Cited by 887Regulation of Appetite and ObesityAdipokines, Inflammation, and Metabolic DiseasesCytokine Signaling Pathways and Interactions

The DOI matches its Crossref record; 29 of the 29 references it cites were found in a registry or an index.

Two defects contribute to hypothalamic leptin resistance in mice with diet-induced obesity

Open access

El-Haschimi, Karim, Pierroz, Dominique D., Hileman, Stanley M., Bjørbæk, Christian, Flier, Jeffrey S.·2000·Journal of Clinical Investigation

DOI 10.1172/jci9842PMC PMC378516

Open this paper in CoChat — free account Open PDF

Abstract

Obesity in humans and in rodents is usually associated with high circulating leptin levels and leptin resistance. To examine the molecular basis for leptin resistance, we determined the ability of leptin to induce hypothalamic STAT3 (signal transducer and activator of transcription) signaling in C57BL/6J mice fed either low-fat or high-fat diets. In mice fed the low-fat diet, leptin activated STAT3 signaling when administered via the intraperitoneal (ip) or the intracerebroventricular (icv) route, with the half-maximal dose being 30-fold less when given by the icv route. The high-fat diet increased body-weight gain and plasma leptin levels. After 4 weeks on the diet, hypothalamic STAT3 signaling after ip leptin administration was equivalent in both diet groups. In contrast, peripherally administered leptin was completely unable to activate hypothalamic STAT3 signaling, as measured by gel shift assay after 15 weeks of high-fat diet. Despite the absence of detectable signaling after peripheral leptin at 15 weeks, the mice fed the high-fat diet retained the capacity to respond to icv leptin, although the magnitude of STAT3 activation was substantially reduced. These results suggest that leptin resistance induced by a high-fat diet evolves during the course of the diet and has at least two independent causes: an apparent defect in access to sites of action in the hypothalamus that markedly limits the ability of peripheral leptin to activate hypothalamic STAT signaling, and an intracellular signaling defect in leptin-responsive hypothalamic neurons that lies upstream of STAT3 activation.

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

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

Integrity signals

Registry

Crossref · 10.1172/jci9842

Cites

29 of 29 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

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

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

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

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

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

Positional cloning of the mouse obese gene and its human homologue
Zhang, Y., Proenca, R., Maffei, M., Barone, M., Leopold, L., & Friedman, J. M. (1994) · Nature · doi:10.1038/372425a0 · Cited by 13,419
Serum Immunoreactive-Leptin Concentrations in Normal-Weight and Obese Humans
Considine, R. V., Sinha, M. K., Heiman, M. L., Kriauciunas, A., Stephens, T. W., Nyce, M. R., Ohannesian, J. P., Marco, C. C., McKee, L. J., Bauer, T. L., et al. (1996) · New England Journal of Medicine · doi:10.1056/nejm199602013340503 · Cited by 6,326
Weight-Reducing Effects of the Plasma Protein Encoded by the obese Gene
Halaas, J. L., Gajiwala, K. S., Maffei, M., Cohen, S. L., Chait, B. T., Rabinowitz, D., Lallone, R. L., Burley, S. K., & Friedman, J. M. (1995) · Science · doi:10.1126/science.7624777 · Cited by 4,451
Rapid detection of octamer binding proteins with ‘mini extracts’, prepared from a small number of cells
Schreiber, E. H., Matthias, P., Müller, M. M., & Schaffner, W. (1989) · Nucleic Acids Research · doi:10.1093/nar/17.15.6419 · Cited by 4,179
Effects of the obese Gene Product on Body Weight Regulation in ob / ob Mice
Pelleymounter, M. A., Cullen, M. J., Baker, M. B., Hecht, R., Winters, D., Boone, T., & Collins, F. (1995) · Science · doi:10.1126/science.7624776 · Cited by 4,017
Recombinant Mouse OB Protein: Evidence for a Peripheral Signal Linking Adiposity and Central Neural Networks
Campfield, L. A., Smith, F. J., Guisez, Y., Devos, R., & Burn, P. (1995) · Science · doi:10.1126/science.7624778 · Cited by 3,243
Role of leptin in the neuroendocrine response to fasting
Ahima, R. S., Prabakaran, D., Mantzoros, C., Qu, D., Lowell, B., Maratos-Flier, E., & Flier, J. S. (1996) · Nature · doi:10.1038/382250a0 · Cited by 3,117
Self-citation
Abnormal splicing of the leptin receptor in diabetic mice
Lee, G.-H., Proenca, R., Montez, J. M., Carroll, K. M., Darvishzadeh, J. G., Lee, J. I., & Friedman, J. M. (1996) · Nature · doi:10.1038/379632a0 · Cited by 2,327
Evidence That the Diabetes Gene Encodes the Leptin Receptor: Identification of a Mutation in the Leptin Receptor Gene in db/db Mice
Chen, H., Charlat, O., Tartaglia, L. A., Woolf, E. A., Weng, X., Ellis, S. J., Lakey, N. D., Culpepper, J., More, K. J., Breitbart, R. E., et al. (1996) · Cell · doi:10.1016/s0092-8674(00)81294-5 · Cited by 2,214
Leptin levels reflect body lipid content in mice: Evidence for diet-induced resistance to leptin action
Frederich, R. C., Hamann, A., Anderson, S., Löllmann, B., Lowell, B. B., & Flier, J. S. (1995) · Nature Medicine · doi:10.1038/nm1295-1311 · Cited by 1,660
Self-citation

