Diet-Induced Obesity Causes Severe but Reversible Leptin Resistance in Arcuate Melanocortin Neurons
Open accessAbstract
Despite high leptin levels, most obese humans and rodents lack responsiveness to its appetite-suppressing effects. We demonstrate that leptin modulates NPY/AgRP and alpha-MSH secretion from the ARH of lean mice. High-fat diet-induced obese (DIO) mice have normal ObRb levels and increased SOCS-3 levels, but leptin fails to modulate peptide secretion and any element of the leptin signaling cascade. Despite this leptin resistance, the melanocortin system downstream of the ARH in DIO mice is over-responsive to melanocortin agonists, probably due to upregulation of MC4R. Lastly, we show that by decreasing the fat content of the mouse's diet, leptin responsiveness of NPY/AgRP and POMC neurons recovered simultaneously, with mice regaining normal leptin sensitivity and glycemic control. These results highlight the physiological importance of leptin sensing in the melanocortin circuits and show that their loss of leptin sensing likely contributes to the pathology of leptin resistance.
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?
In one study, only about half of male C57/BL6J mice became obese on a palatable high-fat diet, but reward functions were not assessed.
“In one such study, only about half of male C57/BL6J mice became obese on a palatable high-fat diet ([55](#B55)), but reward functions were not assessed.”
From Food reward, hyperphagia, and obesity (2011) · cites this paper as [55]
The ability of leptin to activate pSTAT3 is impaired in rodent models of diet-induced obesity, specifically in the hypothalamic arcuate nucleus.
“the ability of leptin to activate pSTAT3, a marker of leptin signaling (49), is impaired in rodent models of DIO, specifically in the hypothalamic ARC (56, 124).”
From Leptin and the Central Nervous System Control of Glucose Metabolism (2011) · cites this paper as [56]
Cites
The Mouse Brain in Stereotaxic Coordinates
Paxinos, G. (2001) · Cited by 12,859 · see citing works
Serum Immunoreactive-Leptin Concentrations in Normal-Weight and Obese Humans
Considine, R. V., Sinha, M. K., Heiman, M. L., Kriauciunas, A., Stephens, T. W., Nyce, M. R., Ohannesian, J. P., Marco, C. C., McKee, L. J., Bauer, T. L., et al. (1996) · New England Journal of Medicine · doi:10.1056/nejm199602013340503 · Cited by 6,326 · see citing works
Weight-Reducing Effects of the Plasma Protein Encoded by the <i>obese</i> Gene
Halaas, J. L., Gajiwala, K. S., Maffei, M., Cohen, S. L., Chait, B. T., Rabinowitz, D., Lallone, R. L., Burley, S. K., & Friedman, J. M. (1995) · Science · doi:10.1126/science.7624777 · Cited by 4,451 · see citing works
Obesity and the regulation of energy balance
Spiegelman, B. M., & Flier, J. S. (2001) · Cell · doi:10.1016/s0092-8674(01)00240-9 · Cited by 2,398 · see citing works
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 · see citing works
Self-citationChen, H., Charlat, O., Tartaglia, L. A., Woolf, E. A., Weng, X., Ellis, S. J., Lakey, N. D., Culpepper, J., More, K. J., Breitbart, R. E., et al. (1996) · Cell · doi:10.1016/s0092-8674(00)81294-5 · Cited by 2,214 · see citing works
Anatomy and regulation of the central melanocortin system
Cone, R. D. (2005) · Nature Neuroscience · doi:10.1038/nn1455 · Cited by 1,583 · 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
Identification of SOCS-3 as a Potential Mediator of Central Leptin Resistance
Bjørbæk, C., Elmquist, J. K., Frantz, J. D., Shoelson, S. E., & Flier, J. S. (1998) · Molecular Cell · doi:10.1016/s1097-2765(00)80062-3 · Cited by 1,014 · see citing works
STAT3 signalling is required for leptin regulation of energy balance but not reproduction
Bates, S. H., Stearns, W. H., Dundon, T. A., Schubert, M., Tso, A. W. K., Wang, Y., Banks, A. S., Lavery, H. J., Haq, A. K., Maratos-Flier, E., et al. (2003) · Nature · doi:10.1038/nature01388 · Cited by 1,010 · cited 2× · see citing works
“It is believed to be essential for mediating leptin’s effects on homeostatic energy regulation (Bates et al., 2003).”
