Hyperleptinemia Is Required for the Development of Leptin Resistance
Open accessAbstract
Leptin regulates body weight by signaling to the brain the availability of energy stored as fat. This negative feedback loop becomes disrupted in most obese individuals, resulting in a state known as leptin resistance. The physiological causes of leptin resistance remain poorly understood. Here we test the hypothesis that hyperleptinemia is required for the development of leptin resistance in diet-induced obese mice. We show that mice whose plasma leptin has been clamped to lean levels develop obesity in response to a high-fat diet, and the magnitude of this obesity is indistinguishable from wild-type controls. Yet these obese animals with constant low levels of plasma leptin remain highly sensitive to exogenous leptin even after long-term exposure to a high fat diet. This shows that dietary fats alone are insufficient to block the response to leptin. The data also suggest that hyperleptinemia itself can contribute to leptin resistance by downregulating cellular response to leptin as has been shown for other hormones.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Following a switch to a high-fat diet, wild-type and leptin-infused ob/ob mice displayed similar weight gain despite markedly higher plasma leptin levels in the wild-type group.
“Following the switch to a HFD, wild-type and leptin-infused ob/ob mice displayed similar weight gain despite markedly higher plasma leptin levels in the former group (94).”
From Leptin and the Central Nervous System Control of Glucose Metabolism (2011) · cites this paper as [94]
Wild-type mice exposed to a high-fat diet were resistant to the ability of leptin to reduce food intake and body weight and to induce hypothalamic pSTAT3 relative to leptin-infused ob/ob mice fed a high-fat diet.
“wild-type mice exposed to a HFD were resistant to the ability of leptin to reduce food intake and body weight and to induce hypothalamic pSTAT3 relative to leptin-infused ob/ob mice fed a HFD.”
From Leptin and the Central Nervous System Control of Glucose Metabolism (2011) · cites this paper as [94]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
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-citationWeight-Reducing Effects of the Plasma Protein Encoded by the <i>obese</i> 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-citationEffects of the <i>obese</i> Gene Product on Body Weight Regulation in <i>ob</i> / <i>ob</i> 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
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-citationCongenital leptin deficiency is associated with severe early-onset obesity in humans
Montague, C. T., Farooqi, I. S., Whitehead, J. P., Soos, M. A., Rau, H., Wareham, N. J., Sewter, C. P., Digby, J. E., Mohammed, S. N., Hurst, J. A., et al. (1997) · Nature · doi:10.1038/43185 · Cited by 2,936 · see citing works
Effects of Recombinant Leptin Therapy in a Child with Congenital Leptin Deficiency
Farooqi, I. S., Jebb, S. A., Langmack, G., Lawrence, E., Cheetham, C. H., Prentice, A. M., Hughes, I. A., McCamish, M. A., & O'Rahilly, S. (1999) · New England Journal of Medicine · doi:10.1056/nejm199909163411204 · Cited by 1,998 · see citing works
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
Hypothalamic IKKβ/NF-κB and ER Stress Link Overnutrition to Energy Imbalance and Obesity
Zhang, X., Zhang, G., Zhang, H., Karin, M., Bai, H., & Cai, D. (2008) · Cell · doi:10.1016/j.cell.2008.07.043 · Cited by 1,350 · see citing works
Trophic Action of Leptin on Hypothalamic Neurons That Regulate Feeding
Bouret, S. G., Draper, S. J., & Simerly, R. B. (2004) · Science · doi:10.1126/science.1095004 · Cited by 1,219 · see citing works
A translational profiling approach for the molecular characterization of CNS cell types
Heiman, M., Schaefer, A., Gong, S., Peterson, J. D., Day, M., Ramsey, K. E., Suárez-Fariñas, M., Schwarz, C., Stephan, D. A., Surmeier, D. J., et al. (2008) · Cell · doi:10.1016/j.cell.2008.10.028 · Cited by 1,134 · see citing works
Milanski, M., Degasperi, G., Coope, A., Morari, J., Denis, R., Cintra, D. E., Tsukumo, D. M. L., Anhe, G., Amaral, M. E., Takahashi, H. K., et al. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.2760-08.2009 · Cited by 1,125 · 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-citationMechanisms of leptin action and leptin resistance.
Myers, M. G., Cowley, M. A., & Münzberg, H. (2008) · Annual Review of Physiology · doi:10.1146/annurev.physiol.70.113006.100707 · Cited by 1,074 · see citing works
Physiological response to long-term peripheral and central leptin infusion in lean and obese mice.
