进食行为的迷走神经调控机制
Vagal Regulatory Mechanism of Feeding Behavior
摘要: 进食行为是一个高度复杂的动态过程,需要整合机体内稳态信号与环境中的享乐信号,以实现自适应平衡。肠神经系统(ENS)作为人体的“第二大脑”,通过肠–脑轴与中枢神经系统(CNS)进行信号交换,在调节进食行为中发挥重要作用,其中迷走神经(VN)作为肠脑对话的关键纽带,调控着进食的稳态与享乐过程。本文综述了迷走神经在稳态进食中的两大核心系统——内感受系统和外周饱腹系统,以及在享乐进食中的两类驱动线索——感官愉悦线索和营养价值线索的作用机制。同时,结合现代食物环境下的肥胖易感性,探讨了迷走神经相关的干预策略,为优化进食行为调控提供理论依据与实践指导。
Abstract: Eating behavior is a highly complex and dynamic process that requires the integration of homeostatic signals and hedonic cues from the environment to achieve adaptive balance. The enteric nervous system (ENS), known as the “second brain,” plays a vital role in regulating eating behavior by exchanging signals with the central nervous system (CNS) via the gut-brain axis. The vagus nerve (VN), as a key mediator of gut-brain communication, governs both homeostatic and hedonic aspects of eating. This review examines the role of the vagus nerve in regulating homeostatic eating through two major systems—the interoceptive system and the peripheral satiety system—and its involvement in hedonic eating via sensory pleasure and nutritional value cues. Additionally, the susceptibility to obesity in the modern food environment and vagus nerve-based intervention strategies are discussed, providing theoretical insights and practical guidance for optimizing the regulation of eating behavior.
文章引用:胡美琪. 进食行为的迷走神经调控机制[J]. 社会科学前沿, 2025, 14(2): 262-270. https://doi.org/10.12677/ass.2025.142121

参考文献

[1] Berthoud, H., Münzberg, H. and Morrison, C.D. (2017) Blaming the Brain for Obesity: Integration of Hedonic and Homeostatic Mechanisms. Gastroenterology, 152, 1728-1738. [Google Scholar] [CrossRef] [PubMed]
[2] de Araujo, I.E., Schatzker, M. and Small, D.M. (2020) Rethinking Food Reward. Annual Review of Psychology, 71, 139-164. [Google Scholar] [CrossRef] [PubMed]
[3] Morales, I. (2022) Brain Regulation of Hunger and Motivation: The Case for Integrating Homeostatic and Hedonic Concepts and Its Implications for Obesity and Addiction. Appetite, 177, Article ID: 106146. [Google Scholar] [CrossRef] [PubMed]
[4] Rossi, M.A. and Stuber, G.D. (2018) Overlapping Brain Circuits for Homeostatic and Hedonic Feeding. Cell Metabolism, 27, 42-56. [Google Scholar] [CrossRef] [PubMed]
[5] Saper, C.B., Chou, T.C. and Elmquist, J.K. (2002) The Need to Feed: Homeostatic and Hedonic Control of Eating. Neuron, 36, 199-211. [Google Scholar] [CrossRef] [PubMed]
[6] Bai, L., Mesgarzadeh, S., Ramesh, K.S., Huey, E.L., Liu, Y., Gray, L.A., et al. (2019) Genetic Identification of Vagal Sensory Neurons That Control Feeding. Cell, 179, 1129-1143.e23. [Google Scholar] [CrossRef] [PubMed]
[7] Berthoud, H., Albaugh, V.L. and Neuhuber, W.L. (2021) Gut-Brain Communication and Obesity: Understanding Functions of the Vagus Nerve. Journal of Clinical Investigation, 131, e143770. [Google Scholar] [CrossRef] [PubMed]
[8] Ahmed, U., Chang, Y., Zafeiropoulos, S., Nassrallah, Z., Miller, L. and Zanos, S. (2022) Strategies for Precision Vagus Neuromodulation. Bioelectronic Medicine, 8, Article No. 9. [Google Scholar] [CrossRef] [PubMed]
[9] Prescott, S.L. and Liberles, S.D. (2022) Internal Senses of the Vagus Nerve. Neuron, 110, 579-599. [Google Scholar] [CrossRef] [PubMed]
[10] Paintal, A.S. (1973) Vagal Sensory Receptors and Their Reflex Effects. Physiological Reviews, 53, 159-227. [Google Scholar] [CrossRef] [PubMed]
