{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T16:40:48Z","timestamp":1774975248818,"version":"3.50.1"},"reference-count":85,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T00:00:00Z","timestamp":1774224000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"content-version":"vor","delay-in-days":8,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000025","name":"U.S. Department of Health & Human Services | NIH | National Institute of Mental Health","doi-asserted-by":"publisher","award":["R21-MH128574"],"award-info":[{"award-number":["R21-MH128574"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["W81XWH2210084"],"award-info":[{"award-number":["W81XWH2210084"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Transl Psychiatry"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Anorexia nervosa (AN) is an eating disorder observed primarily in girls and women, and is characterized by a low body weight, hypophagia, and hyperactivity. The activity-based anorexia (ABA) paradigm models aspects of AN, and refers to the progressive weight loss, hypophagia, and hyperactivity developed by rodents subjected to fixed-time food restriction and running wheel access. Recent metabolic studies identified white adipose tissue (WAT) as a primary location of the \u2018metabolic memory\u2019 of prior obesity, and implicated WAT-derived signals as drivers of relapse to obesity following weight loss. Thus, we examined whether an obese WAT transplant could attenuate ABA-induced weight loss in normal female mice. Recipient mice received a WAT transplant harvested from either standard chow-fed, or high-fat diet (HFD)-fed obese mice. Obese fat recipient (OFR) and control fat recipient (CFR) mice were then tested for ABA. OFR mice \u201csurvived\u201d longer than CFR mice in the ABA paradigm, defined as maintaining 75% of their initial body weight. Next, we tested whether agouti-related peptide (AgRP) neurons, which regulate feeding-related behaviors and metabolism, mediate obese WAT transplant-induced resilience against ABA. CFR and OFR mice received either control or neonatal AgRP ablation, and were assessed for ABA. OFR intact mice maintained higher body weights than CFR intact mice during ABA, but this effect was abolished by neonatal AgRP ablation. Furthermore, ablation reduced survival in OFR, but not CFR mice. In summary, obese WAT transplants signal to AgRP neurons to protect against ABA. Obese WAT-derived factors may provide targets for treatment development in AN.<\/jats:p>","DOI":"10.1038\/s41398-026-03970-2","type":"journal-article","created":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T17:34:27Z","timestamp":1774287267000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The mitigation of activity-based anorexia by obese adipose tissue transplant is abolished by neonatal AgRP neuron ablation"],"prefix":"10.1038","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-8318-3173","authenticated-orcid":false,"given":"Dongmin J.","family":"Yoon","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rizaldy C.","family":"Zapata","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martina","family":"Ulivieri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Avraham M.","family":"Libster","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1898-2933","authenticated-orcid":false,"given":"Matthew S.","family":"McMurray","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olivia","family":"Osborn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1281-782X","authenticated-orcid":false,"given":"Stephanie C.","family":"Dulawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,3,23]]},"reference":[{"key":"3970_CR1","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1146\/annurev.med.050208.200745","volume":"61","author":"E Attia","year":"2010","unstructured":"Attia E. Anorexia nervosa: Current status and future directions. Annu Rev Med. 2010;61:425\u201335.","journal-title":"Annu Rev Med"},{"key":"3970_CR2","doi-asserted-by":"publisher","first-page":"432","DOI":"10.1002\/erv.2553","volume":"25","author":"K Schaumberg","year":"2017","unstructured":"Schaumberg K, Welch E, Breithaupt L, Hubel C, Baker JH, Munn-Chernoff MA, et al. The science behind the academy for eating disorders\u2019 nine truths about eating disorders. Eur Eat Disord Rev. 2017;25:432\u201350.","journal-title":"Eur Eat Disord Rev"},{"key":"3970_CR3","doi-asserted-by":"publisher","first-page":"1181","DOI":"10.1002\/eat.23503","volume":"54","author":"L Di Lodovico","year":"2021","unstructured":"Di Lodovico L, Hatteea H, Couton C, Duriez P, Treasure J, Gorwood P. Physical exercise-related endophenotypes in anorexia nervosa. Int J Eat Disord. 