Flagged first, then by citations

Show all 29 references

Sorted by citations

Items 301–400 of 885

Leptin, body fat content and energy expenditure in intact and gonadectomized adult cats: a preliminary study
Martin, L., Siliart, B., Dumon, H., Backus, R., Biourge, V., & Nguyen, P. (2001) · Journal of Animal Physiology and Animal Nutrition · doi:10.1046/j.1439-0396.2001.00322.x · Cited by 66
Physical activity and estrogen treatment reduce visceral body fat and serum levels of leptin in an additive manner in a diet induced animal model of obesity
Zoth, N., Weigt, C., Laudenbach-Leschowsky, U., & Diel, P. R. (2010) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2010.03.029 · Cited by 66
Leptin receptor gene expression and number in the brain are regulated by leptin level and nutritional status
Mitchell, S. E., Nogueiras, R., Morris, A. C., Tovar, S. A., Grant, C., Cruickshank, M., Rayner, D. V., Diéguez, C., & Williams, L. M. (2009) · The Journal of Physiology · doi:10.1113/jphysiol.2009.173328 · Cited by 68
Region-specific diet-induced and leptin-induced cellular leptin resistance includes the ventral tegmental area in rats
Matheny, M. E., Shapiro, A. M., Tümer, N., & Scarpace, P. J. (2010) · Neuropharmacology · doi:10.1016/j.neuropharm.2010.11.002 · Cited by 64
Emerging role of glial cells in the control of body weight
García‐Cáceres, C., Fuente-Martín, E., Argente, J., & Chowen, J. A. (2012) · Molecular Metabolism · doi:10.1016/j.molmet.2012.07.001 · Cited by 69
Leptin Expression in Hypothalamic PVN Reverses Dietary Obesity and Hyperinsulinemia but Stimulates Ghrelin*
Bagnasco, M., Dube, M. G., Katz, A. A., Kalra, P. S., & Kalra, S. P. (2003) · Obesity Research · doi:10.1038/oby.2003.196 · Cited by 65
Towards a “Metabolic” Subtype of Major Depressive Disorder: Shared Pathophysiological Mechanisms May Contribute to Cognitive Dysfunction
Liu, C., Carvalho, A., & McIntyre, R. (2015) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/1871527313666141130204031 · Cited by 61
Cardiovascular and sympathetic effects of leptin
Rahmouni, K., Haynes, W. G., & Mark, A. L. (2002) · Current Hypertension Reports · doi:10.1007/s11906-002-0036-z · Cited by 63
Energy imbalance alters Ca2+ handling and excitability of POMC neurons
Paeger, L., Pippow, A., Heß, S., Paehler, M., Klein, A., Husch, A., Pouzat, C., Brüning, J. C., & Kloppenburg, P. (2017) · eLife · doi:10.7554/elife.25641 · Cited by 64
Central melanocortin signaling restores skeletal muscle AMP-activated protein kinase phosphorylation in mice fed a high-fat diet
Tanaka, T., Masuzaki, H., Yasue, S., Ebihara, K., Shiuchi, T., Ishii, T., Arai, N., Hirata, M., Yamamoto, H., Hayashi, T., et al. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.04.004 · Cited by 62
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
Central regulation of energy balance: inputs, outputs and leptin resistance
Arch, J. R. S. (2005) · Proceedings of The Nutrition Society · doi:10.1079/pns2004407 · Cited by 62
Integration of reward signalling and appetite regulating peptide systems in the control of food‐cue responses
Reichelt, A. C., Westbrook, R. F., & Morris, M. J. (2015) · British Journal of Pharmacology · doi:10.1111/bph.13321 · Cited by 62
Central leptin gene delivery evokes persistent leptin signal transduction in young and aged-obese rats but physiological responses become attenuated over time in aged-obese rats
Scarpace, P. J., Matheny, M. E., Zhang, Y., Tümer, N., Frase, C. D., Shek, E. W., Hong, B., Prima, V., & Zolotukhin, S. (2002) · Neuropharmacology · doi:10.1016/s0028-3908(02)00003-5 · Cited by 62
High-fat diet-induced changes in body mass and hypothalamic gene expression in wild-type and leptin-deficient mice
Townsend, K. L., Lorenzi, M. M., & Widmaier, E. P. (2008) · Endocrine · doi:10.1007/s12020-008-9070-1 · Cited by 61
Three Months of High-Fructose Feeding Fails to Induce Excessive Weight Gain or Leptin Resistance in Mice
