Cited by 420Regulation of Appetite and ObesityHypothalamic control of reproductive hormonesAdipokines, Inflammation, and Metabolic Diseases

The DOI matches its Crossref record; 53 of the 54 references it cites were found in a registry or an index.

PI3K integrates the action of insulin and leptin on hypothalamic neurons

Open access

Xu, A. W.·2005·Journal of Clinical Investigation

DOI 10.1172/jci200524301PMC PMC1062894

Open this paper in CoChat — free account Open PDF

Abstract

Central control of energy balance depends on the ability of proopiomelanocortin (POMC) or agouti-related protein (Agrp) hypothalamic neurons to sense and respond to changes in peripheral energy stores. Leptin and insulin have been implicated as circulating indicators of adiposity, but it is not clear how changes in their levels are perceived or integrated by individual neuronal subtypes. We developed mice in which a fluorescent reporter for PI3K activity is targeted to either Agrp or POMC neurons and used 2-photon microscopy to measure dynamic regulation of PI3K by insulin and leptin in brain slices. We show that leptin and insulin act in parallel to stimulate PI3K in POMC neurons but in opposite ways on Agrp neurons. These results suggest a new view of hypothalamic circuitry, in which the effects of leptin and insulin are integrated by anorexigenic but not by orexigenic neurons.

Integrity signals

Registry

Crossref · 10.1172/jci200524301

Cites

53 of 53 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

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?

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
The phosphoinositide 3-kinase pathway
Cantley, L. C. (2002) · Science · doi:10.1126/science.296.5573.1655 · Cited by 5,621
Generalized lacZ expression with the ROSA26 Cre reporter strain
Soriano, P. (1999) · Nature Genetics · doi:10.1038/5007 · Cited by 5,237
A simplified system for generating recombinant adenoviruses
He, T., Zhou, S., da Costa, L. T., Yu, J., Kinzler, K. W., & Vogelstein, B. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.5.2509 · Cited by 3,209
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
Role of Brain Insulin Receptor in Control of Body Weight and Reproduction
Brüning, J. C., Gautam, D., Burks, D. J., Gillette, J., Schubert, M., Orban, P. C., Klein, R., Krone, W., Müller-Wieland, D., & Kahn, C. R. (2000) · Science · doi:10.1126/science.289.5487.2122 · Cited by 2,235
Targeted disruption of the mouse Stat3 gene leads to early embryonic lethality
Takeda, K., Noguchi, K., Shi, W., Tanaka, T., Matsumoto, M., Yoshida, N., Kishimoto, T., & Akira, S. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.8.3801 · Cited by 1,323
Insulin receptors are widely distributed in the central nervous system of the rat
Havránková, J., Roth, J., & Brownstein, M. (1978) · Nature · doi:10.1038/272827a0 · Cited by 1,116
Chronic intracerebroventricular infusion of insulin reduces food intake and body weight of baboons
Woods, S. C., Lotter, E. C., McKay, L. D., & Porte, D. (1979) · Nature · doi:10.1038/282503a0 · Cited by 1,114
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