2021;54:1181\u20138.","journal-title":"Int J Eat Disord"},{"key":"3970_CR4","doi-asserted-by":"publisher","DOI":"10.3389\/fnbeh.2021.700645","volume":"15","author":"LL Smith","year":"2021","unstructured":"Smith LL. The central role of hypothermia and hyperactivity in anorexia nervosa: A hypothesis. Front Behav Neurosci. 2021;15:700645.","journal-title":"Front Behav Neurosci"},{"key":"3970_CR5","doi-asserted-by":"publisher","first-page":"400","DOI":"10.3109\/15622975.2011.602720","volume":"12","author":"M Aigner","year":"2011","unstructured":"Aigner M, Treasure J, Kaye W, Kasper S. Disorders WTFOE. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the pharmacological treatment of eating disorders. World J Biol Psychiatry. 2011;12:400\u201343.","journal-title":"World J Biol Psychiatry"},{"key":"3970_CR6","doi-asserted-by":"publisher","first-page":"3167","DOI":"10.3390\/biomedicines10123167","volume":"10","author":"J Pruccoli","year":"2022","unstructured":"Pruccoli J, Bergonzini L, La Tempa A, Parmeggiani A. Antipsychotics in the treatment of children and adolescents with anorexia nervosa: A systematic review. Biomedicines. 2022;10:3167.","journal-title":"Biomedicines"},{"key":"3970_CR7","doi-asserted-by":"crossref","unstructured":"Crow SJ, Mitchell JE, Roerig JD, Steffen K. What potential role is there for medication treatment in anorexia nervosa? Int J Eat Disorder. 2009;42:1\u20138.","DOI":"10.1002\/eat.20576"},{"key":"3970_CR8","doi-asserted-by":"publisher","first-page":"1207","DOI":"10.1038\/s41588-019-0439-2","volume":"51","author":"HJ Watson","year":"2019","unstructured":"Watson HJ, Yilmaz Z, Thornton LM, Hubel C, Coleman JRI, Gaspar HA, et al. Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa. Nat Genet. 2019;51:1207\u201314.","journal-title":"Nat Genet"},{"key":"3970_CR9","doi-asserted-by":"publisher","first-page":"850","DOI":"10.1176\/appi.ajp.2017.16121402","volume":"174","author":"L Duncan","year":"2017","unstructured":"Duncan L, Yilmaz Z, Gaspar H, Walters R, Goldstein J, Anttila V, et al. Significant locus and metabolic genetic correlations revealed in genome-wide association study of anorexia nervosa. Am J Psychiatry. 2017;174:850\u20138.","journal-title":"Am J Psychiatry"},{"key":"3970_CR10","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1016\/0031-9384(76)90215-8","volume":"16","author":"GP Vincent","year":"1976","unstructured":"Vincent GP, Pare WP. Activity-stress ulcer in the rat, hamster, gerbil and guinea pig. Physiol Behav. 1976;16:557\u201360.","journal-title":"Physiol Behav"},{"key":"3970_CR11","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1002\/(SICI)1098-108X(1997)21:4<307::AID-EAT1>3.0.CO;2-S","volume":"21","author":"JL Treasure","year":"1997","unstructured":"Treasure JL, Owen JB. Intriguing links between animal behavior and anorexia nervosa. Int J Eat Disorder. 1997;21:307\u201311.","journal-title":"Int J Eat Disorder"},{"key":"3970_CR12","doi-asserted-by":"publisher","first-page":"449","DOI":"10.3758\/BF03337853","volume":"5","author":"GP Vincent","year":"1977","unstructured":"Vincent GP, Pare WP, Isom KE, Reeves JM. Activity-stress gastric lesions in Chipmunk (Tamias-Striatus). Physiol Psychol. 1977;5:449\u201352.","journal-title":"Physiol Psychol"},{"key":"3970_CR13","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1037\/h0060276","volume":"47","author":"JF Hall","year":"1954","unstructured":"Hall JF, Hanford PV. Activity as a function of a restricted feeding schedule. J Comp Physiol Psychol. 1954;47:362\u20133.","journal-title":"J Comp Physiol Psychol"},{"key":"3970_CR14","doi-asserted-by":"publisher","first-page":"803","DOI":"10.1016\/j.biopsych.2021.10.002","volume":"90","author":"SC Dulawa","year":"2021","unstructured":"Dulawa SC. Overlapping neural circuitry links cognitive flexibility and activity-based anorexia. Biol Psychiatry. 2021;90:803\u20135.","journal-title":"Biol Psychiatry"},{"key":"3970_CR15","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1007\/978-1-61779-458-2_25","volume":"829","author":"SJ Klenotich","year":"2012","unstructured":"Klenotich SJ, Dulawa SC. The activity-based anorexia mouse model. Methods Mol Biol. 2012;829:377\u201393.","journal-title":"Methods Mol Biol"},{"key":"3970_CR16","doi-asserted-by":"crossref","unstructured":"Foldi CJ. Taking better advantage of the activity-based anorexia model. Trends Mol Med. 2023;30:330\u20138.","DOI":"10.1016\/j.molmed.2023.11.011"},{"key":"3970_CR17","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1002\/eat.22095","volume":"46","author":"E Gutierrez","year":"2013","unstructured":"Gutierrez E. A rat in the labyrinth of anorexia nervosa: contributions of the activity-based anorexia rodent model to the understanding of anorexia nervosa. Int J Eat Disord. 