{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T20:04:14Z","timestamp":1789416254183,"version":"build-2803163510"},"reference-count":73,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research and Development Agency","award":["2023\u201321231357"],"award-info":[{"award-number":["2023\u201321231357"]}]},{"award":["2023\u201321231357"],"award-info":[{"award-number":["2023\u201321231357"]}],"id":[{"id":"https:\/\/ror.org\/02ap3w078","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005916","name":"Universidad de La Frontera","doi-asserted-by":"crossref","award":["DIUFRO DI24-0029"],"award-info":[{"award-number":["DIUFRO DI24-0029"]}],"id":[{"id":"10.13039\/501100005916","id-type":"DOI","asserted-by":"crossref"}]},{"award":["DIUFRO DI24-0029"],"award-info":[{"award-number":["DIUFRO DI24-0029"]}],"id":[{"id":"https:\/\/ror.org\/04v0snf24","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Adverse childhood experiences are associated with long-term metabolic disturbances, yet their effects on the exocrine pancreas remain poorly understood. Using maternal separation (MS) as a model of early-life stress, this study examined whether MS modifies the exocrine pancreatic response to a post-weaning high-fat diet (HFD) in male C57BL\/6 mice. Animals were exposed to MS or standard rearing conditions and fed a control diet or HFD for 16 weeks. Body and pancreatic mass, plasma amylase and lipase activities, exocrine pancreatic histopathology, and apoptosis were assessed. HFD increased body mass and reduced the pancreas-to-body mass ratio independently of MS, without altering absolute pancreatic mass. Lipase activity increased significantly in response to both MS and HFD, whereas amylase showed a non-significant upward trend. Histopathological analysis revealed condition-dependent exocrine pancreatic remodeling, including acinar hypertrophy, autophagic vacuolization, focal necrosis, vascular alterations, interstitial edema, and ductal changes. These alterations were mild in HFD-only mice but more pronounced in MS-exposed animals, particularly when combined with HFD. Apoptosis was strongly influenced by early-life stress and modulated by diet, with significant effects of MS and the MS \u00d7 diet interaction. Overall, early-life stress induces persistent structural and functional alterations in the exocrine pancreas, increasing susceptibility to nutritional challenges in adulthood.<\/jats:p>","DOI":"10.3390\/biology15151297","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T08:14:46Z","timestamp":1785917686000},"page":"1297","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Double-Hit Model of Early-Life Stress and High-Fat Feeding Reveals Enhanced Exocrine Pancreatic Remodeling"],"prefix":"10.3390","volume":"15","author":[{"given":"Laura","family":"Garc\u00eda-Orozco","sequence":"first","affiliation":[{"name":"Doctoral Program in Morphological Sciences, Faculty of Medicine, Universidad de La Frontera, Temuco 4780000, Chile"},{"name":"Health Knowledge Management Research Group, Medical Science Faculty, Corporaci\u00f3n Universitaria Empresarial Alexander Von Humboldt (UNIHUMBOLDT), Armenia 630004, Quind\u00edo, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4134-7978","authenticated-orcid":false,"given":"Carlos Alberto","family":"Mandarim-de-Lacerda","sequence":"additional","affiliation":[{"name":"Laboratory of Morphometry, Metabolism, and Cardiovascular Disease, Institute of Biology, Biomedical Center, The University of the State of Rio de Janeiro, Rio de Janeiro 20551-030, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4106-3548","authenticated-orcid":false,"given":"B\u00e9lgica","family":"V\u00e1squez","sequence":"additional","affiliation":[{"name":"Doctoral Program in Morphological Sciences, Faculty of Medicine, Universidad de La Frontera, Temuco 4780000, Chile"},{"name":"Center of Excellence in Morphological and Surgical Studies, Universidad de La Frontera, Temuco 4811230, Chile"},{"name":"Department of Basic Sciences, Faculty of Medicine, Universidad de La Frontera, Avenida Francisco Salazar 01145, Temuco 4811230, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1016\/j.jad.2024.10.074","article-title":"The impact of adverse childhood experiences on adult physical, mental health, and abuse behaviors: A sex-stratified nationwide latent class analysis in Japan","volume":"369","author":"Hirai","year":"2025","journal-title":"J. Affect. Disord."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.1093\/ije\/dyad054","article-title":"A longitudinal study evaluating adverse childhood experiences and obesity in adulthood using the Canadian Longitudinal Study on Aging (CLSA)","volume":"52","author":"Gonzalez","year":"2023","journal-title":"Int. J. Epidemiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ypmed.2017.12.013","article-title":"Using path analysis to examine the relationship between sexual abuse in childhood and diabetes in adulthood in a sample of US adults","volume":"108","author":"Campbell","year":"2018","journal-title":"Prev. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1016\/j.jdiacomp.2018.09.006","article-title":"The differential impact of adverse childhood experiences in the development of pre-diabetes in a longitudinal cohort of US adults","volume":"32","author":"Campbell","year":"2018","journal-title":"J. Diabetes Complicat."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1007\/s00213-010-2096-0","article-title":"Early life stress paradigms in rodents: Potential animal models of depression?","volume":"214","author":"Schmidt","year":"2011","journal-title":"Psychopharmacology"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Nishi, M. (2020). Effects of early-life stress on the brain and behaviors: Implications of early maternal separation in rodents. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21197212"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1038\/s41386-022-01493-0","article-title":"Effects of early life stress and subsequent re-exposure to stress on neuronal activity in the lateral habenula","volume":"48","author":"Webster","year":"2023","journal-title":"Neuropsychopharmacology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/S0091-3057(02)00781-5","article-title":"Long-lasting changes in stress-induced corticosterone response and anxiety-like behaviors as a consequence of neonatal maternal separation in Long-Evans rats","volume":"73","author":"Kalinichev","year":"2002","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"113399","DOI":"10.1016\/j.physbeh.2021.113399","article-title":"Chronic stress caused by maternal separation is a possible risk factor for the development of 7,12-dimethyl benzo anthracene-induced breast tumors in rats","volume":"235","year":"2021","journal-title":"Physiol. Behav."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"R353","DOI":"10.1152\/ajpregu.00216.2022","article-title":"High-fat\/high-sucrose diet worsens metabolic outcomes and widespread hypersensitivity following early-life stress exposure in female mice","volume":"324","author":"Frick","year":"2023","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"100879","DOI":"10.1016\/j.bbih.2024.100879","article-title":"Early-life obesogenic environment integrates immunometabolic and epigenetic signatures governing neuroinflammation","volume":"42","author":"Simon","year":"2024","journal-title":"Brain Behav. Immun. Health"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"100360","DOI":"10.1016\/j.ynstr.2021.100360","article-title":"Adult food choices depend on sex and exposure to early-life stress: Underlying brain circuitry, adipose tissue adaptations and metabolic responses","volume":"15","author":"Ruigrok","year":"2021","journal-title":"Neurobiol. Stress"},{"key":"ref_13","first-page":"691","article-title":"Postnatal maternal separation modifies the response to an obesogenic diet in adulthood in rats","volume":"5","author":"Paternain","year":"2012","journal-title":"Dis. Models Mech."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Jaimes-Hoy, L., Romero, F., Charli, J.L., and Joseph-Bravo, P. (2019). Sex dimorphic responses of the hypothalamus\u2013pituitary\u2013thyroid axis to maternal separation and palatable diet. Front. Endocrinol., 10.","DOI":"10.3389\/fendo.2019.00445"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Mela, V., Llorente-Berzal, \u00c1., D\u00edaz, F., Argente, J., Viveros, M.P., and Chowen, J.A. (2012). Maternal deprivation exacerbates the response to a high fat diet in a sexually dimorphic manner. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0048915"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Garc\u00eda-Orozco, L., Rivadeneira, J., and V\u00e1squez, B. (2025). Impact of early postnatal maternal separation stress on pancreatic function in rodents: A systematic review and meta-analysis. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26209927"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Overton, D.L., and Mastracci, T.L. (2022). Exocrine-endocrine crosstalk: The influence of pancreatic cellular communications on organ growth, function and disease. Front. Endocrinol., 13.","DOI":"10.3389\/fendo.2022.904004"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1038\/s41392-024-02098-3","article-title":"Pancreatic endocrine and exocrine signaling and crosstalk in physiological and pathological status","volume":"10","author":"Hu","year":"2025","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1007\/s12192-019-00988-y","article-title":"Impact of chronic exercise on counteracting chronic stress-induced functional and morphological pancreatic changes in male albino rats","volume":"24","author":"Elbassuoni","year":"2019","journal-title":"Cell Stress Chaperones"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1007\/s12192-020-01169-y","article-title":"Sex differences impact the