{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T02:11:42Z","timestamp":1792462302948,"version":"4.5.0"},"reference-count":40,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,12,15]],"date-time":"2017-12-15T00:00:00Z","timestamp":1513296000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,12,15]],"date-time":"2017-12-15T00:00:00Z","timestamp":1513296000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Regular overconsumption of sugar is associated with obesity and type-2 diabetes, but how genetic factors contribute to variable sugar preferences and intake levels remains mostly unclear. Here we provide evidence for the usefulness of a <jats:italic>Drosophila<\/jats:italic> larva model to investigate genetic influence on vulnerability to sugar overconsumption. Using genetic and RNA interference approaches, we show that the activity of the <jats:italic>Oamb<\/jats:italic> gene, which encodes a receptor for octopamine (OA, the invertebrate homologue of norepinephrine), plays a major role in controlled sugar consumption. Furthermore, Oamb appears to suppress sugar food intake in fed larvae in an acute manner, and neurons expressing this Oamb receptor do not overlap with neurons expressing Oct\u03b23R, another OA receptor previously implicated in hunger-driven exuberant sugar intake. Together, these results suggest that two separate sub-circuits, defined by Oamb and Oct\u03b23R respectively, co-regulate sugar consumption according to changes in energy needs. We propose that the noradrenergic-like system defines an ancient regulatory mechanism for prevention of sugar overload.<\/jats:p>","DOI":"10.1038\/s41598-017-17760-w","type":"journal-article","created":{"date-parts":[[2017,12,11]],"date-time":"2017-12-11T11:52:58Z","timestamp":1512993178000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Genetic and Neurobiological Analyses of the Noradrenergic-like System in Vulnerability to Sugar Overconsumption Using a Drosophila Model"],"prefix":"10.1038","volume":"7","author":[{"given":"Audrey","family":"Branch","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiwen","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,12,15]]},"reference":[{"key":"17760_CR1","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1038\/414799a","volume":"414","author":"AR Saltiel","year":"2001","unstructured":"Saltiel, A. R. & Kahn, C. R. Insulin signalling and the regulation of glucose and lipid metabolism. Nature \n                           414, 799\u2013806, https:\/\/doi.org\/10.1038\/414799a (2001).","journal-title":"Nature"},{"key":"17760_CR2","doi-asserted-by":"publisher","first-page":"1118","DOI":"10.1126\/science.1070058","volume":"296","author":"EJ Rulifson","year":"2002","unstructured":"Rulifson, E. J., Kim, S. K. & Nusse, R. Ablation of insulin-producing neurons in flies: growth and diabetic phenotypes. Science \n                           296, 1118\u20131120, https:\/\/doi.org\/10.1126\/science.1070058 (2002).","journal-title":"Science"},{"key":"17760_CR3","doi-asserted-by":"publisher","first-page":"e18292","DOI":"10.1371\/journal.pone.0018292","volume":"6","author":"Y Matsumoto","year":"2011","unstructured":"Matsumoto, Y., Sumiya, E., Sugita, T. & Sekimizu, K. An Invertebrate Hyperglycemic Model for the Identification of Anti-Diabetic Drugs. PLoS ONE \n                           6, e18292\u201318212, https:\/\/doi.org\/10.1371\/journal.pone.0018292 (2011).","journal-title":"PLoS ONE"},{"key":"17760_CR4","doi-asserted-by":"publisher","first-page":"2477","DOI":"10.2337\/dc10-1079","volume":"33","author":"VS Malik","year":"2010","unstructured":"Malik, V. S. et al. Sugar-Sweetened Beverages and Risk of Metabolic Syndrome and Type 2 Diabetes. Diabetes Care \n                           33, 2477\u20132483 (2010).","journal-title":"Diabetes Care"},{"key":"17760_CR5","doi-asserted-by":"publisher","first-page":"15431","DOI":"10.1073\/pnas.1308816110","volume":"110","author":"T Zhang","year":"2013","unstructured":"Zhang, T., Branch, A. & Shen, P. Octopamine-mediated circuit mechanism underlying controlled appetite for palatable food in Drosophila. Proceedings of the National Academy of Sciences of the United States of America \n                           110, 15431\u201315436, https:\/\/doi.org\/10.1073\/pnas.1308816110 (2013).","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"17760_CR6","doi-asserted-by":"publisher","first-page":"13289","DOI":"10.1073\/pnas.0501914102","volume":"102","author":"Q Wu","year":"2005","unstructured":"Wu, Q., Zhang, Y., Xu, J. & Shen, P. Regulation of hunger-driven behaviors by neural ribosomal S6 