Cited by 164Regulation of Appetite and ObesityPancreatic function and diabetesAdipokines, Inflammation, and Metabolic Diseases

The DOI matches its Crossref record; 51 of the 51 references it cites were found in a registry or an index.

Hypothalamic Leptin Signaling Regulates Hepatic Insulin Sensitivity via a Neurocircuit Involving the Vagus Nerve

Open access

German, Jonathan, Kim, Francis, Schwartz, Gary J., Havel, Peter J., Rhodes, Christopher J., Schwartz, Michael W., Morton, Gregory J.·2009·Endocrinology

DOI 10.1210/en.2009-0445PMC PMC2754686

Open this paper in CoChat — free account

Abstract

Recent evidence suggests that hormones such as insulin and leptin act in the hypothalamus to regulate energy balance and glucose metabolism. Here we show that in leptin receptor-deficient Koletsky (fak/fak) rats, adenovirally induced expression of leptin receptors in the area of the hypothalamic arcuate nucleus improved peripheral insulin sensitivity via enhanced suppression of hepatic glucose production, with no change of insulin-stimulated glucose uptake or disposal. This effect was associated with increased insulin signal transduction via phosphatidylinositol-3-OH kinase (as measured by pY-insulin receptor substrate-1 and pS-PKB/Akt) in liver, but not skeletal muscle, and with reduced hepatic expression of the gluconeogenic genes, glucose-6-phosphatase and phosphoenolpyruvate kinase. Moreover, the beneficial effects of hypothalamic leptin signaling on hepatic insulin sensitivity were blocked by selective hepatic vagotomy. We conclude that hypothalamic leptin action increases peripheral insulin sensitivity primarily via effects on the liver and that the mechanism underlying this effect is dependent on the hepatic branch of the vagus nerve.

Integrity signals

Registry

Crossref · 10.1210/en.2009-0445

Cites

51 of 51 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?

A SIMPLE METHOD FOR THE ISOLATION AND PURIFICATION OF TOTAL LIPIDES FROM ANIMAL TISSUES
Folch, J., Lees, M., & Stanley, G. H. S. (1957) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)64849-5 · Cited by 65,189
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
Nonalcoholic Fatty Liver Disease
Angulo, P. (2002) · New England Journal of Medicine · doi:10.1056/nejmra011775 · Cited by 5,228
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
Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase
Minokoshi, Y., Kim, Y.-B., Peroni, O. D., Fryer, L. G. D., Müller, C., Carling, D., & Kahn, B. B. (2002) · Nature · doi:10.1038/415339a · Cited by 2,053
Nonalcoholic fatty liver disease
Adams, L. A. (2005) · Canadian Medical Association Journal · doi:10.1503/cmaj.045232 · Cited by 1,658
Leptin reverses insulin resistance and diabetes mellitus in mice with congenital lipodystrophy
Shimomura, I., Hammer, R. E., Ikemoto, S., Brown, M. S., & Goldstein, J. L. (1999) · Nature · doi:10.1038/43448 · Cited by 1,038
Specificity of Leptin Action on Elevated Blood Glucose Levels and Hypothalamic Neuropeptide Y Gene Expression in ob/ob Mice
Schwartz, M. W., Baskin, D. G., Bukowski, T. R., Kuijper, J. L., Foster, D., Lasser, G., Prunkard, D. E., Porte, D., Woods, S. C., Seeley, R. J., et al. (1996) · Diabetes · doi:10.2337/diab.45.4.531 · Cited by 904
Self-citation
Hypothalamic insulin signaling is required for inhibition of glucose production
Obici, S., Zhang, B. B., Karkanias, G., & Rossetti, L. (2002) · Nature Medicine · doi:10.1038/nm1202-798 · Cited by 904
Leptin Receptor Signaling in Midbrain Dopamine Neurons Regulates Feeding
Hommel, J. D., Trinko, R., Sears, R. M., Georgescu, D., Liu, Z.-W., Gao, X.-B., Thurmon, J. J., Marinelli, M., & DiLeone, R. J. (2006) · Neuron · doi:10.1016/j.neuron.2006.08.023 · Cited by 902