pancreatic response to chronic immobilization stress in rats","volume":"26","author":"Allam","year":"2021","journal-title":"Cell Stress Chaperones"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1097\/MPA.0000000000000129","article-title":"Pancreatic fat accumulation, fibrosis, and acinar cell injury in the Zucker diabetic fatty rat fed a chronic high-fat diet","volume":"43","author":"Matsuda","year":"2014","journal-title":"Pancreas"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Souto, M., C\u00fardia Gon\u00e7alves, T., and Cotter, J. (2025). Obesity and pancreatic diseases: From inflammation to oncogenesis and the impact of weight loss interventions. Nutrients, 17.","DOI":"10.3390\/nu17142310"},{"key":"ref_23","unstructured":"Russell, W.M.S., and Burch, R.L. (1992). The Principles of Humane Experimental Technique, Universities Federation for Animal Welfare."},{"key":"ref_24","unstructured":"Institute for Laboratory Animal Research (2011). Guide for the Care and Use of Laboratory Animals, National Academies Press."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1939","DOI":"10.1093\/jn\/123.11.1939","article-title":"AIN-93 purified diets for laboratory rodents: Final report of the American Institute of Nutrition ad hoc writing committee on the reformulation of the AIN-76A rodent diet","volume":"123","author":"Reeves","year":"1993","journal-title":"J. Nutr."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1038\/laban0109-35","article-title":"A method for gender determination in newborn dark pigmented mice","volume":"38","author":"Meerding","year":"2009","journal-title":"Lab Anim."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"George, E.D., Bordner, K.A., Elwafi, H.M., and Simen, A.A. (2010). Maternal separation with early weaning: A novel mouse model of early life neglect. BMC Neurosci., 11.","DOI":"10.1186\/1471-2202-11-123"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1136\/vr.116.16.431","article-title":"Guidelines on the recognition of pain, distress and discomfort in experimental animals and an hypothesis for assessment","volume":"116","author":"Morton","year":"1985","journal-title":"Vet. Rec."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1002\/dev.20292","article-title":"Effects of early deprivation and maternal separation on pup-directed behavior and HPA axis measures in the juvenile female rat","volume":"50","author":"Rees","year":"2008","journal-title":"Dev. Psychobiol."},{"key":"ref_30","first-page":"L148","article-title":"Recent stereological methods for cell biology: A brief survey","volume":"258","author":"Weibel","year":"1990","journal-title":"Am. J. Physiol."},{"key":"ref_31","unstructured":"Canadian Council on Animal Care (1993). Guide to the Care and Use of Experimental Animals, Canadian Council on Animal Care. [2nd ed.]. Available online: https:\/\/ccac.ca\/Documents\/Standards\/Guidelines\/Guide_to_the_Care_and_Use_of_Experimental_Animals_Vol1.pdf."},{"key":"ref_32","first-page":"1135","article-title":"Histopathology and pathogenesis of caerulein-, duct ligation-, and arginine-induced acute pancreatitis in Sprague-Dawley rats and C57BL\/6 mice","volume":"29","author":"Zhang","year":"2014","journal-title":"Histol. Histopathol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.taap.2014.01.021","article-title":"High fat diet and GLP-1 drugs induce pancreatic injury in mice","volume":"276","author":"Rouse","year":"2014","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1482","DOI":"10.4067\/S0717-95022017000401482","article-title":"Tips for Studies with Quantitative Morphology (Morphometry and Stereology)","volume":"35","year":"2017","journal-title":"Int. J. Morphol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1080\/01926230490465874","article-title":"Relationships between organ weight and body\/brain weight in the rat: What is the best analytical endpoint?","volume":"32","author":"Bailey","year":"2004","journal-title":"Toxicol. Pathol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"del Sol, M., Navarrete, J., Garc\u00eda-Orozco, L., S\u00f3cola-Barsallo, Z., Sandoval, C., and V\u00e1squez, B. (2025). When timing matters: Effects of maternal separation and post-weaning high-fat diet on liver morphology in a rodent model. Nutrients, 17.","DOI":"10.3390\/nu17101619"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Han, J., Nepal, P., Odelade, A., Freely, F.D., Belton, D.M., Graves, J.L., and Maldonado-Devincci, A.M. (2021). High-fat diet-induced weight gain, behavioral deficits, and dopamine changes in young C57BL\/6J mice. Front. Nutr., 7.","DOI":"10.3389\/fnut.2020.591161"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1538\/expanim.19-0148","article-title":"High fat diet induced obesity model using four strains of mice: Kunming, C57BL\/6, BALB\/c and ICR","volume":"69","author":"Li","year":"2020","journal-title":"Exp. Anim."