Tillman, E. J., Morgan, D. A., Rahmouni, K., & Swoap, S. J. (2014) · PLoS ONE · doi:10.1371/journal.pone.0107206 · Cited by 67
The role of leptin and ghrelin in the regulation of appetite in obesity
Skoracka, K., Hryhorowicz, S., Schulz, P., Zawada, A. E., Ratajczak, A. E., Rychter, A. M., Słomski, R., Dobrowolska, A., & Krela‐Kaźmierczak, I. (2025) · Peptides · doi:10.1016/j.peptides.2025.171367 · Cited by 79
Pregnancy Induces Resistance to the Anorectic Effect of Hypothalamic Malonyl-CoA and the Thermogenic Effect of Hypothalamic AMPK Inhibition in Female Rats
de Morentin, P. B. M., Lage, R., González‐García, I., Ruíz-Pino, F., Martins, L., Fernández-Mallo, D., Gallego, R., Fernø, J., Señarís, R. M., Saha, A. K., et al. (2014) · Endocrinology · doi:10.1210/en.2014-1611 · Cited by 60
Serum leptin is associated with cardiometabolic risk and predicts metabolic syndrome in Taiwanese adults
Li, W.-C., Hsiao, K., Chen, I., Chang, Y., Wang, S., & Wu, K.-H. (2011) · Cardiovascular Diabetology · doi:10.1186/1475-2840-10-36 · Cited by 62
Combined Neural Inactivation of Suppressor of Cytokine Signaling-3 and Protein-Tyrosine Phosphatase-1B Reveals Additive, Synergistic, and Factor-Specific Roles in the Regulation of Body Energy Balance
Briançon, N., McNay, D. E. G., Maratos–Flier, E., & Flier, J. S. (2010) · Diabetes · doi:10.2337/db10-0481 · Cited by 61
Self-citation
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
Obesity impairs lactation performance in mice by inducing prolactin resistance
Buonfiglio, D. D. C., Ramos-Lobo, A. M., Freitas, V. M., Zampieri, T. T., Nagaishi, V. S., Magalhães, M., Cipolla‐Neto, J., Cella, N., & Donato, J. (2016) · Scientific Reports · doi:10.1038/srep22421 · Cited by 60
Activation of the Hypothalamic Arcuate Nucleus Predicts the Anorectic Actions of Ciliary Neurotrophic Factor and Leptin in Intact and Gold Thioglucose‐Lesioned Mice
Anderson, K. D., Lambert, P., Corcoran, T. L., Murray, J. D., Thabet, K., Yancopoulos, G. D., & Wiegand, S. J. (2003) · Journal of Neuroendocrinology · doi:10.1046/j.1365-2826.2003.01043.x · Cited by 60
A complex interaction pattern of CIS and SOCS2 with the leptin receptor
Lavens, D., Montoye, T., Piessevaux, J., Zabeau, L., Vandekerckhove, J. S., Gevaert, K., Becker, W. B., Eyckerman, S., & Tavernier, J. H. (2006) · Journal of Cell Science · doi:10.1242/jcs.02947 · Cited by 60
The Multiple Facets of the Fat Tissue
Rocha, V. Z., & Libby, P. (2008) · Thyroid · doi:10.1089/thy.2007.0296 · Cited by 61
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
Expression of DGAT2 in White Adipose Tissue Is Regulated by Central Leptin Action
Suzuki, R., Tobe, K., Aoyama, M., Sakamoto, K., Ohsugi, M., Kamei, N., Nemoto, S., Inoue, A., Ito, Y., Uchida, S., et al. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m410955200 · Cited by 58
Skeletal Muscle AMP-Activated Protein Kinase Phosphorylation Parallels Metabolic Phenotype in Leptin Transgenic Mice Under Dietary Modification
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 60
Differential leptin access into the brain — A hierarchical organization of hypothalamic leptin target sites?
Münzberg, H. (2008) · Physiology & Behavior · doi:10.1016/j.physbeh.2008.04.020 · Cited by 61
Interplay Between Galanin and Leptin in the Hypothalamic Control of Feeding via Corticotropin-Releasing Hormone and Neuropeptide Y
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
Nuclear factor κB (NF-κB) suppresses food intake and energy expenditure in mice by directly activating the Pomc promoter
Shi, X., Wang, X., Li, Q., Su, M. Y.-F., Chew, E. G. Y., Wong, E. T., Lacza, Z., Radda, G. K., Tergaonkar, V., & Han, W. (2013) · Diabetologia · doi:10.1007/s00125-013-2831-2 · Cited by 58
Towards the therapeutic use of intranasal neuropeptide administration in metabolic and cognitive disorders