[11] Zhao, Q., Yu, C.D., Wang, R., Xu, Q.J., Dai Pra, R., Zhang, L., et al. (2022) A Multidimensional Coding Architecture of the Vagal Interoceptive System. Nature, 603, 878-884. [Google Scholar] [CrossRef] [PubMed]
[12] Howland, R.H. (2014) Vagus Nerve Stimulation. Current Behavioral Neuroscience Reports, 1, 64-73. [Google Scholar] [CrossRef] [PubMed]
[13] Levinthal, D.J. and Strick, P.L. (2020) Multiple Areas of the Cerebral Cortex Influence the Stomach. Proceedings of the National Academy of Sciences of the United States of America, 117, 13078-13083. [Google Scholar] [CrossRef] [PubMed]
[14] Müller, S.J., Teckentrup, V., Rebollo, I., Hallschmid, M. and Kroemer, N.B. (2022) Vagus Nerve Stimulation Increases Stomach-Brain Coupling via a Vagal Afferent Pathway. Brain Stimulation, 15, 1279-1289. [Google Scholar] [CrossRef] [PubMed]
[15] Rebollo, I., Devauchelle, A., Béranger, B. and Tallon-Baudry, C. (2018) Stomach-Brain Synchrony Reveals a Novel, Delayed-Connectivity Resting-State Network in Humans. eLife, 7, e33321. [Google Scholar] [CrossRef] [PubMed]
[16] Berthoud, H.R., Blackshaw, L.A., Brookes, S.J.H. and Grundy, D. (2004) Neuroanatomy of Extrinsic Afferents Supplying the Gastrointestinal Tract. Neurogastroenterology & Motility, 16, 28-33. [Google Scholar] [CrossRef] [PubMed]
[17] Betley, J.N., Xu, S., Cao, Z.F.H., Gong, R., Magnus, C.J., Yu, Y., et al. (2015) Neurons for Hunger and Thirst Transmit a Negative-Valence Teaching Signal. Nature, 521, 180-185. [Google Scholar] [CrossRef] [PubMed]
[18] Chen, J., Cheng, M., Wang, L., Zhang, L., Xu, D., Cao, P., et al. (2020) A Vagal-NTS Neural Pathway That Stimulates Feeding. Current Biology, 30, 3986-3998.e5. [Google Scholar] [CrossRef] [PubMed]
[19] Kim, K., Seeley, R.J. and Sandoval, D.A. (2018) Signalling from the Periphery to the Brain That Regulates Energy Homeostasis. Nature Reviews Neuroscience, 19, 185-196. [Google Scholar] [CrossRef] [PubMed]
[20] Williams, E.K., Chang, R.B., Strochlic, D.E., Umans, B.D., Lowell, B.B. and Liberles, S.D. (2016) Sensory Neurons That Detect Stretch and Nutrients in the Digestive System. Cell, 166, 209-221. [Google Scholar] [CrossRef] [PubMed]
[21] Cork, S.C. (2018) The Role of the Vagus Nerve in Appetite Control: Implications for the Pathogenesis of Obesity. Journal of Neuroendocrinology, 30, e12643. [Google Scholar] [CrossRef] [PubMed]
[22] D’Agostino, G., Lyons, D.J., Cristiano, C., Burke, L.K., Madara, J.C., Campbell, J.N., et al. (2016) Appetite Controlled by a Cholecystokinin Nucleus of the Solitary Tract to Hypothalamus Neurocircuit. eLife, 5, e12225. [Google Scholar] [CrossRef] [PubMed]
[23] Hussain, S.S. and Bloom, S.R. (2012) The Regulation of Food Intake by the Gut-Brain Axis: Implications for Obesity. International Journal of Obesity, 37, 625-633. [Google Scholar] [CrossRef] [PubMed]
[24] Kaelberer, M.M., Buchanan, K.L., Klein, M.E., Barth, B.B., Montoya, M.M., Shen, X., et al. (2018) A Gut-Brain Neural Circuit for Nutrient Sensory Transduction. Science, 361, eaat5236. [Google Scholar] [CrossRef] [PubMed]
[25] de Lartigue, G. and Diepenbroek, C. (2016) Novel Developments in Vagal Afferent Nutrient Sensing and Its Role in Energy Homeostasis. Current Opinion in Pharmacology, 31, 38-43. [Google Scholar] [CrossRef] [PubMed]
[26] Han, W., Tellez, L.A., Perkins, M.H., Perez, I.O., Qu, T., Ferreira, J., et al. (2018) A Neural Circuit for Gut-Induced Reward. Cell, 175, 665-678.e23. [Google Scholar] [CrossRef] [PubMed]