BackgroundLeptin receptor signaling in POMC neurons is required for normal body weight homeostasis
Balthasar, N., Coppari, R., McMinn, J., Liu, S. M., Lee, C. E., Tang, V., Kenny, C. D., McGovern, R. A., Chua, S. C., Elmquist, J. K., et al. (2004) · Neuron · doi:10.1016/j.neuron.2004.06.004 · Cited by 935 · see citing works
Leptin Differentially Regulates NPY and POMC Neurons Projecting to the Lateral Hypothalamic Area
Elias, C. F., Aschkenasi, C., Lee, C., Kelly, J., Ahima, R. S., Bjorbæk, C., Flier, J. S., Saper, C. B., & Elmquist, J. K. (1999) · Neuron · doi:10.1016/s0896-6273(01)80035-0 · Cited by 924 · 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
Leptin Increases Hypothalamic Pro-opiomelanocortin mRNA Expression in the Rostral Arcuate Nucleus
Schwartz, M. W., Seeley, R. J., Woods, S. C., Weigle, D. S., Campfield, L. A., Burn, P., & Baskin, D. G. (1997) · Diabetes · doi:10.2337/diab.46.12.2119 · Cited by 879 · 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
Mori, H., Hanada, R., Hanada, T., Aki, D., Mashima, R., Nishinakamura, H., Torisu, T., Chien, K. R., Yasukawa, H., & Yoshimura, A. (2004) · Nature Medicine · doi:10.1038/nm1071 · Cited by 651 · see citing works
Health consequences of obesity in the elderly: a review of four unresolved questions
Zamboni, M. M., Mazzali, G., Zoico, E., Harris, T. B., Meigs, J. B., Francesco, V. D., Fantin, F., Bissoli, L., & Bosello, O. (2005) · International Journal of Obesity · doi:10.1038/sj.ijo.0803005 · Cited by 649 · see citing works
Rosenbaum, M. (2005) · Journal of Clinical Investigation · doi:10.1172/jci25977 · Cited by 575 · see citing works
Development of high fat diet-induced obesity and leptin resistance in C57Bl/6J mice
Lin, S., Thomas, T. C., Storlien, L., & Huang, X. (2000) · International Journal of Obesity · doi:10.1038/sj.ijo.0801209 · Cited by 570 · see citing works
Molecular and anatomical determinants of central leptin resistance
Münzberg, H., & Myers, M. G. (2005) · Nature Neuroscience · doi:10.1038/nn1454 · Cited by 550 · see citing works
Selective breeding for diet-induced obesity and resistance in Sprague-Dawley rats
Levin, B. E., Dunn-Meynell, A. A., Balkan, B., & Keesey, R. E. (1997) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1997.273.2.r725 · Cited by 536 · see citing works
Howard, J. K., Cave, B. J., Oksanen, L. J., Tzameli, I., Bjørbæk, C., & Flier, J. S. (2004) · Nature Medicine · doi:10.1038/nm1072 · Cited by 490 · see citing works
Coppari, 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
Orexigen-sensitive NPY/AgRP pacemaker neurons in the hypothalamic arcuate nucleus
van den Top, M., Lee, K., Whyment, A. D., Blanks, A. M., & Spanswick, D. (2004) · Nature Neuroscience · doi:10.1038/nn1226 · Cited by 435 · see citing works
de Luca, C., Kowalski, T. J., Zhang, Y., Elmquist, J. K., Lee, C., Kilimann, M. W., Ludwig, T. E., Liu, S.-M., & Chua, S. C. (2005) · Journal of Clinical Investigation · doi:10.1172/jci24059 · Cited by 383 · see citing works
Liu, H., Kishi, T., Roseberry, A. G., Cai, X., Lee, C. E., Montez, J. M., Friedman, J. M., & Elmquist, J. K. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-18-07143.2003 · Cited by 375 · see citing works