Show all 54 references

Sorted by citations

Items 201–300 of 420

Insulin action in the hypothalamus and dorsal vagal complex
Abraham, M. A., Filippi, B., Kang, G. M., Kim, M., & Lam, T. K. T. (2014) · Experimental Physiology · doi:10.1113/expphysiol.2014.079962 · Cited by 44
PI3K signaling in the pathogenesis of obesity: The cause and the cure
Beretta, M., Bauer, M. W., & Hirsch, E. (2014) · Advances in Biological Regulation · doi:10.1016/j.jbior.2014.11.004 · Cited by 42
Where Does Insulin Resistance Start?
Pagotto, U. (2009) · Diabetes Care · doi:10.2337/dc09-s305 · Cited by 45
ROCK1 in AgRP Neurons Regulates Energy Expenditure and Locomotor Activity in Male Mice
Hu, H., Lee, S., Ye, C., Sousa‐Lima, I., Oh, B., Lowell, B. B., Zabolotny, J. M., & Kim, Y. (2013) · Endocrinology · doi:10.1210/en.2013-1343 · Cited by 41
Rapid linkage of innate immunological signals to adaptive immunity by the brain-fat axis
Kim, M. S., Yan, J., Wu, W., Zhang, G., Zhang, Y., & Cai, D. (2015) · Nature Immunology · doi:10.1038/ni.3133 · Cited by 40
Endocannabinoid Regulation of Neuroendocrine Systems
Tasker, J. G., Chen, C., Fisher, M. O., Fu, X., Rainville, J. R., & Weiss, G. L. (2015) · International review of neurobiology · doi:10.1016/bs.irn.2015.09.003 · Cited by 41
Hunger-promoting hypothalamic neurons modulate effector and regulatory T-cell responses
Matarese, G., Procaccini, C., Menale, C., Kim, J. G., Kim, J. D., Diano, S., Diano, N., Rosa, V. D., Dietrich, M. O., & Horváth, T. L. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1210644110 · Cited by 42
Integration of metabolic stimuli in the hypothalamic arcuate nucleus
van den Top, M., & Spanswick, D. C. (2006) · Progress in brain research · doi:10.1016/s0079-6123(06)53008-0 · Cited by 42
Hypothalamic inflammation and the central nervous system control of energy homeostasis
Pimentel, G. D., Ganeshan, K., & Carvalheira, J. B. C. (2014) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2014.06.005 · Cited by 42
PI3Kα inactivation in leptin receptor cells increases leptin sensitivity but disrupts growth and reproduction.
García-Galiano, D., Borges, B., Donato, J., Allen, S. J., Bellefontaine, N., Wang, M., Zhao, J. J., Kozloff, K., Hill, J. W., & Elias, C. (2017) · JCI Insight · doi:10.1172/jci.insight.96728 · Cited by 33
Eat, sleep, repeat: the role of the circadian system in balancing sleep–wake control with metabolic need
Northeast, R. C., Vyazovskiy, V. V., & Bechtold, D. A. (2020) · Current Opinion in Physiology · doi:10.1016/j.cophys.2020.02.003 · Cited by 39
PI3K integrates the effects of insulin and leptin on large-conductance Ca2+-activated K+ channels in neuropeptide Y neurons of the hypothalamic arcuate nucleus
Yang, M., Wang, F., Wang, J., Wu, W., Hu, Z., Jin, C. S., Yu, D., Long, L., Fu, H. Q., Xie, N., et al. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00155.2009 · Cited by 39
Leptin-dependent Phosphorylation of PTEN Mediates Actin Restructuring and Activation of ATP-sensitive K+ Channels
Ning, K., Miller, L. C., Laidlaw, H. A., Watterson, K. R., Gallagher, J. R., Sutherland, C. D., & Ashford, M. L. J. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m806774200 · Cited by 39
Hypothalamic pregnenolone mediates recognition memory in the context of metabolic disorders
Ramírez, S., Haddad-Tóvolli, R., Radosevic, M., Toledo, M., Pané, A., Alcolea, D. A., Ribas, V., Milà‐Guasch, M., Pozo, M., Obri, A., et al. (2022) · Cell Metabolism · doi:10.1016/j.cmet.2021.12.023 · Cited by 42
Leptin and the central control of feeding behavior
Pénicaud, L., Meillon, S., & Brondel, L. (2012) · Biochimie · doi:10.1016/j.biochi.2012.04.013 · Cited by 49
Neurocircuits integrating hormone and nutrient signaling in control of glucose metabolism
Rother, E., Könner, A. C., & Brüning, J. C. (2008) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00685.2007 · Cited by 38
Hypothalamic redox balance and leptin signaling - Emerging role of selenoproteins
Gong, T., Torres, D. J., Berry, M. J., & Pitts, M. W. (2018) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2018.02.038 · Cited by 38
Augmented Insulin and Leptin Resistance of High Fat Diet-Fed APPswe/PS1dE9 Transgenic Mice Exacerbate Obesity and Glycemic Dysregulation