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"109690","DOI":"10.1016\/j.jnutbio.2024.109690","article-title":"A high-fat diet induces changes in mesenteric adipose tissue accelerating early-stage pancreatic carcinogenesis in mice","volume":"131","author":"Ead","year":"2024","journal-title":"J. Nutr. Biochem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2714","DOI":"10.1210\/en.2008-0038","article-title":"Hypermetabolic syndrome as a consequence of repeated psychological stress in mice","volume":"149","author":"Depke","year":"2008","journal-title":"Endocrinology"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"104693","DOI":"10.1016\/j.isci.2022.104693","article-title":"The metabolic stress response: Adaptation to acute-, repeated- and chronic challenges in mice","volume":"25","author":"Kuti","year":"2022","journal-title":"iScience"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Murthy, S., and Gould, E. (2018). Early Life Stress in Rodents: Animal Models of Illness or Resilience?. Front. Behav. Neurosci., 12.","DOI":"10.3389\/fnbeh.2018.00157"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1203\/01.PDR.0000135998.08025.FB","article-title":"Developmental Origins of Disease Paradigm: A Mechanistic and Evolutionary Perspective","volume":"56","author":"Gluckman","year":"2004","journal-title":"Pediatr. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1016\/j.devcel.2018.05.024","article-title":"Postnatal exocrine pancreas growth by cellular hypertrophy correlates with a shorter lifespan in mammals","volume":"45","author":"Anzi","year":"2018","journal-title":"Dev. Cell"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"12643","DOI":"10.1038\/s41598-017-12721-9","article-title":"Acinar cells in the neonatal pancreas grow by self-duplication and not by neogenesis from duct cells","volume":"7","author":"Houbracken","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_46","first-page":"209","article-title":"Biphasic development of the postnatal mouse pancreas","volume":"40","author":"Dore","year":"1981","journal-title":"Biol. Neonate"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Zhang, T., Gan, Y., and Zhu, S. (2023). Association between autophagy and acute pancreatitis. Front. Genet., 14.","DOI":"10.3389\/fgene.2023.998035"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1177\/0192623313486967","article-title":"Autophagy in pancreatic acinar cells in caerulein-treated mice: Immunolocalization of related proteins and their potential as markers of pancreatitis","volume":"42","author":"Zhang","year":"2014","journal-title":"Toxicol. Pathol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"8172714","DOI":"10.1155\/2020\/8172714","article-title":"High-fat diet aggravates acute pancreatitis via TLR4-mediated necroptosis and inflammation in rats","volume":"2020","author":"Hong","year":"2020","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.biopsych.2008.06.026","article-title":"Early life stress alters behavior, immunity, and microbiota in rats: Implications for irritable bowel syndrome and psychiatric illnesses","volume":"65","author":"Marchesi","year":"2009","journal-title":"Biol. Psychiatry"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.cobeha.2019.01.016","article-title":"Early life stress and metabolism","volume":"28","author":"Malik","year":"2019","journal-title":"Curr. Opin. Behav. Sci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1006\/bbrc.1998.8519","article-title":"Induction of apoptosis in pancreatic acinar cells reduces the severity of acute pancreatitis","volume":"246","author":"Bhatia","year":"1998","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"G189","DOI":"10.1152\/ajpgi.00304.2003","article-title":"Apoptosis versus necrosis in acute pancreatitis","volume":"286","author":"Bhatia","year":"2004","journal-title":"Am. J. Physiol.-Gastrointest. Liver Physiol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1053\/j.gastro.2009.04.003","article-title":"Impaired autolysosome formation correlates with Lamp-2 depletion: Role of apoptosis, autophagy, and necrosis in pancreatitis","volume":"137","author":"Fortunato","year":"2009","journal-title":"Gastroenterology"},{"key":"ref_55","first-page":"3340","article-title":"Impaired autophagic flux mediates acinar cell vacuole formation and trypsinogen activation in rodent models of acute pancreatitis","volume":"119","author":"Mareninova","year":"2009","journal-title":"J. Clin. Investig."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"G993","DOI":"10.1152\/ajpgi.00122.2012","article-title":"Autophagy and pancreatitis","volume":"303","author":"Gukovskaya","year":"2012","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2699","DOI":"10.1089\/ars.2011.4068","article-title":"Organellar dysfunction in the pathogenesis of pancreatitis","volume":"15","author":"Gukovsky","year":"2011","journal-title":"Antioxid. Redox Signal."