2013;46:289\u2013301.","journal-title":"Int J Eat Disord"},{"key":"3970_CR18","doi-asserted-by":"publisher","first-page":"1620","DOI":"10.1038\/npp.2012.7","volume":"37","author":"SJ Klenotich","year":"2012","unstructured":"Klenotich SJ, Seiglie MP, McMurray MS, Roitman JD, Le Grange D, Dugad P, et al. Olanzapine, but not fluoxetine, treatment increases survival in activity-based anorexia in mice. Neuropsychopharmacology. 2012;37:1620\u201331.","journal-title":"Neuropsychopharmacology"},{"key":"3970_CR19","doi-asserted-by":"publisher","first-page":"414","DOI":"10.1037\/h0025205","volume":"64","author":"A Routtenberg","year":"1967","unstructured":"Routtenberg A, Kuznesof AW. Self-starvation of rats living in activity wheels on a restricted feeding schedule. J Comp Physiol Psychol. 1967;64:414\u201321.","journal-title":"J Comp Physiol Psychol"},{"key":"3970_CR20","doi-asserted-by":"publisher","first-page":"1217","DOI":"10.1093\/jn\/123.7.1217","volume":"123","author":"VR Burden","year":"1993","unstructured":"Burden VR, White BD, Dean RG, Martin RJ. Activity of the hypothalamic-pituitary-adrenal axis is elevated in rats with activity-based anorexia. J Nutr. 1993;123:1217\u201325.","journal-title":"J Nutr"},{"key":"3970_CR21","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1016\/j.jneumeth.2017.09.018","volume":"293","author":"L Frintrop","year":"2018","unstructured":"Frintrop L, Trinh S, Liesbrock J, Paulukat L, Kas MJ, Tolba R, et al. Establishment of a chronic activity-based anorexia rat model. J Neurosci Methods. 2018;293:191\u20138.","journal-title":"J Neurosci Methods"},{"key":"3970_CR22","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1016\/j.jadohealth.2022.06.010","volume":"71","author":"LM Ranzenhofer","year":"2022","unstructured":"Ranzenhofer LM, Jablonski M, Davis L, Posner J, Walsh BT, Steinglass JE. Early course of symptom development in anorexia nervosa. J Adolesc Health. 2022;71:587\u201393.","journal-title":"J Adolesc Health"},{"key":"3970_CR23","doi-asserted-by":"publisher","first-page":"1","DOI":"10.12968\/hmed.2020.0099","volume":"81","author":"J Neale","year":"2020","unstructured":"Neale J, Hudson LD. Anorexia nervosa in adolescents. Br J Hosp Med (Lond). 2020;81:1\u20138.","journal-title":"Br J Hosp Med (Lond)"},{"key":"3970_CR24","doi-asserted-by":"publisher","first-page":"728","DOI":"10.1038\/ijo.2017.266","volume":"42","author":"A Hernandez-Carretero","year":"2018","unstructured":"Hernandez-Carretero A, Weber N, La Frano MR, Ying W, Lantero Rodriguez J, Sears DD, et al. Obesity-induced changes in lipid mediators persist after weight loss. Int J Obes (Lond). 2018;42:728\u201336.","journal-title":"Int J Obes (Lond)"},{"key":"3970_CR25","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1016\/j.molmet.2015.12.001","volume":"5","author":"J Schmitz","year":"2016","unstructured":"Schmitz J, Evers N, Awazawa M, Nicholls HT, Bronneke HS, Dietrich A, et al. Obesogenic memory can confer long-term increases in adipose tissue but not liver inflammation and insulin resistance after weight loss. Mol Metab. 2016;5:328\u201339.","journal-title":"Mol Metab"},{"key":"3970_CR26","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1111\/obr.12255","volume":"16","author":"PS MacLean","year":"2015","unstructured":"MacLean PS, Higgins JA, Giles ED, Sherk VD, Jackman MR. The role for adipose tissue in weight regain after weight loss. Obes Rev. 2015;16:45\u201354.","journal-title":"Obes Rev"},{"key":"3970_CR27","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1038\/s41574-018-0148-4","volume":"15","author":"MA van Baak","year":"2019","unstructured":"van Baak MA, Mariman ECM. Mechanisms of weight regain after weight loss - the role of adipose tissue. Nat Rev Endocrinol. 