{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T08:44:01Z","timestamp":1793954641466,"version":"4.8.0"},"reference-count":57,"publisher":"Springer Science and Business Media LLC","issue":"9","license":[{"start":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T00:00:00Z","timestamp":1750723200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T00:00:00Z","timestamp":1750723200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100004312","name":"Eli Lilly and Company","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004312","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Med"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Tirzepatide induces weight reduction but the underlying mechanisms are unknown. This 6-week phase 1 study investigated early effects of tirzepatide on energy intake. Male and female adults without diabetes (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009114) and a body mass index from 27 to 50\u2009kg per m\n                    <jats:sup>2<\/jats:sup>\n                    were randomized 1:1:1 to blinded once-weekly tirzepatide or placebo, or open-label once-daily liraglutide. The primary outcome was change from baseline to week 3 in energy intake during an ad libitum lunch with tirzepatide versus placebo. Secondary outcomes assessed self-reported ingestive behavior and blood-oxygenation-level-dependent functional magnetic resonance imaging with food photos. Tirzepatide reduced energy intake versus placebo at week 3 (estimated treatment difference \u2212524.6\u2009kcal (95% confidence interval \u2212648.1 to \u2212401.0),\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.0001). With regard to secondary outcomes versus placebo, tirzepatide decreased overall appetite, food cravings, tendency to overeat, perceived hunger and reactivity to foods in the environment but did not impact volitional restriction of dietary intake. At week 3 versus placebo, tirzepatide did not statistically significantly impact blood-oxygenation-level-dependent activation to highly palatable food photos (aggregated category of high-fat, high-sugar foods and high-fat, high-carbohydrate foods) but decreased activation to high-fat, high-sugar food photos in the medial frontal and cingulate gyri, orbitofrontal cortex and hippocampus. Our results suggest tirzepatide reduces food intake, potentially by impacting ingestive behavior. ClinicalTrials.gov registration:\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04311411\" ext-link-type=\"uri\">NCT04311411<\/jats:ext-link>\n                    .\n                  <\/jats:p>","DOI":"10.1038\/s41591-025-03774-9","type":"journal-article","created":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T05:03:48Z","timestamp":1750741428000},"page":"3141-3150","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":70,"title":["Tirzepatide on ingestive behavior in adults with overweight or obesity: a randomized 6-week phase 1 trial"],"prefix":"10.1038","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8125-4015","authenticated-orcid":false,"given":"Corby K.","family":"Martin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Owen T.","family":"Carmichael","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Carnell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5033-3642","authenticated-orcid":false,"given":"Robert V.","family":"Considine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Kareken","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrike","family":"Dydak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard D.","family":"Mattes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Scott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergey","family":"Shcherbinin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Nishiyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alastair","family":"Knights","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shweta","family":"Urva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukasz","family":"Biernat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4449-6231","authenticated-orcid":false,"given":"Edward","family":"Pratt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4502-0470","authenticated-orcid":false,"given":"Axel","family":"Haupt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Mintun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Otero