The critical role of gut–brain signalling in eating behaviour and obesity

Watts, A. G., Kanoski, S. E., Sanchez-Watts, G. & Langhans, W. The physiological control of eating: signals, neurons, and networks. Physiol. Rev. 102, 689–813 (2022).

Article  CAS  PubMed  Google Scholar 

Chen, W. G. et al. The emerging science of interoception: sensing, integrating, interpreting, and regulating signals within the self. Trends Neurosci. 44, 3–16 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Prescott, S. L. & Liberles, S. D. Internal senses of the vagus nerve. Neuron 110, 579–599 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

de Araujo, I. E., Schatzker, M. & Small, D. M. Rethinking food reward. Annu. Rev. Psychol. 71, 139–164 (2020).

Article  PubMed  Google Scholar 

Alcantara, I. C., Tapia, A. P. M., Aponte, Y. & Krashes, M. J. Acts of appetite: neural circuits governing the appetitive, consummatory, and terminating phases of feeding. Nat. Metab. 4, 836–847 (2022).

Article  PubMed  PubMed Central  Google Scholar 

Yapici, N., Cohn, R., Schusterreiter, C., Ruta, V. & Vosshall, L. B. A taste circuit that regulates ingestion by integrating food and hunger signals. Cell 165, 715–729 (2016).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Horio, N. & Liberles, S. D. Hunger enhances food-odour attraction through a neuropeptide Y spotlight. Nature 592, 262–266 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Inagaki, H. K., Panse, K. M. & Anderson, D. J. Independent, reciprocal neuromodulatory control of sweet and bitter taste sensitivity during starvation in Drosophila. Neuron 84, 806–820 (2014).

Article  CAS  PubMed  PubMed Central  Google Scholar 

McDougle, M. et al. Separate gut-brain circuits for fat and sugar reinforcement combine to promote overeating. Cell Metab. 36, 393–407.e397 (2024).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Williams, E. K. et al. Sensory neurons that detect stretch and nutrients in the digestive system. Cell 166, 209–221 (2016).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Daly, D. M., Park, S. J., Valinsky, W. C. & Beyak, M. J. Impaired intestinal afferent nerve satiety signalling and vagal afferent excitability in diet induced obesity in the mouse. J. Physiol. 589, 2857–2870 (2011).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Han, W. et al. A neural circuit for gut-induced reward. Cell 175, 665–678.e23 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

de Lartigue, G., Ronveaux, C. C. & Raybould, H. E. Deletion of leptin signaling in vagal afferent neurons results in hyperphagia and obesity. Mol. Metab. 3, 595–607 (2014).

Article  PubMed  PubMed Central  Google Scholar 

Goldstein, N. et al. Hypothalamic detection of macronutrients via multiple gut-brain pathways. Cell Metab. 33, 676–687.e5 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Serlin, H. K. & Fox, E. A. Abdominal vagotomy reveals majority of small intestinal mucosal afferents labeled in nav1.8cre-rosa26tdTomato mice are vagal in origin. J. Comp. Neurol. 528, 816–839 (2020).

Article  PubMed  Google Scholar 

McDougle, M. et al. Intact vagal gut-brain signalling prevents hyperphagia and excessive weight gain in response to high-fat high-sugar diet. Acta Physiol. 231, e13530 (2021).

Article  CAS  Google Scholar 

Covasa, M. & Ritter, R. C. Adaptation to high-fat diet reduces inhibition of gastric emptying by CCK and intestinal oleate. Am. J. Physiol. Regul. Integr. Comp. Physiol 278, R166–R170 (2000).

Article  CAS  PubMed  Google Scholar 

Berthoud, H. R. Vagal and hormonal gut-brain communication: from satiation to satisfaction. Neurogastroenterol. Motil. 20, (Suppl. 1), 64–72 (2008).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Mendez-Hernandez, R., Braga, I., Bali, A., Yang, M. & de Lartigue, G. Vagal sensory gut-brain pathways that control eating-satiety and beyond. Compr. Physiol. 15, e70010 (2025).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Smith, G. P., Jerome, C., Cushin, B. J., Eterno, R. & Simansky, K. J. Abdominal vagotomy blocks the satiety effect of cholecystokinin in the rat. Science 213, 1036–1037 (1981).

Article  CAS  PubMed  Google Scholar 

Walls, E. K., Phillips, R. J., Wang, F. B., Holst, M. C. & Powley, T. L. Suppression of meal size by intestinal nutrients is eliminated by celiac vagal deafferentation. Am. J. Physiol. 269, R1410–R1419 (1995).

CAS  PubMed  Google Scholar 

Phillips, R. J. & Powley, T. L. Gastric volume detection after selective vagotomies in rats. Am. J. Physiol. 274, R1626–R1638 (1998).

CAS  PubMed  Google Scholar 

Fox, E. A. Vagal afferent controls of feeding: a possible role for gastrointestinal BDNF. Clin. Autonomic Res. 23, 15–31 (2013).

Article  Google Scholar 

Diepenbroek, C. et al. Validation and characterization of a novel method for selective vagal deafferentation of the gut. Am. J. Physiol. Gastrointest. Liver Physiol. 313, G342–G352 (2017).

Article  CAS  PubMed  PubMed Central  Google Scholar 

de Lartigue, G., Singh, A., de Araujo, A., Maske, C. B. & Vergara, M. Lessons Learned about Metabolism from Traditional and Novel Tools for Studying the Structure and Function of the Vagus Nerve 1st edn (CRC Press, 2021).

Bai, L. et al. Genetic identification of vagal sensory neurons that control feeding. Cell 179, 1129–1143.e3 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Brierley, D. I. et al. Central and peripheral GLP-1 systems independently suppress eating. Nat. Metab. 3, 258–273 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Smith, J. A. et al. Oxytocin and cardiometabolic interoception: knowing oneself affects ingestive and social behaviors. Appetite 175, 106054 (2022).

Article  PubMed  PubMed Central  Google Scholar 

Krieger, J. P. et al. Knockdown of GLP-1 receptors in vagal afferents affects normal food intake and glycemia. Diabetes 65, 34–43 (2016).

Article  CAS  PubMed  Google Scholar 

Lee, S. J. et al. Blunted vagal cocaine- and amphetamine-regulated transcript promotes hyperphagia and weight gain. Cell Rep. 30, 2028–2039.e24 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Scott, K. A. et al. Mechanosensation of the heart and gut elicits hypometabolism and vigilance in mice. Nat. Metab. 7, 263–275 (2025).

Article  CAS  PubMed  PubMed Central  Google Scholar 

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