Differential Sensitivity to Central Leptin and Insulin in Male and Female Rats
Abstract
The distribution of fat in the body differs between the male and female sexes and is associated with the relative secretion of the two “adiposity” hormones leptin and insulin. We now report that the brains of male and female rats are differentially sensitive to the catabolic actions of small doses of these two hormones. Leptin (1 or 3.5 μg/2 μl) or saline (2 μl) was administered into the third cerebral ventricle of age- and weight-matched male and female rats. Leptin significantly reduced food intake in female and male rats over 4 h; however, leptin reduced 24-h intake in female but not in male rats. When the same rats were administered insulin (1 or 4 mU/2 μl) or saline (2 μl), male but not female rats had a robust reduction in food intake over 24 h. Previous research demonstrates the melanocortins are a central mediator of the effects of both leptin and insulin. However, we found no sex differences in sensitivity to the melanocortin agonist MTII (0.01, 0.1, 0.3, and 1.0 nmol/2 μl). These results suggest that the sex differences in sensitivity to leptin and insulin at the doses that we injected occur upstream of the melanocortin receptors. Because insulin and leptin reflect different fat beds and are differentially distributed in the male and female sexes, the implication is that the male and female sexes regulate adiposity-relevant parameters differently.
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Intracerebroventricular injection of insulin markedly reduced food intake in male rodents, whereas feeding was unaffected in female rodents.
“Intracerebroventricular injection of insulin markedly reduced food intake in male rodents, whereas feeding was unaffected in female rodents23.”
From Brain insulin action on peripheral insulin sensitivity in women depends on menstrual cycle phase (2023) · cites this paper as [23]
Experimental studies suggest considerable sex differences in brain insulin sensitivity.
“Of note, experimental studies suggest considerable sex differences in brain insulin sensitivity.”
From Brain insulin action on peripheral insulin sensitivity in women depends on menstrual cycle phase (2023) · cites this paper as [23]
Male rats are more sensitive to the anorectic action of insulin injected in the brain.
“Male rats, however, are more sensitive to the anorectic action of insulin injected in the brain [32], an observation that translates to humans.”
From Sex differences in metabolic homeostasis, diabetes, and obesity (2015) · cites this paper as [32]
Female rats are more sensitive to the anorectic action of centrally injected leptin than males.
“Accordingly, female rats are more sensitive to the anorectic action of centrally injected leptin than males [32].”
From Sex differences in metabolic homeostasis, diabetes, and obesity (2015) · cites this paper as [32]
Cites
Central nervous system control of food intake
Schwartz, M. W., Woods, S. C., Porte, D., Seeley, R. J., & Baskin, D. G. (2000) · Nature · doi:10.1038/35007534 · Cited by 6,451 · see citing works
Self-citationOverweight and obesity in the United States: prevalence and trends, 1960–1994
Flegal, K., Carroll, M., Kuczmarski, R., & Johnson, C. (1998) · International Journal of Obesity · doi:10.1038/sj.ijo.0800541 · Cited by 3,045 · see citing works
Subcutaneous and visceral adipose tissue: their relation to the metabolic syndrome
Wajchenberg, B. L. (2000) · Endocrine Reviews · doi:10.1210/edrv.21.6.0415 · Cited by 2,961 · see citing works
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
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 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
Signals That Regulate Food Intake and Energy Homeostasis
Woods, S. C., Seeley, R. J., Porte, D., & Schwartz, M. W. (1998) · Science · doi:10.1126/science.280.5368.1378 · Cited by 1,169 · see citing works
Self-citationLeptin 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
Self-citationThe Obesity Epidemic Is a Worldwide Phenomenon
Popkin, B. M., & Doak, C. M. (2009) · Nutrition Reviews · doi:10.1111/j.1753-4887.1998.tb01722.x · Cited by 859 · see citing works
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 · cited 8× · see citing works
“DIABETES, VOL. 52, MARCH 2003 683 D ow nloaded from http://diabetesjournals.org/diabetes/article-pdf/52/3/682/373103/db0303000682.pdf by guest on 04 M arch 2022 I3vt leptin reduces food intake and body weight to a greater extent in female than male rats (experiment 2).”