Lee, Y.-H., Hsu, H.-C., Kao, P.-C., Shiao, Y., Yeh, S. H., Shie, F., Hsu, S.-M., Yeh, C.-W., Liu, H., Yang, S., et al. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19082333 · Cited by 37
Phosphoinositide 3-Kinase Is Integral for the Acute Activity of Leptin and Insulin in Male Arcuate NPY/AgRP Neurons
Huang, Y., He, Z., Gao, Y., Lieu, L., Yao, T. S., Sun, J. M., Liu, T., Javadi, C. S., Box, M., Afrin, S., et al. (2018) · Journal of the Endocrine Society · doi:10.1210/js.2018-00061 · Cited by 35
Signal Transducer and Activator of Transcription (Stat) Binding Sites But Not Stat3 Are Required for Fasting-Induced Transcription of Agouti-Related Protein Messenger Ribonucleic Acid
Kaelin, C. B., Gong, L., Xu, A. W., Yao, F., Hockman, K., Morton, G. J., Schwartz, M. W., Barsh, G. S., & MacKenzie, R. G. (2006) · Molecular Endocrinology · doi:10.1210/me.2006-0107 · Cited by 35
Self-citation
Functional Consequences of the Human Leptin Receptor (LEPR) Q223R Transversion
Stratigopoulos, G., LeDuc, C. A., Matsuoka, N., Gutman, R., Rausch, R. N., Robertson, S., Myers, M. G., Chung, W. K., Chua, S. C., & Leibel, R. L. (2008) · Obesity · doi:10.1038/oby.2008.489 · Cited by 33
New Insights of SF1 Neurons in Hypothalamic Regulation of Obesity and Diabetes
Fosch, A., Zagmutt, S., Casals, N., & Rodríguez‐Rodríguez, R. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22126186 · Cited by 33
The Mechanism of Leptin Resistance in Obesity and Therapeutic Perspective
Engin, A. (2024) · Advances in experimental medicine and biology · doi:10.1007/978-3-031-63657-8_16 · Cited by 42
Erk1/2 Mediates Leptin Receptor Signaling in the Ventral Tegmental Area
Trinko, R., Gan, G., Gao, X., Sears, R. M., Guarnieri, D. J., & Dileone, R. (2011) · PLoS ONE · doi:10.1371/journal.pone.0027180 · Cited by 33
Chronic central leptin infusion modifies the response to acute central insulin injection by reducing the interaction of the insulin receptor with IRS2 and increasing its association with SOCS3
Burgos‐Ramos, E., Chowen, J. A., Arilla, E., Canelles, S., Argente, J., & Barrios, V. (2011) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2011.07191.x · Cited by 33
Action of Neurotransmitter: A Key to Unlock the AgRP Neuron Feeding Circuit
Liu, T., Wang, Q., Berglund, E. D., & Tong, Q. (2013) · Frontiers in Neuroscience · doi:10.3389/fnins.2012.00200 · Cited by 34
Uncoupled protein 3 and p38 signal pathways are involved in anti-obesity activity of Solanum tuberosum L. cv. Bora Valley
Yoon, S.-S., Rhee, Y., Lee, H., Lee, E., Lee, M., Ahn, K.-S., Lim, H., & Kim, S. (2008) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2008.05.014 · Cited by 32
Hypothalamic Control of Hepatic Glucose Production and Its Potential Role in Insulin Resistance
Buettner, C., & Camacho, R. C. (2008) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2008.09.001 · Cited by 31
Obesity
Capel, F. (2007) · CRC Press eBooks · doi:10.3109/9781420020137 · Cited by 31
The Brain-Gut-Islet Connection
Woods, S. C., Benoit, S. C., & Clegg, D. J. (2006) · Diabetes · doi:10.2337/db06-s015 · Cited by 30
O controle hipotalâmico da fome e da termogênese: implicações no desenvolvimento da obesidade
Velloso, L. A. (2006) · Arquivos Brasileiros de Endocrinologia & Metabologia · doi:10.1590/s0004-27302006000200003 · Cited by 29
PI3K signaling: A key pathway in the control of sympathetic traffic and arterial pressure by leptin
Harlan, S. M., & Rahmouni, K. (2013) · Molecular Metabolism · doi:10.1016/j.molmet.2013.03.004 · Cited by 30
TRPCing around the hypothalamus
Kelly, M. J., Qiu, J., & Rønnekleiv, O. K. (2018) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2018.05.004 · Cited by 29
Neuronal suppressor of cytokine signaling-3 deficiency enhances hypothalamic leptin-dependent phosphatidylinositol 3-kinase signaling
Metlakunta, A. S., Sahu, M., Yasukawa, H., Dhillon, S. S., Belsham, D. D., Yoshimura, A., & Sahu, A. (2011) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00794.2010 · Cited by 27
Gamma-protocadherins regulate the functional integrity of hypothalamic feeding circuitry in mice
Su, H., Marcheva, B., Meng, S., Liang, F. A., Kohsaka, A., Kobayashi, Y., Xu, A. W., Bass, J. T., & Wang, X. (2009) · Developmental Biology · doi:10.1016/j.ydbio.2009.12.010 · Cited by 27