Halaas, J. L., Boozer, C., Blair-West, J., Fidahusein, N., Denton, D. A., & Friedman, J. M. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.16.8878 · Cited by 1,033 · see citing works
Self-citationCerebrospinal 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
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
Rapid Rewiring of Arcuate Nucleus Feeding Circuits by Leptin
Pinto, S., Roseberry, A. G., Liu, H., Diano, S., Shanabrough, M., Cai, X., Friedman, J. M., & Horvath, T. L. (2004) · Science · doi:10.1126/science.1089459 · Cited by 987 · see citing works
Self-citationTwo defects contribute to hypothalamic leptin resistance in mice with diet-induced obesity
El-Haschimi, K., Pierroz, D. D., Hileman, S. M., Bjørbæk, C., & Flier, J. S. (2000) · Journal of Clinical Investigation · doi:10.1172/jci9842 · Cited by 887 · see citing works
Endoplasmic Reticulum Stress Plays a Central Role in Development of Leptin Resistance
Ozcan, L., Ergin, A. S., Lu, A., Chung, J., Sarkar, S., Nie, D., Myers, M. G., & Ozcan, U. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2008.12.004 · Cited by 875 · see citing works
Region-Specific Leptin Resistance within the Hypothalamus of Diet-Induced Obese Mice
Münzberg, H., Flier, J. S., & Bjørbæk, C. (2004) · Endocrinology · doi:10.1210/en.2004-0726 · Cited by 737 · 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-citationMori, H., Hanada, R., Hanada, T., Aki, D., Mashima, R., Nishinakamura, H., Torisu, T., Chien, K. R., Yasukawa, H., & Yoshimura, A. (2004) · Nature Medicine · doi:10.1038/nm1071 · Cited by 651 · see citing works
The Hormonal Control of Food Intake
Coll, A. P., Farooqi, I. S., & O’Rahilly, S. (2007) · Cell · doi:10.1016/j.cell.2007.04.001 · Cited by 605 · see citing works
Posey, K. A., Clegg, D. J., Printz, R. L., Byun, J., Morton, G. J., Vivekanandan-Giri, A., Pennathur, S., Baskin, D. G., Heinecke, J. W., Woods, S. C., et al. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90377.2008 · Cited by 586 · see citing works
Development of high fat diet-induced obesity and leptin resistance in C57Bl/6J mice
Lin, S., Thomas, T. C., Storlien, L., & Huang, X. (2000) · International Journal of Obesity · doi:10.1038/sj.ijo.0801209 · Cited by 570 · see citing works
Diet-Induced Obesity Causes Severe but Reversible Leptin Resistance in Arcuate Melanocortin Neurons
Enriori, P. J., Evans, A. E., Sinnayah, P., Jobst, E. E., Tonelli-Lemos, L., Billes, S. K., Glavas, M. M., Grayson, B. E., Perello, M., Nillni, E. A., et al. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.02.004 · Cited by 552 · see citing works
SOCS3 Mediates Feedback Inhibition of the Leptin Receptor via Tyr985
Bjørbæk, C., Lavery, H. J., Bates, S. H., Olson, R. K., Davis, S. M., Flier, J. S., & Myers, M. G. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m007577200 · Cited by 537 · see citing works
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
Collins, S., Martin, T. L., Surwit, R. S., & Robidoux, J. (2004) · Physiology & Behavior · doi:10.1016/j.physbeh.2004.02.006 · Cited by 486 · see citing works
Kleinridders, A., Schenten, D., Könner, A. C., Belgardt, B. F., Mauer, J., Okamura, T., Wunderlich, F. T., Medzhitov, R., & Brüning, J. C. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2009.08.013 · Cited by 483 · see citing works
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
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
Leptin therapy in insulin-deficient type I diabetes
Wang, M.-Y., Chen, L., Clark, G. O., Lee, Y., Stevens, R. D., Ilkayeva, O. R., Wenner, B. R., Bain, J. R., Charron, M. J., Newgard, C. B., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0909422107 · Cited by 327 · see citing works
Diet-induced Obesity Alters AMP Kinase Activity in Hypothalamus and Skeletal Muscle
Martin, T. L., Alquier, T., Asakura, K., Furukawa, N., Preitner, F., & Kahn, B. B. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m512831200 · Cited by 283 · see citing works
Antidiabetic Effects of IGFBP2, a Leptin-Regulated Gene
Hedbacker, K., Birsoy, K., Wysocki, R. W., Asilmaz, E., Ahima, R. S., Farooqi, I. S., & Friedman, J. M. (2010) · Cell Metabolism · doi:10.1016/j.cmet.2009.11.007 · Cited by 280 · see citing works
Self-citationKievit, P., Howard, J. K., Badman, M. K., Balthasar, N., Coppari, R., Mori, H., Lee, C. E., Elmquist, J. K., Yoshimura, A., & Flier, J. S. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.06.010 · Cited by 242 · see citing works
Making insulin-deficient type 1 diabetic rodents thrive without insulin
Yu, X., Park, B.-H., Wang, M.-Y., Wang, Z. V., & Unger, R. H. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0806993105 · Cited by 219 · see citing works
Endoplasmic Reticulum Stress Induces Leptin Resistance
Hosoi, T., Sasaki, M., Miyahara, T., Hashimoto, C., Matsuo, S., Yoshii, M., & Ozawa, K. (2008) · Molecular Pharmacology · doi:10.1124/mol.108.050070 · Cited by 202 · see citing works
Ernst, M. B., Wunderlich, C. M., Hess, S., Paehler, M., Mesaros, A., Koralov, S. B., Kleinridders, A., Husch, A., Münzberg, H., Hampel, B., et al. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.5712-08.2009 · Cited by 185 · see citing works
Mice lacking inhibitory leptin receptor signals are lean with normal endocrine function
Björnholm, M., Münzberg, H., Leshan, R. L., Villanueva, E. C., Bates, S. H., Louis, G. W., Jones, J. C., Ishida-Takahashi, R., Bjørbaek, C., & Myers, M. G. (2007) · Journal of Clinical Investigation · doi:10.1172/jci30688 · Cited by 183 · see citing works
White, M. F. (2006) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/y06-008 · Cited by 163 · see citing works
Won, J. C., Jang, P., Namkoong, C., Koh, E. H., Kim, S. K., Park, J., Lee, K., & Kim, M. (2009) · Obesity · doi:10.1038/oby.2009.194 · Cited by 153 · cited 1× · see citing works
“In addition, ER stress is a common byproduct of inflammation, and ER stress has been shown to contribute independently to the development of leptin resistance[23,24,25].”