Svaldi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zvonko","family":"Milicevic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2481-133X","authenticated-orcid":false,"given":"Tamer","family":"Coskun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,6,24]]},"reference":[{"key":"3774_CR1","doi-asserted-by":"crossref","unstructured":"Bray, G. A., Kim, K. K., Wilding, J. P. H. & World Obesity Federation. Obesity: a chronic relapsing progressive disease process. A position statement of the World Obesity Federation. Obes. Rev. 18, 715\u2013723 (2017).","DOI":"10.1111\/obr.12551"},{"key":"3774_CR2","unstructured":"Obesity and Overweight Key Facts. 2021 (World Health Organization, accessed 16 February 2024); www.who.int\/news-room\/fact-sheets\/detail\/obesity-and-overweight"},{"key":"3774_CR3","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1111\/j.1467-789X.2011.00927.x","volume":"13","author":"S Carnell","year":"2012","unstructured":"Carnell, S., Gibson, C., Benson, L., Ochner, C. N. & Geliebter, A. Neuroimaging and obesity: current knowledge and future directions. Obes. Rev. 13, 43\u201356 (2012).","journal-title":"Obes. Rev."},{"key":"3774_CR4","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/j.eprac.2023.12.010","volume":"30","author":"AK Chetty","year":"2024","unstructured":"Chetty, A. K., Rafi, E., Bellini, N. J., Buchholz, N. & Isaacs, D. A review of incretin therapies approved and in late-stage development for overweight and obesity management. Endocr. Pract. 30, 292\u2013303 (2024).","journal-title":"Endocr. Pract."},{"key":"3774_CR5","doi-asserted-by":"publisher","first-page":"418","DOI":"10.1038\/s41366-024-01500-y","volume":"49","author":"S Bettadapura","year":"2025","unstructured":"Bettadapura, S., Dowling, K., Jablon, K., Al-Humadi, A. W. & le Roux, C. W. Changes in food preferences and ingestive behaviors after glucagon-like peptide-1 analog treatment: techniques and opportunities. Int. J. Obes. 49, 418\u2013426 (2025).","journal-title":"Int. J. Obes."},{"key":"3774_CR6","doi-asserted-by":"publisher","first-page":"784","DOI":"10.1038\/ijo.2013.162","volume":"38","author":"J van Can","year":"2014","unstructured":"van Can, J. et al. Effects of the once-daily GLP-1 analog liraglutide on gastric emptying, glycemic parameters, appetite and energy metabolism in obese, non-diabetic adults. Int. J. Obes. 38, 784\u2013793 (2014).","journal-title":"Int. J. Obes."},{"key":"3774_CR7","doi-asserted-by":"crossref","first-page":"1242","DOI":"10.1111\/dom.12932","volume":"19","author":"J Blundell","year":"2017","unstructured":"Blundell, J. et al. Effects of once-weekly semaglutide on appetite, energy intake, control of eating, food preference and body weight in subjects with obesity. Diabetes Obes. Metab. 19, 1242\u20131251 (2017).","journal-title":"Diabetes Obes. Metab."},{"key":"3774_CR8","doi-asserted-by":"crossref","first-page":"4186","DOI":"10.2337\/db14-0849","volume":"63","author":"L van Bloemendaal","year":"2014","unstructured":"van Bloemendaal, L. et al. GLP-1 receptor activation modulates appetite- and reward-related brain areas in humans. Diabetes 63, 4186\u20134196 (2014).","journal-title":"Diabetes"},{"key":"3774_CR9","doi-asserted-by":"crossref","first-page":"1804","DOI":"10.2337\/dc15-2706","volume":"39","author":"R Eldor","year":"2016","unstructured":"Eldor, R. et al. Discordance between central (brain) and pancreatic action of exenatide in lean and obese subjects. Diabetes Care 39, 1804\u20131810 (2016).","journal-title":"Diabetes Care"},{"key":"3774_CR10","doi-asserted-by":"publisher","first-page":"954","DOI":"10.1007\/s00125-016-3874-y","volume":"59","author":"OM Farr","year":"2016","unstructured":"Farr, O. M. et al. GLP-1 receptors exist in the parietal cortex, hypothalamus and medulla of human brains and the GLP-1 analogue liraglutide alters brain activity related to highly desirable food cues in individuals with diabetes: a crossover, randomised, placebo-controlled trial. Diabetologia 59, 954\u2013965 (2016).","journal-title":"Diabetologia"},{"key":"3774_CR11","doi-asserted-by":"crossref","first-page":"214","DOI":"10.2337\/dc15-0772","volume":"39","author":"JS Ten Kulve","year":"2016","unstructured":"Ten Kulve, J. S. et al. Liraglutide reduces CNS activation in response to visual food cues only after short-term treatment in patients with type 2 diabetes. Diabetes Care 39, 214\u2013221 (2016).","journal-title":"Diabetes Care"},{"key":"3774_CR12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1530\/JOE-15-0461","volume":"229","author":"JS Ten Kulve","year":"2016","unstructured":"Ten Kulve, J. S. et al. Endogenous GLP1 and GLP1 analogue alter CNS responses to palatable food consumption. J. Endocrinol. 