Self-citation
Exendin-4 reduces food intake via the PI3K/AKT signaling pathway in the hypothalamus
Yang, Y., Choi, P. P., Smith, W. W., Xu, W., Ma, D., Cordner, Z. A., Liang, N., & Moran, T. H. (2017) · Scientific Reports · doi:10.1038/s41598-017-06951-0 · Cited by 27
Leptin Promotes the Proliferation and Neuronal Differentiation of Neural Stem Cells through the Cooperative Action of MAPK/ERK1/2, JAK2/STAT3 and PI3K/AKT Signaling Pathways
Tan, R., Hu, X., Wang, X., Sun, M., Cai, Z., Zhang, Z., Fu, Y., Chen, X., An, J., & Lü, H. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242015151 · Cited by 26
PI3K p110β subunit in leptin receptor expressing cells is required for the acute hypophagia induced by endotoxemia
Borges, B., García-Galiano, D., Rorato, R., Elias, L., & Elias, C. (2016) · Molecular Metabolism · doi:10.1016/j.molmet.2016.03.003 · Cited by 27
PI3K and AKT at the Interface of Signaling and Metabolism
Solinas, G., & Becattini, B. (2022) · Current topics in microbiology and immunology · doi:10.1007/978-3-031-06566-8_13 · Cited by 27
Central Regulation of Energy Homeostasis
Porte, D. (2006) · Diabetes · doi:10.2337/db06-s019 · Cited by 26
Precise pattern of recombination in serotonergic and hypothalamic neurons in a Pdx1-cre transgenic mouse line
Honig, G., Liou, A., Berger, M., German, M. S., & Tecott, L. H. (2010) · Journal of Biomedical Science · doi:10.1186/1423-0127-17-82 · Cited by 23
PI 3K signalling in leptin receptor cells: Role in growth and reproduction
García-Galiano, D., Borges, B. C., Allen, S. J., & Elias, C. F. (2019) · Journal of Neuroendocrinology · doi:10.1111/jne.12685 · Cited by 24
Regulación central de la ingestión alimentaria y el gasto energético: acciones moleculares de la insulina, la leptina y el ejercicio físico
Cintra, D. E., Ropelle, E. R., & Pauli, J. R. (2007) · Revista de Neurología · doi:10.33588/rn.4511.2006612 · Cited by 24
Protein tyrosine phosphatase 1B in metabolic and cardiovascular diseases: from mechanisms to therapeutics
Sun, Y., Dinenno, F. A., Tang, P., & Kontaridis, M. I. (2024) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2024.1445739 · Cited by 25
Central Leptin and Tumor Necrosis Factor-α (TNFα) in Diurnal Control of Blood Pressure and Hypertension
Han, C., Wu, W., Alé, A., Kim, M. S., & Cai, D. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.730408 · Cited by 23
Fasting-Induced Lipolysis and Hypothalamic Insulin Signaling Are Regulated by Neuronal Glucosylceramide Synthase
Herzer, S., Meldner, S., Gröne, H., & Nordström, V. (2015) · Diabetes · doi:10.2337/db14-1726 · Cited by 24
Sodium tungstate regulates food intake and body weight through activation of the hypothalamic leptin pathway
Amigó-Correig, M., Barceló-Batllori, S., Piquer, S., Soty, M., Pujadas, G., Gasa, R., Bortolozzi, A. A., Carmona, M. C., & Gomis, R. (2010) · Diabetes Obesity and Metabolism · doi:10.1111/j.1463-1326.2010.01339.x · Cited by 22
For Better or Worse: The Potential for Dose Limiting the On-Target Toxicity of PI 3-Kinase Inhibitors
Buchanan, C. M., Lee, K., & Shepherd, P. (2019) · Biomolecules · doi:10.3390/biom9090402 · Cited by 25
The central melanocortin system as a treatment target for obesity and diabetes: A brief overview
Goit, R. K., Taylor, A. W., & Lo, A. (2022) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2022.174956 · Cited by 22
Autophagy in the control of food intake
Singh, R. (2012) · Adipocyte · doi:10.4161/adip.18966 · Cited by 23
Involvement of brain ketone bodies and the noradrenergic pathway in diabetic hyperphagia in rats
Iwata, K., Kinoshita, M., Yamada, S., Imamura, T., Uenoyama, Y., Tsukamura, H., & Maeda, K.-I. (2011) · The Journal of Physiological Sciences · doi:10.1007/s12576-010-0127-6 · Cited by 22
Leptin Monotherapy Rescues Spermatogenesis in Male Akita Type 1 Diabetic Mice
Schoeller, E. L., Chi, M. M.-Y., Drury, A. M., Bertschinger, A., Esakky, P., & Moley, K. H. (2014) · Endocrinology · doi:10.1210/en.2014-1119 · Cited by 21
Physiologic and Neural Controls of Eating
Moran, T. H., & Ladenheim, E. E. (2016) · Gastroenterology Clinics of North America · doi:10.1016/j.gtc.2016.07.009 · Cited by 22
