{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T22:24:20Z","timestamp":1785450260634,"version":"3.56.0"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,10,19]],"date-time":"2022-10-19T00:00:00Z","timestamp":1666137600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Nutr."],"abstract":"<jats:p>Fasting with varying intensities is used to treat obesity-related diseases. Re-feeding after fasting exhibits hyperphagia and often rebound weight gain. However, the mechanisms underlying the hyperphagia and rebound remain elusive. Here we show that 24 h food restriction (24 h FR) and milder 50% FR, both depress synaptic transmission in the hypothalamic paraventricular nucleus (PVN) and induce acute hyperphagia in rats. 24 h FR is followed by weight rebound but 50% FR is not. Orexigenic neuropeptide Y (NPY) <jats:italic>via<\/jats:italic> the Y1 receptor (Y1R) inhibited the miniature excitatory postsynaptic current (mEPSC) on anorexigenic oxytocin neurons in the PVN. 24 h FR and 50% FR activated this neuronal pathway to induce acute hyperphagia on Days 1\u20133 and Days 1\u20132 after FR, respectively. 24 h FR induced large mEPSC depression, recurrent hyperphagia on Days 9\u201312 and rebound weight gain on Days 12\u201317, whereas 50% FR induced moderate mEPSC depression and sustained weight reduction. Transverse data analysis on Day 1 after 24 h FR and 50% FR demonstrated saturation kinetics for the mEPSC depression-hyperphagiacurve, implying hysteresis. The results reveal FR-driven synaptic plasticity in the NPY-Y1R-oxytocin neurocircuit that drives acute hyperphagia. FR with the intensity that regulates the synapse-feeding relay without hysteresis is the key for successful dieting.<\/jats:p>","DOI":"10.3389\/fnut.2022.994827","type":"journal-article","created":{"date-parts":[[2022,10,19]],"date-time":"2022-10-19T17:52:24Z","timestamp":1666201944000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Fasting inhibits excitatory synaptic input on paraventricular oxytocin neurons via neuropeptide Y and Y1 receptor, inducing rebound hyperphagia, and weight gain"],"prefix":"10.3389","volume":"9","author":[{"given":"Lei","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigetomo","family":"Suyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha A.","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoichi","family":"Ueta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutaka","family":"Seino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geoffrey W. G.","family":"Sharp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihiko","family":"Yada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,10,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1048","DOI":"10.1016\/j.cmet.2016.06.001","article-title":"Fasting, circadian rhythms, and time-restricted feeding in healthy lifespan.","volume":"23","author":"Longo","year":"2016","journal-title":"Cell Metab."},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3390\/nu11102442","article-title":"Effectiveness of intermittent fasting and time-restricted feeding compared to continuous energy restriction for weight loss.","volume":"1","author":"Rynders","year":"2019","journal-title":"Nutrients."},{"key":"B3","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1152\/physiol.00030","article-title":"Intermittent fasting: physiological implications on outcomes in mice and men.","volume":"35","author":"Lee","year":"2020","journal-title":"Physiology."},{"key":"B4","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/0196-9781(89)90082-x","article-title":"Influence of oxytocin on feeding behavior in the rat.","volume":"10","author":"Arletti","year":"1989","journal-title":"Peptides."},{"key":"B5","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1016\/j.cmet.2009.09.002","article-title":"Nesfatin-1-regulated oxytocinergic signaling in the paraventricular nucleus causes anorexia through a leptin-independent melanocortin pathway.","volume":"10","author":"Maejima","year":"2009","journal-title":"Cell Metab."},{"key":"B6","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1097\/MED.0b013e3283422f0a","article-title":"Neuropeptide Y and peptide Y.Y.: important regulators of energy metabolism.","volume":"18","author":"Nguyen","year":"2011","journal-title":"Curr Opin Endocrinol Diabetes Obes."},{"key":"B7","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1038\/nn.2739","article-title":"AGRP neurons are sufficient to orchestrate feeding behavior rapidly and without training.","volume":"14","author":"Aponte","year":"2011","journal-title":"Nat Neurosci."},{"key":"B8","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1038\/nature11270","article-title":"Deconstruction of a neural circuit for hunger.","volume":"488","author":"Atasoy","year":"2012","journal-title":"Nature."},{"key":"B9","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/0006-8993(93)91192-U","article-title":"Neuropeptide Y projection from arcuate nucleus to parvocellular division of paraventricular nucleus: specific relation to the ingestion of carbohydrate.","volume":"631","author":"Jhanwar-Uniyal","year":"1993","journal-title":"Brain Res."},{"key":"B10","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1038\/1082","article-title":"Coexpression of Agrp and NPY in fasting-activated hypothalamic neurons.","volume":"1","author":"Hahn","year":"1998","journal-title":"Nat Neurosci."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1210\/en.2004-1397","article-title":"Fasting induces a large, leptin-dependent increase in the intrinsic action potential frequency of orexigenic arcuate nucleus neuropeptide Y\/Agouti-related protein neurons.","volume":"146","author":"Takahashi","year":"2005","journal-title":"Endocrinology."},{"key":"B12","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1016\/j.cbpb.2005.04.015","article-title":"Neuropeptide Y content in the hypothalamic paraventricular nucleus responds to fasting and refeeding in broiler chickens.","volume":"141","author":"Zhou","year":"2005","journal-title":"Comp Biochem Physiol Mol Integr Physiol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1016\/j.neuron.2011.11.027","article-title":"Fasting activation of AgRP neurons requires NMDA receptors and involves spinogenesis and increased excitatory tone.","volume":"73","author":"Liu","year":"2012","journal-title":"Neuron."