229, 1\u201312 (2016).","journal-title":"J. Endocrinol."},{"key":"3774_CR13","doi-asserted-by":"crossref","first-page":"2459","DOI":"10.1111\/dom.13827","volume":"21","author":"OM Farr","year":"2019","unstructured":"Farr, O. M. et al. Longer-term liraglutide administration at the highest dose approved for obesity increases reward-related orbitofrontal cortex activation in response to food cues: implications for plateauing weight loss in response to anti-obesity therapies. Diabetes Obes. Metab. 21, 2459\u20132464 (2019).","journal-title":"Diabetes Obes. Metab."},{"key":"3774_CR14","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.molmet.2018.09.009","volume":"18","author":"T Coskun","year":"2018","unstructured":"Coskun, T. et al. LY3298176, a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus: from discovery to clinical proof of concept. Mol. Metab. 18, 3\u201314 (2018).","journal-title":"Mol. Metab."},{"key":"3774_CR15","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1056\/NEJMoa2206038","volume":"387","author":"AM Jastreboff","year":"2022","unstructured":"Jastreboff, A. M. et al. Tirzepatide once weekly for the treatment of obesity. N. Engl. J. Med. 387, 205\u2013216 (2022).","journal-title":"N. Engl. J. Med."},{"key":"3774_CR16","doi-asserted-by":"crossref","unstructured":"Martin, C. K. et al. 128-OR: the effect of tirzepatide during weight loss on food intake, appetite, food preference, and food craving in people with obesity. Diabetes 72, 128-OR (2023).","DOI":"10.2337\/db23-128-OR"},{"key":"3774_CR17","doi-asserted-by":"crossref","unstructured":"Ravussin, E. et al. 127-OR: the effect of tirzepatide during weight loss on metabolic adaption, fat oxidation, and food intake in people with obesity. Diabetes 72, 127-OR (2023).","DOI":"10.2337\/db23-127-OR"},{"key":"3774_CR18","doi-asserted-by":"crossref","first-page":"998","DOI":"10.2337\/dc22-1710","volume":"46","author":"T Heise","year":"2023","unstructured":"Heise, T. et al. Tirzepatide reduces appetite, energy intake, and fat mass in people with type 2 diabetes. Diabetes Care 46, 998\u20131004 (2023).","journal-title":"Diabetes Care"},{"key":"3774_CR19","doi-asserted-by":"crossref","first-page":"2005","DOI":"10.1002\/oby.22653","volume":"27","author":"AM Chao","year":"2019","unstructured":"Chao, A. M. et al. Effects of liraglutide and behavioral weight loss on food cravings, eating behaviors, and eating disorder psychopathology. Obesity 27, 2005\u20132010 (2019).","journal-title":"Obesity"},{"key":"3774_CR20","doi-asserted-by":"crossref","first-page":"1552","DOI":"10.1210\/clinem\/dgz140","volume":"105","author":"H Kadouh","year":"2020","unstructured":"Kadouh, H. et al. GLP-1 analog modulates appetite, taste preference, gut hormones, and regional body fat stores in adults with obesity. J. Clin. Endocrinol. Metab. 105, 1552\u20131563 (2020).","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"3774_CR21","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.appet.2005.01.002","volume":"45","author":"DA Williamson","year":"2005","unstructured":"Williamson, D. A. et al. Microanalysis of eating behavior of three leptin deficient adults treated with leptin therapy. Appetite 45, 75\u201380 (2005).","journal-title":"Appetite"},{"key":"3774_CR22","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1016\/j.cmet.2019.07.013","volume":"30","author":"AE Adriaenssens","year":"2019","unstructured":"Adriaenssens, A. E. et al. Glucose-dependent insulinotropic polypeptide receptor-expressing cells in the hypothalamus regulate food intake. Cell Metab. 30, 987\u2013996.e6 (2019).","journal-title":"Cell Metab."