[27] Liu, C., Bookout, A.L., Lee, S., Sun, K., Jia, L., Lee, C., et al. (2014) PPARγ in Vagal Neurons Regulates High-Fat Diet Induced Thermogenesis. Cell Metabolism, 19, 722-730. [Google Scholar] [CrossRef] [PubMed]
[28] Li, M., Tan, H., Lu, Z., Tsang, K.S., Chung, A.J. and Zuker, C.S. (2022) Gut-Brain Circuits for Fat Preference. Nature, 610, 722-730. [Google Scholar] [CrossRef] [PubMed]
[29] Liu, W.W. and Bohórquez, D.V. (2022) The Neural Basis of Sugar Preference. Nature Reviews Neuroscience, 23, 584-595. [Google Scholar] [CrossRef] [PubMed]
[30] de Lartigue, G. (2016) Role of the Vagus Nerve in the Development and Treatment of Diet‐induced Obesity. The Journal of Physiology, 594, 5791-5815. [Google Scholar] [CrossRef] [PubMed]
[31] Lee, P.C. and Dixon, J.B. (2017) Food for Thought: Reward Mechanisms and Hedonic Overeating in Obesity. Current Obesity Reports, 6, 353-361. [Google Scholar] [CrossRef] [PubMed]
[32] Small, D.M. and Prescott, J. (2005) Odor/Taste Integration and the Perception of Flavor. Experimental Brain Research, 166, 345-357. [Google Scholar] [CrossRef] [PubMed]
[33] Holman, G.L. (1969) Intragastric Reinforcement Effect. Journal of Comparative and Physiological Psychology, 69, 432-441. [Google Scholar] [CrossRef] [PubMed]
[34] Gutierrez, R., Fonseca, E. and Simon, S.A. (2020) The Neuroscience of Sugars in Taste, Gut-Reward, Feeding Circuits, and Obesity. Cellular and Molecular Life Sciences, 77, 3469-3502. [Google Scholar] [CrossRef] [PubMed]
[35] Jin, H., Fishman, Z.H., Ye, M., Wang, L. and Zuker, C.S. (2021) Top-Down Control of Sweet and Bitter Taste in the Mammalian Brain. Cell, 184, 257-271.e16. [Google Scholar] [CrossRef] [PubMed]
[36] Veldhuizen, M.G., Douglas, D., Aschenbrenner, K., Gitelman, D.R. and Small, D.M. (2011) The Anterior Insular Cortex Represents Breaches of Taste Identity Expectation. The Journal of Neuroscience, 31, 14735-14744. [Google Scholar] [CrossRef] [PubMed]
[37] Ootani, S., Umezaki, T., Shin, T. and Murata, Y. (1995) Convergence of Afferents from the SLN and GPN in Cat Medullary Swallowing Neurons. Brain Research Bulletin, 37, 397-404. [Google Scholar] [CrossRef] [PubMed]
[38] Spector, A.C. (2000) Linking Gustatory Neurobiology to Behavior in Vertebrates. Neuroscience & Biobehavioral Reviews, 24, 391-416. [Google Scholar] [CrossRef] [PubMed]
[39] Ackroff, K., Yiin, Y. and Sclafani, A. (2010) Post-Oral Infusion Sites That Support Glucose-Conditioned Flavor Preferences in Rats. Physiology & Behavior, 99, 402-411. [Google Scholar] [CrossRef] [PubMed]
[40] Boakes, R.A., Colagiuri, B. and Mahon, M. (2010) Learned Avoidance of Flavors Signaling Reduction in a Nutrient. Journal of Experimental Psychology: Animal Behavior Processes, 36, 117-125. [Google Scholar] [CrossRef] [PubMed]
[41] Berthoud, H., Morrison, C.D., Ackroff, K. and Sclafani, A. (2021) Learning of Food Preferences: Mechanisms and Implications for Obesity & Metabolic Diseases. International Journal of Obesity, 45, 2156-2168. [Google Scholar] [CrossRef] [PubMed]
[42] Sclafani, A. and Ackroff, K. (2012) Role of Gut Nutrient Sensing in Stimulating Appetite and Conditioning Food Preferences. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 302, R1119-R1133. [Google Scholar] [CrossRef] [PubMed]
[43] Beutler, L.R., Chen, Y., Ahn, J.S., Lin, Y., Essner, R.A. and Knight, Z.A. (2017) Dynamics of Gut-Brain Communication Underlying Hunger. Neuron, 96, 461-475.e5. [Google Scholar] [CrossRef] [PubMed]