BackgroundWhite, C. L., Whittington, A., Barnes, M. J., Wang, Z., Bray, G. A., & Morrison, C. D. (2008) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90513.2008 · Cited by 146 · see citing works
Hypothalamic inflammation and energy homeostasis: Resolving the paradox
Thaler, J. P., Choi, S. J., Schwartz, M. W., & Wisse, B. E. (2010) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2009.10.002 · Cited by 144 · see citing works
Scarpace, P. J., Matheny, M. E., Tümer, N., Cheng, K., & Zhang, Y. (2005) · Diabetologia · doi:10.1007/s00125-005-1763-x · Cited by 93 · see citing works
Trevaskis, J. L., Lei, C., Koda, J. E., Weyer, C., Parkes, D. G., & Roth, J. D. (2009) · Obesity · doi:10.1038/oby.2009.187 · Cited by 89 · see citing works
Wolfgang, M. J., & Lane, M. D. (2006) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.25.050304.092532 · Cited by 84 · see citing works
Does Hypothalamic Inflammation Cause Obesity?
Wisse, B. E., & Schwartz, M. W. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2009.09.003 · Cited by 62 · see citing works
Townsend, K. L., Lorenzi, M. M., & Widmaier, E. P. (2008) · Endocrine · doi:10.1007/s12020-008-9070-1 · Cited by 61 · see citing works
Tanaka, T., Hidaka, S., Masuzaki, H., Yasue, S., Minokoshi, Y., Ebihara, K., Chusho, H., Ogawa, Y., Toyoda, T., Sato, K., et al. (2005) · Diabetes · doi:10.2337/diabetes.54.8.2365 · Cited by 58 · see citing works
Surwit, R. S., Edwards, C. L., Murthy, S., & Petro, A. E. (2000) · Diabetes · doi:10.2337/diabetes.49.7.1203 · Cited by 40 · see citing works
Mechanism of attenuation of leptin signaling under chronic ligand stimulation
Knobelspies, H., Zeidler, J., Hekerman, P., Bamberg‐Lemper, S., & Becker, W. (2010) · BMC Biochemistry · doi:10.1186/1471-2091-11-2 · Cited by 35 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Adapting to obesity with adipose tissue inflammation
Reilly, S. M., & Saltiel, A. R. (2017) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2017.90 · Cited by 1,204 · see citing works
Obesity and leptin resistance: distinguishing cause from effect
Myers, M. G., Leibel, R. L., Seeley, R. J., & Schwartz, M. W. (2010) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2010.08.002 · Cited by 906 · see citing works
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-citationStructure, production and signaling of leptin
Münzberg, H., & Morrison, C. D. (2014) · Metabolism · doi:10.1016/j.metabol.2014.09.010 · Cited by 455 · see citing works
Leptin resistance and diet-induced obesity: central and peripheral actions of leptin
Sáinź, N., Barrenetxe, J., Moreno-Aliaga, M. J., & Martínez, J. A. (2014) · Metabolism · doi:10.1016/j.metabol.2014.10.015 · Cited by 423 · see citing works
Leptin signaling and leptin resistance
Zhou, Y., & Rui, L. (2013) · Frontiers of Medicine · doi:10.1007/s11684-013-0263-5 · Cited by 417 · see citing works
Amylin: Pharmacology, Physiology, and Clinical Potential
Hay, D. L., Chen, S., Lutz, T. A., Parkes, D. G., & Roth, J. D. (2015) · Pharmacological Reviews · doi:10.1124/pr.115.010629 · Cited by 400 · see citing works
Adiponectin, Leptin and Cardiovascular Disorders
Zhao, S., Kusminski, C. M., & Scherer, P. E. (2021) · Circulation Research · doi:10.1161/circresaha.120.314458 · Cited by 398 · see citing works
Peripheral Cannabinoid-1 Receptor Inverse Agonism Reduces Obesity by Reversing Leptin Resistance
Tam, J., Çınar, R., Liu, J., Godlewski, G., Wesley, D., Jourdan, T., Szanda, G., Mukhopadhyay, B., Chedester, L., Liow, J., et al. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.07.002 · Cited by 359 · see citing works
Leptin Mediates the Increase in Blood Pressure Associated with Obesity
Simonds, S. E., Pryor, J. T., Ravussin, É., Greenway, F. L., Dileone, R., Allen, A. M., Bassi, J. K., Elmquist, J. K., Keogh, J. M., Henning, E., et al. (2014) · Cell · doi:10.1016/j.cell.2014.10.058 · Cited by 347 · see citing works
Leptin and the maintenance of elevated body weight
Pan, W. W., & Myers, M. G. (2018) · Nature reviews. Neuroscience · doi:10.1038/nrn.2017.168 · Cited by 344 · see citing works
Leptin and the Central Nervous System Control of Glucose Metabolism
Morton, G. J., & Schwartz, M. W. (2011) · Physiological Reviews · doi:10.1152/physrev.00007.2010 · Cited by 338 · see citing works
“Following the switch to a HF diet, wild-type and leptin-infused ob/ob mice displayed similar weight gain despite markedly higher plasma leptin levels in the former group (94).”