},{"key":"3774_CR23","doi-asserted-by":"crossref","DOI":"10.1016\/j.appet.2019.104397","volume":"143","author":"JL Dorling","year":"2019","unstructured":"Dorling, J. L. et al. Change in self-efficacy, eating behaviors and food cravings during two years of calorie restriction in humans without obesity. Appetite 143, 104397 (2019).","journal-title":"Appetite"},{"key":"3774_CR24","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1016\/j.gtc.2023.08.002","volume":"52","author":"K Alabduljabbar","year":"2023","unstructured":"Alabduljabbar, K., Bonanos, E., Miras, A. D. & le Roux, C. W. Mechanisms of action of bariatric surgery on body weight regulation. Gastroenterol. Clin. North Am. 52, 691\u2013705 (2023).","journal-title":"Gastroenterol. Clin. North Am."},{"key":"3774_CR25","doi-asserted-by":"crossref","DOI":"10.1016\/j.appet.2019.104575","volume":"150","author":"EJ Bryant","year":"2020","unstructured":"Bryant, E. J., Malik, M. S., Whitford-Bartle, T. & Waters, G. M. The effects of bariatric surgery on psychological aspects of eating behaviour and food intake in humans. Appetite 150, 104575 (2020).","journal-title":"Appetite"},{"key":"3774_CR26","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.cpr.2017.12.004","volume":"60","author":"H Kober","year":"2018","unstructured":"Kober, H. & Boswell, R. G. Potential psychological & neural mechanisms in binge eating disorder: implications for treatment. Clin. Psychol. Rev. 60, 32\u201344 (2018).","journal-title":"Clin. Psychol. Rev."},{"key":"3774_CR27","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.cpr.2016.02.001","volume":"44","author":"EM Schulte","year":"2016","unstructured":"Schulte, E. M., Grilo, C. M. & Gearhardt, A. N. Shared and unique mechanisms underlying binge eating disorder and addictive disorders. Clin. Psychol. Rev. 44, 125\u2013139 (2016).","journal-title":"Clin. Psychol. Rev."},{"key":"3774_CR28","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1146\/annurev-nutr-110420-111710","volume":"41","author":"AN Gearhardt","year":"2021","unstructured":"Gearhardt, A. N. & Schulte, E. M. Is food addictive? A review of the science. Annu. Rev. Nutr. 41, 387\u2013410 (2021).","journal-title":"Annu. Rev. Nutr."},{"key":"3774_CR29","doi-asserted-by":"crossref","first-page":"e170671","DOI":"10.1172\/jci.insight.170671","volume":"8","author":"V Chuong","year":"2023","unstructured":"Chuong, V. et al. The glucagon-like peptide-1 (GLP-1) analogue semaglutide reduces alcohol drinking and modulates central GABA neurotransmission. JCI Insight 8, e170671 (2023).","journal-title":"JCI Insight"},{"key":"3774_CR30","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1111\/bph.15677","volume":"179","author":"MK Klausen","year":"2022","unstructured":"Klausen, M. K., Thomsen, M., Wortwein, G. & Fink-Jensen, A. The role of glucagon-like peptide 1 (GLP-1) in addictive disorders. Br. J. Pharmacol. 179, 625\u2013641 (2022).","journal-title":"Br. J. Pharmacol."},{"key":"3774_CR31","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.7326\/M23-2718","volume":"177","author":"W Wang","year":"2024","unstructured":"Wang, W. et al. Association of semaglutide with tobacco use disorder in patients with type 2 diabetes: target trial emulation using real-world data. Ann. Intern. Med. 177, 1016\u20131027 (2024).","journal-title":"Ann. Intern. Med."},{"key":"3774_CR32","doi-asserted-by":"publisher","first-page":"2587","DOI":"10.1038\/s41380-024-02498-5","volume":"29","author":"W Wang","year":"2024","unstructured":"Wang, W. et al. Association of semaglutide with reduced incidence and relapse of cannabis use disorder in real-world populations: a retrospective cohort study. Mol. Psychiatry 29, 2587\u20132598 (2024).","journal-title":"Mol. Psychiatry"},{"key":"3774_CR33","doi-asserted-by":"crossref","first-page":"2254","DOI":"10.1210\/clinem\/dgac299","volume":"107","author":"CL Roth","year":"2022","unstructured":"Roth, C. L. et al. Impaired brain satiety responses after weight loss in children with obesity. J. Clin. Endocrinol. Metab. 107, 2254\u20132266 (2022).","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"3774_CR34","doi-asserted-by":"crossref","first-page":"2709","DOI":"10.1016\/j.neuroimage.2011.10.071","volume":"59","author":"DL Murdaugh","year":"2012","unstructured":"Murdaugh, D. L., Cox, J. E., Cook, E. W. III & Weller, R. E. fMRI reactivity to high-calorie food pictures predicts short- and long-term outcome in a weight-loss program. Neuroimage 59, 2709\u20132721 (2012).","journal-title":"Neuroimage"},{"key":"3774_CR35","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1111\/obr.12354","volume":"17","author":"RG Boswell","year":"2016","unstructured":"Boswell, R. G. & Kober, H. Food cue reactivity and craving predict eating and weight gain: a meta-analytic review. Obes. Rev. 17, 159\u2013177 (2016).","journal-title":"Obes. Rev."