[44] Berthoud, H. (2011) Metabolic and Hedonic Drives in the Neural Control of Appetite: Who Is the Boss? Current Opinion in Neurobiology, 21, 888-896. [Google Scholar] [CrossRef] [PubMed]
[45] Schultz, W. (2015) Neuronal Reward and Decision Signals: From Theories to Data. Physiological Reviews, 95, 853-951. [Google Scholar] [CrossRef] [PubMed]
[46] Joshi, A., Schott, M., la Fleur, S.E. and Barrot, M. (2022) Role of the Striatal Dopamine, GABA and Opioid Systems in Mediating Feeding and Fat Intake. Neuroscience & Biobehavioral Reviews, 139, Article ID: 104726. [Google Scholar] [CrossRef] [PubMed]
[47] Tellez, L.A., Medina, S., Han, W., Ferreira, J.G., Licona-Limón, P., Ren, X., et al. (2013) A Gut Lipid Messenger Links Excess Dietary Fat to Dopamine Deficiency. Science, 341, 800-802. [Google Scholar] [CrossRef] [PubMed]
[48] Berland, C., Castel, J., Terrasi, R., Montalban, E., Foppen, E., Martin, C., et al. (2022) Identification of an Endocannabinoid Gut-Brain Vagal Mechanism Controlling Food Reward and Energy Homeostasis. Molecular Psychiatry, 27, 2340-2354. [Google Scholar] [CrossRef] [PubMed]
[49] Cluny, N., Vemuri, V., Chambers, A., Limebeer, C., Bedard, H., Wood, J., et al. (2010) A Novel Peripherally Restricted Cannabinoid Receptor Antagonist, AM6545, Reduces Food Intake and Body Weight, but Does Not Cause Malaise, in Rodents. British Journal of Pharmacology, 161, 629-642. [Google Scholar] [CrossRef] [PubMed]
[50] DiPatrizio, N.V. (2021) Endocannabinoids and the Gut-Brain Control of Food Intake and Obesity. Nutrients, 13, Article 1214. [Google Scholar] [CrossRef] [PubMed]
[51] Bellono, N.W., Bayrer, J.R., Leitch, D.B., Castro, J., Zhang, C., O’Donnell, T.A., et al. (2017) Enterochromaffin Cells Are Gut Chemosensors That Couple to Sensory Neural Pathways. Cell, 170, 185-198.e16. [Google Scholar] [CrossRef] [PubMed]
[52] Buchanan, K.L., Rupprecht, L.E., Kaelberer, M.M., Sahasrabudhe, A., Klein, M.E., Villalobos, J.A., et al. (2022) The Preference for Sugar over Sweetener Depends on a Gut Sensor Cell. Nature Neuroscience, 25, 191-200. [Google Scholar] [CrossRef] [PubMed]
[53] Lu, V.B., Rievaj, J., O’Flaherty, E.A., Smith, C.A., Pais, R., Pattison, L.A., et al. (2019) Adenosine Triphosphate Is Co-Secreted with Glucagon-Like Peptide-1 to Modulate Intestinal Enterocytes and Afferent Neurons. Nature Communications, 10, Article No. 1029. [Google Scholar] [CrossRef] [PubMed]
[54] Tan, H., Sisti, A.C., Jin, H., Vignovich, M., Villavicencio, M., Tsang, K.S., et al. (2020) The Gut-Brain Axis Mediates Sugar Preference. Nature, 580, 511-516. [Google Scholar] [CrossRef] [PubMed]
[55] Appleton, K.M., Tuorila, H., Bertenshaw, E.J., de Graaf, C. and Mela, D.J. (2018) Sweet Taste Exposure and the Subsequent Acceptance and Preference for Sweet Taste in the Diet: Systematic Review of the Published Literature. The American Journal of Clinical Nutrition, 107, 405-419. [Google Scholar] [CrossRef] [PubMed]
[56] Heinze, J.M., Costanzo, A., Baselier, I., Fritsche, A., Frank-Podlech, S. and Keast, R. (2018) Detection Thresholds for Four Different Fatty Stimuli Are Associated with Increased Dietary Intake of Processed High-Caloric Food. Appetite, 123, 7-13. [Google Scholar] [CrossRef] [PubMed]
[57] Maliphol, A.B., Garth, D.J. and Medler, K.F. (2013) Diet-Induced Obesity Reduces the Responsiveness of the Peripheral Taste Receptor Cells. PLOS ONE, 8, e79403. [Google Scholar] [CrossRef] [PubMed]