},{"key":"B14","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.neuron.2016.05.025","article-title":"A Postsynaptic AMPK\u2192p21-activated kinase pathway drives fasting-induced synaptic plasticity in AgRP neurons.","volume":"91","author":"Kong","year":"2016","journal-title":"Neuron."},{"key":"B15","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/j.npep.2015.08.008","article-title":"Fasted\/fed states regulate postsynaptic hub protein DYNLL2 and glutamatergic transmission in oxytocin neurons in the hypothalamic paraventricular nucleus.","volume":"56","author":"Suyama","year":"2016","journal-title":"Neuropeptides."},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.25755","article-title":"Plasticity of calcium-permeable AMPA glutamate receptors in Pro-opiomelanocortin neurons.","volume":"6","author":"Suyama","year":"2017","journal-title":"Elife."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.neulet.2014.09.004","article-title":"Differences in acid-induced currents between oxytocin-mRFP1 and vasopressin-eGFP neurons isolated from the supraoptic and paraventricular nuclei of transgenic rats.","volume":"583","author":"Ohkubo","year":"2014","journal-title":"Neurosci Lett."},{"key":"B18","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1016\/j.bbr.2016.05.010","article-title":"Neuronal activity and the expression of hypothalamic oxytocin and vasopressin in social versus cocaine conditioning.","volume":"310","author":"Liu","year":"2016","journal-title":"Behav Brain Res."},{"key":"B19","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1016\/j.cbpa.2018.08.015","article-title":"Fasting and refeeding induce differential changes in hypothalamic mRNA abundance of appetite-associated factors in 7-day-old Japanese quail, Coturnix japonica.","volume":"227","author":"McConn","year":"2019","journal-title":"Comp Biochem Physiol Mol Integr Physiol."},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0040191","article-title":"Y1 and Y5 receptors are both required for the regulation of food intake and energy homeostasis in mice.","volume":"7","author":"Nguyen","year":"2012","journal-title":"PLoS One."},{"key":"B21","doi-asserted-by":"publisher","first-page":"e1131","DOI":"10.1152\/ajpendo.00491.2002","article-title":"NPY ablation in C57BL\/6 mice leads to mild obesity and to an impaired refeeding response to fasting.","volume":"284","author":"Segal-Lieberman","year":"2003","journal-title":"Am J Physiol Endocrinol Metab."},{"key":"B22","doi-asserted-by":"publisher","first-page":"863","DOI":"10.1016\/j.cell.2011.08.031","article-title":"Synaptic plasticity of feeding circuits: hormones and hysteresis.","volume":"146","author":"Dietrich","year":"2011","journal-title":"Cell."},{"key":"B23","doi-asserted-by":"publisher","first-page":"992","DOI":"10.1016\/j.cell.2011.07.039","article-title":"Hunger states switch a flip-flop memory circuit via a synaptic AMPK-dependent positive feedback loop.","volume":"146","author":"Yang","year":"2011","journal-title":"Cell."},{"key":"B24","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1016\/0896-6273(92)90119-x","article-title":"Slow voltage-dependent changes in channel open-state probability underlie hysteresis of NMDA responses in Mg(2+)-free solutions.","volume":"8","author":"Nowak","year":"1992","journal-title":"Neuron."},{"key":"B25","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1210\/en.2012-1421","article-title":"Calorie-restricted weight loss reverses high-fat diet-induced ghrelin resistance, which contributes to rebound weight gain in a ghrelin-dependent manner.","volume":"154","author":"Briggs","year":"2013","journal-title":"Endocrinology."},{"key":"B26","doi-asserted-by":"publisher","first-page":"10960","DOI":"10.1073\/pnas.1706517114","article-title":"Butyrylcholinesterase gene transfer in obese mice prevents postdieting body weight rebound by suppressing ghrelin signaling.","volume":"114","author":"Chen","year":"2017","journal-title":"Proc Natl Acad Sci U.S.A."},{"key":"B27","doi-asserted-by":"publisher","first-page":"4404","DOI":"10.1016\/j.febslet.2014.10.010","article-title":"Oxytocinergic circuit from paraventricular and supraoptic nuclei to arcuate POMC neurons in hypothalamus.","volume":"588","author":"Maejima","year":"2014","journal-title":"FEBS Lett."},{"key":"B28","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1038\/s41586-020-2563-7","article-title":"Rescue of oxytocin response and social behaviour in a mouse model of autism.","volume":"584","author":"H\u00f6rnberg","year":"2020","journal-title":"Nature."},{"key":"B29","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1093\/ajcn\/36.3.444","article-title":"Refeeding after fasting in the rat: effects on body composition and food efficiency.","volume":"36","author":"Bj\u00f6rntorp","year":"1982","journal-title":"Am J Clin Nutr."},{"key":"B30","doi-asserted-by":"publisher","first-page":"4329","DOI":"10.1210\/en.2008-0411","article-title":"Differential effects of refeeding on melanocortin-responsive neurons in the hypothalamic paraventricular nucleus.","volume":"149","author":"S\u00e1nchez","year":"2008","journal-title":"Endocrinology."}],"container-title":["Frontiers in Nutrition"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2022.994827\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,19]],"date-time":"2022-10-19T17:52:27Z","timestamp":1666201947000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2022.994827\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,19]]},"references-count":30,"alternative-id":["10.3389\/fnut.2022.994827"],"URL":"https:\/\/doi.org\/10.3389\/fnut.2022.994827","relation":{},"ISSN":["2296-861X"],"issn-type":[{"value":"2296-861X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,19]]},"article-number":"994827"}}