi:10.1016/s0753-3322(97)88048-1 · Cited by 57
F-DIO obesity-prone rat is insulin resistant before obesity onset
Levin, B. E., Magnan, C., Migrenne, S., Chua, S. C., & Dunn-Meynell, A. A. (2005) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00216.2005 · Cited by 56
“Since leptin reduces ARC NPY expression (43), these results suggested that DIO rats might be leptin resistant.”
BackgroundBivariate genetic analysis of fasting insulin and glucose levels
Snieder, H., Boomsma, D. I., van Doornen, L. J. P., & Neale, M. C. (1999) · Genetic Epidemiology · doi:10.1002/(sici)1098-2272(1999)16:4 · Cited by 56
Long-term cigarette smoke exposure increases uncoupling protein expression but reduces energy intake
Chen, H., Hansen, M. J., Jones, J. E. C., Vlahos, R., Anderson, G. P., & Morris, M. J. (2008) · Brain Research · doi:10.1016/j.brainres.2008.06.067 · Cited by 57
“5).”
BackgroundRelation of leptin and neuropeptide Y in human blood and cerebrospinal fluid
Dötsch, J., Adelmann, M., Englaro, P., Dötsch, A., Hänze, J., Blum, W. F., Kiess, W., & Rascher, W. (1997) · Journal of the Neurological Sciences · doi:10.1016/s0022-510x(97)00116-0 · Cited by 52
Role of neuropeptide Y in diet-, chemical- and genetic-induced obesity of mice
Hollopeter, G., Erickson, J. C., & Palmiter, R. D. (1998) · International Journal of Obesity · doi:10.1038/sj.ijo.0800615 · Cited by 55
Morimoto, I., Yamamoto, S., Kai, K., Fujihira, T., Morita, E., & Eto, S. (2000) · Neuroendocrinology · doi:10.1159/000054557 · Cited by 53
“The hypothalamus is the regulatory center of feeding behavior and thermogenesis, controlling energy balance in vivo. Several lines of evidence suggest that the hypothalamus is the primary brain site targeted by leptin [”
BackgroundYau, S. W., Henry, B. A., Russo, V. C., McConell, G. K., Clarke, I. J., Werther, G. A., & Sabin, M. A. (2014) · Endocrinology · doi:10.1210/en.2013-2099 · Cited by 54
Kim, D., Woods, S. C., & Seeley, R. J. (2010) · Diabetes · doi:10.2337/db09-1141 · Cited by 54
“Expression of NPY and AgRP is inhibited by leptin (39,40), whereas expression of POMC is increased by leptin (41–43).”
BackgroundSelf-citationBeck, B., Richy, S., Dimitrov, T., & Stricker‐Krongrad, A. (2001) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2001.5420 · Cited by 54
Masaki, T., Chiba, S., Yoshimichi, G., et al. (2003) · Endocrinology · doi:10.1210/en.2003-0031 · Cited by 54
“There is increasing evidence that the effects of leptin are governed by a number of hypothalamic mediators including orexigenic substances such as neuropeptide Y (4), melanin-concentrating hormone (5), and agouti-related protein (6) in addition to anorexigenic substances, such as CRH (7), cocaine-amphetamine-regulated…”
BackgroundA role for dietary fat in leptin receptor, OB-Rb, function
Heshka, J. T., & Jones, P. J. H. (2001) · Life Sciences · doi:10.1016/s0024-3205(01)01201-2 · Cited by 53
“Others have found that CART mRNA levels are low at times when leptin levels are low, such as during starvation [48].”
BackgroundLu, H., Duanmu, Z., Houck, C., Jen, K. ‐. C., Buison, A. M., & Dunbar, J. C. (1998) · Brain Research Bulletin · doi:10.1016/s0361-9230(98)00086-0 · Cited by 54
Cloning and expression of the porcineobesegene
Bidwell, C. A., Ji, S., Frank, G. R., Cornelius, S. G., Willis, G. M., & Spurlock, M. E. (1997) · Animal Biotechnology · doi:10.1080/10495399709525882 · Cited by 53
Neuroscience and Appetitive Behavior Research: 25 Years
Hoebel, B. G. (1997) · Appetite · doi:10.1006/appe.1997.0126 · Cited by 53
Adipokines and Cardiovascular Risk in Cushing’s Syndrome
Valassi, E., Biller, B. M. K., Klibanski, A., & Misra, M. (2011) · Neuroendocrinology · doi:10.1159/000330416 · Cited by 54
Hypothalamic neuropeptide Y and plasma leptin after long-term high-fat feeding in the rat
Stricker‐Krongrad, A., Cumin, F., Burlet, C. R., & Beck, B. (1998) · Neuroscience Letters · doi:10.1016/s0304-3940(98)00678-8 · Cited by 52
Chen, S.-C., Kochan, J. P., Campfield, L. A., Burn, P., & Smeyne, R. J. (1999) · Journal of Receptors and Signal Transduction · doi:10.3109/10799899909036649 · Cited by 53
SOCS-3 expression in leptin-sensitive neurons of the hypothalamus of fed and fasted rats
Baskin, D. G., Breininger, J. F., & Schwartz, M. W. (2000) · Regulatory Peptides · doi:10.1016/s0167-0115(00)00143-9 · Cited by 54
Self-citation
Metadata
- Authors
- 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., & Weigle, D. S.
- Affiliations
- Departments of Medicine Seattle, Washington
- Biological Structure, and Psychology Seattle, Washington
- Seagen (Canada) (CA)
- University of Washington (US)
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 1996-04-01
- Volume
- 45
- Issue
- 4
- Pages
- 531-535
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2154555913
- Semantic Scholar
- c410a5e2a945c2b99b27f91a7924c39febf099ae
- Cited by
- 904
- References
- 0
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 5 · 2023: 8 · 2022: 12 · 2021: 14 · 2020: 11 · 2019: 12 · 2018: 13 · 2017: 18 · 2016: 26 · 2015: 22 · 2014: 33 · 2013: 28 · 2012: 23
- FWCI
- 25.10
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Novo Nordisk
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 12829, DK17844, DK-17047, R01DK012829, P30DK017047)
- 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/ob mice, neuropeptide Y, hypothalamus, arcuate nucleus, hyperglycemia, insulin, obesity, db/db mice, corticotropin-releasing factor, paraventricular nucleus, dietary intake, body weight, leptin resistance, pair feeding, glucose homeostasis, insulin resistance
- MeSH terms
- Insulin Secretion, Animals, Arcuate Nucleus of Hypothalamus, Blood Glucose, Cerebral Cortex, Corticotropin-Releasing Hormone, Cricetinae, Hippocampus, Hypothalamus, Insulin, Kidney, Mice, Inbred C57BL, Mice, Obese, Neuropeptide Y, Obesity, Proteins, Recombinant Proteins, RNA, Messenger, Transfection, Gene Expression, In Situ Hybridization, Leptin, Mice
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