Hallschmid, M., Benedict, C., Schultes, B., Perras, B., Fehm, H., Kern, W., & Jan Born, A. (2008) · Regulatory Peptides · doi:10.1016/j.regpep.2007.06.012 · Cited by 55
Leptin Receptors
Cottrell, E. C., & Mercer, J. G. (2011) · Handbook of experimental pharmacology · doi:10.1007/978-3-642-24716-3_1 · Cited by 56
Unabated anorexic and enhanced thermogenic responses to melanotan II in diet-induced obese rats despite reduced melanocortin 3 and 4 receptor expression
Li, G., Zhang, Y., Wilsey, J., & Scarpace, P. (2004) · Journal of Endocrinology · doi:10.1677/joe.0.1820123 · Cited by 56
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
Raspberry ketone and Garcinia Cambogia rebalanced disrupted insulin resistance and leptin signaling in rats fed high fat fructose diet
Attia, R. T., Abdel–Mottaleb, Y., Abdallah, D. M., El-Abhar, H. S., & El‐Maraghy, N. N. (2018) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2018.11.079 · Cited by 57
Leptin regulates interleukin-1β expression in the brain via the STAT3-independent mechanisms
Hosoi, T., Okuma, Y., & Nomura, Y. (2002) · Brain Research · doi:10.1016/s0006-8993(02)02974-8 · Cited by 56
A Mathematical Model of Murine Metabolic Regulation by Leptin: Energy Balance and Defense of a Stable Body Weight
Tam, J., Fukumura, D., & Jain, R. K. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2008.11.005 · Cited by 52
Anorexigenic Hormones Leptin, Insulin, and α-Melanocyte-Stimulating Hormone Directly Induce Neurotensin (NT) Gene Expression in Novel NT-Expressing Cell Models
Cui, H., Cai, F., & Belsham, D. D. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.2269-05.2005 · Cited by 55
Ontogeny and insulin regulation of fetal ovine white adipose tissue leptin expression
Devaskar, S. U., Anthony, R. V., & Hay, W. W. (2002) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.2002.282.2.r431 · Cited by 54
Leptin resistance in mice is determined by gender and duration of exposure to high-fat diet
Harris, R. B. S., Bowen, H. M., & Mitchell, T. D. (2003) · Physiology & Behavior · doi:10.1016/s0031-9384(03)00035-0 · Cited by 53
Staying Slim with Insulin in Mind
Schwartz, M. W. (2000) · Science · doi:10.1126/science.289.5487.2066 · Cited by 52
A 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
Diet composition, not calorie intake, rapidly alters intrinsic excitability of hypothalamic AgRP/NPY neurons in mice
Wei, W., Pham, K., Gammons, J. W., Sutherland, D., Liu, Y., Smith, A., Kaczorowski, C. C., & O’Connell, K. M. S. (2015) · Scientific Reports · doi:10.1038/srep16810 · Cited by 55
Regulation of Memory Function by Feeding-Relevant Biological Systems: Following the Breadcrumbs to the Hippocampus
Suarez, A. N., Noble, E. E., & Kanoski, S. E. (2019) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2019.00101 · Cited by 55
Biochemical markers of psoriasis as a metabolic disease
Gerkowicz, A., Pietrzak, A., Szepietowski, J. C., Radej, S., & Chodorowska, G. (2012) · Folia Histochemica et Cytobiologica · doi:10.5603/fhc.2012.0025 · Cited by 49
Improvement of diabetes, obesity and hypertension in type 2 diabetic KKAy mice by bis(allixinato)oxovanadium(IV) complex
Adachi, Y., Yoshikawa, Y., Yoshida, J., Kodera, Y., Katoh, A., Takada, J., & Sakurai, H. (2006) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2006.05.003 · Cited by 51
Cellular Leptin Resistance Impairs the Leptin-Mediated Suppression of Neuropeptide Y Secretion in Hypothalamic Neurons
Dhillon, S. S., McFadden, S. A., Chalmers, J. A., Centeno, M.-L., Kim, G. L., & Belsham, D. D. (2011) · Endocrinology · doi:10.1210/en.2011-0178 · Cited by 52
A critical period for the trophic actions of leptin on AgRP neurons in the arcuate nucleus of the hypothalamus
Kamitakahara, A. K., Bouyer, K., Wang, C.-Y., & Simerly, R. B. (2017) · The Journal of Comparative Neurology · doi:10.1002/cne.24327 · Cited by 52
Leptin Resistance During Pregnancy in the Rat
Ladyman, S. R. (2007) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2007.01628.x · Cited by 50
