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

Central nervous system control of food intake and body weight
Morton, G. J., Cummings, D. E., Baskin, D. G., Barsh, G. S., & Schwartz, M. W. (2006) · Nature · doi:10.1038/nature05026 · Cited by 2,503
Self-citation
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
Mechanisms 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
Pancreatic regulation of glucose homeostasis.
Röder, P. V., Wu, B., Liu, Y., & Han, W. (2016) · Experimental & Molecular Medicine · doi:10.1038/emm.2016.6 · Cited by 985
Insulin Action in AgRP-Expressing Neurons Is Required for Suppression of Hepatic Glucose Production
Könner, A. C., Janoschek, R., Plum, L., Jordan, S. D., Rother, E., Ma, X., Xu, C., Enriori, P., Hampel, B., Barsh, G. S., et al. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.05.004 · Cited by 695
Self-citation
Neuroendocrine control of food intake
Valassi, E., Scacchi, M., & Cavagnini, F. (2008) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2007.06.004 · Cited by 649
The Brain, Appetite, and Obesity
Berthoud, H., & Morrison, C. D. (2007) · Annual Review of Psychology · doi:10.1146/annurev.psych.59.103006.093551 · Cited by 699
Neuronal PTP1B regulates body weight, adiposity and leptin action
Bence, K. K., Delibegovic, M., Xue, B., Gorgun, C. Z., Hotamisligil, G. S., Neel, B. G., & Kahn, B. B. (2006) · Nature Medicine · doi:10.1038/nm1435 · Cited by 633
Gonadal Hormones Determine Sensitivity to Central Leptin and Insulin
Clegg, D. J., Brown, L. M., Woods, S. C., & Benoit, S. C. (2006) · Diabetes · doi:10.2337/diabetes.55.04.06.db05-1339 · Cited by 552
Mitofusin 2 in POMC neurons connects ER stress with leptin resistance and energy imbalance
Schneeberger, M., Dietrich, M. O., Sebastián, D., Imbernón, M., Castaño, C., Garcia, A., Esteban, Y., Gonzalez-Franquesa, A., Rodríguez, I. C., Bortolozzi, A., et al. (2013) · Cell · doi:10.1016/j.cell.2013.09.003 · Cited by 519
AMPK is essential for energy homeostasis regulation and glucose sensing by POMC and AgRP neurons
Claret, M., Smith, M. A., Batterham, R. L., Selman, C., Choudhury, A. I., Fryer, L. G. D., Clements, M., Al‐Qassab, H., Heffron, H., Xu, A. W., et al. (2007) · Journal of Clinical Investigation · doi:10.1172/jci31516 · Cited by 522
Self-citation
Lipophagy: Connecting Autophagy and Lipid Metabolism
Singh, R., & Cuervo, A. M. (2012) · International Journal of Cell Biology · doi:10.1155/2012/282041 · Cited by 497
Disruption of Intraflagellar Transport in Adult Mice Leads to Obesity and Slow-Onset Cystic Kidney Disease
Davenport, J. R., Watts, A. J., Roper, V. C., Croyle, M. J., van Groen, T., Wyss, J. M., Nagy, T. R., Kesterson, R. A., & Yoder, B. K. (2007) · Current Biology · doi:10.1016/j.cub.2007.08.034 · Cited by 482
Recent advances in understanding leptin signaling and leptin resistance
Morris, D. L., & Rui, L. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00274.2009 · Cited by 484
Critical role for the p110α phosphoinositide-3-OH kinase in growth and metabolic regulation
Foukas, L. C., Claret, M., Pearce, W., Okkenhaug, K., Meek, S., Peskett, E., Sancho, S., Smith, A. J. H., Withers, D. J., & Vanhaesebroeck, B. (2006) · Nature · doi:10.1038/nature04694 · Cited by 463
Forkhead protein FoxO1 mediates Agrp-dependent effects of leptin on food intake
Kitamura, T., Feng, Y., Kitamura, Y., Chua, S. C., Xu, A. W., Barsh, G. S., Rossetti, L., & Accili, D. (2006) · Nature Medicine · doi:10.1038/nm1392 · Cited by 458