BackgroundInfluentialStojsavljević, S. (2014) · World Journal of Gastroenterology · doi:10.3748/wjg.v20.i48.18070 · Cited by 325 · see citing works
Karczewski, J., Śledzińska, E., Baturo, A., Jończyk, I., Maleszko, A., Maleszko, A., Samborski, P., Krasińska, B., & Dobrowolska, A. (2018) · European Cytokine Network · doi:10.1684/ecn.2018.0415 · Cited by 314 · see citing works
Partial Leptin Reduction as an Insulin Sensitization and Weight Loss Strategy
Zhao, S., Zhu, Y., Schultz, R. D., Li, N., He, Z., Zhang, Z., Caron, A., Zhu, Q., Sun, K., Xiong, W., et al. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.08.005 · Cited by 295 · see citing works
Leptin revisited: its mechanism of action and potential for treating diabetes
Coppari, R., & Bjørbæk, C. (2012) · Nature Reviews Drug Discovery · doi:10.1038/nrd3757 · Cited by 295 · see citing works
Friedman, J. M. (2016) · Journal of Clinical Investigation · doi:10.1172/jci91578 · Cited by 279 · see citing works
Self-citationLeal, V. D. O., & Mafra, D. (2013) · Clinica Chimica Acta · doi:10.1016/j.cca.2013.02.003 · Cited by 275 · see citing works
20 YEARS OF LEPTIN: Leptin at 20: an overview
Friedman, J. M. (2014) · Journal of Endocrinology · doi:10.1530/joe-14-0405 · Cited by 249 · see citing works
Self-citationChallenges and Opportunities of Defining Clinical Leptin Resistance
Myers, M. G., Heymsfield, S. B., Haft, C. R., Kahn, B. B., Laughlin, M. R., Leibel, R. L., Tschöp, M. H., & Yanovski, J. A. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.01.002 · Cited by 241 · see citing works
Appetite regulation and weight control: the role of gut hormones
Perry, B., & Wang, Y. (2012) · Nutrition and Diabetes · doi:10.1038/nutd.2011.21 · Cited by 216 · see citing works
Adipose tissue: an endocrine organ playing a role in metabolic regulation
Booth, A. D., Magnuson, A. M., Fouts, J. K., & Foster, M. T. (2016) · Hormone Molecular Biology and Clinical Investigation · doi:10.1515/hmbci-2015-0073 · Cited by 215 · see citing works
Role of Leptin in Obesity, Cardiovascular Disease, and Type 2 Diabetes
Vilariño‐García, T., Polonio-González, M., Pérez‐Pérez, A., Ribalta, J., Arrieta, F., Aguilar‐Diosdado, M., Obaya, J. C., Gimeno-Orna, J. A., Iglesias, P., Navarro, J., et al. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25042338 · Cited by 172 · see citing works
Voss, M. W., Carr, L. J., Clark, R., & Weng, T. (2014) · Mental health and physical activity · doi:10.1016/j.mhpa.2014.01.001 · Cited by 164 · see citing works
Duntas, L. H., & Biondi, B. (2012) · Thyroid · doi:10.1089/thy.2011.0499 · Cited by 162 · see citing works
The therapeutic potential of second and third generation CB1R antagonists
Çınar, R., Iyer, M. R., & Kunos, G. (2020) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2020.107477 · Cited by 151 · see citing works
Crujeiras, A., Zulet, M. D. L. Á., Lopez-Legarrea, P., de la Iglesia, R., Pardo, M., Carreira, M., Martinez, J., & Casanueva, F. (2014) · Metabolism: Clinical and Experimental · doi:10.1016/j.metabol.2013.12.007 · Cited by 143 · see citing works
Diet-Induced Obese Mice Retain Endogenous Leptin Action
Ottaway, N., Mahbod, P., Rivero‐Gutiérrez, B., Norman, L. W., Gertler, A., D’Alessio, D. A., & Pérez–Tilve, D. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.04.015 · Cited by 137 · see citing works
Control of energy homeostasis by amylin
Lutz, T. A. (2011) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-011-0905-1 · Cited by 136 · see citing works