2019;15:274\u201387.","journal-title":"Nat Rev Endocrinol"},{"key":"3970_CR28","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1242\/dmm.008698","volume":"4","author":"JR Speakman","year":"2011","unstructured":"Speakman JR, Levitsky DA, Allison DB, Bray MS, de Castro JM, Clegg DJ, et al. Set points, settling points and some alternative models: theoretical options to understand how genes and environments combine to regulate body adiposity. Dis Model Mech. 2011;4:733\u201345.","journal-title":"Dis Model Mech"},{"key":"3970_CR29","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1186\/s10020-023-00705-7","volume":"29","author":"RC Zapata","year":"2023","unstructured":"Zapata RC, Nasamran CA, Chilin-Fuentes DR, Dulawa SC, Osborn O. Identification of adipose tissue transcriptomic memory of anorexia nervosa. Mol Med. 2023;29:109.","journal-title":"Mol Med"},{"key":"3970_CR30","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-32764-5","volume":"13","author":"RC Zapata","year":"2022","unstructured":"Zapata RC, Carretero M, Reis FCG, Chaudry BS, Ofrecio J, Zhang D, et al. Adipocytes control food intake and weight regain via Vacuolar-type H(+) ATPase. Nat Commun. 2022;13:5092.","journal-title":"Nat Commun"},{"key":"3970_CR31","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/j.mce.2009.08.031","volume":"318","author":"TJ Bartness","year":"2010","unstructured":"Bartness TJ, Shrestha YB, Vaughan CH, Schwartz GJ, Song CK. Sensory and sympathetic nervous system control of white adipose tissue lipolysis. Mol Cell Endocrinol. 2010;318:34\u201343.","journal-title":"Mol Cell Endocrinol"},{"key":"3970_CR32","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1186\/1743-7075-11-27","volume":"11","author":"W Zhang","year":"2014","unstructured":"Zhang W, Cline MA, Gilbert ER. Hypothalamus-adipose tissue crosstalk: neuropeptide Y and the regulation of energy metabolism. Nutr Metab (Lond). 2014;11:27.","journal-title":"Nutr Metab (Lond)"},{"key":"3970_CR33","doi-asserted-by":"publisher","first-page":"191","DOI":"10.5114\/aoms.2013.33181","volume":"9","author":"M Coelho","year":"2013","unstructured":"Coelho M, Oliveira T, Fernandes R. Biochemistry of adipose tissue: an endocrine organ. Arch Med Sci. 2013;9:191\u2013200.","journal-title":"Arch Med Sci"},{"key":"3970_CR34","doi-asserted-by":"publisher","first-page":"1424","DOI":"10.1172\/JCI46229","volume":"121","author":"MJ Krashes","year":"2011","unstructured":"Krashes MJ, Koda S, Ye C, Rogan SC, Adams AC, Cusher DS, et al. Rapid, reversible activation of AgRP neurons drives feeding behavior in mice. J Clin Invest. 2011;121:1424\u20138.","journal-title":"J Clin Invest"},{"key":"3970_CR35","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1038\/nn.2739","volume":"14","author":"Y Aponte","year":"2011","unstructured":"Aponte Y, Atasoy D, Sternson SM. AGRP neurons are sufficient to orchestrate feeding behavior rapidly and without training. Nat Neurosci. 2011;14:351\u20135.","journal-title":"Nat Neurosci"},{"key":"3970_CR36","doi-asserted-by":"publisher","first-page":"8678","DOI":"10.1523\/JNEUROSCI.0798-17.2017","volume":"37","author":"RA Essner","year":"2017","unstructured":"Essner RA, Smith AG, Jamnik AA, Ryba AR, Trutner ZD, Carter ME. AgRP neurons can increase food intake during conditions of appetite suppression and inhibit anorexigenic parabrachial neurons. J Neurosci. 2017;37:8678\u201387.","journal-title":"J Neurosci"},{"key":"3970_CR37","doi-asserted-by":"publisher","first-page":"734","DOI":"10.1038\/nn.4274","volume":"19","author":"SL Padilla","year":"2016","unstructured":"Padilla SL, Qiu J, Soden ME, Sanz E, Nestor CC, Barker FD, et al. Agouti-related peptide neural circuits mediate adaptive behaviors in the starved state. Nat Neurosci. 2016;19:734\u201341.","journal-title":"Nat Neurosci"},{"key":"3970_CR38","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1038\/s42255-024-00987-z","volume":"6","author":"AJ De Solis","year":"2024","unstructured":"De Solis AJ, Del Rio-Martin A, Radermacher J, Chen W, Steuernagel L, Bauder CA, et al. Reciprocal activity of AgRP and POMC neurons governs coordinated control of feeding and metabolism. Nat Metab. 2024;6:473\u201393.","journal-title":"Nat Metab"},{"key":"3970_CR39","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/j.conb.2020.08.009","volume":"65","author":"SM Sternson","year":"2020","unstructured":"Sternson SM. Exploring internal state-coding across the rodent brain. Curr Opin Neurobiol. 2020;65:20\u20136.","journal-title":"Curr Opin Neurobiol"},{"key":"3970_CR40","doi-asserted-by":"publisher","first-page":"e22848","DOI":"10.7554\/eLife.22848","volume":"6","author":"LK Burke","year":"2017","unstructured":"Burke LK, Darwish T, Cavanaugh AR, Virtue S, Roth E, Morro J, et al. mTORC1 in AGRP neurons integrates exteroceptive and interoceptive food-related cues in the modulation of adaptive energy expenditure in mice. Elife. 2017;6:e22848.","journal-title":"Elife"},{"key":"3970_CR41","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/j.molmet.2018.08.011","volume":"18","author":"Z He","year":"2018","unstructured":"He Z, Gao Y, Alhadeff AL, Castorena CM, Huang Y, Lieu L, et al. Cellular and synaptic reorganization of arcuate NPY\/AgRP and POMC neurons after exercise. Mol Metab. 