BackgroundInfluentialMetabolic fuels and reproduction in female mammals
Wade, G. N., & Schneider, J. E. (1992) · Neuroscience & Biobehavioral Reviews · doi:10.1016/s0149-7634(05)80183-6 · Cited by 686 · see citing works
Melanocortin receptors in leptin effects
Seeley, R. J., Yagaloff, K. A., Fisher, S. L., Burn, P., Thiele, T. E., van Dijk, G., Baskin, D. G., & Schwartz, M. W. (1997) · Nature · doi:10.1038/37016 · Cited by 522 · see citing works
Mizuno, T. M., Kleopoulos, S. P., Bergen, H., Roberts, J. L., Priest, C. A., & Mobbs, C. V. (1998) · Diabetes · doi:10.2337/diab.47.2.294 · Cited by 521 · see citing works
Baura, G. D., Foster, D. M., Porte, D., Kahn, S. E., Bergman, R. N., Cobelli, C., & Schwartz, M. W. (1993) · Journal of Clinical Investigation · doi:10.1172/jci116773 · Cited by 489 · see citing works
Estrogen increases in vivo leptin production in rats and human subjects
Shimizu, H., Shimomura, Y., Nakanishi, Y., Futawatari, T., Ohtani, K., Sato, N., & Mori, M. (1997) · Journal of Endocrinology · doi:10.1677/joe.0.1540285 · Cited by 471 · see citing works
Body fat distribution, insulin resistance, and metabolic diseases
Björntorp, P. (1997) · Nutrition · doi:10.1016/s0899-9007(97)00191-3 · Cited by 470 · see citing works
Gonadal effects on food intake and adiposity: a metabolic hypothesis.
Wade, G., & Gray, J. (1979) · Physiology and Behavior · doi:10.1016/0031-9384(79)90028-3 · Cited by 458 · see citing works
Masuzaki, H., Ogawa, Y., Isse, N., Satoh, N., Okazaki, T., Shigemoto, M., Mori, K., Tamura, N., Hosoda, K., Yoshimasa, Y., et al. (1995) · Diabetes · doi:10.2337/diab.44.7.855 · Cited by 454 · see citing works
The Catabolic Action of Insulin in the Brain Is Mediated by Melanocortins
Benoit, S. C., Air, E. L., Coolen, L. M., Strauss, R., Jackman, A., Clegg, D. J., Seeley, R. J., & Woods, S. C. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-20-09048.2002 · Cited by 417 · see citing works
Self-citationWabitsch, M., Blum, W. F. P., Muche, R., Braun, M., Hube, F., Rascher, W., Heinze, E., Teller, W. M., & Hauner, H. (1997) · Journal of Clinical Investigation · doi:10.1172/jci119595 · Cited by 360 · see citing works
Food Intake and the Regulation of Body Weight
Woods, S. C., Schwartz, M. W., Baskin, D. G., & Seeley, R. J. (2000) · Annual Review of Psychology · doi:10.1146/annurev.psych.51.1.255 · Cited by 332 · see citing works
Self-citationSome effects of ovarian hormones on food intake and body weight in female rats.
Wade, G. N. (1975) · Journal of Comparative and Physiological Psychology · doi:10.1037/h0076186 · Cited by 308 · see citing works
The Insulin Resistance—Dyslipidemic Syndrome of Visceral Obesity: Effect on Patients' Risk
Després, J. (1998) · Obesity Research · doi:10.1002/j.1550-8528.1998.tb00683.x · Cited by 261 · see citing works
Intraventricular Leptin Reduces Food Intake and Body Weight of Lean Rats but Not Obese Zucker Rats
Seeley, R. J., van Dijk, G., Campfield, L. A., Smith, F., Burn, P., Nelligan, J., Bell, S. M., Baskin, D. S., Woods, S. C., & Schwartz, M. W. (1996) · Hormone and Metabolic Research · doi:10.1055/s-2007-979874 · Cited by 253 · see citing works
Self-citationTHE EFFECTS OF OVARIAN STEROIDS ON FOOD AND WATER INTAKE AND BODY WEIGHT IN THE FEMALE RAT
Tarttelin, M. F., & Gorski, R. A. (1973) · European Journal of Endocrinology · doi:10.1530/acta.0.0720551 · Cited by 202 · see citing works
Metabolic hormones and regulation of body weight.
Woods, S. C., Decke, E., & Vasselli, J. (1974) · Psychology Review · doi:10.1037/h0035927 · Cited by 193 · see citing works
Self-citationAcetylation alters the feeding response to MSH and beta-endorphin
Tsujii, S., & Bray, G. A. (1989) · Brain Research Bulletin · doi:10.1016/0361-9230(89)90142-1 · Cited by 161 · see citing works
Cloning and Functional Characterization of a Family of Receptors for the Melanotropic Peptides
Cone, R. D., Mountjoy, K. G., Robbins, L. S., Nadeau, J. H., Johnson, K. R., Roselli-Rehfuss, L., & Mortrud, M. T. (1993) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1993.tb19694.x · Cited by 151 · see citing works
Mizuno, T. M., Kleopoulos, S. P., Bergen, H., Roberts, J. L., Priest, C. A., & Mobbs, C. V. (1998) · Diabetes · doi:10.2337/diabetes.47.2.294 · Cited by 142 · see citing works
Differential effects of melanocortin peptides on neural melanocortin receptors.