There and Back Again: Leptin Actions in White Adipose Tissue
Martínez‐Sánchez, N. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21176039 · Cited by 135 · see citing works
The pleiotropic roles of leptin in metabolism, immunity, and cancer
de Candia, P., Prattichizzo, F., Garavelli, S., Alviggi, C., Cava, A. L., & Matarese, G. (2021) · The Journal of Experimental Medicine · doi:10.1084/jem.20191593 · Cited by 132 · see citing works
Szewczyk‐Golec, K., Woźniak, A., & Reiter, R. J. (2015) · Journal of Pineal Research · doi:10.1111/jpi.12257 · Cited by 153 · see citing works
Leptin and the regulation of endothelial function in physiological and pathological conditions
Bełtowski, J. (2011) · Clinical and Experimental Pharmacology and Physiology · doi:10.1111/j.1440-1681.2011.05623.x · Cited by 127 · see citing works
Appetite Regulation: Hormones, Peptides, and Neurotransmitters and Their Role in Obesity
Miller, G. D. (2017) · American Journal of Lifestyle Medicine · doi:10.1177/1559827617716376 · Cited by 125 · see citing works
Zhao, S., Kusminski, C. M., Elmquist, J. K., & Scherer, P. E. (2020) · Diabetes · doi:10.2337/dbi19-0018 · Cited by 127 · see citing works
Martínez-Sánchez, N., Sweeney, O., Sidarta-Oliveira, D., Caron, A., Stanley, S., & Domingos, A. (2022) · Neuron · doi:10.1016/j.neuron.2022.10.017 · Cited by 105 · see citing works
The Leptin System and Diet: A Mini Review of the Current Evidence
Mendoza-Herrera, K., Florio, A. A., Moore, M., Marrero, A., Taméz, M., Bhupathiraju, S. N., & Mattei, J. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.749050 · Cited by 121 · see citing works
Adipose Tissue: Physiology to Metabolic Dysfunction
Richard, A. J., White, U. A., Elks, C. M., & Stephens, J. M. (2020) · Europe PMC (PubMed Central) · Cited by 118 · see citing works
Obesity causes selective and long-lasting desensitization of AgRP neurons to dietary fat
Beutler, L. R., Corpuz, T. V., Ahn, J. S., Kosar, S., Song, W., Chen, Y., & Knight, Z. A. (2020) · eLife · doi:10.7554/elife.55909 · Cited by 118 · see citing works
Self-citationSTAT3 phosphorylation in central leptin resistance
Liu, H., Du, T., Li, C., & Yang, G. (2021) · Nutrition & Metabolism · doi:10.1186/s12986-021-00569-w · Cited by 124 · see citing works
Hayes, M. R., Kanoski, S. E., Alhadeff, A. L., & Grill, H. J. (2011) · Obesity · doi:10.1038/oby.2011.50 · Cited by 110 · see citing works
High‐Fat Diet Induces Leptin Resistance in Leptin‐Deficient Mice
Koch, C. E., Lowe, C., Pretz, D., Steger, J., Williams, L. M., & Tups, A. (2014) · Journal of Neuroendocrinology · doi:10.1111/jne.12131 · Cited by 111 · see citing works
The Role of Ceramides in Diabetes and Cardiovascular Disease Regulation of Ceramides by Adipokines
Field, B. C., Gordillo, R., & Scherer, P. E. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.569250 · Cited by 111 · see citing works
Role of oxytocin signaling in the regulation of body weight
Blevins, J. E., & Ho, J. M. (2013) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-013-9260-x · Cited by 108 · see citing works
Cognitive and autonomic determinants of energy homeostasis in obesity
Richard, D. (2015) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2015.103 · Cited by 108 · see citing works
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
Self-citationNew therapeutic approaches for the treatment of obesity
Saltiel, A. R. (2016) · Science Translational Medicine · doi:10.1126/scitranslmed.aad1811 · Cited by 100 · see citing works
New insights in leptin resistance mechanisms in mice