},{"key":"3774_CR36","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1007\/BF00235545","volume":"49","author":"SJ Thorpe","year":"1983","unstructured":"Thorpe, S. J., Rolls, E. T. & Maddison, S. The orbitofrontal cortex: neuronal activity in the behaving monkey. Exp. Brain Res. 49, 93\u2013115 (1983).","journal-title":"Exp. Brain Res."},{"key":"3774_CR37","doi-asserted-by":"crossref","first-page":"1970","DOI":"10.1152\/jn.1996.75.5.1970","volume":"75","author":"ET Rolls","year":"1996","unstructured":"Rolls, E. T., Critchley, H. D., Mason, R. & Wakeman, E. A. Orbitofrontal cortex neurons: role in olfactory and visual association learning. J. Neurophysiol. 75, 1970\u20131981 (1996).","journal-title":"J. Neurophysiol."},{"key":"3774_CR38","doi-asserted-by":"crossref","first-page":"nsab083","DOI":"10.1093\/scan\/nsab083","volume":"18","author":"ET Rolls","year":"2023","unstructured":"Rolls, E. T., Feng, R., Cheng, W. & Feng, J. Orbitofrontal cortex connectivity is associated with food reward and body weight in humans. Soc. Cogn. Affect. Neurosci. 18, nsab083 (2023).","journal-title":"Soc. Cogn. Affect. Neurosci."},{"key":"3774_CR39","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.3945\/ajcn.113.080788","volume":"99","author":"WJ Eiler","year":"2014","unstructured":"Eiler, W. J. et al. Ventral frontal satiation-mediated responses to food aromas in obese and normal-weight women. Am. J. Clin. Nutr. 99, 1309\u20131318 (2014).","journal-title":"Am. J. Clin. Nutr."},{"key":"3774_CR40","doi-asserted-by":"crossref","first-page":"609012","DOI":"10.3389\/fnut.2021.609012","volume":"8","author":"E Saruco","year":"2021","unstructured":"Saruco, E. & Pleger, B. A systematic review of obesity and binge eating associated impairment of the cognitive inhibition system. Front. Nutr. 8, 609012 (2021).","journal-title":"Front. Nutr."},{"key":"3774_CR41","doi-asserted-by":"crossref","first-page":"795","DOI":"10.3945\/jn.111.153445","volume":"142","author":"MS Spetter","year":"2012","unstructured":"Spetter, M. S., de Graaf, C., Viergever, M. A. & Smeets, P. A. Anterior cingulate taste activation predicts ad libitum intake of sweet and savory drinks in healthy, normal-weight men. J. Nutr. 142, 795\u2013802 (2012).","journal-title":"J. Nutr."},{"key":"3774_CR42","doi-asserted-by":"crossref","first-page":"1808","DOI":"10.1093\/brain\/awf181","volume":"125","author":"SC Johnson","year":"2002","unstructured":"Johnson, S. C. et al. Neural correlates of self-reflection. Brain 125, 1808\u20131814 (2002).","journal-title":"Brain"},{"key":"3774_CR43","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1093\/scan\/nsp022","volume":"4","author":"MK Johnson","year":"2009","unstructured":"Johnson, M. K., Nolen-Hoeksema, S., Mitchell, K. J. & Levin, Y. Medial cortex activity, self-reflection and depression. Soc. Cogn. Affect. Neurosci. 4, 313\u2013327 (2009).","journal-title":"Soc. Cogn. Affect. Neurosci."},{"key":"3774_CR44","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.tics.2009.11.001","volume":"14","author":"RE Passingham","year":"2010","unstructured":"Passingham, R. E., Bengtsson, S. L. & Lau, H. C. Medial frontal cortex: from self-generated action to reflection on one\u2019s own performance. Trends Cogn. Sci. 14, 16\u201321 (2010).","journal-title":"Trends Cogn. Sci."},{"key":"3774_CR45","first-page":"391","volume":"7","author":"JM Moran","year":"2013","unstructured":"Moran, J. M., Kelley, W. M. & Heatherton, T. F. What can the organization of the brain\u2019s default mode network tell us about self-knowledge? Front. Hum. Neurosci. 7, 391 (2013).","journal-title":"Front. Hum. Neurosci."},{"key":"3774_CR46","doi-asserted-by":"crossref","DOI":"10.14814\/phy2.14639","volume":"8","author":"L Kerem","year":"2021","unstructured":"Kerem, L. et al. Modulation of neural fMRI responses to visual food cues by overeating and fasting interventions: a preliminary study. Physiol. Rep. 8, e14639 (2021).","journal-title":"Physiol. Rep."