Adan, R. A. H., Cone, R. D., Burbach, J. P. H., & Gispen, W. H. (1994) · Molecular Pharmacology · doi:10.1016/s0026-895x(25)09867-0 · Cited by 130 · see citing works
Dua, A., Hennes, M. M. I., Hoffmann, R. G., Maas, D. L., Krakower, G. R., Sonnenberg, G. E., & Kissebah, A. H. (1996) · Diabetes · doi:10.2337/diab.45.11.1635 · Cited by 130 · see citing works
Serum leptin concentration, body composition, and gonadal hormones during puberty
Demerath, E. W., Towne, B., Wisemandle, W., Blangero, J., Chumlea, W. C., & Siervogel, M. (1999) · International Journal of Obesity · doi:10.1038/sj.ijo.0800902 · Cited by 121 · see citing works
Role of food intake in estradiol-induced body weight changes in female rats
Roy, E. J., & Wade, G. N. (1977) · Hormones and Behavior · doi:10.1016/0018-506x(77)90001-0 · Cited by 115 · see citing works
Intraventricular insulin and the level of maintained body weight in rats.
Chavez, M., Kaiyala, K. J., Madden, L. J., Schwartz, M. W., & Woods, S. C. (1995) · Behavioral Neuroscience · doi:10.1037//0735-7044.109.3.528 · Cited by 111 · see citing works
Self-citationLeptin receptors in estrogen receptor-containing neurons of the female rat hypothalamus
Diano, S., Kalra, S. P., Sakamoto, H., & Horváth, T. L. (1998) · Brain Research · doi:10.1016/s0006-8993(98)00936-6 · Cited by 107 · see citing works
Intraventricular insulin and the level of maintained body weight in rats.
Chavez, M., Kaiyala, K. J., Madden, L. J., et al. (1995) · Behavioral Neuroscience · doi:10.1037/0735-7044.109.3.528 · Cited by 96 · see citing works
Diano, S., Kalra, S. P., & Horváth, T. L. (1998) · Journal of Neuroendocrinology · doi:10.1046/j.1365-2826.1998.00261.x · Cited by 91 · see citing works
Regulation of serum leptin levels by gonadal function in rats
Pinilla, L., Seoane, L. M., Gonzalez, L., Carro, E., Aguilar, E., Casanueva, F. F., & Diéguez, C. (1999) · European Journal of Endocrinology · doi:10.1530/eje.0.1400468 · Cited by 91 · see citing works
The Meal Patterns of the Oestrous Cycle and Their Motivational Significance
Drewett, R. F. (1974) · Quarterly Journal of Experimental Psychology · doi:10.1080/14640747408400438 · Cited by 68 · see citing works
The Influence of Ovariectomy onobGene Expression in Rats
Yoneda, N., Saito, S., Kimura, M., Yamada, M., Iida, M., Murakami, T., Irahara, M., Shima, K., & Aono, T. (1998) · Hormone and Metabolic Research · doi:10.1055/s-2007-978880 · Cited by 66 · see citing works
CIGOLINI, M., Seidell, J. C., Targher, G., Deslypère, J. P., Ellsinger, B. M., Charzewska, J., Cruz, A., & Björntorp, P. A. (1995) · Metabolism · doi:10.1016/0026-0495(95)90286-4 · Cited by 47 · see citing works
Effects of Exogenous Gonadal Steroids on Leptin Homeostasis in Rats
Wu‐Peng, S., ROSENBAUM, M. S., Nicolson, M. A., Chua, S. C., & Leibel, R. L. (1999) · Obesity Research · doi:10.1002/j.1550-8528.1999.tb00718.x · Cited by 45 · see citing works
Effects of Estradiol Implants on Body Weight Regulation in Castrated and Intact Female Rats
Dubuc, P. U. (1974) · Endocrinology · doi:10.1210/endo-95-6-1733 · Cited by 17 · see citing works
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Sex and Gender Differences in Risk, Pathophysiology and Complications of Type 2 Diabetes Mellitus
Kautzky-Willer, A., Harreiter, J., & Pacini, G. (2016) · Endocrine Reviews · doi:10.1210/er.2015-1137 · Cited by 2,043 · see citing works
The role of estrogens in control of energy balance and glucose homeostasis
Mauvais-Jarvis, F., Clegg, D. J., & Hevener, A. L. (2013) · Endocrine Reviews · doi:10.1210/er.2012-1055 · Cited by 1,329 · see citing works
Self-citationAnimal models of obesity and diabetes mellitus
Kleinert, M., Clemmensen, C., Hofmann, S. M., Moore, M. C., Renner, S., Woods, S. C., Huypens, P., Beckers, J., de Angelis, M. H., Schürmann, A., et al. (2018) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2017.161 · Cited by 853 · see citing works
Self-citationIntranasal insulin improves memory in humans
Benedict, C., Hallschmid, M., Hatke, A., Schultes, B., Fehm, H. L., Born, J., & Kern, W. (2004) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2004.04.003 · Cited by 699 · see citing works
Sex differences in metabolic homeostasis, diabetes, and obesity
Mauvais-Jarvis, F. (2015) · Biology of Sex Differences · doi:10.1186/s13293-015-0033-y · Cited by 626 · see citing works
“Male rats, however, are more sensitive to the anorectic action of insulin injected in the brain [32], an observation that translates to humans.”