Show all 49 references

Sorted by citations

The role of fatty acids in insulin resistance
Sears, B., & Perry, M. (2015) · Lipids in Health and Disease · doi:10.1186/s12944-015-0123-1 · Cited by 589
Structure, production and signaling of leptin
Münzberg, H., & Morrison, C. D. (2014) · Metabolism · doi:10.1016/j.metabol.2014.09.010 · Cited by 486
Biology's response to dieting: the impetus for weight regain
MacLean, P. S., Bergouignan, A., Cornier, M., & Jackman, M. R. (2011) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00755.2010 · Cited by 471
Direct Insulin and Leptin Action on Pro-opiomelanocortin Neurons Is Required for Normal Glucose Homeostasis and Fertility
Hill, J. W., Elias, C. F., Fukuda, M., Williams, K. W., Berglund, E. D., Holland, W. L., Cho, Y.-R., Chuang, J.-C., Xu, Y., Choi, M., et al. (2010) · Cell Metabolism · doi:10.1016/j.cmet.2010.03.002 · Cited by 391
Sixteen years and counting: an update on leptin in energy balance
Gautron, L., & Elmquist, J. K. (2011) · Journal of Clinical Investigation · doi:10.1172/jci45888 · Cited by 367
Direct leptin action on POMC neurons regulates glucose homeostasis and hepatic insulin sensitivity in mice
Berglund, E. D., Vianna, C. R., Donato, J., Kim, M. H., Chuang, J.-C., Lee, C. E., Lauzon, D. A., Lin, P., Brule, L. J., Scott, M. M., et al. (2012) · Journal of Clinical Investigation · doi:10.1172/jci59816 · Cited by 352
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
“Moreover, adenoviralinduced overexpression of IGFBP2 normalized blood glucose levels in ob/ob mice via improved hepatic insulin sensitivity, accompanied by reduced hepatic expression of the gluconeogenic genes, G6Pase and Pepck, along with a significant reduction of hepatic steatosis (80).”
BackgroundMethodInfluentialSelf-citation
Hypothalamic nutrient sensing in the control of energy homeostasis
Blouet, C., & Schwartz, G. J. (2009) · Behavioural Brain Research · doi:10.1016/j.bbr.2009.12.024 · Cited by 343
Self-citation
Leptin revisited: its mechanism of action and potential for treating diabetes
Coppari, R., & Bjørbæk, C. (2012) · Nature Reviews Drug Discovery · doi:10.1038/nrd3757 · Cited by 308
Fibroblast Growth Factor 21 Action in the Brain Increases Energy Expenditure and Insulin Sensitivity in Obese Rats
Sarruf, D. A., Thaler, J. P., Morton, G. J., German, J. P., Fischer, J. D., Ogimoto, K., & Schwartz, M. W. (2010) · Diabetes · doi:10.2337/db09-1878 · Cited by 287
Self-citation
Brain Insulin Controls Adipose Tissue Lipolysis and Lipogenesis
Scherer, T., O’Hare, J., Diggs‐Andrews, K. A., Schweiger, M., Cheng, B., Lindtner, C., Zieliński, E., Vempati, P., Su, K., Dighe, S. V., et al. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.01.008 · Cited by 270
Leptin in nonalcoholic fatty liver disease: A narrative review
Polyzos, S. A., Kountouras, J., & Mantzoros, C. S. (2015) · Metabolism · doi:10.1016/j.metabol.2014.10.012 · Cited by 235
The role of leptin in the control of insulin-glucose axis
Amitani, M. S., Asakawa, A., Amitani, H., & Inui, A. (2013) · Frontiers in Neuroscience · doi:10.3389/fnins.2013.00051 · Cited by 242
The role of the autonomic nervous liver innervation in the control of energy metabolism
Yi, C., la Fleur, S. E., Fliers, E., & Kalsbeek, A. (2010) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2010.01.006 · Cited by 240
Inhibition of Hypothalamic Inflammation Reverses Diet-Induced Insulin Resistance in the Liver
Milanski, M., Arruda, A. P., Coope, A., Ignácio-Souza, L. M., Nuñez, C. E. C., Roman, E. A., Romanatto, T., Pascoal, L. B., Caricilli, A. M., Torsoni, M. A., et al. (2012) · Diabetes · doi:10.2337/db11-0390 · Cited by 233
FGF19 action in the brain induces insulin-independent glucose lowering
Morton, G. J., Matsen, M. E., Bracy, D. P., Meek, T. H., Hồng, N. T., Stefanovski, D., Bergman, R. N., Wasserman, D. H., & Schwartz, M. W. (2013) · Journal of Clinical Investigation · doi:10.1172/jci70710 · Cited by 218
Self-citation
Leptin therapy improves insulin-deficient type 1 diabetes by CNS-dependent mechanisms in mice
Fujikawa, T., Chuang, J.-C., Sakata, I., Ramadori, G., & Coppari, R. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1008025107 · Cited by 225