Self-citation
Central insulin action in energy and glucose homeostasis
Plum, L. (2006) · Journal of Clinical Investigation · doi:10.1172/jci29063 · Cited by 444
Leptin signaling and leptin resistance
Zhou, Y., & Rui, L. (2013) · Frontiers of Medicine · doi:10.1007/s11684-013-0263-5 · Cited by 358
Brain Regulation of Appetite and Satiety
Ahima, R. S., & Antwi, D. A. (2008) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2008.08.005 · Cited by 412
Hypothalamic pathways linking energy balance and reproduction
Hill, J. W., Elmquist, J. K., & Elias, C. F. (2008) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00670.2007 · Cited by 367
Segregation of Acute Leptin and Insulin Effects in Distinct Populations of Arcuate Proopiomelanocortin Neurons
Williams, K. W., Margatho, L. O., Lee, C. E., Choi, M., Lee, S., Scott, M. M., Elias, C. F., & Elmquist, J. K. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.3118-09.2010 · Cited by 352
Acute effects of leptin require PI3K signaling in hypothalamic proopiomelanocortin neurons in mice
Hill, J. W., Williams, K. W., Ye, C., Luo, J., Balthasar, N., Coppari, R., Cowley, M. A., Cantley, L. C., Lowell, B. B., & Elmquist, J. K. (2008) · Journal of Clinical Investigation · doi:10.1172/jci32964 · Cited by 362
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
“Complicating matters further, leptin reduces PI3K signaling in AgRP cells, whereas insulin increases it (204), yet both hormones inhibit AgRP neuronal firing.”
BackgroundInfluential
Collective and individual functions of leptin receptor modulated neurons controlling metabolism and ingestion
van de Wall, E., Leshan, R., Xu, A. W., Balthasar, N., Coppari, R., Liu, S. M., Jo, Y. H., MacKenzie, R. G., Allison, D. B., Dun, N. J., et al. (2008) · Endocrinology · doi:10.1210/en.2007-1132 · Cited by 338
Self-citation
Role of hypothalamic Foxo1 in the regulation of food intake and energy homeostasis
Kim, M.-S., Pak, Y. K., Jang, P., NamKoong, C., Choi, Y.-S., Won, J. C., Kim, K., Kim, S., Kim, H.-S., Park, J., et al. (2006) · Nature Neuroscience · doi:10.1038/nn1731 · Cited by 330
Enhanced PIP3 signaling in POMC neurons causes KATP channel activation and leads to diet-sensitive obesity
Plum, L. (2006) · Journal of Clinical Investigation · doi:10.1172/jci27123 · Cited by 326
Autophagy in the CNS and Periphery Coordinate Lipophagy and Lipolysis in the Brown Adipose Tissue and Liver
Martínez-López, N., Macia, M. G., Sahu, S., Athonvarangkul, D., Liebling, E. J., Merlo, P., Cecconi, F., Schwartz, G. J., & Singh, R. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.10.008 · Cited by 302
Hypothalamic and brainstem neuronal circuits controlling homeostatic energy balance.
Schneeberger, M., Gomis, R., & Claret, M. (2014) · Journal of Endocrinology · doi:10.1530/joe-13-0398 · Cited by 301
Leptin regulates insulin sensitivity via phosphatidylinositol-3-OH kinase signaling in mediobasal hypothalamic neurons
Morton, G. J., Gelling, R. W., Niswender, K. D., Morrison, C. D., Rhodes, C. J., & Schwartz, M. W. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2005.10.009 · Cited by 292
O-GlcNAc Transferase Enables AgRP Neurons to Suppress Browning of White Fat
Ruan, H.-B., Dietrich, M. O., Liu, Z.-W., Zimmer, M. R., Li, M.-D., Singh, J. P., Zhang, K., Yin, R., Wu, J., Horvath, T. L., et al. (2014) · Cell · doi:10.1016/j.cell.2014.09.010 · Cited by 281
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 287
Targeting PI3K/AKT signaling pathway in obesity.