BackgroundBrain Insulin Resistance at the Crossroads of Metabolic and Cognitive Disorders in Humans
Kullmann, S., Heni, M., Hallschmid, M., Fritsche, A., Preissl, H. T., & Häring, H. (2016) · Physiological Reviews · doi:10.1152/physrev.00032.2015 · Cited by 632 · see citing works
Power, M. L., & Schulkin, J. A. (2007) · British Journal Of Nutrition · doi:10.1017/s0007114507853347 · Cited by 610 · see citing works
Gonadal Hormones Determine Sensitivity to Central Leptin and Insulin
Clegg, D. J., Brown, L. M., Woods, S. C., & Benoit, S. C. (2006) · Diabetes · doi:10.2337/diabetes.55.04.06.db05-1339 · Cited by 552 · see citing works
Self-citationModulation of appetite by gonadal steroid hormones
Asarian, L., & Geary, N. (2006) · Philosophical Transactions of the Royal Society B: Biological Sciences · doi:10.1098/rstb.2006.1860 · Cited by 506 · 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
Leeners, B., Geary, N., Tobler, P. N., & Asarian, L. (2017) · Human Reproduction Update · doi:10.1093/humupd/dmw045 · Cited by 407 · see citing works
Sex and gender differences in developmental programming of metabolism
Dearden, L., Bouret, S. G., & Ozanne, S. E. (2018) · Molecular Metabolism · doi:10.1016/j.molmet.2018.04.007 · Cited by 353 · see citing works
Sex differences in developmental programming models
Aiken, C., & Ozanne, S. E. (2012) · Reproduction · doi:10.1530/rep-11-0489 · Cited by 340 · see citing works
Central effects of estradiol in the regulation of food intake, body weight, and adiposity
Brown, L. M., & Clegg, D. J. (2010) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2009.12.005 · Cited by 331 · see citing works
Self-citationPlum, L. (2006) · Journal of Clinical Investigation · doi:10.1172/jci27123 · Cited by 326 · see citing works
Neuroendocrinology of nutritional infertility
Wade, G. N., & Jones, J. E. (2004) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00475.2004 · Cited by 296 · see citing works
Benedict, C., Kern, W., Schultes, B., Born, J., & Hallschmid, M. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2007-2606 · Cited by 296 · see citing works
Insulin in the Brain: Sources, Localization and Functions
Ghasemi, R., Haeri, A., Dargahi, L., Mohamed, Z., & Ahmadiani, A. (2012) · Molecular Neurobiology · doi:10.1007/s12035-012-8339-9 · Cited by 291 · see citing works
Intranasal Insulin Reduces Body Fat in Men but not in Women
Hallschmid, M., Benedict, C., Schultes, B., Fehm, H.-L., Born, J., & Kern, W. (2004) · Diabetes · doi:10.2337/diabetes.53.11.3024 · Cited by 281 · see citing works
Estradiol-Dependent Decrease in the Orexigenic Potency of Ghrelin in Female Rats
Clegg, D., Brown, L. M., Zigman, J., Kemp, C., Strader, A., Benoit, S., Woods, S. C., Mangiaracina, M., & Geary, N. (2007) · Diabetes · doi:10.2337/db06-0015 · Cited by 275 · see citing works
Self-citationPancreatic signals controlling food intake; insulin, glucagon and amylin
Woods, S. C., Lutz, T. A., Geary, N., & Langhans, W. (2006) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2006.1858 · Cited by 286 · see citing works
Self-citationSex Differences in the Regulation of Body Weight
Shi, H., & Clegg, D. J. (2009) · Physiology and Behavior · doi:10.1016/j.physbeh.2009.02.017 · Cited by 273 · see citing works
Self-citationInsulin and its evolving partnership with leptin in the hypothalamic control of energy homeostasis
Niswender, K. D., Baskin, D. G., & Schwartz, M. W. (2004) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2004.07.009 · Cited by 250 · see citing works
Suarez, E. C. (2008) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2008.01.011 · Cited by 248 · see citing works
Wang, G.-J., Volkow, N. D., Telang, F., Jayne, M., Ma, Y., Pradhan, K., Zhu, W., Wong, C. T., Thanos, P. K., Geliebter, A., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0807423106 · Cited by 242 · see citing works
Sexual differences in the control of energy homeostasis
Shi, H., Seeley, R. J., & Clegg, D. J. (2009) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2009.03.004 · Cited by 242 · see citing works
“While both leptin and insulin cross into the brain via dedicated transport processes to act on specific receptors to regulate energy balance and elicit net catabolic responses, there are sexually dimorphic responses to their actions [29], [30] and [65].”
