Fasting inhibits excitatory synaptic input on paraventricular oxytocin neurons via neuropeptide Y and Y1 receptor, inducing rebound hyperphagia, and weight gain
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,...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-10-01
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| Series: | Frontiers in Nutrition |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnut.2022.994827/full |
| _version_ | 1828142986754523136 |
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| author | Lei Wang Lei Wang Lei Wang Lei Wang Shigetomo Suyama Shigetomo Suyama Samantha A. Lee Samantha A. Lee Yoichi Ueta Yutaka Seino Geoffrey W. G. Sharp Toshihiko Yada Toshihiko Yada Toshihiko Yada Toshihiko Yada |
| author_facet | Lei Wang Lei Wang Lei Wang Lei Wang Shigetomo Suyama Shigetomo Suyama Samantha A. Lee Samantha A. Lee Yoichi Ueta Yutaka Seino Geoffrey W. G. Sharp Toshihiko Yada Toshihiko Yada Toshihiko Yada Toshihiko Yada |
| author_sort | Lei Wang |
| collection | DOAJ |
| description | 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) via 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 1–3 and Days 1–2 after FR, respectively. 24 h FR induced large mEPSC depression, recurrent hyperphagia on Days 9–12 and rebound weight gain on Days 12–17, 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. |
| first_indexed | 2024-04-11T19:49:40Z |
| format | Article |
| id | doaj.art-db90368598a54a01b9191d5681a8ce09 |
| institution | Directory Open Access Journal |
| issn | 2296-861X |
| language | English |
| last_indexed | 2024-04-11T19:49:40Z |
| publishDate | 2022-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Nutrition |
| spelling | doaj.art-db90368598a54a01b9191d5681a8ce092022-12-22T04:06:20ZengFrontiers Media S.A.Frontiers in Nutrition2296-861X2022-10-01910.3389/fnut.2022.994827994827Fasting inhibits excitatory synaptic input on paraventricular oxytocin neurons via neuropeptide Y and Y1 receptor, inducing rebound hyperphagia, and weight gainLei Wang0Lei Wang1Lei Wang2Lei Wang3Shigetomo Suyama4Shigetomo Suyama5Samantha A. Lee6Samantha A. Lee7Yoichi Ueta8Yutaka Seino9Geoffrey W. G. Sharp10Toshihiko Yada11Toshihiko Yada12Toshihiko Yada13Toshihiko Yada14Division of Integrative Physiology, Department of Physiology, Jichi Medical University School of Medicine, Shimotsuke, JapanDivision of Integrative Physiology, Center for Integrative Physiology, Kansai Electric Power Medical Research Institute, Kyoto, JapanDivision of Diabetes, Metabolism and Endocrinology, Kobe University Graduate School of Medicine, Kobe, JapanDepartment of Diabetes, Endocrinology and Metabolism/Rheumatology and Clinical Immunology, Gifu University Graduate School of Medicine, Gifu, JapanDivision of Integrative Physiology, Department of Physiology, Jichi Medical University School of Medicine, Shimotsuke, JapanDepartment of Physiology, School of Medicine, Keio University, Tokyo, JapanDivision of Integrative Physiology, Department of Physiology, Jichi Medical University School of Medicine, Shimotsuke, JapanDepartment of Biological Sciences, University of Manitoba, Winnipeg, MB, CanadaDepartment of Physiology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, JapanYutaka Seino Distinguished Center for Diabetes Research, Kansai Electric Power Medical Research Institute, Osaka, JapanDepartment of Molecular Medicine, College of Veterinary Medicine, Cornell University, Ithaca, NY, United StatesDivision of Integrative Physiology, Department of Physiology, Jichi Medical University School of Medicine, Shimotsuke, JapanDivision of Integrative Physiology, Center for Integrative Physiology, Kansai Electric Power Medical Research Institute, Kyoto, JapanDivision of Diabetes, Metabolism and Endocrinology, Kobe University Graduate School of Medicine, Kobe, JapanDepartment of Diabetes, Endocrinology and Metabolism/Rheumatology and Clinical Immunology, Gifu University Graduate School of Medicine, Gifu, JapanFasting 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) via 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 1–3 and Days 1–2 after FR, respectively. 24 h FR induced large mEPSC depression, recurrent hyperphagia on Days 9–12 and rebound weight gain on Days 12–17, 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.https://www.frontiersin.org/articles/10.3389/fnut.2022.994827/fullfood restrictionneuropeptide YY1 receptorparaventricular nucleusoxytocinsynaptic plasticity |
| spellingShingle | Lei Wang Lei Wang Lei Wang Lei Wang Shigetomo Suyama Shigetomo Suyama Samantha A. Lee Samantha A. Lee Yoichi Ueta Yutaka Seino Geoffrey W. G. Sharp Toshihiko Yada Toshihiko Yada Toshihiko Yada Toshihiko Yada Fasting inhibits excitatory synaptic input on paraventricular oxytocin neurons via neuropeptide Y and Y1 receptor, inducing rebound hyperphagia, and weight gain Frontiers in Nutrition food restriction neuropeptide Y Y1 receptor paraventricular nucleus oxytocin synaptic plasticity |
| title | Fasting inhibits excitatory synaptic input on paraventricular oxytocin neurons via neuropeptide Y and Y1 receptor, inducing rebound hyperphagia, and weight gain |
| title_full | Fasting inhibits excitatory synaptic input on paraventricular oxytocin neurons via neuropeptide Y and Y1 receptor, inducing rebound hyperphagia, and weight gain |
| title_fullStr | Fasting inhibits excitatory synaptic input on paraventricular oxytocin neurons via neuropeptide Y and Y1 receptor, inducing rebound hyperphagia, and weight gain |
| title_full_unstemmed | Fasting inhibits excitatory synaptic input on paraventricular oxytocin neurons via neuropeptide Y and Y1 receptor, inducing rebound hyperphagia, and weight gain |
| title_short | Fasting inhibits excitatory synaptic input on paraventricular oxytocin neurons via neuropeptide Y and Y1 receptor, inducing rebound hyperphagia, and weight gain |
| title_sort | fasting inhibits excitatory synaptic input on paraventricular oxytocin neurons via neuropeptide y and y1 receptor inducing rebound hyperphagia and weight gain |
| topic | food restriction neuropeptide Y Y1 receptor paraventricular nucleus oxytocin synaptic plasticity |
| url | https://www.frontiersin.org/articles/10.3389/fnut.2022.994827/full |
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