},{"key":"3774_CR47","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/j.appet.2017.09.025","volume":"120","author":"CN Kahathuduwa","year":"2018","unstructured":"Kahathuduwa, C. N. et al. Effects of 3-week total meal replacement vs. typical food-based diet on human brain functional magnetic resonance imaging food-cue reactivity and functional connectivity in people with obesity. Appetite 120, 431\u2013441 (2018).","journal-title":"Appetite"},{"key":"3774_CR48","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1097\/SLA.0b013e318203a289","volume":"253","author":"CN Ochner","year":"2011","unstructured":"Ochner, C. N. et al. Selective reduction in neural responses to high calorie foods following gastric bypass surgery. Ann. Surg. 253, 502\u2013507 (2011).","journal-title":"Ann. Surg."},{"key":"3774_CR49","doi-asserted-by":"crossref","first-page":"17","DOI":"10.3389\/fpsyg.2018.00017","volume":"9","author":"JL King","year":"2018","unstructured":"King, J. L. et al. Perceptual characterization of the Macronutrient Picture System (MaPS) for food image fMRI. Front. Psychol. 9, 17 (2018).","journal-title":"Front. Psychol."},{"key":"3774_CR50","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1016\/j.cmet.2023.02.015","volume":"35","author":"SE Thanarajah","year":"2023","unstructured":"Thanarajah, S. E. et al. Habitual daily intake of a sweet and fatty snack modulates reward processing in humans. Cell Metab. 35, 571\u2013584.e6 (2023).","journal-title":"Cell Metab."},{"key":"3774_CR51","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1038\/nn.2519","volume":"13","author":"PM Johnson","year":"2010","unstructured":"Johnson, P. M. & Kenny, P. J. Dopamine D2 receptors in addiction-like reward dysfunction and compulsive eating in obese rats. Nat. Neurosci. 13, 635\u2013641 (2010).","journal-title":"Nat. Neurosci."},{"key":"3774_CR52","unstructured":"Saxenda US, Package Insert (Novo Nordisk, 2018); www.accessdata.fda.gov\/drugsatfda_docs\/label\/2018\/206321s007lbl.pdf"},{"key":"3774_CR53","unstructured":"Wegovy US, Package Insert (Novo Nordisk, 2021); www.accessdata.fda.gov\/drugsatfda_docs\/label\/2021\/215256s000lbl.pdf"},{"key":"3774_CR54","doi-asserted-by":"crossref","first-page":"3140","DOI":"10.1007\/s40615-022-01487-0","volume":"10","author":"CN Johnson-Mann","year":"2023","unstructured":"Johnson-Mann, C. N. et al. A systematic review on participant diversity in clinical trials\u2014have we made progress for the management of obesity and its metabolic sequelae in diet, drug, and surgical trials. J. Racial Ethn. Health Disparities 10, 3140\u20133149 (2023).","journal-title":"J. Racial Ethn. Health Disparities"},{"key":"3774_CR55","doi-asserted-by":"crossref","first-page":"617","DOI":"10.3389\/fpsyg.2014.00617","volume":"5","author":"J Blechert","year":"2014","unstructured":"Blechert, J., Meule, A., Busch, N. A. & Ohla, K. Food-pics: an image database for experimental research on eating and appetite. Front. Psychol. 5, 617 (2014).","journal-title":"Front. Psychol."},{"key":"3774_CR56","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1016\/S0031-9384(97)00542-8","volume":"63","author":"PJ Geiselman","year":"1998","unstructured":"Geiselman, P. J. et al. Reliability and validity of a macronutrient self-selection paradigm and a food preference questionnaire. Physiol. Behav. 63, 919\u2013928 (1998).","journal-title":"Physiol. Behav."},{"key":"3774_CR57","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1006\/nimg.2001.0978","volume":"15","author":"N Tzourio-Mazoyer","year":"2002","unstructured":"Tzourio-Mazoyer, N. et al. Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain. Neuroimage 15, 273\u2013289 (2002).","journal-title":"Neuroimage"}],"container-title":["Nature Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41591-025-03774-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41591-025-03774-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41591-025-03774-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T11:03:35Z","timestamp":1788519815000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41591-025-03774-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,24]]},"references-count":57,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2025,9]]}},"alternative-id":["3774"],"URL":"https:\/\/doi.org\/10.1038\/s41591-025-03774-9","relation":{},"ISSN":["1078-8956","1546-170X"],"issn-type":[{"value":"1078-8956","type":"print"},{"value":"1546-170X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,24]]},"assertion":[{"value":"11 