Differential responses of circulating amylin to high‐fat vs. high‐carbohydrate meal in healthy men
Eller, L. K., Ainslie, P. N., Poulin, M. J., & Reimer, R. A. (2008) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2007.03129.x · Cited by 20
Avian Neuropeptide Y: Beyond Feed Intake Regulation
Greene, E. S., Abdelli, N., Dridi, J. S., & Dridi, S. (2022) · Veterinary Sciences · doi:10.3390/vetsci9040171 · Cited by 24
Protein Phosphatase 1 (PP-1)-Dependent Inhibition of Insulin Secretion by Leptin in INS-1 Pancreatic β-Cells and Human Pancreatic Islets
Kühnen, P., Laubner, K., Raile, K., Schöfl, C., Jakob, F. J., Pilz, I. H., Päth, G., & Seufert, J. (2011) · Endocrinology · doi:10.1210/en.2010-1094 · Cited by 20
Expanding neurotransmitters in the hypothalamic neurocircuitry for energy balance regulation
Xu, Y., & Tong, Q. (2011) · Protein & Cell · doi:10.1007/s13238-011-1112-4 · Cited by 20
Phosphatidylinositol 3‐kinase is an Upstream Regulator of the Phosphodiesterase 3B Pathway of Leptin Signalling that may not Involve Activation of Akt in the Rat Hypothalamus
Sahu, A., Koshinaka, K., & Sahu, M. (2012) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2012.02386.x · Cited by 20
Shared pathological pathways of Alzheimer's disease with specific comorbidities: current perspectives and interventions
Nday, C. M., Eleftheriadou, D., & Jackson, G. E. (2017) · Journal of Neurochemistry · doi:10.1111/jnc.14256 · Cited by 21
The transcriptional regulator PRDM12 is critical for Pomc expression in the mouse hypothalamus and controlling food intake, adiposity, and body weight
Hael, C. E., Rojo, D., Orquera, D. P., Low, M. J., & Rubinstein, M. (2020) · Molecular Metabolism · doi:10.1016/j.molmet.2020.01.007 · Cited by 20
Deleterious effects of lard-enriched diet on tissues fatty acids composition and hypothalamic insulin actions
Dornellas, A. P. S., Watanabe, R. L. H., Pimentel, G. D., Boldarine, V. T., Nascimento, C. M. O., Oyama, L. M., Ghebremeskel, K., Wang, Y., Bueno, A. A., & Ribeiro, E. B. (2015) · Prostaglandins, Leukotrienes and Essential Fatty Acids · doi:10.1016/j.plefa.2015.10.003 · Cited by 18
Maternal Brain Adaptations in Pregnancy
Brunton, P. J., & Russell, J. A. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-397175-3.00044-2 · Cited by 18
Pro-opiomelanocortin (POMC) neuron translatome signatures underlying obesogenic gestational malprogramming in mice
Haddad-Tóvolli, R., Altirriba, J., Obri, A., Eyre, E., Chivite, Í., Milà‐Guasch, M., Ramírez, S., Gómez-Valadés, A. G., Pozo, M., Burguet, J., et al. (2020) · Molecular Metabolism · doi:10.1016/j.molmet.2020.02.006 · Cited by 18
Hypothalamic lipophagy and energetic balance
Singh, R. (2011) · Aging · doi:10.18632/aging.100393 · Cited by 19
Regulation of Energy Balance by the Hypothalamic Lipoprotein Lipase Regulator Angptl3
Kim, H.-K., Shin, M., Youn, B., Kang, G. M., Gil, S. Y., Lee, C. H., Choi, J. H., Lim, H. S., Yoo, H. J., & Kim, M.-S. (2014) · Diabetes · doi:10.2337/db14-0647 · Cited by 18
Phosphoinositide Signalling Pathways in Metabolic Regulation
Foukas, L. C., & Withers, D. J. (2010) · Current topics in microbiology and immunology · doi:10.1007/82_2010_59 · Cited by 19
Leptin Induces Mitosis and Activates the Canonical Wnt/β-Catenin Signaling Pathway in Neurogenic Regions of Xenopus Tadpole Brain
Bender, M. C., Sifuentes, C. J., & Denver, R. J. (2017) · Frontiers in Endocrinology · doi:10.3389/fendo.2017.00099 · Cited by 18
Overcoming neuroendocrine and metabolic barriers to puberty: the role of melatonin in advancing puberty in ewe lambs
Pool, K., Rickard, J. P., & de Graaf, S. P. (2020) · Domestic Animal Endocrinology · doi:10.1016/j.domaniend.2020.106457 · Cited by 19
Is “Leptin Resistance” Another Key Resistance to Manage Type 2 Diabetes?
Salazar, J. J., Chávez-Castillo, M., Rojas, J., Ortega, Á., Nava, M., Pérez, J. L., Rojas, M., Díaz, C. I. E., Chacín, M., Herazo, Y., et al. (2019) · Current Diabetes Reviews · doi:10.2174/1573399816666191230111838 · Cited by 17
Fasting-induced suppression of LH secretion does not require activation of ATP-sensitive potassium channels
Huang, W., Acosta‐Martínez, M., Horton, T. H., & Levine, J. E. (2008) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90615.2008 · Cited by 17