Balland, É., & Cowley, M. A. (2015) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2015.09.004 · Cited by 101 · see citing works
Fairbrother, U. L., Kidd, E., Malagamuwa, T., & Walley, A. J. (2018) · Current Diabetes Reports · doi:10.1007/s11892-018-1053-x · Cited by 96 · see citing works
Leptin resensitisation: a reversion of leptin-resistant states
Andreoli, M. F., Donato, J., Çakır, I., & Perelló, M. (2019) · Journal of Endocrinology · doi:10.1530/joe-18-0606 · Cited by 95 · see citing works
Obesity-related kidney disease: Beyond hypertension and insulin-resistance
Arabi, T. Z., Shafqat, A., Sabbah, B. N., Ashraf, N., Shah, H., Abdulkader, H. S., Razak, A., Sabbah, A. N., & Arabi, Z. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.1095211 · Cited by 98 · see citing works
Gamber, K. M., Huo, L., Ha, S., Hairston, J. E., Greeley, S., & Bjørbæk, C. (2012) · PLoS ONE · doi:10.1371/journal.pone.0030485 · Cited by 94 · see citing works
Boonloh, K., Kukongviriyapan, V., Kongyingyoes, B., Kukongviriyapan, U., Thawornchinsombut, S., & Pannangpetch, P. (2015) · Nutrients · doi:10.3390/nu7085292 · Cited by 89 · see citing works
Diet-Induced Obesity and the Mechanism of Leptin Resistance
Engin, A. (2017) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-48382-5_16 · Cited by 87 · see citing works
Maziarz, M. P., Preisendanz, S., Juma, S., Imrhan, V., Prasad, C., & Vijayagopal, P. (2017) · Nutrition Journal · doi:10.1186/s12937-017-0235-8 · Cited by 84 · see citing works
Contrasting Effects of Leptin on Food Anticipatory and Total Locomotor Activity
Ribeiro, A. C. D. M., Ceccarini, G., Dupré, C., Friedman, J. M., Pfaff, D. W., & Mark, A. L. (2011) · PLoS ONE · doi:10.1371/journal.pone.0023364 · Cited by 81 · see citing works
Self-citationPartial leptin deficiency confers resistance to diet-induced obesity in mice
Zhao, S., Li, N., Zhu, Y., Straub, L. G., Zhang, Z., Wang, M.-Y., Zhu, Q., Kusminski, C. M., Elmquist, J. K., & Scherer, P. E. (2020) · Molecular Metabolism · doi:10.1016/j.molmet.2020.100995 · Cited by 83 · see citing works
Lee, C., Hsiao, W., & Lee, O. K. (2016) · Translational research · doi:10.1016/j.trsl.2016.11.003 · Cited by 83 · see citing works
Villanueva-Carmona, T., Cedó, L., Madeira, A., Ceperuelo‐Mallafré, V., Rodríguez‐Peña, M., Núñez‐Roa, C., Maymó‐Masip, E., Repollés-de-Dalmau, M., Badia, J., Keiran, N., et al. (2023) · Cell Metabolism · doi:10.1016/j.cmet.2023.03.004 · Cited by 82 · see citing works
Morton, G. J., Kaiyala, K. J., Fisher, J. D., Ogimoto, K., Schwartz, M. W., & Wisse, B. E. (2010) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00546.2010 · Cited by 81 · see citing works
Mészáros, M., & Bikov, A. (2022) · Biomedicines · doi:10.3390/biomedicines10112754 · Cited by 81 · see citing works
Peripheral cannabinoid-1 receptor blockade restores hypothalamic leptin signaling
Tam, J., Szanda, G., Drori, A., Liu, Z., Çınar, R., Kashiwaya, Y., Reitman, M. L., & Kunos, G. (2017) · Molecular Metabolism · doi:10.1016/j.molmet.2017.06.010 · Cited by 78 · see citing works
Structural insights into the mechanism of leptin receptor activation
Saxton, R. A., Caveney, N. A., Moya-Garzón, M. D., Householder, K. D., Rodriguez, G. E., Burdsall, K. A., Long, J. Z., & García, K. C. (2023) · Nature Communications · doi:10.1038/s41467-023-37169-6 · Cited by 76 · see citing works
Sahu, A. (2011) · Neuroendocrinology · doi:10.1159/000326785 · Cited by 74 · see citing works
Impaired Leptin Signalling in Obesity: Is Leptin a New Thermolipokine?