Agrarian diet and diseases of affluence – Do evolutionary novel dietary lectins cause leptin resistance?
Jönsson, T., Olsson, S., Åhrén, B., Bøg-Hansen, T. C., Dole, A., & Lindeberg, S. (2005) · BMC Endocrine Disorders · doi:10.1186/1472-6823-5-10 · Cited by 53
Large-scale preparation of biologically active mouse and rat leptins and their L39A/D40A/F41A muteins which act as potent antagonists
Salomon, G., Niv‐Spector, L., Gussakovsky, E. E., & Gertler, A. (2005) · Protein Expression and Purification · doi:10.1016/j.pep.2005.09.016 · Cited by 52
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 52
Effects of High-Fat Diet and Body Mass on Bone Morphology and Mechanical Properties in 1100 Advanced Intercross Mice
Silva, M. J., Eekhoff, J. D., Patel, T. K., Kenney‐Hunt, J. P., Brodt, M. D., Steger-May, K., Scheller, E. L., & Cheverud, J. M. (2019) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.3648 · Cited by 50
Is the Brain a Key Player in Glucose Regulation and Development of Type 2 Diabetes?
Lundqvist, M., Almby, K. E., Abrahamsson, N., & Eriksson, J. W. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2019.00457 · Cited by 55
Leptin, sympathetic nervous system, and baroreflex function
Grassi, G. M. (2004) · Current Hypertension Reports · doi:10.1007/s11906-004-0075-8 · Cited by 50
Hypothalamic Phosphatidylinositol 3‐Kinase‐Phosphodiesterase 3B‐Cyclic AMP Pathway of Leptin Signalling is Impaired Following Chronic Central Leptin Infusion
Sahu, A., & Metlakunta, A. S. (2005) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2005.01362.x · Cited by 50
Maternal Obesity in Sheep Increases Fatty Acid Synthesis, Upregulates Nutrient Transporters, and Increases Adiposity in Adult Male Offspring after a Feeding Challenge
Long, N., Rule, D. C., Tuersunjiang, N., Nathanielsz, P. W., & Ford, S. P. (2015) · PLoS ONE · doi:10.1371/journal.pone.0122152 · Cited by 49
Physiological role for leptin in the control of thermal conductance
Kaiyala, K. J., Ogimoto, K., Nelson, J. T., Muta, K., & Morton, G. J. (2016) · Molecular Metabolism · doi:10.1016/j.molmet.2016.07.005 · Cited by 48
Amylin and Leptin: Co-Regulators of Energy Homeostasis and Neuronal Development
Levin, B. E., & Lutz, T. A. (2016) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2016.11.004 · Cited by 50
SORCS1 and SORCS3 control energy balance and orexigenic peptide production
Subkhangulova, A., Malik, A. R., Hermey, G., Popp, O., Dittmar, G., Rathjen, T., Poy, M. N., Stumpf, A., Beed, P. S., Schmitz, D., et al. (2018) · EMBO Reports · doi:10.15252/embr.201744810 · Cited by 53
Effects of lipopolysaccharide on leptin transport across the blood–brain barrier
Nonaka, N., Hileman, S. M., Shioda, S., Vo, T. Q., & Banks, W. A. (2004) · Brain Research · doi:10.1016/j.brainres.2004.04.066 · Cited by 49
Self-citation
The Impact of Dysmetabolic Sarcopenia Among Insulin Sensitive Tissues: A Narrative Review
Armandi, A., Rosso, C., Caviglia, G. P., Ribaldone, D. G., & Bugianesi, E. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.716533 · Cited by 48
Leptin Potentiates Thermogenic Sympathetic Responses to Hypothermia
Hausberg, M., Morgan, D. A., Mitchell, J., Sivitz, W. I., Mark, A. L., & Haynes, W. G. (2002) · Diabetes · doi:10.2337/diabetes.51.8.2434 · Cited by 48
Moderate Long-Term Modulation of Neuropeptide Y in Hypothalamic Arcuate Nucleus Induces Energy Balance Alterations in Adult Rats
Sousa-Ferreira, L., Garrido, M., Nascimento-Ferreira, I., Nóbrega, C., Santos-Carvalho, A., Álvaro, A. R., Rosmaninho‐Salgado, J., Kaster, M. P., Kügler, S., de Almeida, L. P., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0022333 · Cited by 48
A Treasure Trove of Hypothalamic Neurocircuitries Governing Body Weight Homeostasis
Vianna, C. R., & Coppari, R. (2010) · Endocrinology · doi:10.1210/en.2010-0778 · Cited by 51