Insights into leptin signaling and male reproductive health: the missing link between overweight and subfertility?
Moreira, B. P., Monteiro, M. P., Sousa, M., Oliveira, P. F., & Alves, M. G. (2018) · Biochemical Journal · doi:10.1042/bcj20180631 · Cited by 18
Estrogenic regulation of reproduction and energy homeostasis by a triumvirate of hypothalamic arcuate neurons
Stincic, T. L., & Kelly, M. J. (2022) · Journal of Neuroendocrinology · doi:10.1111/jne.13145 · Cited by 18
Enterostatin affects cyclic AMP and ERK signaling pathways to regulate Agouti-related Protein (AgRP) expression
Park, M., Oh, H., & York, D. A. (2008) · Peptides · doi:10.1016/j.peptides.2008.11.005 · Cited by 17
4-hydroxy-3-methoxycinnamic acid regulates orexigenic peptides and hepatic glucose homeostasis through phosphorylation of FoxO1
Kinyua, A. W., Ko, C. M., Doan, K. V., Yang, D. J., Huynh, M. K. Q., Moh, S. H., Choi, Y., & Kim, K. W. (2018) · Experimental & Molecular Medicine · doi:10.1038/emm.2017.253 · Cited by 18
Acute injection of ASP in the third ventricle inhibits food intake and locomotor activity in rats
Roy, C., Roy, M.-C., Gauvreau, D., Poulin, A.-M., Tom, F.-Q., Timofeeva, E., Richard, D., & Cianflone, K. (2011) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00476.2010 · Cited by 16
Leptin and Its Role in Oxidative Stress and Apoptosis: An Overview
Gelen, V., Kükürt, A., Şengül, E., & Deveci, H. A. (2021) · IntechOpen eBooks · doi:10.5772/intechopen.101237 · Cited by 16
Preventive Leptin Administration Protects Against Sepsis Through Improving Hypotension, Tachycardia, Oxidative Stress Burst, Multiple Organ Dysfunction, and Increasing Survival
Vallejos, A., Olivares, P., Varela, D., Echeverría, C., Cabello‐Verrugio, C., Perez‐Leighton, C. E., & Simón, F. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.01800 · Cited by 16
Reduced Anorexigenic Efficacy of Leptin, But Not of the Melanocortin Receptor Agonist Melanotan-II, Predicts Diet-Induced Obesity in Rats
van Dijk, G., de Vries, K., Nyakas, C. J., Buwalda, B., Adage, T., Kuipers, F., Kas, M. J., Adan, R. A. H., Wilkinson, C. W., Thiele, T. E., et al. (2005) · Endocrinology · doi:10.1210/en.2005-0472 · Cited by 16
Mediobasal hypothalamic PTEN modulates hepatic insulin resistance independently of food intake in rats
Sumita, T., Ono, H., Suzuki, T., Sakai, G., Inukai, K., Katagiri, H., Asano, T., Katayama, S., & Awata, T. (2014) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00361.2013 · Cited by 16
RETRACTED: Glucose regulates the effects of leptin on hypothalamic POMC neurons
Ma, X., Zubcevic, L., & Ashcroft, F. M. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0800952105 · Cited by 14
Retracted
Preserved Energy Balance in Mice Lacking FoxO1 in Neurons of Nkx2.1 Lineage Reveals Functional Heterogeneity of FoxO1 Signaling Within the Hypothalamus
Heinrich, G., Meece, K., Wardlaw, S. L., & Accili, D. (2014) · Diabetes · doi:10.2337/db13-0651 · Cited by 15
Hypothesis: Musculin is a hormone secreted by skeletal muscle, the body's largest endocrine organ. Evidence for actions on the endocrine pancreas to restrain the beta-cell mass and to inhibit insulin secretion and on the hypothalamus to co-ordinate the neuroendocrine and appetite responses to exercise.
Engler, D. (2007) · Acta bio-medica dell'Ateneo parmense/Acta biomedica · Cited by 15
Using Intermittent Fasting as a Non-pharmacological Strategy to Alleviate Obesity-Induced Hypothalamic Molecular Pathway Disruption
Oliveira, L. D. C., Morais, G. P., Ropelle, E. R., de Moura, L. P., Cintra, D. E., Pauli, J. R., de Freitas, E. C., Rorato, R. C., & da Silva, A. S. R. (2022) · Frontiers in Nutrition · doi:10.3389/fnut.2022.858320 · Cited by 17
Caloric restriction selectively reduces the GABAergic phenotype of mouse hypothalamic proopiomelanocortin neurons
Jarvie, B. C., King, C. M., Hughes, A. R., Dicken, M. S., Dennison, C. S., & Hentges, S. T. (2016) · The Journal of Physiology · doi:10.1113/jp273020 · Cited by 14
Differential Desensitization Observed at Multiple Effectors of Somatic μ-Opioid Receptors Underlies Sustained Agonist-Mediated Inhibition of Proopiomelanocortin Neuron Activity