Genchi, V. A., D’Oria, R., Palma, G., Caccioppoli, C., Cignarelli, A., Natalicchio, A., Laviola, L., Giorgino, F., & Perrini, S. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22126445 · Cited by 75 · see citing works
Histone deacetylase 6 inhibition restores leptin sensitivity and reduces obesity
Çakır, I., Hadley, C. K., Pan, P. L., Bagchi, R. A., Ghamari‐Langroudi, M., Porter, D. T., Wang, Q., Litt, M. J., Jana, S., Hagen, S. E., et al. (2022) · Nature Metabolism · doi:10.1038/s42255-021-00515-3 · Cited by 74 · see citing works
Bandyopadhyay, G. K., Vu, C. U., Gentile, S., Lee, H., Biswas, N., Chi, N., O’Connor, D. T., & Mahata, S. K. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.335877 · Cited by 72 · see citing works
The emerging role of the endocannabinoid system in the pathogenesis and treatment of kidney diseases
Tam, J. (2015) · Journal of Basic and Clinical Physiology and Pharmacology · doi:10.1515/jbcpp-2015-0055 · Cited by 73 · see citing works
New Pharmacological Perspectives for the Leptin Receptor in the Treatment of Obesity
Roujeau, C., Jockers, R., & Dam, J. (2014) · Frontiers in Endocrinology · doi:10.3389/fendo.2014.00167 · Cited by 70 · see citing works
A gut–brain neural circuit controlled by intestinal gluconeogenesis is crucial in metabolic health
Soty, M., Penhoat, A., Amigó-Correig, M., Vinera, J., Sardella, A., Vulin-Bouilloux, F., Zitoun, C., Houberdon, I., & Mithieux, G. (2014) · Molecular Metabolism · doi:10.1016/j.molmet.2014.12.009 · Cited by 67 · see citing works
Tsunekawa, T., Banno, R., Mizoguchi, A., Sugiyama, M., Tominaga, T., Onoue, T., Hagiwara, D., Ito, Y., Iwama, S., Goto, M., et al. (2017) · EBioMedicine · doi:10.1016/j.ebiom.2017.01.007 · Cited by 63 · see citing works
Rahman, H. A., Sahib, N. G., Saari, N., Abas, F., Ismail, A., Mumtaz, M. W., & Hamid, A. A. (2017) · BMC Complementary and Alternative Medicine · doi:10.1186/s12906-017-1640-4 · Cited by 63 · see citing works
Effects of gut microbiota on leptin expression and body weight are lessened by high-fat diet in mice
Yao, H., Fan, C., Fan, X., Lu, Y., Wang, Y., Wang, R., Tang, T., & Qi, K. (2020) · British Journal Of Nutrition · doi:10.1017/s0007114520001117 · Cited by 63 · see citing works
Naito, M., Fujikura, J., Ebihara, K., Miyanaga, F., Yokoi, H., Kusakabe, T., Yamamoto, Y., Son, C., Mukoyama, M., Hosoda, K., et al. (2011) · Diabetes · doi:10.2337/db10-1795 · Cited by 58 · see citing works
Teasaponin Reduces Inflammation and Central Leptin Resistance in Diet-Induced Obese Male Mice
Yu, Y., Wu, Y., Szabo, A., Wu, Z., Wang, H., Li, D., & Huang, X. (2013) · Endocrinology · doi:10.1210/en.2013-1218 · Cited by 59 · see citing works
Newton, A. J., Heß, S., Paeger, L., Vogt, M. C., Lascano, J. F., Nillni, E. A., Brüning, J. C., Kloppenburg, P., & Xu, A. W. (2012) · Endocrinology · doi:10.1210/en.2012-1643 · Cited by 58 · see citing works
Serum leptin and loss of control eating in children and adolescents
Miller, R., Tanofsky‐Kraff, M., Shomaker, L. B., Field, S. E., Hannallah, L. M., Reina, S. A., Mooreville, M., Sedaka, N. M., Brady, S. M., Condarco, T. A., et al. (2013) · International Journal of Obesity · doi:10.1038/ijo.2013.126 · Cited by 57 · see citing works
Central and peripheral leptin resistance in obesity and improvements of exercise
Peng, J., Yin, L., & Wang, X. (2021) · Hormones and Behavior · doi:10.1016/j.yhbeh.2021.105006 · Cited by 56 · see citing works
Low Glycemic Load Experimental Diet More Satiating Than High Glycemic Load Diet
Chang, K. T., Lampe, J. W., Schwarz, Y., Breymeyer, K. L., Noar, K. A., Song, X., & Neuhouser, M. L. (2012) · Nutrition and Cancer · doi:10.1080/01635581.2012.676143 · Cited by 56 · see citing works
Rajamani, U., Gross, A. R., Hjelm, B. E., Sequeira, A., Vawter, M. P., Tang, J., Gangalapudi, V., Wang, Y., Andres, A. M., Gottlieb, R. A., et al. (2018) · Cell stem cell · doi:10.1016/j.stem.2018.03.009 · Cited by 55 · see citing works
Boyle, C., Rossier, M., & Lutz, T. (2011) · Physiology and Behavior · doi:10.1016/j.physbeh.2011.04.044 · Cited by 59 · see citing works
Metabolic Reserve as a Determinant of Cognitive Aging
Stranahan, A. M., & Mattson, M. P. (2012) · Journal of Alzheimer s Disease · doi:10.3233/jad-2011-110899 · Cited by 54 · see citing works
Rhythmic Leptin Is Required for Weight Gain from Circadian Desynchronized Feeding in the Mouse
Arble, D. M., Vitaterna, M. H., & Turek, F. W. (2011) · PLoS ONE · doi:10.1371/journal.pone.0025079 · Cited by 54 · see citing works
Misdistribution of iron and oxidative stress in chronic kidney disease