Transcription factors and coactivators controlling nutrient and hormonal regulation of hepatic gluconeogenesis
Jitrapakdee, S. (2011) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2011.10.001 · Cited by 202
Hypothalamic-autonomic control of energy homeostasis
Seoane‐Collazo, P., Fernø, J., González, F., Diéguez, C., Leis, R., Nogueiras, R., & López, M. (2015) · Endocrine · doi:10.1007/s12020-015-0658-y · Cited by 189
Leptin Activates a Novel CNS Mechanism for Insulin-Independent Normalization of Severe Diabetic Hyperglycemia
German, J. P., Thaler, J. P., Wisse, B. E., Oh-I, S., Sarruf, D. A., Matsen, M. E., Fischer, J. D., Taborsky, G. J., Schwartz, M. W., & Morton, G. J. (2011) · Endocrinology · doi:10.1210/en.2010-0890 · Cited by 169
Self-citation
Leptin Deficiency Causes Insulin Resistance Induced by Uncontrolled Diabetes
German, J. P., Wisse, B. E., Thaler, J. P., Oh-I, S., Sarruf, D. A., Ogimoto, K., Kaiyala, K. J., Fischer, J. D., Matsen, M. E., Taborsky, G. J., et al. (2010) · Diabetes · doi:10.2337/db09-1918 · Cited by 159
Self-citation
Hypothalamic control of energy metabolism via the autonomic nervous system
Kalsbeek, A., Bruinstroop, E., Yi, C., Klieverik, L. P., la Fleur, S. E., & Fliers, E. (2010) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2010.05800.x · Cited by 152
The role of leptin in glucose homeostasis
Denroche, H. C., Huynh, F. K., & Kieffer, T. J. (2012) · Journal of Diabetes Investigation · doi:10.1111/j.2040-1124.2012.00203.x · Cited by 153
Leptin Rapidly Improves Glucose Homeostasis in Obese Mice by Increasing Hypothalamic Insulin Sensitivity
Koch, C. E., Augustine, R. A., Steger, J., Ganjam, G. K., Benzler, J., Pracht, C., Lowe, C., Schwartz, M. W., Shepherd, P. R., Anderson, G. M., et al. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.3202-10.2010 · Cited by 139
Self-citation
Recent Trends in Therapeutic Approaches for Diabetes Management: A Comprehensive Update
Tiwari, P. (2015) · Journal of Diabetes Research · doi:10.1155/2015/340838 · Cited by 140
Leptin Engages a Hypothalamic Neurocircuitry to Permit Survival in the Absence of Insulin
Fujikawa, T., Berglund, E. D., Patel, V. R., Ramadori, G., Vianna, C. R., Vong, L., Thorel, F., Chera, S., Herrera, P. L., Lowell, B. B., et al. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.08.004 · Cited by 135
Central Inhibition of IKKβ/NF-κB Signaling Attenuates High-Fat Diet–Induced Obesity and Glucose Intolerance
Benzler, J., Ganjam, G. K., Pretz, D., Oelkrug, R., Koch, C. E., Legler, K., Stöhr, S., Culmsee, C., Williams, L. M., & Tups, A. (2015) · Diabetes · doi:10.2337/db14-0093 · Cited by 129
Leptin Therapy Reverses Hyperglycemia in Mice With Streptozotocin-Induced Diabetes, Independent of Hepatic Leptin Signaling
Denroche, H. C., Levi, J., Wideman, R. D., Sequeira, R. M., Huynh, F. K., Covey, S. D., & Kieffer, T. J. (2011) · Diabetes · doi:10.2337/db10-0958 · Cited by 126
The Bidirectional Relationship between Diabetes and Depression: A Literature Review
Alzoubi, A., Abunaser, R., Khassawneh, A., Alfaqih, M. A., Khasawneh, A. G., & Abdo, N. M. (2018) · Korean Journal of Family Medicine · doi:10.4082/kjfm.2018.39.3.137 · Cited by 130
Wired on sugar: the role of the CNS in the regulation of glucose homeostasis
Grayson, B. E., Seeley, R. J., & Sandoval, D. A. (2012) · Nature reviews. Neuroscience · doi:10.1038/nrn3409 · Cited by 125
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
Galantamine Alleviates Inflammation and Other Obesity-Associated Complications in High-Fat Diet-Fed Mice
Satapathy, S. K., Ochani, M., Dancho, M. E., Hudson, L., Rosas‐Ballina, M., Valdés‐Ferrer, S. I., Olofsson, P. S., Harris, Y., Roth, J., Chavan, S. S., et al. (2011) · Molecular Medicine · doi:10.2119/molmed.2011.00083 · Cited by 119
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
Modulation of glucose metabolism by the renin-angiotensin-aldosterone system
Favre, G. A., Esnault, V. L. M., & Van Obberghen, E. (2015) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00391.2014 · Cited by 114