Changes in Gene Expression Foreshadow Diet-Induced Obesity in Genetically Identical Mice
Koza, R. A., Nikonova, L. V., Hogan, J. C., Rim, J., Mendoza, T. M., Faulk, C. D., Skaf, J. S., & Kozak, L. P. (2006) · PLoS Genetics · doi:10.1371/journal.pgen.0020081 · Cited by 344 · see citing works
Heterogeneous metabolic adaptation of C57BL/6J mice to high-fat diet
Burcelin, R., Crivelli, V., Dacosta, A., Roy-Tirelli, A., & Thorens, B. (2002) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00332.2001 · Cited by 292 · see citing works
Wang, H., Storlien, L. H., & Huang, X. (2002) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00230.2001 · Cited by 280 · see citing works
The role of leptin in leptin resistance and obesity
Zhang, Y., & Scarpace, P. J. (2006) · Physiology & Behavior · doi:10.1016/j.physbeh.2006.05.038 · Cited by 253 · see citing works
Kievit, P., Howard, J. K., Badman, M. K., Balthasar, N., Coppari, R., Mori, H., Lee, C. E., Elmquist, J. K., Yoshimura, A., & Flier, J. S. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.06.010 · Cited by 245 · see citing works
Monitoring of stored and available fuel by the CNS: implications for obesity
Seeley, R. J., & Woods, S. C. (2003) · Nature reviews. Neuroscience · doi:10.1038/nrn1245 · Cited by 228 · see citing works
Rodent obesity models: An overview
Tschöp, M. H., & Heiman, M. L. (2001) · Experimental and Clinical Endocrinology & Diabetes · doi:10.1055/s-2001-17297 · Cited by 220 · see citing works
Leptin Regulates Prothyrotropin-releasing Hormone Biosynthesis
Nillni, E. A., Vaslet, C. A., Harris, M., Hollenberg, A. N., Bjørbæk, C., & Flier, J. S. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m003549200 · Cited by 208 · see citing works
Self-citationPierroz, D. D., Ziotopoulou, M., Ungsunan, L., Moschos, S. J., Flier, J. S., & Mantzoros, C. S. (2002) · Diabetes · doi:10.2337/diabetes.51.5.1337 · Cited by 208 · see citing works
Physiological and Anatomical Circuitry between Agouti-Related Protein and Leptin Signaling
Wilson, B. D., Bagnol, D., Kaelin, C. B., Ollmann, M. M., Gantz, I., Watson, S. J., & Barsh, G. S. (1999) · Endocrinology · doi:10.1210/endo.140.5.6728 · Cited by 203 · see citing works
Reversal of diet-induced obesity and diabetes in C57BL/6J mice
Parekh, P. I., Petro, A. E., Tiller, J. M., Feinglos, M. N., & Surwit, R. S. (1998) · Metabolism · doi:10.1016/s0026-0495(98)90283-9 · Cited by 197 · see citing works
The role of leptin in leptin resistance and obesity
Enriori, P. J., Evans, A. E., Sinnayah, P., & Cowley, M. A. (2006) · Obesity · Cited by 197 · see citing works
Self-citationLeptin receptor, NPY, POMC mRNA expression in the diet-induced obese mouse brain
Lin, S., Storlien, L. H., & Huang, X. (2000) · Brain Research · doi:10.1016/s0006-8993(00)02580-4 · Cited by 194 · see citing works
Huang, X., Han, M., South, T., & Storlien, L. H. (2003) · Brain Research · doi:10.1016/j.brainres.2003.08.019 · Cited by 113 · see citing works
Commins, S. P., Marsh, D. J., Thomas, S. A., Watson, P. M., Padgett, M. A., Palmiter, R., & Gettys, T. W. (1999) · Endocrinology · doi:10.1210/endo.140.10.7043 · Cited by 107 · see citing works
Banks, W. A. (2003) · Current Pharmaceutical Design · doi:10.2174/1381612033455350 · Cited by 101 · see citing works