2018;18:107\u201319.","journal-title":"Mol Metab"},{"key":"3970_CR42","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1152\/physiolgenomics.00042.2023","volume":"56","author":"ML Ritter","year":"2024","unstructured":"Ritter ML, Wagner VA, Balapattabi K, Opichka MA, Lu KT, Wackman KK, et al. Kruppel-like factor 4 in transcriptional control of the three unique isoforms of Agouti-related peptide in mice. Physiol Genomics. 2024;56:265\u201375.","journal-title":"Physiol Genomics"},{"key":"3970_CR43","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2022.101455","volume":"59","author":"Y Qi","year":"2022","unstructured":"Qi Y, Lee NJ, Ip CK, Enriquez R, Tasan R, Zhang L, et al. NPY derived from AGRP neurons controls feeding via Y1 and energy expenditure and food foraging behaviour via Y2 signalling. Mol Metab. 2022;59:101455.","journal-title":"Mol Metab"},{"key":"3970_CR44","doi-asserted-by":"publisher","first-page":"2362","DOI":"10.1111\/febs.16176","volume":"289","author":"JD Deem","year":"2022","unstructured":"Deem JD, Faber CL, Morton GJ. AgRP neurons: Regulators of feeding, energy expenditure, and behavior. FEBS J. 2022;289:2362\u201381.","journal-title":"FEBS J"},{"key":"3970_CR45","doi-asserted-by":"publisher","first-page":"1204","DOI":"10.1038\/s42255-020-00300-8","volume":"2","author":"MC Miletta","year":"2020","unstructured":"Miletta MC, Iyilikci O, Shanabrough M, Sestan-Pesa M, Cammisa A, Zeiss CJ, et al. AgRP neurons control compulsive exercise and survival in an activity-based anorexia model. Nat Metab. 2020;2:1204\u201311.","journal-title":"Nat Metab"},{"key":"3970_CR46","doi-asserted-by":"publisher","first-page":"1622","DOI":"10.1038\/s41380-022-01932-w","volume":"28","author":"AK Sutton Hickey","year":"2023","unstructured":"Sutton Hickey AK, Duane SC, Mickelsen LE, Karolczak EO, Shamma AM, Skillings A, et al. AgRP neurons coordinate the mitigation of activity-based anorexia. Mol Psychiatry. 2023;28:1622\u201335.","journal-title":"Mol Psychiatry"},{"key":"3970_CR47","doi-asserted-by":"publisher","first-page":"4276","DOI":"10.1038\/emboj.2012.250","volume":"31","author":"A Joly-Amado","year":"2012","unstructured":"Joly-Amado A, Denis RG, Castel J, Lacombe A, Cansell C, Rouch C, et al. Hypothalamic AgRP-neurons control peripheral substrate utilization and nutrient partitioning. EMBO J. 2012;31:4276\u201388.","journal-title":"EMBO J"},{"key":"3970_CR48","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-08239-x","volume":"10","author":"JP Cavalcanti-de-Albuquerque","year":"2019","unstructured":"Cavalcanti-de-Albuquerque JP, Bober J, Zimmer MR, Dietrich MO. Regulation of substrate utilization and adiposity by Agrp neurons. Nat Commun. 2019;10:311.","journal-title":"Nat Commun"},{"key":"3970_CR49","first-page":"379","volume":"12","author":"K Goto","year":"2003","unstructured":"Goto K, Inui A, Takimoto Y, Yuzuriha H, Asakawa A, Kawamura Y, et al. Acute intracerebroventricular administration of either carboxyl-terminal or amino-terminal fragments of agouti-related peptide produces a long-term decrease in energy expenditure in rats. Int J Mol Med. 2003;12:379\u201383.","journal-title":"Int J Mol Med"},{"key":"3970_CR50","doi-asserted-by":"publisher","DOI":"10.1007\/s11920-019-0988-1","volume":"21","author":"CA Timko","year":"2019","unstructured":"Timko CA, DeFilipp L, Dakanalis A. Sex differences in adolescent anorexia and bulimia nervosa: Beyond the signs and symptoms. Curr Psychiatry Rep. 2019;21:1.","journal-title":"Curr Psychiatry Rep"},{"key":"3970_CR51","doi-asserted-by":"publisher","first-page":"683","DOI":"10.1126\/science.1115524","volume":"310","author":"S Luquet","year":"2005","unstructured":"Luquet S, Perez FA, Hnasko TS, Palmiter RD. NPY\/AgRP neurons are essential for feeding in adult mice but can be ablated in neonates. Science. 2005;310:683\u20135.","journal-title":"Science"},{"key":"3970_CR52","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1016\/j.cmet.2008.04.004","volume":"7","author":"TT Tran","year":"2008","unstructured":"Tran TT, Yamamoto Y, Gesta S, Kahn CR. Beneficial effects of subcutaneous fat transplantation on metabolism. Cell Metab. 2008;7:410\u201320.","journal-title":"Cell Metab"},{"key":"3970_CR53","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/B978-0-12-411619-1.00006-9","volume":"537","author":"SD Parlee","year":"2014","unstructured":"Parlee SD, Lentz SI, Mori H, MacDougald OA. Quantifying size and number of adipocytes in adipose tissue. Methods Enzymol. 