Savova, M., Mihaylova, L., Tews, D., Wabitsch, M., & Georgiev, M. (2023) · Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · doi:10.1016/j.biopha.2023.114244 · Cited by 260
Leptin signalling pathways in hypothalamic neurons
Kwon, O., Kim, K. W., & Kim, M. (2016) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-016-2133-1 · Cited by 306
Pancreatic signals controlling food intake; insulin, glucagon and amylin
Woods, S. C., Lutz, T. A., Geary, N., & Langhans, W. (2006) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2006.1858 · Cited by 301
The melanocortin pathway and control of appetite-progress and therapeutic implications
Baldini, G., & Phelan, K. D. (2019) · Journal of Endocrinology · doi:10.1530/joe-18-0596 · Cited by 300
Peptides and Food Intake
Crespo, C. S., Cachero, A. P., Puebla, L., Barrios, V., & Arilla, E. (2014) · Frontiers in Endocrinology · doi:10.3389/fendo.2014.00058 · Cited by 274
Cross-talk between estrogen and leptin signaling in the hypothalamus
Gao, Q., & Horváth, T. L. (2008) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00733.2007 · Cited by 251
Hormone and glucose signalling in POMC and AgRP neurons
Belgardt, B., Okamura, T., & Brüning, J. C. (2009) · The Journal of Physiology · doi:10.1113/jphysiol.2009.179192 · Cited by 257
The role of insulin receptor substrate 2 in hypothalamic and β cell function
Choudhury, A. I., Heffron, H., Smith, M. A., Al‐Qassab, H., Xu, A. W., Selman, C., Simmgen, M., Clements, M., Claret, M., MacColl, G., et al. (2005) · Journal of Clinical Investigation · doi:10.1172/jci24445 · Cited by 244
Self-citation
Leptin Increases Adult Hippocampal Neurogenesis in Vivo and in Vitro
Garza, J. C., Guo, M., Zhang, W., & Lu, X. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m800053200 · Cited by 241
Leptin receptor signaling and the regulation of mammalian physiology
Villanueva, E. C., & Myers, M. G. (2008) · International Journal of Obesity · doi:10.1038/ijo.2008.232 · Cited by 237
Insulin Excites Anorexigenic Proopiomelanocortin Neurons via Activation of Canonical Transient Receptor Potential Channels
Qiu, J., Zhang, C., Borgquist, A., Nestor, C. C., Smith, A. W., Bosch, M. A., Ku, S., Wagner, E. J., Rønnekleiv, O. K., & Kelly, M. J. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.03.004 · Cited by 244
De Novo Neurogenesis in Adult Hypothalamus as a Compensatory Mechanism to Regulate Energy Balance
Pierce, A. A., & Xu, A. W. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.2479-09.2010 · Cited by 224
Self-citation
Agrp Neurons Mediate Sirt1's Action on the Melanocortin System and Energy Balance: Roles for Sirt1 in Neuronal Firing and Synaptic Plasticity
Dietrich, M. O., Antunes, C., Geliang, G., Liu, Z.-W., Borók, E., Nie, Y., Xu, A. W., Souza, D. O., Gao, Q., Diano, S., et al. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.2234-10.2010 · Cited by 229
Self-citation
Uncoupling the mechanisms of obesity and hypertension by targeting hypothalamic IKK-β and NF-κB
Purkayastha, S., Zhang, G., & Cai, D. (2011) · Nature Medicine · doi:10.1038/nm.2372 · Cited by 220
PTP1B and SHP2 in POMC neurons reciprocally regulate energy balance in mice
Banno, R., Zimmer, D., De Jonghe, B. C., Atienza, M., Rak, K., Yang, W., & Bence, K. K. (2010) · Journal of Clinical Investigation · doi:10.1172/jci39620 · Cited by 214