Central GLP-2 Enhances Hepatic Insulin Sensitivity via Activating PI3K Signaling in POMC Neurons
Shi, X., Zhou, F., Li, X., Chang, B. H.-J., Li, D., Wang, Y., Tong, Q., Xu, Y., Fukuda, M., Zhao, J. J., et al. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.06.014 · Cited by 106
Brain insulin action augments hepatic glycogen synthesis without suppressing glucose production or gluconeogenesis in dogs
Ramnanan, C. J., Saraswathi, V., Smith, M. S., Donahue, E. P., Farmer, B., Farmer, T. D., Neal, D. W., Williams, P. E., Lautz, M., Mari, A., et al. (2011) · Journal of Clinical Investigation · doi:10.1172/jci45472 · Cited by 96
Modulation of the central melanocortin system by leptin, insulin, and serotonin: Co-ordinated actions in a dispersed neuronal network
Williams, K. W., Scott, M. M., & Elmquist, J. K. (2011) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2010.11.042 · Cited by 96
Role of Leptin in Non-Alcoholic Fatty Liver Disease
Jiménez‐Cortegana, C., García-Galey, A., Tami, M., Bellido, P. D. P., Carmona, I., López, S., Álba, G., & Sánchez‐Margalet, V. (2021) · Biomedicines · doi:10.3390/biomedicines9070762 · Cited by 100
Differential contribution of POMC and AgRP neurons to the regulation of regional autonomic nerve activity by leptin
Bell, B. B., Harlan, S. M., Morgan, D., Guo, D., Cui, H.-X., & Rahmouni, K. (2017) · Molecular Metabolism · doi:10.1016/j.molmet.2017.12.006 · Cited by 77
Vagal control of satiety and hormonal regulation of appetite
Owyang, C., & Heldsinger, A. (2011) · Journal of Neurogastroenterology and Motility · doi:10.5056/jnm.2011.17.4.338 · Cited by 87
Subcutaneous administration of leptin normalizes fasting plasma glucose in obese type 2 diabetic UCD-T2DM rats
Cummings, B. P., Bettaieb, A., Graham, J. L., Stanhope, K. L., Dill, R., Morton, G. J., Haj, F. G., & Havel, P. J. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1107163108 · Cited by 87
Self-citation
Hypothalamic AMP-Activated Protein Kinase Regulates Glucose Production
Yang, C. S., Lam, C. K. L., Chari, M., Cheung, G. W. C., Kokorovic, A., Gao, S., Leclerc, I., Rutter, G. A., & Lam, T. K. T. (2010) · Diabetes · doi:10.2337/db10-0221 · Cited by 86
Vagal Stimulation Modulates Inflammation through a Ghrelin Mediated Mechanism in Traumatic Brain Injury
Bansal, V., Ryu, S. Y., Lopez, N., Allexan, S. S., Krzyżaniak, M., Eliceiri, B. P., Baird, A., & Coimbra, R. S. M. (2011) · Inflammation · doi:10.1007/s10753-011-9307-7 · Cited by 87
Obesity surgery and gut–brain communication
Berthoud, H., Shin, A. C., & Zheng, H. (2011) · Physiology & Behavior · doi:10.1016/j.physbeh.2011.01.023 · Cited by 85
Lipid Sensing and Insulin Resistance in the Brain
Yue, J. T. Y., & Lam, T. K. T. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.01.013 · Cited by 83
The Potential Adverse Role of Leptin Resistance in Nonalcoholic Fatty Liver Disease
Pοlyzos, S. A., Kountouras, J., Zavos, C., & Deretzi, G. (2010) · Journal of Clinical Gastroenterology · doi:10.1097/mcg.0b013e3181ec5c66 · Cited by 84
Leptin Receptor Signaling in the Hypothalamus Regulates Hepatic Autonomic Nerve Activity via Phosphatidylinositol 3-Kinase and AMP-Activated Protein Kinase
Tanida, M., Yamamoto, N., Morgan, D., Kurata, Y., Shibamoto, T., & Rahmouni, K. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.1828-14.2015 · Cited by 68
The influence of fasting and energy-restricted diets on leptin and adiponectin levels in humans: A systematic review and meta-analysis
Kord-Varkaneh, H., Tinsley, G. M., Santos, H. O., Zand, H., Nazary, A., Fatahi, S., Mokhtari, Z., Salehi‐Sahlabadi, A., Tan, S. C., Rahmani, J., et al. (2020) · Clinical Nutrition · doi:10.1016/j.clnu.2020.10.034 · Cited by 85
Melatonin acts through MT1/MT2 receptors to activate hypothalamic Akt and suppress hepatic gluconeogenesis in rats
Faria, J. A., Kinote, A. P. B. D. M., Ignácio-Souza, L. M., de Araújo, T. M., Razolli, D. S., Doneda, D. L., Paschoal, L. B., Lellis‐Santos, C., Bertolini, G. L., Velloso, L. A., et al. (2013) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00094.2013 · Cited by 82
Histamine Regulation in Glucose and Lipid Metabolism via Histamine Receptors
Wang, K., Tanimoto, A., Yamada, S., Guo, X., Ding, Y., Watanabe, T., Watanabe, T., Kohno, K., Hirano, K., Tsukada, H., et al. (2010) · American Journal Of Pathology · doi:10.2353/ajpath.2010.091198 · Cited by 83
Glucose Transporter-1 in the Hypothalamic Glial Cells Mediates Glucose Sensing to Regulate Glucose Production In Vivo
Chari, M., Yang, C. S., Lam, C., Lee, K., Mighiu, P. I., Kokorovic, A., Cheung, G. W. C., Lai, T. Y. Y., Wang, P. Y. T., & Lam, T. K. T. (2011) · Diabetes · doi:10.2337/db11-0120 · Cited by 80
Review of the role of the nervous system in glucose homoeostasis and future perspectives towards the management of diabetes
Güemes, A., & Georgiou, P. (2018) · Bioelectronic Medicine · doi:10.1186/s42234-018-0009-4 · Cited by 79
Vagal mechanisms as neuromodulatory targets for the treatment of metabolic disease
Berthoud, H., & Neuhuber, W. (2019) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.14182 · Cited by 74
Disruption of Hepatic Leptin Signaling Protects Mice From Age- and Diet-Related Glucose Intolerance
Huynh, F. K., Levi, J., Denroche, H. C., Gray, S. L., Voshol, P. J., Neumann, U. H., Speck, M., Chua, S. C., Covey, S. D., & Kieffer, T. J. (2010) · Diabetes · doi:10.2337/db10-0074 · Cited by 79
Hypothalamic glycogen synthase kinase 3β has a central role in the regulation of food intake and glucose metabolism
Benzler, J., Ganjam, G. K., Krüger, M., Pinkenburg, O., Kutschke, M., Stöhr, S., Steger, J., Koch, C. E., Oelkrug, R., Schwartz, M. W., et al. (2012) · Biochemical Journal · doi:10.1042/bj20120834 · Cited by 70
Self-citation
Leptin Activates Hepatic 5′-AMP-activated Protein Kinase through Sympathetic Nervous System and α1-Adrenergic Receptor
Miyamoto, L., Ebihara, K., Kusakabe, T., Aotani, D., Yamamoto‐Kataoka, S., Sakai, T., Aizawa‐Abe, M., Yamamoto, Y., Fujikura, J., Hayashi, T., et al. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.384545 · Cited by 74
Cyclic AMP sensor EPAC proteins and energy homeostasis
Almahariq, M. F., Mei, F. C., & Cheng, X. (2013) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2013.10.004 · Cited by 73
The CNS glucagon-like peptide-2 receptor in the control of energy balance and glucose homeostasis
Guan, X. (2014) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00096.2014 · Cited by 70
Leptin Increases Hepatic Triglyceride Export via a Vagal Mechanism in Humans
Metz, M., Beghini, M., Wolf, P. S., Pfleger, L., Hackl, M. T., Bastian, M., Freudenthaler, A., Harreiter, J., Zeyda, M., Baumgartner-Parzer, S. M., et al. (2022) · Cell Metabolism · doi:10.1016/j.cmet.2022.09.020 · Cited by 65
Adipokines and Hepatic Insulin Resistance
Yu, L. J., Ding, L., Hassan, W., Daoud, A., & Shang, J. (2013) · Journal of Diabetes Research · doi:10.1155/2013/170532 · Cited by 64
Extracellular Signal–Regulated Kinase in the Ventromedial Hypothalamus Mediates Leptin-Induced Glucose Uptake in Red-Type Skeletal Muscle
Toda, C., Shiuchi, T., Kageyama, H., Okamoto, S., Coutinho, E. A., Sato, T., Okamatsu‐Ogura, Y., Yokota, S., Takagi, K., Tang, L., et al. (2013) · Diabetes · doi:10.2337/db12-1629 · Cited by 62
Hypothalamic Nutrient Sensing Activates a Forebrain-Hindbrain Neuronal Circuit to Regulate Glucose Production In Vivo
Lam, C., Chari, M., Rutter, G. A., & Lam, T. K. T. (2010) · Diabetes · doi:10.2337/db10-0994 · Cited by 61
GDH-Dependent Glutamate Oxidation in the Brain Dictates Peripheral Energy Substrate Distribution
Karaca, M., Frigerio, F., Migrenne, S., Martin-Levilain, J., Skytt, D. M., Pajecka, K., Martin-del-Rio, R., Gruetter, R., Tamarit-Rodriguez, J., Waagepetersen, H. S., et al. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.09.003 · Cited by 60
Evidence That the Sympathetic Nervous System Elicits Rapid, Coordinated, and Reciprocal Adjustments of Insulin Secretion and Insulin Sensitivity During Cold Exposure
Morton, G. J., Muta, K., Kaiyala, K., Rojas, J. M., Scarlett, J., Matsen, M. E., Nelson, J. T., Acharya, N., Piccinini, F., Stefanovski, D., et al. (2017) · Diabetes · doi:10.2337/db16-1351 · Cited by 45
Self-citation
Impact of Melatonin and Molecular Clockwork Components on the Expression of Thyrotropin β-Chain (Tshb) and the Tsh Receptor in the Mouse Pars Tuberalis
Unfried, C., Ansari, N., Yasuo, S., Korf, H., & von Gall, C. (2009) · Endocrinology · doi:10.1210/en.2009-0609 · Cited by 59
Male fertility and obesity: are ghrelin, leptin and glucagon-like peptide-1 pharmacologically relevant?
Alves, M. G., Jesus, T. T., Sousa, M., Goldberg, E., Silva, B. M., & Oliveira, P. F. (2016) · Current Pharmaceutical Design · doi:10.2174/1381612822666151209151550 · Cited by 59
Brain-liver connections: role of the preautonomic PVN neurons
O’Hare, J., & Zsombok, A. (2015) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00302.2015 · Cited by 54
Ginsenoside Rb1 increases insulin sensitivity by activating AMP-activated protein kinase in male rats
Shen, L., Haas, M., Wang, D. Q. ‐., May-Zhang, A. A., Lo, C. C., Obici, S., Tso, P., Woods, S. C., & Liu, M. (2015) · Physiological Reports · doi:10.14814/phy2.12543 · Cited by 54
Should I Lay or Should I Grow: Photoperiodic Versus Metabolic Cues in Chickens
Hanlon, C., Ramachandran, R., Zuidhof, M. J., & Bédécarrats, G. Y. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2020.00707 · Cited by 48
Central Activating Transcription Factor 4 (ATF4) Regulates Hepatic Insulin Resistance in Mice via S6K1 Signaling and the Vagus Nerve
Zhang, Q., Yu, J., Liu, B., Lv, Z., Xia, T., Xiao, F., Chen, S., & Guo, F. (2013) · Diabetes · doi:10.2337/db12-1050 · 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
Self-citation
Acute Disruption of Leptin Signaling in Vivo Leads to Increased Insulin Levels and Insulin Resistance
Levi, J., Gray, S. L., Speck, M., Huynh, F. K., Babich, S. L., Gibson, W. T., & Kieffer, T. J. (2011) · Endocrinology · doi:10.1210/en.2011-0185 · Cited by 48
Intracerebroventricular Leptin Infusion Improves Glucose Homeostasis in Lean Type 2 Diabetic MKR Mice via Hepatic Vagal and Non-Vagal Mechanisms
Li, X., Wu, X., Camacho, R. C., Schwartz, G. J., & LeRoith, D. (2011) · PLoS ONE · doi:10.1371/journal.pone.0017058 · Cited by 45
Self-citation
Insulin and glucagon signaling in the central nervous system
Filippi, B., Abraham, M. A., Yue, J. T. Y., & Lam, T. K. T. (2013) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-013-9258-4 · Cited by 43
A critical update on the l eptin‐melanocortin system
Lavoie, O., Michael, N. J., & Caron, A. (2023) · Journal of Neurochemistry · doi:10.1111/jnc.15765 · Cited by 43
CNS Control of Glucose Metabolism: Response to Environmental Challenges
Arble, D. M., & Sandoval, D. A. (2013) · Frontiers in Neuroscience · doi:10.3389/fnins.2013.00020 · Cited by 44
How Should We Think About the Role of the Brain in Glucose Homeostasis and Diabetes?
Deem, J. D., Muta, K., Scarlett, J. M., Morton, G. J., & Schwartz, M. W. (2017) · Diabetes · doi:10.2337/dbi16-0067 · Cited by 42
Self-citation
Interplay between the brain and adipose tissue: a metabolic conversation
Díaz‐Castro, F., Morselli, E., & Claret, M. (2024) · EMBO Reports · doi:10.1038/s44319-024-00321-4 · Cited by 44
Leptin, 20years of searching for glucose homeostasis
Fernández-Formoso, G., Perez‐Sieira, S., González-Touceda, D., Diéguez, C., & Tovar, S. A. (2015) · Life Sciences · doi:10.1016/j.lfs.2015.02.008 · Cited by 39
Effect of body weight loss and normalization on blood pressure in overweight non-obese patients with stage 1 hypertension
Fogari, R., Zoppi, A., Corradi, L., Preti, P. S., Mugellini, A., Lazzari, P., & Derosa, G. (2010) · Hypertension Research · doi:10.1038/hr.2009.220 · Cited by 37
Hypothalamic glucagon signals through the KATP channels to regulate glucose production
Abraham, M. A., Yue, J. T. Y., LaPierre, M. P., Rutter, G. A., Light, P. E., Filippi, B., & Lam, T. K. T. (2013) · Molecular Metabolism · doi:10.1016/j.molmet.2013.11.007 · Cited by 35
Bardoxolone methyl prevents insulin resistance and the development of hepatic steatosis in mice fed a high-fat diet
Camer, D., Yu, Y., Szabo, A., Dinh, C. H. L., Wang, H., Cheng, L., & Huang, X. (2015) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2015.05.018 · Cited by 34
Reversing diet-induced metabolic dysregulation by diet switching leads to altered hepatic de novo lipogenesis and glycerolipid synthesis
Kowalski, G. M., Hamley, S., Selathurai, A., Kloehn, J., Souza, D. P. D., O’Callaghan, S., Nijagal, B., Tull, D., McConville, M. J., & Bruce, C. R. (2016) · Scientific Reports · doi:10.1038/srep27541 · Cited by 33
Central effects of humanin on hepatic triglyceride secretion
Gong, Z., Su, K., Cui, L., Tas, E., Zhang, T., Dong, H. H., Yakar, S., & Muzumdar, R. H. (2015) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00043.2015 · Cited by 34
CNS Regulation of Glucose Homeostasis: Role of the Leptin-Melanocortin System
da Silva, A. A., do Carmo, J. M., & Hall, J. E. (2020) · Current Diabetes Reports · doi:10.1007/s11892-020-01311-1 · Cited by 30
Subdiaphragmatic Vagotomy With Pyloroplasty Ameliorates the Obesity Caused by Genetic Deletion of the Melanocortin 4 Receptor in the Mouse
Dezfuli, G., Gillis, R. A., Tatge, J. E., Duncan, K. R., Dretchen, K. L., Jackson, P. G., Verbalis, J. G., & Sahibzada, N. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00104 · Cited by 29
Leptin levels predict the development of insulin resistance in a sample of adult men–The Olivetti Heart Study
D’Elia, L., Strazzullo, P., Iacone, R., Russo, O., & Galletti, F. (2018) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2018.10.003 · Cited by 29
Adipose Tissue and Biological Factors. Possible Link between Lymphatic System Dysfunction and Obesity
Antoniak-Pietrynczak, K., Hansdorfer-Korzon, R., Mrugacz, M., & Zorena, K. (2021) · Metabolites · doi:10.3390/metabo11090617 · Cited by 28
The hypothalamus as a key regulator of glucose homeostasis: emerging roles of the brain renin-angiotensin system
Pan, S., Worker, C. J., & Feng, Y. (2023) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00533.2022 · Cited by 31
Whole-Body and Hepatic Insulin Resistance in Obese Children
Ibarra‐Reynoso, L. D. R., Pisarchyk, L., Pérez-Luque, E. L., Garay‐Sevilla, M. E., & Malacara, J. M. (2014) · PLoS ONE · doi:10.1371/journal.pone.0113576 · Cited by 27
Hepatic leptin signalling and subdiaphragmatic vagal efferents are not required for leptin-induced increases of plasma IGF binding protein-2 (IGFBP-2) in ob/ob mice
Levi, J., Huynh, F. K., Denroche, H. C., Neumann, U. H., Glavas, M. M., Covey, S. D., & Kieffer, T. J. (2011) · Diabetologia · doi:10.1007/s00125-011-2426-8 · Cited by 26
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
Leptin Is Required for Glucose Homeostasis after Roux-en-Y Gastric Bypass in Mice
Mokadem, M., Zechner, J. F., Uchida, A., & Aguirre, V. (2015) · PLoS ONE · doi:10.1371/journal.pone.0139960 · Cited by 25
Ablation of LMO4 in glutamatergic neurons impairs leptin control of fat metabolism
Zhou, X. C., Gomez-Smith, M., Qin, Z., Duquette, P. M., Cárdenas‐Blanco, A., Rai, P. S., Harper, M., Tsai, E. C., Anisman, H., & Chen, H. (2011) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-011-0794-3 · Cited by 26
Hormonal Control of Metabolism by the Hypothalamus-Autonomic Nervous System-Liver Axis
Kalsbeek, A., Bruinstroop, E., Yi, C., Klieverik, L. P., Liu, J., & Fliers, E. (2014) · Frontiers of hormone research · doi:10.1159/000358312 · Cited by 25
Living without insulin: the role of leptin signaling in the hypothalamus
Fujikawa, T., & Coppari, R. (2015) · Frontiers in Neuroscience · doi:10.3389/fnins.2015.00108 · Cited by 24
Leptin therapy in type 2 diabetes
Cummings, B. P. (2012) · Diabetes Obesity and Metabolism · doi:10.1111/dom.12048 · Cited by 24
Leptin deficiency affects glucose homeostasis and results in adiposity in zebrafish
He, J., Ding, Y., Nowik, N., Jager, C., Eeza, M. N. H., Alia, A., Baelde, H. J., & Spaink, H. P. (2021) · Journal of Endocrinology · doi:10.1530/joe-20-0437 · Cited by 23
Brain-mediated antidiabetic, anorexic, and cardiovascular actions of leptin require melanocortin-4 receptor signaling
da Silva, A. A., Spradley, F. T., Granger, J. P., Hall, J. E., & do Carmo, J. M. (2015) · Journal of Neurophysiology · doi:10.1152/jn.00911.2014 · Cited by 21
Autonomic Regulation of Hepatic Glucose Production
Bisschop, P. H. L. T., Fliers, E., & Kalsbeek, A. (2014) · Comprehensive physiology · doi:10.1002/cphy.c140009 · Cited by 25