kinase in Drosophila. Proceedings of the National Academy of Sciences of the United States of America \n                           102, 13289\u201313294 (2005).","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"17760_CR7","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1111\/j.1471-4159.2005.03251.x","volume":"94","author":"B Maqueira","year":"2005","unstructured":"Maqueira, B., Chatwin, H. & Evans, P. D. Identification and characterization of a novel family of Drosophila beta-adrenergic-like octopamine G-protein coupled receptors. Journal of neurochemistry \n                           94, 547\u2013560, https:\/\/doi.org\/10.1111\/j.1471-4159.2005.03251.x (2005).","journal-title":"Journal of neurochemistry"},{"key":"17760_CR8","doi-asserted-by":"publisher","first-page":"3650","DOI":"10.1016\/0896-6273(90)90047-J","volume":"18","author":"K-A Han","year":"1998","unstructured":"Han, K.-A., Millar, N. S. & Davis, R. L. A Novel Octopamine Receptor with Preferential Expression inDrosophila Mushroom Bodies. The Journal of Neuroscience \n                           18, 3650\u20133658, https:\/\/doi.org\/10.1016\/0896-6273(90)90047-J (1998).","journal-title":"The Journal of Neuroscience"},{"key":"17760_CR9","doi-asserted-by":"publisher","first-page":"1466","DOI":"10.1016\/j.cub.2013.06.028","volume":"23","author":"D Mishra","year":"2013","unstructured":"Mishra, D. et al. The Molecular Basis of Sugar Sensing in Drosophila Larvae. Current Biology \n                           23, 1466\u20131471, https:\/\/doi.org\/10.1016\/j.cub.2013.06.028 (2013).","journal-title":"Current Biology"},{"key":"17760_CR10","doi-asserted-by":"publisher","first-page":"e1003710","DOI":"10.1371\/journal.pgen.1003710","volume":"9","author":"P Masek","year":"2013","unstructured":"Masek, P. & Keene, A. C. Drosophila fatty acid taste signals through the PLC pathway in sugar-sensing neurons. PLoS genetics \n                           9, e1003710, https:\/\/doi.org\/10.1371\/journal.pgen.1003710 (2013).","journal-title":"PLoS genetics"},{"key":"17760_CR11","doi-asserted-by":"publisher","DOI":"10.1038\/srep02120","volume":"3","author":"G Gasque","year":"2013","unstructured":"Gasque, G., Conway, S., Huang, J., Rao, Y. & Vosshall, L. B. Small molecule drug screening in Drosophila identifies the 5HT2A receptor as a feeding modulation target. Scientific Reports \n                           3, srep02120, https:\/\/doi.org\/10.1038\/srep02120 (2013).","journal-title":"Scientific Reports"},{"key":"17760_CR12","doi-asserted-by":"publisher","first-page":"820","DOI":"10.1016\/j.celrep.2013.02.003","volume":"3","author":"Y Wang","year":"2013","unstructured":"Wang, Y., Pu, Y. & Shen, P. Neuropeptide-gated perception of appetitive olfactory inputs in Drosophila larvae. Cell Reports \n                           3, 820\u2013830, https:\/\/doi.org\/10.1016\/j.celrep.2013.02.003 (2013).","journal-title":"Cell Reports"},{"key":"17760_CR13","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1016\/j.physbeh.2006.05.033","volume":"88","author":"DR Reed","year":"2006","unstructured":"Reed, D. R., Tanaka, T. & McDaniel, A. H. Diverse tastes: Genetics of sweet and bitter perception. Physiology & behavior \n                           88, 215\u2013226, https:\/\/doi.org\/10.1016\/j.physbeh.2006.05.033 (2006).","journal-title":"Physiology & behavior"},{"key":"17760_CR14","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1023\/A:1025692031673","volume":"27","author":"DR Reed","year":"1997","unstructured":"Reed, D. R., Bachmanov, A. A., Beauchamp, G. K., Tordoff, M. G. & Price, R. A. Heritable Variation in Food Preferences and Their Contribution to Obesity. Behavior genetics \n                           27, 373\u2013387 (1997).","journal-title":"Behavior genetics"},{"key":"17760_CR15","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1101\/lm.71604","volume":"11","author":"R Scheiner","year":"2004","unstructured":"Scheiner, R., Sokolowski, M. B. & Erber, J. Activity of cGMP-Dependent Protein Kinase (PKG) Affects Sucrose Responsiveness and Habituation in Drosophila melanogaster. Learning & Memory \n                           11, 303\u2013311, https:\/\/doi.org\/10.1101\/lm.71604 (2004).","journal-title":"Learning & Memory"},{"key":"17760_CR16","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1016\/S0166-4328(02)00205-X","volume":"136","author":"R Scheiner","year":"2002","unstructured":"Scheiner, R., Pluckhahn, S., Oney, B., Blenau, W. & Erber, J. Behavioural pharmacology of octopamine, tyramine and dopamine in honey bees. Behav Brain Res \n                           136, 545\u2013553 (2002).","journal-title":"Behav Brain Res"},{"key":"17760_CR17","doi-asserted-by":"publisher","first-page":"1703","DOI":"10.1073\/pnas.0610506104","volume":"104","author":"AB Barron","year":"2007","unstructured":"Barron, A. B., Maleszka, R., Vander Meer, R. K. & Robinson, G. E. Octopamine modulates honey bee dance behavior. Proc Natl Acad Sci USA \n                           104, 1703\u20131707, https:\/\/doi.org\/10.1073\/pnas.0610506104 (2007).","journal-title":"Proc Natl Acad Sci USA"},{"key":"17760_CR18","doi-asserted-by":"crossref","first-page":"10495","DOI":"10.1523\/JNEUROSCI.23-33-10495.2003","volume":"23","author":"M Schwaerzel","year":"2003","unstructured":"Schwaerzel, M. et al. Dopamine and octopamine differentiate between aversive and appetitive olfactory memories in Drosophila. The Journal of neuroscience: the official journal of the Society for Neuroscience \n                           23, 10495\u201310502 (2003).","journal-title":"The Journal of neuroscience: the official journal of the Society for Neuroscience"},{"key":"17760_CR19","doi-asserted-by":"publisher","first-page":"1741","DOI":"10.1016\/j.cub.2006.07.023","volume":"16","author":"C Schroll","year":"2006","unstructured":"Schroll, C. et al. Light-induced activation of distinct modulatory neurons triggers appetitive or aversive learning in Drosophila larvae. Current biology: CB \n                           16, 1741\u20131747, https:\/\/doi.org\/10.1016\/j.cub.2006.07.023 (2006).","journal-title":"Current biology: CB"},{"key":"17760_CR20","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1016\/0006-8993(80)91037-9","volume":"201","author":"SF Leibowitz","year":"1980","unstructured":"Leibowitz, S. F. & Brown, L. L. Histochemical and pharmacological analysis of noradrenergic projections to the paraventricular hypothalamus in relation to feeding stimulation. Brain research \n                           201, 289\u2013314, https:\/\/doi.org\/10.1016\/0006-8993(80)91037-9 (1980).","journal-title":"Brain research"},{"key":"17760_CR21","doi-asserted-by":"publisher","first-page":"829","DOI":"10.1016\/0031-9384(80)90301-7","volume":"25","author":"SF Leibowitz","year":"1980","unstructured":"Leibowitz, S. F., Hammer, N. J. & Brown, L. L. Analysis of behavioral deficits produced by lesions in the dorsal and ventral midbrain tegmentum. Physiology &amp; Behavior \n                           25, 829\u2013843, https:\/\/doi.org\/10.1016\/0031-9384(80)90301-7 (1980).","journal-title":"Physiology &amp; Behavior"},{"key":"17760_CR22","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1016\/S0074-7742(02)51007-2","volume":"51","author":"BE Levin","year":"2002","unstructured":"Levin, B. E., Dunn-Meynell, A. A. & Routh, V. H. CNS sensing and regulation of peripheral glucose levels. International review of neurobiology \n                           51, 219\u2013258 (2002).","journal-title":"International review of neurobiology"},{"key":"17760_CR23","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1016\/0361-9230(85)90105-4","volume":"14","author":"SF Leibowitz","year":"1985","unstructured":"Leibowitz, S. F., Weiss, G. F., Yee, F. & Tretter, J. B. Noradrenergic innervation of the paraventricular nucleus: specific role in control of carbohydrate ingestion. Brain research bulletin \n                           14, 561\u2013567 (1985).","journal-title":"Brain research bulletin"},{"key":"17760_CR24","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1016\/0024-3205(93)90243-V","volume":"53","author":"PJD Wellman","year":"1993","unstructured":"Wellman, P. J. D., Marien, B. T. & McMahon, A. L. Modulation of feeding by hypothalamic paraventricular nucleus alpha1 and alpha2-adrenergic receptors. Life Sciences \n                           53, 669\u2013679 (1993).","journal-title":"Life Sciences"},{"key":"17760_CR25","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/0006-8993(82)90933-7","volume":"233","author":"SF Leibowitz","year":"1982","unstructured":"Leibowitz, S. F., Jhanwar-Uniyal, M., Dvorkin, B. & Makman, M. H. Distribution of alpha-adrenergic, beta-adrenergic and dopaminergic receptors in discrete hypothalamic areas of rat. Brain research \n                           233, 97\u2013114 (1982).","journal-title":"Brain research"},{"key":"17760_CR26","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/0014-2999(85)90578-3","volume":"115","author":"CK Goldman","year":"1985","unstructured":"Goldman, C. K., Marino, L. & Leibowitz, S. F. Postsynaptic alpha2-noradrenergic receptors mediate feeding induced by paraventricular nucleus injection of norepinephrine and clonidien. European