Effects of Hypothalamic Neurodegeneration on Energy Balance
Xu, A. W., Kaelin, C. B., Morton, G. J., Ogimoto, K., Stanhope, K. L., Graham, J. L., Baskin, D. G., Havel, P. J., Schwartz, M. W., & Barsh, G. S. (2005) · PLoS Biology · doi:10.1371/journal.pbio.0030415 · Cited by 211
Self-citation
Leptin inhibits hypothalamic Npy and Agrp gene expression via a mechanism that requires phosphatidylinositol 3-OH-kinase signaling
Morrison, C. D., Morton, G. J., Niswender, K. D., Gelling, R. W., & Schwartz, M. W. (2005) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00094.2005 · Cited by 228
Neuropeptide exocytosis involving synaptotagmin-4 and oxytocin in hypothalamic programming of body weight and energy balance
Zhang, G., Bai, H., Zhang, H., Dean, C., Wu, Q., Li, J., Guariglia, S., Meng, Q., & Cai, D. (2011) · Neuron · doi:10.1016/j.neuron.2010.12.036 · Cited by 208
Metabolic syndrome as a risk factor for neurological disorders
Farooqui, A. A., Farooqui, T., Panza, F., & Frisardi, V. (2011) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-011-0840-1 · Cited by 213
Brain insulin, energy and glucose homeostasis; genes, environment and metabolic pathologies
Gerozissis, K. (2008) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2008.01.050 · Cited by 204
Leptin signaling and circuits in puberty and fertility
Elias, C. F., & Purohit, D. (2012) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-012-1095-1 · Cited by 200
Functional relationship between obesity and male reproduction: from humans to animal models
Teerds, K. J., de Rooij, D. G., & Keijer, J. (2011) · Human Reproduction Update · doi:10.1093/humupd/dmr017 · Cited by 190
Leptin receptor signaling: pathways to leptin resistance
Wauman, J. (2011) · Frontiers in bioscience · doi:10.2741/3885 · Cited by 182
The FoxO transcription factors and metabolic regulation
Nakae, J., Oki, M., & Cao, Y. (2008) · FEBS Letters · doi:10.1016/j.febslet.2007.11.025 · Cited by 176
Functional Role of Suppressor of Cytokine Signaling 3 Upregulation in Hypothalamic Leptin Resistance and Long-Term Energy Homeostasis
Reed, A. S., Unger, E. K., Olofsson, L. E., Piper, M. L., Myers, M. G., & Xu, A. W. (2010) · Diabetes · doi:10.2337/db09-1024 · Cited by 176
Self-citation
Inflammation during obesity is not all bad: evidence from animal and human studies
Ye, J., & McGuinness, O. P. (2012) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00266.2012 · Cited by 178
The Long Form of the Leptin Receptor Regulates STAT5 and Ribosomal Protein S6 via Alternate Mechanisms
Gong, Y., Ishida-Takahashi, R., Villanueva, E. C., Fingar, D. C., Münzberg, H., & Myers, M. G. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m702838200 · Cited by 173
Minireview: CNS Mechanisms of Leptin Action
Flak, J. N., & Myers, M. G. (2015) · Molecular Endocrinology · doi:10.1210/me.2015-1232 · Cited by 179
AdipoR1 mediates the anorexigenic and insulin/leptin‐like actions of adiponectin in the hypothalamus
Coope, A., Milanski, M., ARAUJO, E. P. D., Tambascia, M. A., Saad, M. J. A., Geloneze, B., & Velloso, L. A. (2008) · FEBS Letters · doi:10.1016/j.febslet.2008.03.037 · Cited by 168
Inactivation of Signal Transducer and Activator of Transcription 3 in Proopiomelanocortin (Pomc) Neurons Causes Decreased Pomc Expression, Mild Obesity, and Defects in Compensatory Refeeding