Fox, P. D., & Hentges, S. T. (2017) · Journal of Neuroscience · doi:10.1523/jneurosci.1030-17.2017 · Cited by 13
ASB4 modulates central melanocortinergic neurons and calcitonin signaling to control satiety and glucose homeostasis
Vagena, E., Crneta, J., Engström, P., He, L., Yulyaningsih, E., Korpel, N. L., Cheang, R. T., Bachor, T. P., Huang, A., Michel, G., et al. (2022) · Science Signaling · doi:10.1126/scisignal.abj8204 · Cited by 13
Self-citation
Local Drd1-neurons input to subgroups of arcuate AgRP/NPY-neurons
Chadwick, S. R., & Güler, A. D. (2022) · iScience · doi:10.1016/j.isci.2022.104605 · Cited by 12
PI3K signaling: A molecular pathway associated with acute hypophagic response during inflammatory challenges
Borges, B. C., Elias, C. F., & Elias, L. L. K. (2016) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2016.07.005 · Cited by 13
The brain leptin signaling system and its functional state in metabolic syndrome and type 2 diabetes mellitus
Shpakov, A. O. (2016) · Journal of Evolutionary Biochemistry and Physiology · doi:10.1134/s0022093016030017 · Cited by 11
The Role of Cdc42 in the Insulin and Leptin Pathways Contributing to the Development of Age-Related Obesity
Umbayev, B. A., Saliev, T. M., Safarova, Y., Yermekova, A., Olzhayev, F., Bulanin, D. S., Tsoy, A., & Askarova, S. (2023) · Nutrients · doi:10.3390/nu15234964 · Cited by 15
FTO promotes weight gain via altering Kif1a splicing and axonal vesicle trafficking in AgRP neurons
Kohno, D., Kawabata‐Iwakawa, R., Ichinose, S., Suyama, S., Ohashi, K., Ariyani, W., Sadakata, T., Yokota‐Hashimoto, H., Kobayashi, R., Horii, T., et al. (2025) · The EMBO Journal · doi:10.1038/s44318-025-00503-3 · Cited by 11
Canonical transient receptor potential channels and hypothalamic control of homeostatic functions
Kelly, M. J., & Wagner, E. J. (2024) · Journal of Neuroendocrinology · doi:10.1111/jne.13392 · Cited by 11
Chronic central leptin infusion modulates the glycemia response to insulin administration in male rats through regulation of hepatic glucose metabolism
Burgos‐Ramos, E., Canelles, S., Rodrı́guez, A., Gómez‐Ambrosi, J., Frago, L. M., Chowen, J. A., Frühbeck, G., Argente, J., & Barrios, V. (2015) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2015.08.014 · Cited by 12
Hypothalamic Akt PKB signaling in regulation of food intake
Kim, D. H. (2012) · Frontiers in Bioscience-Scholar · doi:10.2741/s311 · Cited by 11
Effect of dexamethasone on hypothalamic expression of appetite-related genes in chickens under different diet and feeding conditions
Liu, L., Xu, S., Wang, X., Jiao, H., Zhao, J., & Lin, H. (2016) · Journal of Animal Science and Biotechnology/Journal of animal science and biotechnology · doi:10.1186/s40104-016-0084-x · Cited by 11
Calcium Channel CaV2.3 Subunits Regulate Hepatic Glucose Production by Modulating Leptin-Induced Excitation of Arcuate Pro-opiomelanocortin Neurons
Smith, M. A., Katsouri, L., Virtue, S., Choudhury, A. I., Vidal‐Puig, A., Ashford, M. L. J., & Withers, D. J. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.09.024 · Cited by 11
The increase in fiber size in male rat gastrocnemius after chronic central leptin infusion is related to activation of insulin signaling
Burgos‐Ramos, E., Canelles, S., Rodrı́guez, A., Frago, L. M., Gómez‐Ambrosi, J., Chowen, J. A., Frühbeck, G., Argente, J., & Barrios, V. (2017) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2017.09.029 · Cited by 11
Coordinated Regulation of Hepatic Energy Stores by Leptin and Hypothalamic Agouti-Related Protein
Warne, J. P., Varonin, J. M., Nielsen, S. S., Olofsson, L. E., Kaelin, C. B., Chua, S. C., Barsh, G. S., Koliwad, S. K., & Xu, A. W. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.0830-13.2013 · Cited by 10
Self-citation
Retracted
Leptin directly regulate intrinsic neuronal excitability in hypothalamic POMC neurons but not in AgRP neurons in food restricted mice
Lee, S., Lee, J., Kang, G. M., & Kim, M. (2018) · Neuroscience Letters · doi:10.1016/j.neulet.2018.05.041 · Cited by 10
Sistema leptina-melanocortinas en la regulación de la ingesta y el peso corporal
José Luis Santos, M. (2009) · Revista médica de Chile · doi:10.4067/s0034-98872009000900014 · Cited by 14