Irani, B. G., Dunn-Meynell, A. A., & Levin, B. E. (2006) · Endocrinology · doi:10.1210/en.2006-1126 · Cited by 99 · see citing works
Effects of fasting, leptin, and insulin on AGRP and POMC peptide release in the hypothalamus
Breen, T. L., Conwell, I. M., & Wardlaw, S. L. (2004) · Brain Research · doi:10.1016/j.brainres.2004.11.008 · Cited by 78 · see citing works
Li, J.-Y., Finniss, S., Yang, Y.-K., Zeng, Q., Qu, S.-Y., Barsh, G. S., Dickinson, C. J., & Gantz, I. (2000) · Endocrinology · doi:10.1210/endo.141.6.7462 · Cited by 70 · see citing works
Grove, K. L., Brogan, R. S., & Smith, M. S. (2001) · Endocrinology · doi:10.1210/endo.142.11.8498 · Cited by 65 · see citing works
Self-citationPritchard, L. E., Oliver, R. L., McLoughlin, J. D., Birtles, S., Lawrence, C. B., Turnbull, A. V., & White, A. E. (2003) · Endocrinology · doi:10.1210/en.2002-220866 · Cited by 65 · see citing works
盛, 裕. (2006) · Medical Entomology and Zoology · Cited by 58 · see citing works
Li, G., Zhang, Y., Wilsey, J., & Scarpace, P. (2004) · Journal of Endocrinology · doi:10.1677/joe.0.1820123 · Cited by 56 · see citing works
Divergent Effects of Leptin in Mice Susceptible or Resistant to Obesity
Takahashi, N., Patel, H. R., Qi, Y., Dushay, J. R., & Ahima, R. S. (2002) · Hormone and Metabolic Research · doi:10.1055/s-2002-38251 · Cited by 52 · see citing works
Interaction of genetic and environmental programming of the leptin system and of obesity disposition
Schmidt, I., Schoelch, C., Ziska, T., et al. (2000) · Physiological Genomics · doi:10.1152/physiolgenomics.2000.3.2.113 · Cited by 52 · see citing works
Sahu, A., Nguyen, L., & O'Doherty, R. M. (2002) · Journal of Neuroendocrinology · doi:10.1046/j.1365-2826.2002.00856.x · Cited by 44 · see citing works
Regulation of neuropeptide Y release from hypothalamic slices by melanocortin-4 agonists and leptin
King, P., Widdowson, P. S., Doods, H. N., & Williams, G. (2000) · Peptides · doi:10.1016/s0196-9781(99)00168-0 · Cited by 27 · see citing works
Elmquist (1998) · doi:10.1002/(sici)1096-9861(19980615)395:4
Flagged first, then by citations
Cited by
Sorted by citations
Milanski, M., Degasperi, G., Coope, A., Morari, J., Denis, R., Cintra, D. E., Tsukumo, D. M. L., Anhe, G., Amaral, M. E., Takahashi, H. K., et al. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.2760-08.2009 · Cited by 1,125 · see citing works
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 · see citing works
Self-citationGlucose sensing by POMC neurons regulates glucose homeostasis and is impaired in obesity
Parton, L. E., Ye, C. P., Coppari, R., Enriori, P. J., Choi, B., Zhang, C.-Y., Xu, C., Vianna, C. R., Balthasar, N., Lee, C. E., et al. (2007) · Nature · doi:10.1038/nature06098 · Cited by 700 · see citing works
Self-citationLeptin and the endocrine control of energy balance
Friedman, J. M. (2019) · Nature Metabolism · doi:10.1038/s42255-019-0095-y · Cited by 661 · 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
“Consistent with this observation, the ability of leptin to activate pSTAT3, a marker of leptin signaling (49), is impaired in rodent models of DIO, specifically in the hypothalamic ARC (56, 124).”