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1053\/j.gastro.2007.01.055","article-title":"Acute pancreatitis: Bench to the bedside","volume":"132","author":"Pandol","year":"2007","journal-title":"Gastroenterology"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1055\/s-0028-1119406","article-title":"The combination of a high-fat diet and chronic stress aggravates insulin resistance in Wistar male rats","volume":"117","author":"Fu","year":"2009","journal-title":"Exp. Clin. Endocrinol. Diabetes"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.bbi.2016.08.021","article-title":"Chronic psychological stress and high-fat high-fructose diet disrupt metabolic and inflammatory gene networks in the brain, liver, and gut and promote behavioral deficits in mice","volume":"59","author":"Bekhbat","year":"2017","journal-title":"Brain Behav. Immun."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1530\/JOE-20-0633","article-title":"Chronic social stress lessens the metabolic effects induced by a high-fat diet","volume":"249","author":"Jene","year":"2021","journal-title":"J. Endocrinol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/j.neuroscience.2011.06.072","article-title":"High-fat diet selectively protects against the effects of chronic social stress in the mouse","volume":"192","author":"Finger","year":"2011","journal-title":"Neuroscience"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1053\/j.gastro.2014.12.003","article-title":"Impaired autophagy induces chronic atrophic pancreatitis in mice via sex- and nutrition-dependent processes","volume":"148","author":"Diakopoulos","year":"2015","journal-title":"Gastroenterology"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Hegyi, P., Mal\u00e9th, J., Venglovecz, V., and Rakonczay, Z. (2011). Pancreatic ductal bicarbonate secretion: Challenge of the acinar acid load. Front. Physiol., 2.","DOI":"10.3389\/fphys.2011.00036"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"S13","DOI":"10.1016\/j.pan.2015.03.010","article-title":"The role of pancreatic ducts in the pathogenesis of acute pancreatitis","volume":"15","author":"Hegyi","year":"2015","journal-title":"Pancreatology"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Heindl, M., Tuennemann, J., Sommerer, I., M\u00f6ssner, J., and Hoffmeister, A. (2015). Loss of Bace1 in mice does not alter the severity of caerulein-induced pancreatitis. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0125556"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"7161592","DOI":"10.1155\/2018\/7161592","article-title":"Isoliquiritigenin ameliorates acute pancreatitis in mice via inhibition of oxidative stress and modulation of the Nrf2\/HO-1 pathway","volume":"2018","author":"Liu","year":"2018","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/S0022-2275(20)36904-2","article-title":"Effect of dietary fat on pancreatic lipase levels in the rat","volume":"14","author":"Gidez","year":"1973","journal-title":"J. Lipid Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1111\/j.1432-1033.1989.tb14682.x","article-title":"Changes in mRNA levels of rat pancreatic lipase in the early days of consumption of a high-lipid diet","volume":"180","author":"Wicker","year":"1989","journal-title":"Eur. J. Biochem."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1111\/jnc.15208","article-title":"Sex differences in the neurochemistry of frontal cortex: Impact of early life stress","volume":"157","author":"Perry","year":"2021","journal-title":"J. Neurochem."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"113489","DOI":"10.1016\/j.bbr.2021.113489","article-title":"Sex-specific behavioral and structural alterations caused by early-life stress in C57BL\/6 and BTBR mice","volume":"414","author":"Reshetnikov","year":"2021","journal-title":"Behav. Brain Res."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Maric, I., Krieger, J.P., van der Velden, P., B\u00f6rchers, S., Asker, M., Vujicic, M., Asterholm, I.W., and Skibicka, K.P. (2022). Sex and species differences in the development of diet-induced obesity and metabolic disturbances in rodents. Front. Nutr., 9.","DOI":"10.3389\/fnut.2022.828522"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/s13293-025-00699-3","article-title":"Sex-dependent effects of a high-fat diet on the hypothalamic response in mice","volume":"16","author":"Dreux","year":"2025","journal-title":"Biol. Sex Differ."}],"container-title":["Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-7737\/15\/15\/1297\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T04:14:18Z","timestamp":1786076058000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-7737\/15\/15\/1297"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,5]]},"references-count":73,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["biology15151297"],"URL":"https:\/\/doi.org\/10.3390\/biology15151297","relation":{},"ISSN":["2079-7737"],"issn-type":[{"value":"2079-7737","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,5]]}}}