Acylated Ghrelin as a Multi-Targeted Therapy for Alzheimer's and Parkinson's Disease
Reich, N., & Hölscher, C. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.614828 · Cited by 48
“Additionally, a high-fat diet, in an inflammation-mediated manner, promotes hypothalamic leptin resistance as well (El-Haschimi et al., 2000; Zhang et al., 2008).”
Background
Increased circulating adiponectin levels and decreased leptin/soluble leptin receptor ratio throughout puberty in female ballet dancers: association with body composition and the delay in puberty
Donoso, M. A., Muñoz-Calvo, M. T., Barrios, V., Garrido, G., Hawkins, F. G., & Argente, J. (2010) · European Journal of Endocrinology · doi:10.1530/eje-09-0874 · Cited by 48
The role of leptin in obesity and the potential for leptin replacement therapy
Feng, H., Zheng, L., Feng, Z., Zhao, Y., & Zhang, N. (2012) · Endocrine · doi:10.1007/s12020-012-9865-y · Cited by 47
Expression of Obesity Markers and Persistent Organic Pollutants Levels in Adipose Tissue of Obese Patients: Reinforcing the Obesogen Hypothesis?
Pereira-Fernandes, A., Dirinck, E. L., Dirtu, A. C., Malarvannan, G., Covaci, A., Gaal, L. V., Vanparys, C., Jorens, P. G., & Blust, R. (2014) · PLoS ONE · doi:10.1371/journal.pone.0084816 · Cited by 49
JAK-STAT and feeding
Ladyman, S. R., & Grattan, D. R. (2013) · JAK-STAT · doi:10.4161/jkst.23675 · Cited by 48
Aged-obese rats exhibit robust responses to a melanocortin agonist and antagonist despite leptin resistance
Zhang, Y., Matheny, M. E., Tümer, N., & Scarpace, P. J. (2004) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2004.02.012 · Cited by 47
Obesity-related hypertension: Is there a role for selective leptin resistance?
Correia, M. L. G., & Haynes, W. G. (2004) · Current Hypertension Reports · doi:10.1007/s11906-004-0074-9 · Cited by 46
The role of leptin and low testosterone in obesity
Khodamoradi, K., Khosravizadeh, Z., Seetharam, D., Mallepalli, S. K. R., Farber, N., & Arora, H. (2022) · International Journal of Impotence Research · doi:10.1038/s41443-022-00534-y · Cited by 49
Dietary Factors Affect Food Reward and Motivation to Eat
Pandit, R., Mercer, J. G., Overduin, J., la Fleur, S. E., & Adan, R. A. H. (2012) · Obesity Facts · doi:10.1159/000338073 · Cited by 47
Leptin, diabetes, and the brain
Morton, G. J., & Meek, T. H. (2012) · Indian Journal of Endocrinology and Metabolism · doi:10.4103/2230-8210.105568 · Cited by 47
Running from Disease: Molecular Mechanisms Associating Dopamine and Leptin Signaling in the Brain with Physical Inactivity, Obesity, and Type 2 Diabetes
Ruegsegger, G. N., & Booth, F. W. (2017) · Frontiers in Endocrinology · doi:10.3389/fendo.2017.00109 · Cited by 47
Role for fatty acid amide hydrolase (FAAH) in the leptin-mediated effects on feeding and energy balance
Balsevich, G., Sticht, M. A., Bowles, N. P., Singh, A., Lee, T. T.-Y., Li, Z., Chelikani, P. K., Lee, F. S., Borgland, S. L., Hillard, C. J., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1802251115 · Cited by 46
Potential relationship between dietary long-chain saturated fatty acids and hypothalamic dysfunction in obesity
Sergi, D., & Williams, L. M. (2019) · Nutrition Reviews · doi:10.1093/nutrit/nuz056 · Cited by 48
Immunomodulatory actions of leptin
Juge-Aubry, C. E., & Meier, C. A. (2002) · Molecular and Cellular Endocrinology · doi:10.1016/s0303-7207(02)00191-0 · Cited by 46
Leptin signaling pathways in the central nervous system: interactions between neuropeptide Y and melanocortins
Rahmouni, K., & Haynes, W. G. (2001) · BioEssays · doi:10.1002/bies.10018 · Cited by 46
Molecular Targets for Obesity Therapy in the Brain
Obici, S. (2009) · Endocrinology · doi:10.1210/en.2009-0409 · Cited by 45
Inter-organ metabolic communication involved in energy homeostasis: Potential therapeutic targets for obesity and metabolic syndrome
Yamada, T., Oka, Y., & Katagiri, H. (2007) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2007.09.006 · Cited by 46