Journal of Pharmacology \n                           115, 11\u201319 (1985).","journal-title":"European Journal of Pharmacology"},{"key":"17760_CR27","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/S0149-7634(88)80002-2","volume":"12","author":"SF Leibowitz","year":"1988","unstructured":"Leibowitz, S. F. Hypothalamic Paraventricular Nucleus: Interaction Between c 2-Noradrenergic System and Circulating Hormones and Nutrients in Relation to Energy Balance. Neuroscience & Biobehavioral Reviews \n                           12, 101\u2013109 (1988).","journal-title":"Neuroscience & Biobehavioral Reviews"},{"key":"17760_CR28","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1016\/0024-3205(93)90664-O","volume":"53","author":"A Morien","year":"1993","unstructured":"Morien, A., McMahon, L. & Wellman, P. J. Effects on food and water intake of the alpha 1-adrenoceptor agonists amidephrine and SK&F-89748. Life sciences \n                           53, 169\u2013174 (1993).","journal-title":"Life sciences"},{"key":"17760_CR29","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1016\/j.nut.2004.06.021","volume":"21","author":"EJ Ramos","year":"2005","unstructured":"Ramos, E. J., Meguid, M. M., Campos, A. C. & Coelho, J. C. Neuropeptide Y, alpha-melanocyte-stimulating hormone, and monoamines in food intake regulation. Nutrition \n                           21, 269\u2013279, https:\/\/doi.org\/10.1016\/j.nut.2004.06.021 (2005).","journal-title":"Nutrition"},{"key":"17760_CR30","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1016\/0031-9384(89)90251-5","volume":"46","author":"BG Stanley","year":"1989","unstructured":"Stanley, B. G., Anderson, K. C., Grayson, M. H. & Leibowitz, S. F. Repeated hypothalamic stimulation with neuropeptide Y increases daily carbohydrate and fat intake and body weight gain in female rats. Physiology & behavior \n                           46, 173\u2013177 (1989).","journal-title":"Physiology & behavior"},{"key":"17760_CR31","doi-asserted-by":"publisher","first-page":"889","DOI":"10.1016\/0361-9230(86)90104-8","volume":"17","author":"M Jhanwar-Uniyal","year":"1986","unstructured":"Jhanwar-Uniyal, M. & Leibowitz, S. F. Impact of food deprivation on alpha 1- and alpha 2-noradrenergic receptors in the paraventricular nucleus and other hypothalamic areas. Brain research bulletin \n                           17, 889\u2013896 (1986).","journal-title":"Brain research bulletin"},{"key":"17760_CR32","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1002\/neu.1012","volume":"47","author":"P Shen","year":"2001","unstructured":"Shen, P. & Cai, H. N. 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The Journal of neuroscience: the official journal of the Society for Neuroscience \n                           32, 14281\u201314287, https:\/\/doi.org\/10.1523\/JNEUROSCI.0517-12.2012 (2012).","journal-title":"The Journal of neuroscience: the official journal of the Society for Neuroscience"},{"key":"17760_CR35","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1534\/genetics.105.041848","volume":"171","author":"A Metaxakis","year":"2005","unstructured":"Metaxakis, A., Oehler, S., Klinakis, A. & Savakis, C. Minos as a genetic and genomic tool in Drosophila melanogaster. Genetics \n                           171, 571\u2013581, https:\/\/doi.org\/10.1534\/genetics.105.041848 (2005).","journal-title":"Genetics"},{"key":"17760_CR36","doi-asserted-by":"publisher","first-page":"761","DOI":"10.1534\/genetics.104.026427","volume":"167","author":"HJ Bellen","year":"2004","unstructured":"Bellen, H. J. et al. 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(Cold Spring Harbor Lab Press, 2010).","DOI":"10.1101\/pdb.ip80"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-17760-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-17760-w","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-17760-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T16:27:46Z","timestamp":1671812866000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-17760-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,12,15]]},"references-count":40,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,12]]}},"alternative-id":["17760"],"URL":"https:\/\/doi.org\/10.1038\/s41598-017-17760-w","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,12,15]]},"assertion":[{"value":"8 June 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 November 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 December 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that they have no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"17642"}}