[58] May, C.E., Vaziri, A., Lin, Y.Q., Grushko, O., Khabiri, M., Wang, Q., et al. (2019) High Dietary Sugar Reshapes Sweet Taste to Promote Feeding Behavior in Drosophila Melanogaster. Cell Reports, 27, 1675-1685.e7. [Google Scholar] [CrossRef] [PubMed]
[59] Vaziri, A., Khabiri, M., Genaw, B.T., May, C.E., Freddolino, P.L. and Dus, M. (2020) Persistent Epigenetic Reprogramming of Sweet Taste by Diet. Science Advances, 6, eabc8492. [Google Scholar] [CrossRef] [PubMed]
[60] Wang, Q., Lin, Y.Q., Lai, M., Su, Z., Oyston, L.J., Clark, T., et al. (2020) PGC1α Controls Sucrose Taste Sensitization in Drosophila. Cell Reports, 31, Article ID: 107480. [Google Scholar] [CrossRef] [PubMed]
[61] Weiss, M.S., Hajnal, A., Czaja, K. and Di Lorenzo, P.M. (2019) Taste Responses in the Nucleus of the Solitary Tract of Awake Obese Rats Are Blunted Compared with Those in Lean Rats. Frontiers in Integrative Neuroscience, 13, Article 35. [Google Scholar] [CrossRef] [PubMed]
[62] Meldrum, D.R., Morris, M.A. and Gambone, J.C. (2017) Obesity Pandemic: Causes, Consequences, and Solutions—But Do We Have the Will? Fertility and Sterility, 107, 833-839. [Google Scholar] [CrossRef] [PubMed]
[63] Ifland, J.R., Preuss, H.G., Marcus, M.T., Rourke, K.M., Taylor, W.C., Burau, K., et al. (2009) Refined Food Addiction: A Classic Substance Use Disorder. Medical Hypotheses, 72, 518-526. [Google Scholar] [CrossRef] [PubMed]
[64] Adair, D., Truong, D., Esmaeilpour, Z., Gebodh, N., Borges, H., Ho, L., et al. (2020) Electrical Stimulation of Cranial Nerves in Cognition and Disease. Brain Stimulation, 13, 717-750. [Google Scholar] [CrossRef] [PubMed]
[65] Steidel, K., Krause, K., Menzler, K., Strzelczyk, A., Immisch, I., Fuest, S., et al. (2021) Transcutaneous Auricular Vagus Nerve Stimulation Influences Gastric Motility: A Randomized, Double-Blind Trial in Healthy Individuals. Brain Stimulation, 14, 1126-1132. [Google Scholar] [CrossRef] [PubMed]
[66] von Wrede, R., Rings, T., Schach, S., Helmstaedter, C. and Lehnertz, K. (2021) Transcutaneous Auricular Vagus Nerve Stimulation Induces Stabilizing Modifications in Large-Scale Functional Brain Networks: Towards Understanding the Effects of taVNS in Subjects with Epilepsy. Scientific Reports, 11, Article No. 7906. [Google Scholar] [CrossRef] [PubMed]
[67] Val-Laillet, D., Biraben, A., Randuineau, G. and Malbert, C.H. (2010) Chronic Vagus Nerve Stimulation Decreased Weight Gain, Food Consumption and Sweet Craving in Adult Obese Minipigs. Appetite, 55, 245-252. [Google Scholar] [CrossRef] [PubMed]
[68] Fallgatter, A.J., Neuhauser, B., Herrmann, M.J., Ehlis, A., Wagener, A., Scheuerpflug, P., et al. (2003) Far Field Potentials from the Brain Stem after Transcutaneous Vagus Nerve Stimulation. Journal of Neural Transmission, 110, 1437-1443. [Google Scholar] [CrossRef] [PubMed]
[69] Neuser, M.P., Teckentrup, V., Kühnel, A., Hallschmid, M., Walter, M. and Kroemer, N.B. (2020) Vagus Nerve Stimulation Boosts the Drive to Work for Rewards. Nature Communications, 11, Article No. 3555. [Google Scholar] [CrossRef] [PubMed]
[70] Hong, G., Pintea, B., Lingohr, P., Coch, C., Randau, T., Schaefer, N., et al. (2018) Effect of Transcutaneous Vagus Nerve Stimulation on Muscle Activity in the Gastrointestinal Tract (transVaGa): A Prospective Clinical Trial. International Journal of Colorectal Disease, 34, 417-422. [Google Scholar] [CrossRef] [PubMed]