Xu, A. W., Marie, L. S., Kaelin, C. B., & Barsh, G. S. (2006) · Endocrinology · doi:10.1210/en.2006-1119 · Cited by 169
Self-citation
Genetic rescue of nonclassical ERα signaling normalizes energy balance in obese Erα-null mutant mice
Park, C. J., Zhao, Z., Glidewell-Kenney, C., Lazic, M., Chambon, P., Krust, A., Weiss, J., Clegg, D. J., Dunaif, A., Jameson, J. L., et al. (2011) · Journal of Clinical Investigation · doi:10.1172/jci41702 · Cited by 162
Hormone Interactions Regulating Energy Balance During Pregnancy
Ladyman, S. R., Augustine, R. A., & Grattan, D. R. (2010) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2010.02017.x · Cited by 166
Dominant Role of the p110β Isoform of PI3K over p110α in Energy Homeostasis Regulation by POMC and AgRP Neurons
Al‐Qassab, H., Smith, M. A., Irvine, E. E., Guillermet‐Guibert, J., Claret, M., Choudhury, A. I., Selman, C., Piipari, K., Clements, M., Lingard, S. J., et al. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2009.09.008 · Cited by 165
Brain-Derived Neurotrophic Factor, Food Intake Regulation, and Obesity
Rosas‐Vargas, H., Martínez‐Ezquerro, J. D., & Bienvenu, T. (2011) · Archives of Medical Research · doi:10.1016/j.arcmed.2011.09.005 · Cited by 165
PDK1 Deficiency in POMC-Expressing Cells Reveals FOXO1-Dependent and -Independent Pathways in Control of Energy Homeostasis and Stress Response
Belgardt, B., Husch, A., Rother, E., Ernst, M. B., Wunderlich, F. T., Hampel, B., Klöckener, T., Alessi, D. R., Kloppenburg, P., & Brüning, J. C. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2008.01.006 · Cited by 159
Mechanism involved in insulin resistance via accumulation of β-amyloid and neurofibrillary tangles: link between type 2 diabetes and Alzheimer’s disease
Rad, S. K., Arya, A., Karimian, H., Madhavan, P., Rizwan, F., Koshy, S., & Prabhu, G. (2018) · Drug Design Development and Therapy · doi:10.2147/dddt.s173970 · Cited by 167
Central nervous system regulation of organismal energy and glucose homeostasis
Myers, M. G., Affinati, A. H., Richardson, N. E., & Schwartz, M. W. (2021) · Nature Metabolism · doi:10.1038/s42255-021-00408-5 · Cited by 165
Hypothalamic proopiomelanocortin processing and the regulation of energy balance
Wardlaw, S. L. (2011) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2010.10.107 · Cited by 153
Mitochondrial Dynamics Mediated by Mitofusin 1 Is Required for POMC Neuron Glucose-Sensing and Insulin Release Control
Ramírez, S., Gómez-Valadés, A. G., Schneeberger, M., Varela, L., Haddad-Tóvolli, R., Altirriba, J., Noguera, E., Drougard, A., Flores‐Martínez, Á., Imbernón, M., et al. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.05.010 · Cited by 157
Convergence of the Insulin and Serotonin Programs in the Pancreatic β-Cell
Ohta, Y., Kosaka, Y., Kishimoto, N. Y., Wang, J., Smith, S. B., Honig, G., Kim, H., Gasa, R., Neubauer, N., Liou, A., et al. (2011) · Diabetes · doi:10.2337/db10-1192 · Cited by 149
Divergent Regulation of Energy Expenditure and Hepatic Glucose Production by Insulin Receptor in Agouti-Related Protein and POMC Neurons
Lin, H. V., Plum, L., Ono, H., Juárez, R. G., Shanabrough, M., Borók, E., Horváth, T. L., Rossetti, L., & Accili, D. (2009) · Diabetes · doi:10.2337/db09-1303 · Cited by 162