Nakanishi, T., Kuragano, T., Nanami, M., Nagasawa, Y., & Hasuike, Y. (2018) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2018.06.025 · Cited by 54 · see citing works
The role of dietary salt in metabolism and energy balance: Insights beyond cardiovascular disease
Wu, Q., Burley, G., Li, L., Lin, S., & Shi, Y. (2023) · Diabetes Obesity and Metabolism · doi:10.1111/dom.14980 · Cited by 57 · see citing works
Matias, A. M., Estevam, W. M., Coelho, P. M., Haese, D., Kobi, J. B. B. S., Lima‐Leopoldo, A. P., & Leopoldo, A. S. (2018) · Nutrients · doi:10.3390/nu10081071 · Cited by 53 · see citing works
Insulin and leptin as potential cognitive enhancers in metabolic disorders and Alzheimer's disease
Mejido, D. C. P., Peny, J. A., Vieira, M. N. N., Ferreira, S. T., & Felice, F. G. D. (2020) · Neuropharmacology · doi:10.1016/j.neuropharm.2020.108115 · Cited by 53 · see citing works
Berthoud, H., Morrison, C. D., & Münzberg, H. (2020) · Physiology & Behavior · doi:10.1016/j.physbeh.2020.112959 · Cited by 57 · see citing works
de Oliveira, R. D. V. C., Cerda, Á., Genvigir, F. D. V., Sampaio, M. F., Armaganijan, D., Bernik, M. M. S., Dórea, E. L., Hirata, M. H., Hinuy, H. M., & Hirata, R. D. C. (2013) · Arquivos Brasileiros de Endocrinologia & Metabologia · doi:10.1590/s0004-27302013000900002 · Cited by 52 · see citing works
Leptin Keeps Working, Even in Obesity
Myers, M. G. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.05.017 · Cited by 50 · see citing works
Leptin in normal physiology and leptin resistance
Li, S., & Li, X. (2015) · 中国科学通报：英文版 · doi:10.1007/s11434-015-0951-4 · Cited by 51 · see citing works
Coudriet, G. M., Delmastro-Greenwood, M. M., Previte, D. M., Marré, M. L., O’Connor, E., Novak, E. M., Vincent, G., Mollen, K. P., Lee, S., Dong, H. H., et al. (2017) · Antioxidants · doi:10.3390/antiox6040085 · Cited by 50 · see citing works
The association of short-chain fatty acids and leptin metabolism: a systematic review
Gabriel, F. C., & Fantuzzi, G. (2019) · Nutrition Research · doi:10.1016/j.nutres.2019.08.006 · Cited by 49 · see citing works
Recent advances in understanding the role of leptin in energy homeostasis
Münzberg, H., Singh, P., Heymsfield, S. B., Yu, S., & Morrison, C. D. (2020) · F1000Research · doi:10.12688/f1000research.24260.1 · Cited by 47 · see citing works
Effects of Amylin on Eating and Adiposity
Lutz, T. A. (2011) · Handbook of experimental pharmacology · doi:10.1007/978-3-642-24716-3_10 · Cited by 48 · see citing works
Interactions Between Alcohol and the Endocannabinoid System
Kunos, G. (2020) · Alcoholism Clinical and Experimental Research · doi:10.1111/acer.14306 · Cited by 47 · see citing works
Non-Neuronal Cells in the Hypothalamic Adaptation to Metabolic Signals
Freire‐Regatillo, A., Argente-Arizón, P., Argente, J., García‐Segura, L. M., & Chowen, J. A. (2017) · Frontiers in Endocrinology · doi:10.3389/fendo.2017.00051 · Cited by 45 · see citing works
Evans, M. C., Lord, R. A., & Anderson, G. M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22179210 · Cited by 44 · see citing works
The secretory function of adipose tissues in metabolic regulation
Liu, Y., Qian, S., Tang, Y., & Tang, Q. (2024) · Life Metabolism · doi:10.1093/lifemeta/loae003 · Cited by 48 · see citing works
Chhabra, K. H., Adams, J. M., Jones, G. L., Yamashita, M., Schlapschy, M., Skerra, A., Rubinstein, M., & Low, M. J. (2016) · Molecular Metabolism · doi:10.1016/j.molmet.2016.07.012 · Cited by 43 · see citing works
- Authors
- Knight, Z. A., Hannan, K. S., Greenberg, M. L., & Friedman, J. M.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Friedman, Jeffrey M.
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2010-06-29
- Volume
- 5
- Issue
- 6
- Pages
- e11376
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC2894068
- OpenAlex
- W1974838371
- Cited by
- 311
- References
- 53
- Citations by year
- 2026: 12 · 2025: 17 · 2024: 17 · 2023: 16 · 2022: 21 · 2021: 21 · 2020: 31 · 2019: 21 · 2018: 20 · 2017: 22 · 2016: 19 · 2015: 23 · 2014: 19 · 2013: 14 · 2012: 15
- FWCI
- 7.37
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- eScholarship (California Digital Library) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health (DK083531)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK083531, R00DK083531, DK041096, K99DK083531, 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
- hyperleptinemia, leptin resistance, diet-induced obesity, leptin signaling, high-fat diet, leptin sensitivity, obesity, energy homeostasis
- MeSH terms
- Animals, Energy Intake, Feeding Behavior, Mice, Inbred C57BL, Obesity, 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