2014;537:93\u2013122.","journal-title":"Methods Enzymol"},{"key":"3970_CR54","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2015.109","volume":"5","author":"SJ Klenotich","year":"2015","unstructured":"Klenotich SJ, Ho EV, McMurray MS, Server CH, Dulawa SC. Dopamine D2\/3 receptor antagonism reduces activity-based anorexia. Transl Psychiatry. 2015;5:e613.","journal-title":"Transl Psychiatry"},{"key":"3970_CR55","doi-asserted-by":"publisher","first-page":"3765","DOI":"10.1038\/s41380-019-0633-8","volume":"26","author":"AC Welch","year":"2019","unstructured":"Welch AC, Zhang J, Lyu J, McMurray MS, Javitch JA, Kellendonk C, et al. Dopamine D2 receptor overexpression in the nucleus accumbens core induces robust weight loss during scheduled fasting selectively in female mice. Mol Psychiatry. 2019;26:3765\u201377.","journal-title":"Mol Psychiatry"},{"key":"3970_CR56","doi-asserted-by":"publisher","first-page":"1078","DOI":"10.1016\/j.cmet.2019.01.023","volume":"29","author":"J Cedernaes","year":"2019","unstructured":"Cedernaes J, Huang W, Ramsey KM, Waldeck N, Cheng L, Marcheva B, et al. Transcriptional basis for rhythmic control of hunger and metabolism within the AgRP neuron. Cell Metab. 2019;29:1078\u201391.e1075.","journal-title":"Cell Metab"},{"key":"3970_CR57","doi-asserted-by":"publisher","first-page":"e65317","DOI":"10.1371\/journal.pone.0065317","volume":"8","author":"R Dutia","year":"2013","unstructured":"Dutia R, Kim AJ, Modes M, Rothlein R, Shen JM, Tian YE, et al. Effects of AgRP inhibition on energy balance and metabolism in rodent models. PLoS One. 2013;8:e65317.","journal-title":"PLoS One"},{"key":"3970_CR58","doi-asserted-by":"publisher","first-page":"33295","DOI":"10.1073\/pnas.2005950117","volume":"117","author":"Y Gao","year":"2020","unstructured":"Gao Y, Chen X, He Q, Gimple RC, Liao Y, Wang L, et al. Adipocytes promote breast tumorigenesis through TAZ-dependent secretion of Resistin. Proc Natl Acad Sci USA 2020;117:33295\u2013304.","journal-title":"Proc Natl Acad Sci USA"},{"key":"3970_CR59","doi-asserted-by":"publisher","first-page":"1988","DOI":"10.3390\/cells9091988","volume":"9","author":"L Rios-Colon","year":"2020","unstructured":"Rios-Colon L, Arthur E, Niture S, Qi Q, Moore JT, Kumar D. The role of exosomes in the crosstalk between adipocytes and liver cancer cells. Cells. 2020;9:1988.","journal-title":"Cells"},{"key":"3970_CR60","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.physbeh.2016.12.014","volume":"170","author":"N Achamrah","year":"2017","unstructured":"Achamrah N, Nobis S, Goichon A, Breton J, Legrand R, do Rego JL, et al. Sex differences in response to activity-based anorexia model in C57Bl\/6 mice. Physiol Behav. 2017;170:1\u20135.","journal-title":"Physiol Behav"},{"key":"3970_CR61","doi-asserted-by":"publisher","first-page":"256","DOI":"10.18632\/aging.100738","volume":"7","author":"RA van der Heijden","year":"2015","unstructured":"van der Heijden RA, Sheedfar F, Morrison MC, Hommelberg PP, Kor D, Kloosterhuis NJ, et al. High-fat diet induced obesity primes inflammation in adipose tissue prior to liver in C57BL\/6j mice. Aging (Albany NY). 2015;7:256\u201368.","journal-title":"Aging (Albany NY)"},{"key":"3970_CR62","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1038\/sj.ijo.0801209","volume":"24","author":"S Lin","year":"2000","unstructured":"Lin S, Thomas TC, Storlien LH, Huang XF. Development of high fat diet-induced obesity and leptin resistance in C57Bl\/6J mice. Int J Obes Relat Metab Disord. 2000;24:639\u201346.","journal-title":"Int J Obes Relat Metab Disord"},{"key":"3970_CR63","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1016\/j.biopsych.2005.03.011","volume":"58","author":"JJ Hillebrand","year":"2005","unstructured":"Hillebrand JJ, Koeners MP, de Rijke CE, Kas MJ, Adan RA. Leptin treatment in activity-based anorexia. Biol Psychiatry. 2005;58:165\u201371.","journal-title":"Biol Psychiatry"},{"key":"3970_CR64","doi-asserted-by":"publisher","first-page":"476","DOI":"10.1038\/sj.mp.4000771","volume":"5","author":"C Exner","year":"2000","unstructured":"Exner C, Hebebrand J, Remschmidt H, Wewetzer C, Ziegler A, Herpertz S, et al. Leptin suppresses semi-starvation induced hyperactivity in rats: implications for anorexia nervosa. Mol Psychiatry. 2000;5:476\u201381.","journal-title":"Mol Psychiatry"},{"key":"3970_CR65","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1016\/j.euroneuro.2010.11.006","volume":"21","author":"LA Verhagen","year":"2011","unstructured":"Verhagen LA, Luijendijk MC, Adan RA. Leptin reduces hyperactivity in an animal model for anorexia nervosa via the ventral tegmental area. Eur Neuropsychopharmacol. 