BackgroundInfluentialSelf-citationCentral nervous pathways of insulin action in the control of metabolism and food intake
Kullmann, S., Kleinridders, A., Small, D. M., Fritsche, A., Häring, H.-U., Preissl, H., & Heni, M. (2020) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(20)30113-3 · Cited by 233 · see citing works
Monitoring of stored and available fuel by the CNS: implications for obesity
Seeley, R. J., & Woods, S. C. (2003) · Nature reviews. Neuroscience · doi:10.1038/nrn1245 · Cited by 228 · see citing works
Self-citationBayol, S. A., Simbi, B. H., Bertrand, J. A., & Stickland, N. C. (2008) · The Journal of Physiology · doi:10.1113/jphysiol.2008.153817 · Cited by 225 · see citing works
Claxton, A., Baker, L. D., Wilkinson, C. W., Trittschuh, E. H., Chapman, D., Watson, G. S., Cholerton, B., Plymate, S. R., Arbuckle, M., & Craft, S. (2013) · Journal of Alzheimer’s Disease · doi:10.3233/jad-122308 · Cited by 215 · see citing works
Brain insulin signalling in metabolic homeostasis and disease
Scherer, T., Sakamoto, K., & Buettner, C. (2021) · Nature Reviews Endocrinology · doi:10.1038/s41574-021-00498-x · Cited by 205 · see citing works
The Control of Food Intake: Behavioral versus Molecular Perspectives
Woods, S. C. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2009.04.007 · Cited by 198 · see citing works
Self-citationStockhorst, U., de Fries, D., Steingrüber, H.-J., & Scherbaum, W. A. (2004) · Physiology & Behavior · doi:10.1016/j.physbeh.2004.07.022 · Cited by 191 · see citing works
Consumption of a high-fat diet induces central insulin resistance independent of adiposity
Clegg, D. J., Gotoh, K., Kemp, C., Wortman, M. D., Benoit, S. C., Brown, L. M., D’Alessio, D. A., Tso, P., Seeley, R. J., & Woods, S. C. (2011) · Physiology & Behavior · doi:10.1016/j.physbeh.2011.01.010 · Cited by 187 · see citing works
Self-citationHormonal and Metabolic Effects of Olanzapine and Clozapine Related to Body Weight in Rodents
Albaugh, V. L., Henry, C. R., Bello, N. T., Hajnal, A. S., Lynch, S. L., Halle, B., & Lynch, C. J. (2006) · Obesity · doi:10.1038/oby.2006.6 · Cited by 180 · see citing works
Hallschmid, M., Higgs, S., Thienel, M., Ott, V., & Lehnert, H. (2012) · Diabetes · doi:10.2337/db11-1390 · Cited by 181 · see citing works
Intranasal Insulin to Improve Memory Function in Humans
Benedict, C., Hallschmid, M., Schultes, B., Jan Born, A., & Kern, W. (2007) · Neuroendocrinology · doi:10.1159/000106378 · Cited by 171 · see citing works
Effects of selective estrogen receptor agonists on food intake and body weight gain in rats.
Roesch, D. (2006) · Physiology and Behavior · doi:10.1016/j.physbeh.2005.08.035 · Cited by 183 · see citing works
Hewagalamulage, S. D., Lee, T. K., Clarke, I. J., & Henry, B. A. (2016) · Domestic Animal Endocrinology · doi:10.1016/j.domaniend.2016.03.004 · Cited by 167 · see citing works
Leptin, but not adiponectin, predicts stroke in males
Söderberg, S., Stegmayr, B. G., Stenlund, H. C., Sjöström, L., Ågren, Å., Johansson, L. O. M., Weinehall, L., & Olsson, T. (2004) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2004.01351.x · Cited by 167 · see citing works
Obese men respond to cognitive but not to catabolic brain insulin signaling
Hallschmid, M., Benedict, C., Schultes, B., Born, J., & Kern, W. (2008) · International Journal of Obesity · doi:10.1038/sj.ijo.0803722 · Cited by 165 · see citing works
Metabolic Impact Of Sex Hormones On Obesity
Brown, L. M., Gent, L., Davis, K. E., & Clegg, D. J. (2010) · Brain Research · doi:10.1016/j.brainres.2010.04.056 · Cited by 13 · see citing works
Self-citationEffect of Intranasal Insulin on Cognitive Function: A Systematic Review
Shemesh, E., Rudich, A., Harman-Boehm, I., & Cukierman-Yaffe, T. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-1802 · Cited by 162 · see citing works
The selfish brain: competition for energy resources
Fehm, H. L., Kern, W., & Peters, A. (2006) · Progress in brain research · doi:10.1016/s0079-6123(06)53007-9 · Cited by 162 · see citing works
Sexual Dimorphism in Body Fat Distribution and Risk for Cardiovascular Diseases
Nedungadi, T. P., & Clegg, D. J. (2009) · Journal of Cardiovascular Translational Research · doi:10.1007/s12265-009-9101-1 · Cited by 154 · see citing works
Self-citationIncreased Tumor Growth in Mice with Diet-Induced Obesity: Impact of Ovarian Hormones
Yakar, S., Núñez, N. P., Pennisi, P. A., Brodt, P., Sun, H., Fallavollita, L., Zhao, H., Scavo, L. M., Novosyadlyy, R., Kurshan, N., et al. (2006) · Endocrinology · doi:10.1210/en.2006-0311 · Cited by 152 · see citing works
Gender Differences in the Control of Energy Homeostasis
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Self-citationOtt, V., Benedict, C., Schultes, B., Born, J., & Hallschmid, M. (2012) · Diabetes, Obesity and Metabolism · doi:10.1111/j.1463-1326.2011.01490.x · Cited by 139 · see citing works
Intraventricular insulin and leptin reduce food intake and body weight in C57BL/6J mice
Brown, L. M., Clegg, D. J., Benoit, S. C., & Woods, S. C. (2006) · Physiology & Behavior · doi:10.1016/j.physbeh.2006.08.008 · Cited by 139 · see citing works
Self-citationMechanisms of amylin/leptin synergy in rodent models.