Leptin and the brain: Influences on brain development, cognitive functioning and psychiatric disorders
Farr, O. M., Tsoukas, M. A., & Mantzoros, C. S. (2014) · Metabolism · doi:10.1016/j.metabol.2014.07.004 · Cited by 153
Hypothalamic dysfunction in obesity
Williams, L. M. (2012) · Proceedings of The Nutrition Society · doi:10.1017/s002966511200078x · Cited by 148
Leptin and its receptors
Wada, N., Hirako, S., Takenoya, F., Kageyama, H., Okabe, M., & Shioda, S. (2014) · Journal of Chemical Neuroanatomy · doi:10.1016/j.jchemneu.2014.09.002 · Cited by 156
Insulin and Leptin Induce Glut4 Plasma Membrane Translocation and Glucose Uptake in a Human Neuronal Cell Line by a Phosphatidylinositol 3-Kinase- Dependent Mechanism
Benomar, Y., Naour, N., Aubourg, A., Bailleux, V., Gertler, A., Djiane, J., Guerre-Millo, M., & Taouis, M. (2006) · Endocrinology · doi:10.1210/en.2005-1464 · Cited by 142
Off the Clock: From Circadian Disruption to Metabolic Disease
Maury, E. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20071597 · Cited by 148
Intraventricular insulin and leptin reduce food intake and body weight in C57BL/6J mice
Brown, L. M., Clegg, D. J., Benoit, S. C., & Woods, S. C. (2006) · Physiology & Behavior · doi:10.1016/j.physbeh.2006.08.008 · Cited by 139
Sympathetic nervous system control of triglyceride metabolism: novel concepts derived from recent studies
Geerling, J. J., Boon, M. R., Kooijman, S., Parlevliet, E. T., Havekes, L. M., Romijn, J. A., Meurs, I. M., & Rensen, P. C. N. (2014) · Journal of Lipid Research · doi:10.1194/jlr.r045013 · Cited by 137
Modulation of AgRP-neuronal function by SOCS3 as an initiating event in diet-induced hypothalamic leptin resistance
Olofsson, L. E., Unger, E. K., Cheung, C. C., & Xu, A. W. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1218284110 · Cited by 138
Self-citation
Central nervous control of energy and glucose balance: focus on the central melanocortin system
Xu, Y., Elmquist, J. K., & Fukuda, M. (2011) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2011.06248.x · Cited by 135
TNF-α acts in the hypothalamus inhibiting food intake and increasing the respiratory quotient—Effects on leptin and insulin signaling pathways
Romanatto, T., Cesquini, M., do Amaral, M. E. C., Roman, É. A., Moraes, J. C., Torsoni, M. A., Cruz-Neto, A. P., & Velloso, L. A. (2007) · Peptides · doi:10.1016/j.peptides.2007.03.006 · Cited by 131
Appetite Regulation: An Overview
Dhillo, W. S. (2007) · Thyroid · doi:10.1089/thy.2007.0018 · Cited by 127
Central insulin and leptin-mediated autonomic control of glucose homeostasis
Marino, J. S., Xu, Y., & Hill, J. W. (2011) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2011.03.001 · Cited by 129
Integrative neurobiology of energy homeostasis-neurocircuits, signals and mediators
Sánchez-Lasheras, C., Könner, A. C., & Brüning, J. C. (2009) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2009.08.002 · Cited by 127
A Role for Brain-Specific Homeobox Factor Bsx in the Control of Hyperphagia and Locomotory Behavior
Σάκκου, Μ., Wiedmer, P., Anlag, K., Hamm, A. C., Seuntjens, E., Ettwiller, L. M., Tschöp, M. H., & Treier, M. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.05.007 · Cited by 117