2011;21:274\u201381.","journal-title":"Eur Neuropsychopharmacol"},{"key":"3970_CR66","doi-asserted-by":"publisher","first-page":"588","DOI":"10.1016\/j.cmet.2013.09.009","volume":"18","author":"MJ Krashes","year":"2013","unstructured":"Krashes MJ, Shah BP, Koda S, Lowell BB. Rapid versus delayed stimulation of feeding by the endogenously released AgRP neuron mediators GABA, NPY, and AgRP. Cell Metab. 2013;18:588\u201395.","journal-title":"Cell Metab"},{"key":"3970_CR67","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1038\/nrm729","volume":"3","author":"T Nishi","year":"2002","unstructured":"Nishi T, Forgac M. The vacuolar (H)-atpases - Nature\u2019s most versatile proton pumps. Nat Rev Mol Cell Bio. 2002;3:94\u2013103.","journal-title":"Nat Rev Mol Cell Bio"},{"key":"3970_CR68","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.5440","volume":"6","author":"F Rotondo","year":"2018","unstructured":"Rotondo F, Ho-Palma AC, Remesar X, Fernandez-Lopez JA, Romero MDM, Alemany M. Effect of sex on glucose handling by adipocytes isolated from rat subcutaneous, mesenteric and perigonadal adipose tissue. PeerJ. 2018;6:e5440.","journal-title":"PeerJ"},{"key":"3970_CR69","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.1399","volume":"3","author":"S Arriaran","year":"2015","unstructured":"Arriaran S, Agnelli S, Remesar X, Fernandez-Lopez JA, Alemany M. Effects of sex and site on amino acid metabolism enzyme gene expression and activity in rat white adipose tissue. PeerJ. 2015;3:e1399.","journal-title":"PeerJ"},{"key":"3970_CR70","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2024.159543","volume":"1869","author":"M Riecan","year":"2024","unstructured":"Riecan M, Domanska V, Lupu C, Patel M, Vondrackova M, Rossmeisl M, et al. Tissue-specific sex-dependent difference in the metabolism of fatty acid esters of hydroxy fatty acids. Biochim Biophys Acta Mol Cell Biol Lipids. 2024;1869:159543.","journal-title":"Biochim Biophys Acta Mol Cell Biol Lipids"},{"key":"3970_CR71","doi-asserted-by":"publisher","first-page":"3453","DOI":"10.3390\/cells10123453","volume":"10","author":"ED Queathem","year":"2021","unstructured":"Queathem ED, Welly RJ, Clart LM, Rowles CC, Timmons H, Fitzgerald M, et al. White adipose tissue depots respond to chronic Beta-3 adrenergic receptor activation in a sexually dimorphic and depot divergent manner. Cells. 2021;10:3453.","journal-title":"Cells"},{"key":"3970_CR72","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.112935","volume":"42","author":"K Balapattabi","year":"2023","unstructured":"Balapattabi K, Yavuz Y, Jiang J, Deng G, Mathieu NM, Ritter ML, et al. Angiotensin AT(1A) receptor signal switching in Agouti-related peptide neurons mediates metabolic rate adaptation during obesity. Cell Rep. 2023;42:112935.","journal-title":"Cell Rep"},{"key":"3970_CR73","doi-asserted-by":"publisher","first-page":"857","DOI":"10.1016\/j.cmet.2024.02.007","volume":"36","author":"D Guan","year":"2024","unstructured":"Guan D, Men Y, Bartlett A, Hernandez MAS, Xu J, Yi X, et al. Central inhibition of HDAC6 re-sensitizes leptin signaling during obesity to induce profound weight loss. Cell Metab. 2024;36:857\u201376.e810.","journal-title":"Cell Metab"},{"key":"3970_CR74","doi-asserted-by":"publisher","DOI":"10.1016\/j.npep.2024.102461","volume":"108","author":"J Ajwani","year":"2024","unstructured":"Ajwani J, Hwang E, Portillo B, Lieu L, Wallace B, Kabahizi A, et al. Upregulation of Xbp1 in NPY\/AgRP neurons reverses diet-induced obesity and ameliorates leptin and insulin resistance. Neuropeptides. 2024;108:102461.","journal-title":"Neuropeptides"},{"key":"3970_CR75","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.867929","volume":"13","author":"N Murgia","year":"2022","unstructured":"Murgia N, Ma Y, Najam SS, Liu Y, Przybys J, Guo C, et al. In vivo reductionist approach identifies miR-15a protecting mice from obesity. Front Endocrinol (Lausanne). 2022;13:867929.","journal-title":"Front Endocrinol (Lausanne)"},{"key":"3970_CR76","doi-asserted-by":"publisher","first-page":"1123","DOI":"10.1007\/s40519-021-01257-7","volume":"27","author":"S Gorrell","year":"2022","unstructured":"Gorrell S, Hughes EK, Sawyer SM, Roberts SR, Nagata JM, Yeo M, et al. Gender-based clinical differences in evidence-based treatment for adolescent anorexia nervosa: analysis of aggregated randomized controlled trials. Eat Weight Disord. 