BackgroundDiet-Induced Obesity Causes Ghrelin Resistance in Arcuate NPY/AgRP Neurons
Briggs, D. I., Enriori, P. J., Lemus, M. B., Cowley, M. A., & Andrews, Z. B. (2010) · Endocrinology · doi:10.1210/en.2010-0556 · Cited by 320 · see citing works
Self-citationEffects of glucagon-like peptide 1 on appetite and body weight: focus on the CNS
van Bloemendaal, L., ten Kulve, J. S., la Fleur, S. E., Ijzerman, R. G., & Diamant, M. (2014) · Journal of Endocrinology · doi:10.1530/joe-13-0414 · Cited by 312 · see citing works
Hyperleptinemia Is Required for the Development of Leptin Resistance
Knight, Z. A., Hannan, K. S., Greenberg, M. L., & Friedman, J. M. (2010) · PLoS ONE · doi:10.1371/journal.pone.0011376 · Cited by 311 · see citing works
Food reward, hyperphagia, and obesity
Berthoud, H.-R., Lenard, N. R., & Shin, A. C. (2011) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00028.2011 · Cited by 275 · see citing works
Neuronal control of peripheral insulin sensitivity and glucose metabolism
Ruud, J., Steculorum, S. M., & Brüning, J. C. (2017) · Nature Communications · doi:10.1038/ncomms15259 · Cited by 245 · see citing works
Peripheral oxytocin suppresses food intake and causes weight loss in diet-induced obese rats
Morton, G. J., Thatcher, B. S., Reidelberger, R. D., Ogimoto, K., Wolden-Hanson, T., Baskin, D. G., Schwartz, M. W., & Blevins, J. E. (2012) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00296.2011 · Cited by 213 · see citing works
Baver, S. B., Hope, K., Guyot, S., Bjørbaek, C., Kaczorowski, C., & O'Connell, K. M. S. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.4861-12.2014 · Cited by 203 · see citing works
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 · see citing works
Prior, L. J., Eikelis, N., Armitage, J. A., Davern, P. J., Burke, S. L., Montani, J.-P., Barzel, B., & Head, G. A. (2010) · Hypertension · doi:10.1161/hypertensionaha.109.141119 · Cited by 157 · see citing works
Bouret, S., Levin, B. E., & Ozanne, S. E. (2015) · Physiological Reviews · doi:10.1152/physrev.00007.2014 · Cited by 157 · see citing works
Synaptic plasticity in neuronal circuits regulating energy balance
Zeltser, L. M., Seeley, R. J., & Tschöp, M. H. (2012) · Nature Neuroscience · doi:10.1038/nn.3219 · Cited by 147 · see citing works
Hypothalamic inflammation and energy homeostasis: Resolving the paradox
Thaler, J. P., Choi, S. J., Schwartz, M. W., & Wisse, B. E. (2010) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2009.10.002 · Cited by 144 · see citing works
Putting desire on a budget: dopamine and energy expenditure, reconciling reward and resources
Beeler, J. A., Frazier, C. R. M., & Zhuang, X. (2012) · Frontiers in Integrative Neuroscience · doi:10.3389/fnint.2012.00049 · Cited by 136 · see citing works
Estradiol prevents fat accumulation and overcomes leptin resistance in female high-fat diet mice
Litwak, S. A., Wilson, J. L., Chen, W., Garcia-Rudaz, C., Khaksari, M., Cowley, M. A., & Enriori, P. J. (2014) · Endocrinology · doi:10.1210/en.2014-1342 · Cited by 115 · see citing works
Self-citationEarly-Life Exposure to Testosterone Programs the Hypothalamic Melanocortin System
Nohara, K., Zhang, Y., Waraich, R. S., Laque, A., Tiano, J. P., Tong, J., Münzberg, H., & Mauvais-Jarvis, F. (2011) · Endocrinology · doi:10.1210/en.2010-1288 · Cited by 120 · see citing works
Leptin resistance is a secondary consequence of the obesity in ciliopathy mutant mice