Molecular mechanisms associated with leptin resistance: n-3 polyunsaturated fatty acids induce alterations in the tight junction of the brain
Oh‐I, S., Shimizu, H., Sato, T., Uehara, Y., Okada, S., & Mori, M. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2005.04.004 · Cited by 45
Photoperiod regulates leptin sensitivity in field voles, Microtus agrestis
Król, E., Duncan, J. S., Redman, P., Morgan, P. J., Mercer, J. G., & Speakman, J. R. (2005) · Journal of Comparative Physiology B · doi:10.1007/s00360-005-0037-8 · Cited by 44
Emerging aspects of pharmacotherapy for obesity and metabolic syndrome
Nisoli, E., & Carruba, M. O. (2004) · Pharmacological Research · doi:10.1016/j.phrs.2004.02.004 · Cited by 44
Adipokines: Novel Players in Resistant Hypertension
de Faria, A. P., Modolo, R., Fontana, V., & Moreno, H. (2014) · Journal of Clinical Hypertension · doi:10.1111/jch.12399 · Cited by 44
High fructose intake and the route towards cardiometabolic diseases
Lelis, D. D. F., Andrade, J. M. O., Almenara, C. C. P., Broseghini-Filho, G. B., Mill, J. G., & Baldo, M. P. (2020) · Life Sciences · doi:10.1016/j.lfs.2020.118235 · Cited by 46
Multiple Leptin Signalling Pathways in the Control of Metabolism and Fertility: A Means to Different Ends?
Evans, M. C., Lord, R. A., & Anderson, G. M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22179210 · Cited by 48
Nutritional Regulation of Hypothalamic Leptin Receptor Gene Expression is Defective in Diet‐Induced Obesity
Sahu, A., Nguyen, L., & O'Doherty, R. M. (2002) · Journal of Neuroendocrinology · doi:10.1046/j.1365-2826.2002.00856.x · Cited by 45
Leptin regulation of lipid homeostasis: dietary and metabolic implications
Houseknecht, K. L., & Spurlock, M. E. (2003) · Nutrition Research Reviews · doi:10.1079/nrr200256 · Cited by 44
A Role for the Agouti-Related Protein Promoter in Obesity and Type 2 Diabetes
Mayfield, D. K., Brown, A. M., Page, G. P., Garvey, W. T., Shriver, M. D., & Argyropoulos, G. A. (2001) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2001.5600 · Cited by 43
Neural circuits of long-term thermoregulatory adaptations to cold temperatures and metabolic demands
Mota, C. M. D., & Madden, C. J. (2024) · Nature reviews. Neuroscience · doi:10.1038/s41583-023-00785-8 · Cited by 42
Exercise Training and Calorie Restriction Influence the Metabolic Parameters in Ovariectomized Female Rats
Pósa, A., Szabó, R., Kupai, K., Csonka, A., Szalai, Z., Veszelka, M., Török, S., Daruka, L., & Varga, C. (2015) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2015/787063 · Cited by 42
Interplay between glucose and leptin signalling determines the strength of GABAergic synapses at POMC neurons
Lee, D., Jeong, J. H., Chun, S., Chua, S. C., & Jo, Y. (2015) · Nature Communications · doi:10.1038/ncomms7618 · Cited by 43
The liver in obesity and type 2 diabetes mellitus
Li, Z., Clark, J. M., & Diehl, A. M. (2002) · Clinics in Liver Disease · doi:10.1016/s1089-3261(02)00060-0 · Cited by 42
Hypothalamic Gene Expression Is Altered in Underweight but Obese Juvenile Male Sprague-Dawley Rats Fed a High-Energy Diet
Archer, Z. A., Rayner, D. V., & Mercer, J. G. (2004) · Journal of Nutrition · doi:10.1093/jn/134.6.1369 · Cited by 42
Glucose Enhances Leptin Signaling through Modulation of AMPK Activity
Su, H., Jiang, L., Carter‐Su, C., & Rui, L. (2012) · PLoS ONE · doi:10.1371/journal.pone.0031636 · Cited by 42
Leptin concentrations are a predictor of overweight reduction in a lifestyle intervention
Reinehr, T., Kleber, M., de Sousa, G., & Andler, W. (2009) · International Journal of Pediatric Obesity · doi:10.3109/17477160902952464 · Cited by 40
Perinatal Nutritional and Metabolic Pathways: Early Origins of Chronic Lung Diseases
Kuiper-Makris, C., Selle, J., Nüsken, E., Dötsch, J., & Alcazar, M. A. A. (2021) · Frontiers in Medicine · doi:10.3389/fmed.2021.667315 · Cited by 43