Turek, V., Trevaskis, J., Levin, B., Dunn-Meynell, A., Irani, B. G., Gu, G., Wittmer, C. R., Griffin, P. S., Vu, C., Parkes, D., et al. (2010) · Endocrinology · doi:10.1210/en.2009-0546 · Cited by 144 · see citing works
Sexual dimorphism in insulin sensitivity and susceptibility to develop diabetes in rats
Vital, P., Larrieta‐Carrasco, E., & Hiriart, M. (2006) · Journal of Endocrinology · doi:10.1677/joe.1.06596 · Cited by 135 · see citing works
Dearden, L., & Ozanne, S. E. (2015) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2015.08.001 · Cited by 131 · see citing works
Ghrelin‐induced adiposity is independent of orexigenic effects
Perez-Tilve, D., Heppner, K., Kirchner, H., Lockie, S. K. H., Woods, S. C., Smiley, D., Tschöp, M., & Pfluger, P. (2011) · The FASEB Journal · doi:10.1096/fj.11-183632 · Cited by 132 · see citing works
Self-citationBenedict, C., Brede, S., Schiöth, H. B., Lehnert, H., Schultes, B., Born, J., & Hallschmid, M. (2011) · Diabetes · doi:10.2337/db10-0329 · Cited by 129 · see citing works
The role of hypothalamic estrogen receptors in metabolic regulation
Frank, A., Brown, L. M., & Clegg, D. J. (2014) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2014.05.002 · Cited by 128 · see citing works
“Higher levels of estrogens have been associated with increased leptin sensitivity [84; 85; 86]; however, some studies have failed to observe direct estrogen-leptin interactions [87; 88; 89].”
Self-citationMacKay, H., Patterson, Z. R., Khazall, R., Patel, S., Tsirlin, D., & Abizaid, A. B. (2013) · Endocrinology · doi:10.1210/en.2012-2044 · Cited by 116 · see citing works
The selfish brain: Competition for energy resources
Peters, A. (2010) · American Journal of Human Biology · doi:10.1002/ajhb.21106 · Cited by 115 · see citing works
Impaired estrogen receptor action in the pathogenesis of the metabolic syndrome
Hevener, A. L., Clegg, D. J., & Mauvais-Jarvis, F. (2015) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2015.05.020 · Cited by 112 · see citing works
Self-citationObesity-programmed mice are rescued by early genetic intervention
Bumaschny, V. F., Yamashita, M., Casas-Cordero, R., Otero-Corchón, V., de Souza, F. S. J., Rubinstein, M., & Low, M. J. (2012) · Journal of Clinical Investigation · doi:10.1172/jci62543 · Cited by 107 · see citing works
The utility of animal models to evaluate novel anti‐obesity agents
Vickers, S. P., Jackson, H. C., & Cheetham, S. C. (2011) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2011.01245.x · Cited by 107 · see citing works
Hsu, C., & Tain, Y. (2019) · Nutrients · doi:10.3390/nu11040894 · Cited by 106 · see citing works
Sex and estrogens alter the action of glucagon-like peptide-1 on reward
Richard, J. E., Anderberg, R. H., López-Ferreras, L., Olandersson, K., & Skibicka, K. P. (2016) · Biology of Sex Differences · doi:10.1186/s13293-016-0059-9 · Cited by 102 · see citing works
Adipose Tissue Hormones and the Regulation of Food Intake
Henry, B. A., & Clarke, I. J. (2008) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2008.1730.x · Cited by 102 · see citing works
Leptin Treatment in Activity-Based Anorexia
Hillebrand, J. J., Koeners, M. P., de Rijke, C. E., Kas, M. J., & Adan, R. A. H. (2005) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.03.011 · Cited by 102 · see citing works
Characterization of the metabolic differences between male and female C57BL/6 mice
de Souza, G. O., Wasinski, F., & Donato, J. (2022) · Life Sciences · doi:10.1016/j.lfs.2022.120636 · Cited by 98 · see citing works
Insulin Promotes Neuronal Survival via the Alternatively Spliced Protein Kinase CδII Isoform
Apostolatos, A. H., Song, S., Acosta, S., Peart, M. S., Watson, J. E., Bickford, P. C., Cooper, D. R., & Patel, N. A. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.313080 · Cited by 94 · see citing works
Developmental programming of hypothalamic neuronal circuits: impact on energy balance control
Ramamoorthy, T. G., Begum, G., Harno, E., & White, A. E. (2015) · Frontiers in Neuroscience · doi:10.3389/fnins.2015.00126 · Cited by 96 · see citing works