Leptin Suppresses Ghrelin-Induced Activation of Neuropeptide Y Neurons in the Arcuate Nucleus via Phosphatidylinositol 3-Kinase- and Phosphodiesterase 3-Mediated Pathway
Kohno, D., Nakata, M., Maekawa, F., Fujiwara, K., Maejima, Y., Kuramochi, M., Shimazaki, T., Okano, H., Onaka, T., & Yada, T. (2007) · Endocrinology · doi:10.1210/en.2006-1240 · Cited by 122
Hypothalamic obesity in children
Bereket, A., Kiess, W., Lustig, R. H., Muller, H. L., Goldstone, A. P., Weiss, R., Yavuz, Y., & Hochberg, Z. (2012) · Obesity Reviews · doi:10.1111/j.1467-789x.2012.01004.x · Cited by 117
Lipid phosphatases as drug discovery targets for type 2 diabetes
Lazar, D. F., & Saltiel, A. R. (2006) · Nature Reviews Drug Discovery · doi:10.1038/nrd2007 · Cited by 114
Cilia and ObesityPreprint
Vaisse, C., Reiter, J. F., & Berbari, N. F. (2017) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a028217 · Cited by 116
Freeze-dried jaboticaba peel added to high-fat diet increases HDL-cholesterol and improves insulin resistance in obese rats
Lenquiste, S. A., Batista, Â. G., Marineli, R. D. S., Dragano, N. R. V., & Maróstica, M. R. (2012) · Food Research International · doi:10.1016/j.foodres.2012.07.052 · Cited by 113
Specific Physiological Roles for Signal Transducer and Activator of Transcription 3 in Leptin Receptor-Expressing Neurons
Piper, M. L., Unger, E. K., Myers, M. G., & Xu, A. W. (2007) · Molecular Endocrinology · doi:10.1210/me.2007-0389 · Cited by 113
Self-citation
Unraveling the Central Proopiomelanocortin Neural Circuits
Mercer, A. J., Hentges, S. T., Meshul, C. K., & Low, M. J. (2013) · Frontiers in Neuroscience · doi:10.3389/fnins.2013.00019 · Cited by 118
Hormonal induction of leptin resistance during pregnancy
Grattan, D. R., Ladyman, S. R., & Augustine, R. A. (2007) · Physiology & Behavior · doi:10.1016/j.physbeh.2007.04.005 · Cited by 114
CNS Regulation of Glucose Homeostasis
Lam, C., Chari, M., & Lam, T. K. T. (2009) · Physiology · doi:10.1152/physiol.00003.2009 · Cited by 117
Hypothalamic alterations in fetuses of high fat diet-fed obese female rats
Gupta, A., Srinivasan, M., Thamadilok, S., & Patel, M. S. (2008) · Journal of Endocrinology · doi:10.1677/joe-08-0429 · Cited by 109
A novel leptin signalling pathway via PTEN inhibition in hypothalamic cell lines and pancreatic β‐cells
Ning, K., Miller, L. C., Laidlaw, H. A., Burgess, L. A., Perera, N. M., Downes, C. P., Leslie, N. R., & Ashford, M. L. J. (2006) · The EMBO Journal · doi:10.1038/sj.emboj.7601118 · Cited by 107
Oleic Acid Directly Regulates POMC Neuron Excitability in the Hypothalamus
Jo, Y., Su, Y., Juárez, R. G., & Chua, S. C. (2009) · Journal of Neurophysiology · doi:10.1152/jn.91294.2008 · Cited by 113
Inactivation of SOCS3 in leptin receptor-expressing cells protects mice from diet-induced insulin resistance but does not prevent obesity
Pedroso, J. A. B., Buonfiglio, D. D. C., Cardinali, L. I., Furigo, I. C., Ramos-Lobo, A. M., Tirapegui, J., Elias, C. F., & Donato, J. (2014) · Molecular Metabolism · doi:10.1016/j.molmet.2014.06.001 · Cited by 106
Selective deletion of leptin receptors in adult hippocampus induces depression-related behaviours
Guo, M., Huang, T.-Y., Garza, J. C., Chua, S. C., & Lu, X. (2012) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145712000703 · Cited by 102

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