Berbari, N. F., Pasek, R. C., Malarkey, E. B., Yazdi, S. M. Z., McNair, A. D., Lewis, W. R., Nagy, T. R., Kesterson, R. A., & Yoder, B. K. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1210192110 · Cited by 98 · see citing works
Mechanisms mediating renal sympathetic activation to leptin in obesity
Morgan, D. A., Thedens, D. R., Weiss, R., & Rahmouni, K. (2008) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.90324.2008 · Cited by 89 · see citing works
Activation of temperature-sensitive TRPV1-like receptors in ARC POMC neurons reduces food intake
Jeong, J. H., Lee, D. K., Liu, S.-M., Chua, S. C., Schwartz, G. J., & Jo, Y.-H. (2018) · PLOS Biology · doi:10.1371/journal.pbio.2004399 · Cited by 89 · see citing works
Perello, M., Çakir, I., Cyr, N. E., Romero, A., Stuart, R. C., Chiappini, F., Hollenberg, A. N., & Nillni, E. A. (2010) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00448.2010 · Cited by 80 · see citing works
Tanaka, T., Masuzaki, H., Yasue, S., Ebihara, K., Shiuchi, T., Ishii, T., Arai, N., Hirata, M., Yamamoto, H., Hayashi, T., et al. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.04.004 · Cited by 62 · see citing works
Yosten, G. L. C., & Samson, W. K. (2014) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00396.2013 · Cited by 48 · see citing works
Struik, N. A., Brinkworth, G. D., Thompson, C. H., Buckley, J. D., Wittert, G., & Luscombe-Marsh, N. D. (2020) · The Journal of Nutrition · doi:10.1093/jn/nxz344 · Cited by 19 · see citing works
An overview on how components of the melanocortin system respond to different high energy diets
van den Heuvel, J. K., van Rozen, A. J., Adan, R. A. H., & la Fleur, S. E. (2011) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2010.12.019 · Cited by 17 · see citing works
- Authors
- Enriori, P. J., Evans, A. E., Sinnayah, P., Jobst, E. E., Tonelli-Lemos, L., Billes, S. K., Glavas, M. M., Grayson, B. E., Perello, M., Nillni, E. A., Grove, K. L., & Cowley, M. A.
- Affiliations
- Oregon National Primate Research Center (US)
- Brown University (US)
- Corresponding author
- Cowley, Michael A.
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2007-03
- Volume
- 5
- Issue
- 3
- Pages
- 181-194
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W2169342042
- Cited by
- 552
- References
- 54
- Citations by year
- 2026: 9 · 2025: 18 · 2024: 7 · 2023: 20 · 2022: 28 · 2021: 32 · 2020: 34 · 2019: 27 · 2018: 33 · 2017: 30 · 2016: 28 · 2015: 36 · 2014: 48 · 2013: 34 · 2012: 39
- FWCI
- 12.64
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Victoria University Research Repository (Victoria University) (submittedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (DK 62202, RR 0163, R01 NS 045231, DK 60685 NIH RR 0163)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK 58148)
- 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 resistance, diet-induced obesity, arcuate nucleus, melanocortin system, NPY/AgRP neurons, POMC neurons, alpha-melanocyte-stimulating hormone, SOCS3, melanocortin-4 receptor, leptin signaling, high-fat diet, obesity reversal, appetite regulation, glycemic control
- MeSH terms
- alpha-MSH, Animals, Arcuate Nucleus of Hypothalamus, Body Composition, Diet, Dietary Fats, Dose-Response Relationship, Drug, Gene Expression Regulation, Hypothalamus, Male, Mice, Inbred C57BL, Neurons, Neuropeptide Y, Obesity, Pro-Opiomelanocortin, RNA, Messenger, Signal Transduction, Weight Loss, Leptin, Intercellular Signaling Peptides and Proteins, Mice, Melanocortins, Agouti-Related Protein, In Vitro Techniques
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