Chang, C., Yeh, S., Lee, S. O., & Chang, T. (2013) · Nuclear Receptor Signaling · doi:10.1621/nrs.11001 · Cited by 91 · see citing works
Signals generating anorexia during acute illness
Langhans, W. (2007) · Proceedings of The Nutrition Society · doi:10.1017/s0029665107005587 · Cited by 92 · see citing works
Bruijnzeel, A. W., Corrie, L. W.-C., Rogers, J. A., & Yamada, H. (2011) · Behavioural Brain Research · doi:10.1016/j.bbr.2011.01.020 · Cited by 89 · see citing works
Polymorphisms of the LEP- and LEPR Gene and Obesity in Patients Using Antipsychotic Medication
Gregoor, J. G., van der Weide, J., Mulder, H., Cohen, D., van Megen, H. J. G. M., Egberts, T. C. G., & Heerdink, E. R. (2009) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0b013e31819359be · Cited by 87 · see citing works
Bench-top to clinical therapies: A review of melanocortin ligands from 1954 to 2016
Ericson, M. D., Lensing, C. J., Fleming, K. A., Schlasner, K. N., Doering, S. R., & Haskell‐Luevano, C. (2017) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2017.03.020 · Cited by 86 · see citing works
Sexually different actions of leptin in proopiomelanocortin neurons to regulate glucose homeostasis
Shi, H., Strader, A. D., Sorrell, J. E., Chambers, J. B., Woods, S. C., & Seeley, R. J. (2008) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00704.2007 · Cited by 85 · see citing works
Self-citationGLP-1 and Its Analogs: Does Sex Matter?
Börchers, S., & Skibicka, K. P. (2024) · Endocrinology · doi:10.1210/endocr/bqae165 · Cited by 91 · see citing works
Söderberg, S., Zimmet, P., Tuomilehto, J. O., Chitson, P., Gareeboo, H., Alberti, K. G. M. M., & Shaw, J. E. (2007) · International Journal of Obesity · doi:10.1038/sj.ijo.0803561 · Cited by 79 · see citing works
Yu, I.-C. I., Lin, H., Liu, N.-C., Sparks, J. D., Yeh, S., Fang, L., Chen, L., & Chang, C. (2012) · Diabetes · doi:10.2337/db12-0135 · Cited by 78 · see citing works
Estradiol is a critical regulator of food-reward behavior.
Richard, J. E., López-Ferreras, L., Anderberg, R., Olandersson, K., & Skibicka, K. (2017) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2017.01.014 · Cited by 66 · see citing works
Hallschmid, M., Benedict, C., Jan Born, A., Fehm, H., & Kern, W. (2004) · Physiology & Behavior · doi:10.1016/j.physbeh.2004.07.023 · Cited by 75 · see citing works
Estradiol and high fat diet associate with changes in gut microbiota in female ob/ob mice
Acharya, K. D., Gao, X., Bless, E. P., Chen, J., & Tetel, M. J. (2019) · Scientific Reports · doi:10.1038/s41598-019-56723-1 · Cited by 74 · see citing works
Krug, R., Benedict, C., Jan Born, A., & Hallschmid, M. (2010) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2010-0744 · Cited by 74 · see citing works
Potential role of insulin on the pathogenesis of depression
Zou, X.-H., Sun, L.-H., Yang, W., Li, B.-J., & Cui, R.-J. (2020) · Cell Proliferation · doi:10.1111/cpr.12806 · Cited by 66 · see citing works
Begum, G., Davies, A., Stevens, A., Oliver, M. H., Jaquiery, A. L., Challis, J. R. G., Harding, J. E., Bloomfield, F. H., & White, A. E. (2013) · Endocrinology · doi:10.1210/en.2013-1693 · Cited by 71 · see citing works
Dearden, L., & Balthasar, N. (2014) · Endocrinology · doi:10.1210/en.2014-1131 · Cited by 69 · see citing works
Factors promoting and ameliorating the development of obesity
Levin, B. E. (2005) · Physiology & Behavior · doi:10.1016/j.physbeh.2005.08.054 · Cited by 69 · see citing works
Palou, M., Priego, T., Sánchez, J., Palou, A., & Picó, C. (2010) · Nutrition & Metabolism · doi:10.1186/1743-7075-7-69 · Cited by 69 · see citing works
Underwood, E. L., & Thompson, L. T. (2015) · Neural Plasticity · doi:10.1155/2016/7385314 · Cited by 69 · see citing works
Liu, X., & Shi, H. (2015) · International Journal of Endocrinology · doi:10.1155/2015/949085 · Cited by 70 · see citing works
Lentivirus-mediated downregulation of hypothalamic insulin receptor expression