Authors: El-Haschimi, K., Pierroz, D. D., Hileman, S. M., Bjørbæk, C., & Flier, J. S.
Affiliations: Beth Israel Deaconess Medical Center (US)
Corresponding author: Flier, Jeffrey S.
ORCID: Pierroz, Dominique D.
Hileman, Stanley M.
Flier, Jeffrey S.
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 2000-06-15
Volume: 105
Issue: 12
Pages: 1827-1832
ISSN: 0021-9738 (ISSN-L)
DOI: 10.1172/jci9842
PMC: PMC378516
OpenAlex: W2088666203
Cited by: 887
References: 29
Citations by year: 2026: 8 · 2025: 20 · 2024: 13 · 2023: 14 · 2022: 17 · 2021: 37 · 2020: 29 · 2019: 29 · 2018: 35 · 2017: 39 · 2016: 28 · 2015: 42 · 2014: 43 · 2013: 45 · 2012: 45
FWCI: 12.97
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Clinical Investigation (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Eli Lilly and Company
Joslin Diabetes Center
Deutsche Forschungsgemeinschaft
National Institutes of Health
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
Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
Keywords: leptin resistance, hypothalamus, STAT3 signaling, diet-induced obesity, high-fat diet, C57BL/6J mice
MeSH terms: Animals, Cerebral Ventricles, Dietary Fats, DNA-Binding Proteins, Drug Resistance, Humans, Hypothalamus, Injections, Intraventricular, Male, Mice, Inbred C57BL, Obesity, Trans-Activators, Diet, Fat-Restricted, Leptin, STAT3 Transcription Factor, 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

Two defects contribute to hypothalamic leptin resistance in mice with diet-induced obesity

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks