Leptin regulates insulin sensitivity via phosphatidylinositol-3-OH kinase signaling in mediobasal hypothalamic neurons
Open accessAbstract
To investigate whether phosphatidylinositol-3 kinase (PI3K) signaling mediates the metabolic effects of hypothalamic leptin action, adenoviral gene therapy was used to direct expression of leptin receptors to the area of the hypothalamic arcuate nucleus (ARC). This intervention markedly improved insulin sensitivity in genetically obese, leptin-receptor-deficient Koletsky (fa(k)/fa(k)) rats via a mechanism that was not dependent on reduced food intake but was attenuated by approximately 44% by third-ventricular infusion of the PI3K inhibitor LY294002. Conversely, ARC-directed expression of a constitutively active mutant of protein kinase B (PKB/Akt, an enzyme activated by PI3K) mimicked the insulin-sensitizing effect of restored hypothalamic leptin signaling in these animals, despite having no effect on food intake or body weight. These findings suggest that hypothalamic leptin signaling is an important determinant of glucose metabolism and that the underlying neuronal mechanism involves PI3K.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
Caloric restriction is limited in its ability to improve insulin sensitivity and hyperglycemia in animals with genetic leptin or leptin-receptor deficiency.
“caloric restriction limited in its ability to improve insulin sensitivity and hyperglycemia in animals with genetic leptin or leptin-receptor deficiency (122, 203)”
From Leptin and the Central Nervous System Control of Glucose Metabolism (2011) · cites this paper as [122]
Leptin-stimulated PI3K signaling likely contributes to the mechanism by which leptin regulates glucose homeostasis.
“Leptin-stimulated PI3K signaling likely contributes to this mechanism, based on findings noted above (122)”
From Leptin and the Central Nervous System Control of Glucose Metabolism (2011) · cites this paper as [122]
Leptin signaling limited to the arcuate nucleus of the hypothalamus (ARC) is sufficient to promote normal insulin sensitivity.
“These findings suggest that leptin signaling limited to the ARC is sufficient to promote normal insulin sensitivity”
From Leptin and the Central Nervous System Control of Glucose Metabolism (2011) · cites this paper as [122]
The neuronal signaling mechanism underlying leptin's effect on insulin sensitivity involves PI3K.
“and that the neuronal signaling mechanism underlying this leptin effect involves PI3K.”
From Leptin and the Central Nervous System Control of Glucose Metabolism (2011) · cites this paper as [122]
Selective restoration of leptin receptor signaling to the ARC significantly improves peripheral insulin sensitivity via a mechanism not dependent on reduced food intake or body weight.
“we found that selective restoration of leptin receptor signaling to the ARC significantly improved peripheral insulin sensitivity via a mechanism that was not dependent on reduced food intake or body weight (122).”
From Leptin and the Central Nervous System Control of Glucose Metabolism (2011) · cites this paper as [122]
Hypothalamic effects of both insulin and leptin are dependent on neuronal phosphatidylinositol-3-OH kinase signaling.
“hypothalamic effects of both insulin and leptin are dependent on neuronal phosphatidylinositol-3-OH kinase signaling”
From Leptin Activates a Novel CNS Mechanism for Insulin-Independent Normalization of Severe Diabetic Hyperglycemia (2011) · cites this paper as [35]
A shared neuronal mechanism mediates effects of both insulin and leptin on glucose metabolism.
“suggesting a shared neuronal mechanism mediating effects of both hormones on glucose metabolism (34,35).”
From Leptin Activates a Novel CNS Mechanism for Insulin-Independent Normalization of Severe Diabetic Hyperglycemia (2011) · cites this paper as [35]
Cites
Positional cloning of the mouse obese gene and its human homologue
Zhang, Y., Proenca, R., Maffei, M., Barone, M., Leopold, L., & Friedman, J. M. (1994) · Nature · doi:10.1038/372425a0 · Cited by 13,419 · see citing works
Matsuda, M., & DeFronzo, R. A. (1999) · Diabetes Care · doi:10.2337/diacare.22.9.1462 · Cited by 5,621 · see citing works
Effects of the <i>obese</i> Gene Product on Body Weight Regulation in <i>ob</i> / <i>ob</i> Mice
Pelleymounter, M. A., Cullen, M. J., Baker, M. B., Hecht, R., Winters, D., Boone, T., & Collins, F. (1995) · Science · doi:10.1126/science.7624776 · Cited by 4,017 · see citing works
Identification of targets of leptin action in rat hypothalamus.
Schwartz, M. W., Seeley, R. J., Campfield, L. A., Burn, P., & Baskin, D. G. (1996) · Journal of Clinical Investigation · doi:10.1172/jci118891 · Cited by 1,475 · see citing works
Self-citationLeptin-Replacement Therapy for Lipodystrophy
Oral, E. A., Simha, V., Ruiz, E., Andewelt, A., Premkumar, A., Snell, P., Wagner, A. J., DePaoli, A. M., Reitman, M. L., Taylor, S. I., et al. (2002) · New England Journal of Medicine · doi:10.1056/nejmoa012437 · Cited by 1,247 · see citing works
Coexpression of Agrp and NPY in fasting-activated hypothalamic neurons
Hahn, T. M., Breininger, J. F., Baskin, D. G., & Schwartz, M. W. (1998) · Nature Neuroscience · doi:10.1038/1082 · Cited by 1,164 · see citing works
Self-citationLeptin 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 · see citing works
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 · see citing works
Self-citationHypothalamic 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 · see citing works
Two defects contribute to hypothalamic leptin resistance in mice with diet-induced obesity
El-Haschimi, K., Pierroz, D. D., Hileman, S. M., Bjørbæk, C., & Flier, J. S. (2000) · Journal of Clinical Investigation · doi:10.1172/jci9842 · Cited by 887 · see citing works
Broberger, C., Johansen, J., Johansson, C., Schalling, M., & Hökfelt, T. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.25.15043 · Cited by 798 · see citing works
Shimomura, I., Hammer, R. E., Richardson, J. A., Ikemoto, S., Bashmakov, Y., Goldstein, J. L., & Brown, M. S. (1998) · Genes & Development · doi:10.1101/gad.12.20.3182 · Cited by 790 · see citing works
Diet-induced obese mice develop peripheral, but not central, resistance to leptin.
van Heek, M., Compton, D. S., France, C. F., Tedesco, R. P., Fawzi, A. B., Graziano, M. P., Sybertz, E. J., Strader, C. D., & Davis, H. (1997) · Journal of Clinical Investigation · doi:10.1172/jci119171 · Cited by 752 · see citing works
Region-Specific Leptin Resistance within the Hypothalamus of Diet-Induced Obese Mice
Münzberg, H., Flier, J. S., & Bjørbæk, C. (2004) · Endocrinology · doi:10.1210/en.2004-0726 · Cited by 737 · see citing works
Modulation of Insulin Activities by Leptin
Cohen, B., Novick, D., & Rubinstein, M. (1996) · Science · doi:10.1126/science.274.5290.1185 · Cited by 716 · see citing works
Central Administration of Oleic Acid Inhibits Glucose Production and Food Intake
Obici, S., Feng, Z., Morgan, K., Stein, D., Karkanias, G., & Rossetti, L. (2002) · Diabetes · doi:10.2337/diabetes.51.2.271 · Cited by 654 · see citing works
Hypothalamic KATP channels control hepatic glucose production
Pocai, A., Lam, T. K. T., Gutierrez-Juarez, R., Obici, S., Schwartz, G. J., Bryan, J., Aguilar-Bryan, L., & Rossetti, L. (2005) · Nature · doi:10.1038/nature03439 · Cited by 645 · see citing works
Leptin inhibits hypothalamic neurons by activation of ATP-sensitive potassium channels
Spanswick, D., Smith, M. A., Groppi, V. E., Logan, S. D., & Ashford, M. L. J. (1997) · Nature · doi:10.1038/37379 · Cited by 628 · see citing works
Free Fatty Acids and Pathogenesis of Type 2 Diabetes Mellitus
Bergman, R. N., & Ader, M. (2000) · Trends in Endocrinology and Metabolism · doi:10.1016/s1043-2760(00)00323-4 · Cited by 622 · see citing works
Leptin reverses insulin resistance and hepatic steatosis in patients with severe lipodystrophy
Petersen (2002) · Journal of Clinical Investigation · doi:10.1172/jci0215001 · Cited by 622 · see citing works
Key enzyme in leptin-induced anorexia
Niswender, K. D., Morton, G. J., Stearns, W. H., Rhodes, C. J., Myers, M. G., & Schwartz, M. W. (2001) · Nature · doi:10.1038/35101657 · Cited by 585 · see citing works
Self-citationInhibition of hypothalamic neuropeptide Y gene expression by insulin.
Schwartz, M. W., Sipols, A. J., Marks, J. L., Sanacora, G., White, J. D., Scheurink, A., Kahn, S. E., Baskin, D. G., Woods, S. C., & Figlewicz, D. P. (1992) · Endocrinology · doi:10.1210/endo.130.6.1597158 · Cited by 555 · see citing works
Self-citationObici, S., Feng, Z., Arduini, A., Conti, R., & Rossetti, L. (2003) · Nature Medicine · doi:10.1038/nm873 · Cited by 548 · see citing works
Zarjevski, N., Cusin, I., Vettor, R., Rohner‐Jeanrenaud, F., & Jeanrenaud, B. (1993) · Endocrinology · doi:10.1210/endo.133.4.8404618 · Cited by 476 · see citing works
Insulin Activation of Phosphatidylinositol 3-Kinase in the Hypothalamic Arcuate Nucleus
Niswender, K. D., Morrison, C. D., Clegg, D. J., Olson, R., Baskin, D. G., Myers, M. G., Seeley, R. J., & Schwartz, M. W. (2003) · Diabetes · doi:10.2337/diabetes.52.2.227 · Cited by 476 · see citing works
Self-citationCoppari, R., Ichinose, M., Lee, C. E., Pullen, A. E., Kenny, C. D., McGovern, R. A., Tang, V., Liu, S. M., Ludwig, T., Chua, S. C., et al. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2004.12.004 · Cited by 457 · see citing works
PI3K integrates the action of insulin and leptin on hypothalamic neurons
Xu, A. W. (2005) · Journal of Clinical Investigation · doi:10.1172/jci200524301 · Cited by 420 · see citing works
Mizuno, T. M., & Mobbs, C. V. (1999) · Endocrinology · doi:10.1210/endo.140.2.6491 · Cited by 387 · see citing works
Baskin, D. G., Breininger, J. F., & Schwartz, M. W. (1999) · Diabetes · doi:10.2337/diabetes.48.4.828 · Cited by 351 · see citing works
Self-citationAdipocyte Signaling and Lipid Homeostasis
Yu, Y., & Ginsberg, H. N. (2005) · Circulation Research · doi:10.1161/01.res.0000165803.47776.38 · Cited by 328 · see citing works
Dysregulation of insulin receptor substrate 2 in β cells and brain causes obesity and diabetes
Lin, X., Taguchi, A., Park, S., Kushner, J. A., Li, F., Li, Y., & White, M. F. (2004) · Journal of Clinical Investigation · doi:10.1172/jci22217 · Cited by 313 · see citing works
Leptin action in the forebrain regulates the hindbrain response to satiety signals
Morton, G. J., Blevins, J. E., Williams, D. L., Niswender, K. D., Gelling, R. W., Rhodes, C. J., Baskin, D. G., & Schwartz, M. W. (2005) · Journal of Clinical Investigation · doi:10.1172/jci22081 · Cited by 253 · see citing works
Self-citationProtein Kinase B/Akt Prevents Fatty Acid-induced Apoptosis in Pancreatic β-Cells (INS-1)
Wrede, C. E., Dickson, L. M., Lingohr, M. K., Briaud, I., & Rhodes, C. J. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m208756200 · Cited by 246 · see citing works
Self-citationThe 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 241 · see citing works
Insulin receptor substrate 2 plays a crucial role in β cells and the hypothalamus
Kubota, N., Terauchi, Y., Tobe, K., Yano, W., Suzuki, R., Ueki, K., Takamoto, I., Satoh, H., Maki, T., Kubota, T., et al. (2004) · Journal of Clinical Investigation · doi:10.1172/jci21484 · Cited by 239 · see citing works
Widdowson, P. S., Upton, R., Buckingham, R. E., Arch, J. R. S., & Williams, G. (1997) · Diabetes · doi:10.2337/diab.46.11.1782 · Cited by 210 · see citing works
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 210 · see citing works
Self-citationSite and mechanism of leptin action in a rodent form of congenital lipodystrophy
Asilmaz, E., Cohen, P., Miyazaki, M., Dobrzyn, P., Ueki, K., Fayzikhodjaeva, G., Soukas, A. A., Kahn, C. R., Ntambi, J. M., Socci, N. D., et al. (2004) · Journal of Clinical Investigation · doi:10.1172/jci200419511 · Cited by 210 · see citing works
Nonsense mutation of leptin receptor in the obese spontaneously hypertensive Koletsky rat
Takaya, K., Ogawa, Y., Hiraoka, J., Hosoda, K., Yamori, Y., Nakao, K., & Koletsky, R. J. (1996) · Nature Genetics · doi:10.1038/ng1096-130 · Cited by 207 · see citing works
Site and mechanism of leptin action in a rodent form of congenital lipodystrophy
Asilmaz, E., Cohen, P., Miyazaki, M., Dobrzyń, P., Ueki, K., Fayzikhodjaeva, G., Soukas, A. A., Kahn, C. R., Ntambi, J. M., Socci, N. D., et al. (2004) · Journal of Clinical Investigation · doi:10.1172/jci19511 · Cited by 206 · see citing works
Berti, L., Kellerer, M., Capp, E., & H�ring, H. U. (1997) · Diabetologia · doi:10.1007/s001250050722 · Cited by 204 · see citing works
Obese spontaneously hypertensive rats—A model for study of atherosclerosis
Koletsky, S. (1973) · Experimental and Molecular Pathology · doi:10.1016/0014-4800(73)90040-3 · Cited by 197 · see citing works
Bates, S. H., Kulkarni, R. N., Seifert, M., & Myers, M. G. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2005.02.001 · Cited by 173 · see citing works
Morton, G. J., Niswender, K. D., Rhodes, C. J., Myers, M. G., Blevins, J. E., Baskin, D. G., & Schwartz, M. W. (2003) · Endocrinology · doi:10.1210/en.2002-0115 · Cited by 158 · see citing works
Mercer, J. G., Moar, K. M., Rayner, D. V., Trayhurn, P., & Hoggard, N. (1997) · FEBS Letters · doi:10.1016/s0014-5793(96)01525-6 · Cited by 129 · see citing works
van den Hoek, A. M., Voshol, P. J., Karnekamp, B. N., Buijs, R. M., Romijn, J. A., Havekes, L. M., & Pijl, H. (2004) · Diabetes · doi:10.2337/diabetes.53.10.2529 · Cited by 109 · see citing works
Zarjevski, N., Cusin, I., Vettor, R., Rohner‐Jeanrenaud, F., & Jeanrenaud, B. (1994) · Diabetes · doi:10.2337/diab.43.6.764 · Cited by 105 · see citing works
The influence of age and dietary conditions on diabetes in the db mouse
Wyse, B. M., & Dulin, W. E. (1970) · Diabetologia · doi:10.1007/bf01212237 · Cited by 83 · see citing works
Molecular Pathology in the Obese Spontaneous Hypertensive Koletsky Rat: A Model of Syndrome X
ERNSBERGER, P., KOLETSKY, R. J., & FRIEDMAN, J. E. (1999) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1999.tb07801.x · Cited by 69 · see citing works
Hepatic glycolytic and gluconeogenic enzymes of the obese-hyperglycemic mouse
Seidman, I., Horland, A. A., & Teebor, G. W. (1967) · Biochimica et Biophysica Acta (BBA) - Enzymology · doi:10.1016/0005-2744(67)90249-5 · Cited by 36 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Hypothalamic IKKβ/NF-κB and ER Stress Link Overnutrition to Energy Imbalance and Obesity
Zhang, X., Zhang, G., Zhang, H., Karin, M., Bai, H., & Cai, D. (2008) · Cell · doi:10.1016/j.cell.2008.07.043 · Cited by 1,350 · see citing works
Reward Processing by the Opioid System in the Brain
Le Merrer, J., Becker, J. A. J., Befort, K., & Kieffer, B. L. (2009) · Physiological Reviews · doi:10.1152/physrev.00005.2009 · Cited by 1,013 · see citing works
Neurobiology of food intake in health and disease
Morton, G. J., Meek, T. H., & Schwartz, M. W. (2014) · Nature Reviews Neuroscience · doi:10.1038/nrn3745 · Cited by 748 · see citing works
Self-citationAdipocytokines in Obesity and Metabolic Disease
Cao, H. (2014) · Journal of Endocrinology · doi:10.1530/joe-13-0339 · Cited by 705 · see citing works
Central nervous system control of metabolism
Myers, M. G., & Olson, D. P. (2012) · Nature · doi:10.1038/nature11705 · Cited by 399 · see citing works
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 · see citing works
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 · see citing works
Leptin and the Central Nervous System Control of Glucose Metabolism
Morton, G. J., & Schwartz, M. W. (2011) · Physiological Reviews · doi:10.1152/physrev.00007.2010 · Cited by 338 · see citing works
“Available evidence suggests that leptin signaling in forebrain areas such as the ARC activates a descending projection to the NTS, which in turn enhances the hindbrain response to input from CCK (122).”
BackgroundInfluentialSelf-citationAntidiabetic Effects of IGFBP2, a Leptin-Regulated Gene
Hedbacker, K., Birsoy, K., Wysocki, R. W., Asilmaz, E., Ahima, R. S., Farooqi, I. S., & Friedman, J. M. (2010) · Cell Metabolism · doi:10.1016/j.cmet.2009.11.007 · Cited by 280 · see citing works
Cytokines and abnormal glucose and lipid metabolism
Shi, J., Fan, J., Su, Q., & Yang, Z. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00703 · Cited by 282 · see citing works
Critical role of STAT3 in leptin's metabolic actions
Buettner, C., Pocai, A., Muse, E. D., Etgen, A. M., Myers, M. G., & Rossetti, L. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.04.014 · Cited by 228 · see citing works
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 · see citing works
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 · see citing works
Self-citationGenetic 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 · see citing works
German, J., Kim, F., Schwartz, G. J., Havel, P. J., Rhodes, C. J., Schwartz, M. W., & Morton, G. J. (2009) · Endocrinology · doi:10.1210/en.2009-0445 · Cited by 164 · see citing works
Self-citationLeptin 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 · see citing works
Self-citationObesity, leptin, and Alzheimer's disease
Lee, E. B. (2011) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2011.06274.x · Cited by 126 · see citing works
Neuronal regulation of homeostasis by nutrient sensing
Lam, T. K. T. (2010) · Nature Medicine · doi:10.1038/nm0410-392 · Cited by 125 · see citing works
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 · see citing works
SF-1 in the ventral medial hypothalamic nucleus: A key regulator of homeostasis
Kim, K. W., Sohn, J.-W., Kohno, D., Xu, Y., Williams, K., & Elmquist, J. K. (2011) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2010.11.019 · Cited by 76 · see citing works
Roman, E. A. F. R., Reis, D., Romanatto, T., Maimoni, D., Ferreira, E. A., Santos, G. A., Torsoni, A. S., Velloso, L. A., & Torsoni, M. A. (2010) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2009.08.007 · Cited by 71 · see citing works
Robertson, S., Ishida-Takahashi, R., Tawara, I., Hu, J., Patterson, C. M., Jones, J. C., Kulkarni, R. N., & Myers, M. G. (2010) · Diabetes · doi:10.2337/db09-1556 · Cited by 30 · see citing works
Innervation of skeletal muscle by leptin receptor-containing neurons
Babic, T., Purpera, M. N., Banfield, B. W., Berthoud, H.-R., & Morrison, C. D. (2010) · Brain Research · doi:10.1016/j.brainres.2010.05.042 · Cited by 16 · see citing works
Self-citationCentral Control of Glucose Homeostasis
Puglianiello, A., & Cianfarani, S. (2006) · The Review of Diabetic Studies · doi:10.1900/rds.2006.3.54 · Cited by 14 · see citing works
- Authors
- Morton, G. J., Gelling, R. W., Niswender, K. D., Morrison, C. D., Rhodes, C. J., & Schwartz, M. W.
- Affiliations
- University of Washington (US)
- Corresponding author
- Schwartz, Michael W.
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2005-12
- Volume
- 2
- Issue
- 6
- Pages
- 411-420
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W2128824908
- Semantic Scholar
- 8e27f314b254b88dc4e48cac09f343e75285f943
- Cited by
- 292
- References
- 50
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 4 · 2023: 8 · 2022: 10 · 2021: 8 · 2020: 8 · 2019: 14 · 2018: 11 · 2017: 10 · 2016: 17 · 2015: 16 · 2014: 18 · 2013: 20 · 2012: 23
- FWCI
- 5.74
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (2r01dk012829-36)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 12829, R01DK052989, DK68340, DK-52989)
- National Institute of Neurological Disorders and Stroke (NS-32273)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Keywords
- leptin, insulin sensitivity, phosphatidylinositol 3-kinase signaling, PI3K/Akt signaling, hypothalamic arcuate nucleus, mediobasal hypothalamus, leptin receptor, leptin receptor deficiency, obesity, glucose metabolism, LY294002, adenoviral gene therapy, Akt
- MeSH terms
- Adenoviridae, Animals, Blood Glucose, Body Weight, Chromones, Enzyme Inhibitors, Glucose, Hypothalamus, Insulin, Male, Morpholines, Neurons, Receptors, Cell Surface, Time Factors, Genetic Therapy, Signal Transduction, Phosphatidylinositol 3-Kinases, Leptin, Animals, Genetically Modified, Green Fluorescent Proteins, 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