2022;27:1123\u201330.","journal-title":"Eat Weight Disord"},{"key":"3970_CR77","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1016\/j.bbadis.2013.05.006","volume":"1842","author":"UA White","year":"2014","unstructured":"White UA, Tchoukalova YD. Sex dimorphism and depot differences in adipose tissue function. Biochim Biophys Acta. 2014;1842:377\u201392.","journal-title":"Biochim Biophys Acta"},{"key":"3970_CR78","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1148\/radiol.2242011369","volume":"224","author":"K Arfai","year":"2002","unstructured":"Arfai K, Pitukcheewanont PD, Goran MI, Tavare CJ, Heller L, Gilsanz V. Bone, muscle, and fat: sex-related differences in prepubertal children. Radiology. 2002;224:338\u201344.","journal-title":"Radiology"},{"key":"3970_CR79","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1210\/en.2018-00797","volume":"160","author":"M Varghese","year":"2019","unstructured":"Varghese M, Griffin C, McKernan K, Eter L, Lanzetta N, Agarwal D, et al. Sex differences in inflammatory responses to adipose tissue lipolysis in diet-induced obesity. Endocrinology. 2019;160:293\u2013312.","journal-title":"Endocrinology"},{"key":"3970_CR80","doi-asserted-by":"publisher","first-page":"1108","DOI":"10.1038\/nn.3147","volume":"15","author":"MO Dietrich","year":"2012","unstructured":"Dietrich MO, Bober J, Ferreira JG, Tellez LA, Mineur YS, Souza DO, et al. AgRP neurons regulate development of dopamine neuronal plasticity and nonfood-associated behaviors. Nat Neurosci. 2012;15:1108\u201310.","journal-title":"Nat Neurosci"},{"key":"3970_CR81","doi-asserted-by":"publisher","first-page":"5027","DOI":"10.1128\/MCB.22.14.5027-5035.2002","volume":"22","author":"S Qian","year":"2002","unstructured":"Qian S, Chen H, Weingarth D, Trumbauer ME, Novi DE, Guan XM, et al. Neither agouti-related protein nor neuropeptide Y is critically required for the regulation of energy homeostasis in mice. Mol Cell Biol. 2002;22:5027\u201335.","journal-title":"Mol Cell Biol"},{"key":"3970_CR82","doi-asserted-by":"publisher","first-page":"975","DOI":"10.1016\/j.cmet.2017.03.001","volume":"25","author":"RGP Denis","year":"2017","unstructured":"Denis RGP, Joly-Amado A, Webber E, Langlet F, Schaeffer M, Padilla SL, et al. Palatability can drive feeding independent of AgRP neurons (vol 22, pg 646, 2015). Cell Metabolism. 2017;25:975.","journal-title":"Cell Metabolism"},{"key":"3970_CR83","doi-asserted-by":"publisher","first-page":"1110","DOI":"10.3390\/cells11071110","volume":"11","author":"M Claes","year":"2022","unstructured":"Claes M, De Groef L, Moons L. The DREADDful hurdles and opportunities of the chronic chemogenetic toolbox. Cells. 2022;11:1110.","journal-title":"Cells"},{"key":"3970_CR84","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1111\/epi.16840","volume":"62","author":"MG Goossens","year":"2021","unstructured":"Goossens MG, Boon P, Wadman W, Van den Haute C, Baekelandt V, Verstraete AG, et al. Long-term chemogenetic suppression of seizures in a multifocal rat model of temporal lobe epilepsy. Epilepsia. 2021;62:659\u201370.","journal-title":"Epilepsia"},{"key":"3970_CR85","doi-asserted-by":"publisher","first-page":"5988","DOI":"10.1523\/JNEUROSCI.0444-16.2016","volume":"36","author":"F Carvalho Poyraz","year":"2016","unstructured":"Carvalho Poyraz F, Holzner E, Bailey MR, Meszaros J, Kenney L, Kheirbek MA, et al. Decreasing striatopallidal pathway function enhances motivation by energizing the initiation of goal-directed action. J Neurosci. 2016;36:5988\u20136001.","journal-title":"J Neurosci"}],"container-title":["Translational Psychiatry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41398-026-03970-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41398-026-03970-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41398-026-03970-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T15:03:42Z","timestamp":1774969422000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41398-026-03970-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,23]]},"references-count":85,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["3970"],"URL":"https:\/\/doi.org\/10.1038\/s41398-026-03970-2","relation":{},"ISSN":["2158-3188"],"issn-type":[{"value":"2158-3188","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,23]]},"assertion":[{"value":"17 April 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 February 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 March 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 March 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"199"}}