December 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 May 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 June 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The institution of C.K.M. is supported by NORC Center Grant P30 DK072476 entitled\n                      Nutrition and Metabolic Health Through the Lifespan\n                      sponsored by NIDDK and by grant U54 GM104940 from the National Institute of General Medical Sciences, which funds the Louisiana Clinical and Translational Science Center. C.K.M. declares research funding from Eli Lilly and Company paid to his institution to perform the work described in this paper; research grants or contracts paid to his institution from Pack Health, American Society for Nutrition, RAND Corporation, Richard King Mellon Foundation (RKMF), Evidation Health, Leona M. and Harry B. Helmsley Charitable Trust, State of Louisiana Federal American Rescue Plan (ARP), USDA, The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., University of Rochester (NY), Foundation for Food and Agriculture Research, Kroger Co. Zero Hunger\/Zero Waste Foundation, National Institute for Health Research (NIHR), Weight Watchers, American Diabetes Association, Eli Lilly and Company, National Science Foundation (NSF) and National Institutes of Health (NIH); royalties from ABGIL; personal consulting fees from EHE Health and WondrHealth; honoraria from Obesity Action Coalition, Indiana University Bloomington, University of Alabama at Birmingham, Nutrition Obesity Research Center, Brigham Young University, University of Kansas Medical Center (KUMC), University of Southern California and Commission on Dietetic Registration; travel support from Indiana University Bloomington, University of Alabama at Birmingham, Nutrition Obesity Research Center, Brigham Young University, University of Kansas Medical Center (KUMC), University of Southern California and Commission on Dietetic Registration; provision of research materials from Eli Lilly and Company and Weight Watchers; participation on advisory boards for Duke University (NIH-funded trial) and University of Alabama at Birmingham NIH-funded Nutrition Obesity Research Center; mentorship for a junior investigator at the University of Nebraska\u2013Lincoln who received an NIH-supported training grant; and participation in a Bray Course Planning Committee. O.T.C. declares a research grant from Eli Lilly and Company to his institution to perform the work described in this paper and research grants from NIH and Nestle, Inc., and has served on advisory boards for Novo Nordisk. D.A.K. declares clinical trial and research support from Eli Lilly and Company to his institution to perform the work described in this paper, as well as research support from the NIH. R.V.C. declares clinical trial support from Eli Lilly and Company and research support from Adipo Therapeutics. R.D.M. declares research grants from Grain Foods Foundation, Almond Board of California and Eli Lilly and Company; consulting fees from Mars Foods, General Mills Bright Seed and the Calorie Control Council; honoraria from Clean Label Conference, Columbia University, Sports Nutrition Plus, USDA, Michigan State University, American Diabetes Association, Mediterranean Diet Roundtable, American Society for Nutrition, American Italian Food Coalition and Healthy Aging Science Forum; participation on safety monitoring boards\/advisory boards for NIDCD; and presidency of the American Society for Nutrition. U.D. declares a research grant from Eli Lilly and Company to her institution to perform the work described in this paper and research support from the NIH and the International Manganese Institute. S.C. declares payments to her institution to support the work described in this paper. S.S., H.N., A.K., S.U., L.B., E.P., A.H., M.M., D.O.S., Z.M. and T.C. are employees and shareholders of Eli Lilly and Company. D.S. declares no competing interests.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}]}}