Authors: German, J., Kim, F., Schwartz, G. J., Havel, P. J., Rhodes, C. J., Schwartz, M. W., & Morton, G. J.
Affiliations: University of Washington (US)
Albert Einstein College of Medicine (US)
University of California, Davis (US)
University of Chicago (US)
Corresponding author: Morton, Gregory J.
ORCID: Kim, Francis
Schwartz, Gary J.
Havel, Peter J.
Rhodes, Christopher J.
Schwartz, Michael W.
Morton, Gregory J.
Venue: Endocrinology
Publisher: The Endocrine Society
Published: 2009-07-02
Volume: 150
Issue: 10
Pages: 4502-4511
ISSN: 0013-7227 (ISSN-L)
1945-7170
DOI: 10.1210/en.2009-0445
PMC: PMC2754686
OpenAlex: W2067242542
Cited by: 164
References: 49
Citations by year: 2026: 2 · 2025: 4 · 2024: 3 · 2023: 6 · 2022: 7 · 2021: 4 · 2020: 4 · 2019: 2 · 2018: 6 · 2017: 8 · 2016: 8 · 2015: 22 · 2014: 8 · 2013: 17 · 2012: 18
FWCI: 9.18
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Endocrinology (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
eScholarship (California Digital Library) (submittedVersion)
Funders: National Institutes of Health (1u24dk076126-01, 5r01dk073878-05)
National Institute of Diabetes and Digestive and Kidney Diseases (DK-083042, U24-DK076126, DK068384, DK 035816, DK052989, DK 047208, R01DK052989, DK-020541, R01DK047208, P01DK068384, R01DK055267, R01-DK-073878, DK-073878, P60DK020541, P30DK035816, P30DK017047, P30DK020541, R01DK083042)
Topics: Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
Keywords: leptin signaling, hypothalamus, hepatic insulin sensitivity, vagus nerve, hepatic vagotomy, arcuate nucleus, leptin receptor, hepatic glucose production, gluconeogenesis, glucose-6-phosphatase, PI3K/Akt signaling, IRS-1, energy balance, glucose metabolism
MeSH terms: Animals, Arcuate Nucleus of Hypothalamus, Gluconeogenesis, Glucose, Insulin, Insulin Resistance, Liver, Male, Obesity, Vagotomy, Vagus Nerve, Glucose Clamp Technique, Genetic Therapy, Signal Transduction, Gene Expression, Genes, Reporter, Phosphatidylinositol 3-Kinases, Rats, Receptors, Leptin

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

Hypothalamic Leptin Signaling Regulates Hepatic Insulin Sensitivity via a Neurocircuit Involving the Vagus Nerve

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