Authors: Xu, A. W.
Affiliations: Stanford Medicine (US)
ORCID: Xu, A. W.
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 2005-03-10
Volume: 115
Issue: 4
Pages: 951-958
ISSN: 0021-9738 (ISSN-L)
DOI: 10.1172/jci200524301
PMC: PMC1062894
OpenAlex: W2161418574
Cited by: 420
References: 54
Citations by year: 2026: 2 · 2025: 10 · 2024: 8 · 2023: 8 · 2022: 12 · 2021: 7 · 2020: 7 · 2019: 18 · 2018: 17 · 2017: 24 · 2016: 20 · 2015: 18 · 2014: 24 · 2013: 27 · 2012: 27
FWCI: 12.61
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Clinical Investigation (publishedVersion)
PubMed Central (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health
School of Medicine, Stanford University
Stanford Bio-X
National Institute of Diabetes and Digestive and Kidney Diseases (DK-48506, R01DK048506, P01DK068384, DK-68384)
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 › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
Keywords: PI3K signaling, insulin, leptin, hypothalamic neurons, proopiomelanocortin neurons, energy balance, appetite regulation, anorexigenic neurons, orexigenic neurons, neuronal activity imaging
MeSH terms: Animals, Energy Metabolism, Enzyme Activation, Homeostasis, Hypothalamus, Insulin, Mice, Inbred C57BL, Mice, Transgenic, Synaptic Transmission, Neurons, Pro-Opiomelanocortin, Proteins, Recombinant Fusion Proteins, Gene Expression Regulation, Enzymologic, Genes, Reporter, Mice, Knockout, Microscopy, Confocal, Phosphatidylinositol 3-Kinases, Leptin, Intercellular Signaling Peptides and Proteins, Mice, Agouti-Related Protein

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

PI3K integrates the action of insulin and leptin on hypothalamic neurons

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Related

Metadata

Record

About these checks