Grillo, C. A., Tamashiro, K. L., Piroli, G. G., Melhorn, S. J., Gass, J. T., Newsom, R. J., Reznikov, L. R., Smith, A. C., Wilson, S. P., Sakai, R. R., et al. (2007) · Physiology & Behavior · doi:10.1016/j.physbeh.2007.05.043 · Cited by 67 · see citing works
Berends, L. M., Dearden, L., Tung, Y. L., Voshol, P. J., Fernandez‐Twinn, D. S., & Ozanne, S. E. (2018) · Diabetologia · doi:10.1007/s00125-018-4694-z · Cited by 65 · see citing works
Sexually dimorphic responses to fat loss after caloric restriction or surgical lipectomy
Shi, H., Strader, A. D., Woods, S. C., & Seeley, R. J. (2007) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00710.2006 · Cited by 63 · see citing works
Self-citationEstradiol regulates leptin sensitivity to control feeding via hypothalamic Cited1
González‐García, I., García-Clavé, E., Cebrian-Serrano, A., Thuc, O. L., Contreras, R. E., Xu, Y., Gruber, T., Schriever, S. C., Legutko, B., Lintelmann, J., et al. (2023) · Cell Metabolism · doi:10.1016/j.cmet.2023.02.004 · Cited by 62 · see citing works
Self-citationKuperman, Y., Weiss, M., Dine, J., Staikin, K., Golani, O., Ramot, A., Nahum, T., Kühne, C., Shemesh, Y., Wurst, W., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.04.017 · Cited by 60 · see citing works
Modulation of the satiating effect of amylin by central ghrelin, leptin and insulin
Osto, M., Wielinga, P. Y., Alder, B., Walser, N., & Lutz, T. A. (2007) · Physiology & Behavior · doi:10.1016/j.physbeh.2007.03.017 · Cited by 62 · see citing works
Hallschmid, M., Jauch-Chara, K., Korn, O., Mölle, M., Rasch, B., Born, J., Schultes, B., & Kern, W. (2010) · Diabetes · doi:10.2337/db09-1493 · Cited by 61 · see citing works
Begg, D. P., & Woods, S. C. (2013) · AJP Advances in Physiology Education · doi:10.1152/advan.00167.2012 · Cited by 61 · see citing works
Self-citationObesity-induced increases in sympathetic nerve activity: Sex matters
Brooks, V. L., Shi, Z., Holwerda, S. W., & Fadel, P. J. (2014) · Autonomic Neuroscience · doi:10.1016/j.autneu.2014.11.006 · Cited by 61 · see citing works
Molle, R. D., Fatemi, H., Dagher, A., Levitan, R. D., Silveira, P. P., & Dubé, L. (2016) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.12.028 · Cited by 61 · see citing works
Enhanced Amylin-Mediated Body Weight Loss in Estradiol-Deficient Diet-Induced Obese Rats
Trevaskis, J. L., Turek, V. F., Wittmer, C., Griffin, P. S., Wilson, J., Reynolds, J. M., Zhao, Y., Mack, C. M., Parkes, D. G., & Roth, J. D. (2010) · Endocrinology · doi:10.1210/en.2010-0590 · Cited by 60 · see citing works
Neurophysiological and cognitive changes in pregnancy
Grattan, D. R., & Ladyman, S. R. (2020) · Handbook of clinical neurology · doi:10.1016/b978-0-444-64239-4.00002-3 · Cited by 63 · see citing works
The regulation of food intake by insulin in the central nervous system
Mitchell, C. S., & Begg, D. P. (2021) · Journal of Neuroendocrinology · doi:10.1111/jne.12952 · Cited by 59 · see citing works
- Authors
- Clegg, D. J., Riedy, C. A., Smith, K. A. B., Benoit, S. C., & Woods, S. C.
- Affiliations
- University of Cincinnati (US)
- University of Washington (US)
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2003-03-01
- Volume
- 52
- Issue
- 3
- Pages
- 682-687
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2007895806
- Cited by
- 332
- References
- 42
- Citations by year
- 2026: 1 · 2025: 8 · 2024: 7 · 2023: 8 · 2022: 13 · 2021: 19 · 2020: 23 · 2019: 10 · 2018: 15 · 2017: 15 · 2016: 18 · 2015: 16 · 2014: 15 · 2013: 25 · 2012: 14
- FWCI
- 5.72
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Cincinnati
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (DK17844, DK54080, R01DK054080, P01DK056863, DK-56863)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- leptin, insulin, sex differences, dietary intake, melanocortin peptides, melanotan II, melanocortin receptors, adiposity, rats
- MeSH terms
- alpha-MSH, Animals, Body Composition, Body Weight, Brain, Eating, Female, Injections, Intraventricular, Insulin, Male, Sex Characteristics, Receptors, Corticotropin, Rats, Long-Evans, Leptin, Receptors, Melanocortin, Rats
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