{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T16:39:04Z","timestamp":1790699944741,"version":"4.1.0"},"reference-count":51,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T00:00:00Z","timestamp":1770076800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"SECIHTI"},{"name":"\u201cSistema Nacional de Investigadores\u201d of Mexico","award":["MPII"],"award-info":[{"award-number":["MPII"]}]},{"name":"\u201cSistema Nacional de Investigadores\u201d of Mexico","award":["839415"],"award-info":[{"award-number":["839415"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Background\/Objectives: Type 2 diabetes (T2D) and obesity are chronic metabolic disorders associated with cognitive impairment and neuronal damage. The hippocampus, a region sensitive to nutrient excess, is critical for integrating sensory and metabolic signals. This study aimed to determine the early onset of cognitive and motor deficits induced by obesity and\/or hyperglycemia and to characterize associated hippocampal alterations in Zucker Diabetic Fatty (ZDF) rats. Methods: Male ZDF rats (13 weeks old) were categorized into three groups: lean control, obese normoglycemic (ZDF-NG), and obese hyperglycemic (ZDF-HG). Assessments included zoometric parameters (weight and adiposity), biochemical assays (glucose tolerance, insulin response, and lipid profile), and behavioral tests (Open Field and Novel Object Recognition). Hippocampal health was evaluated through stereological neuronal density analysis and redox balance markers. Results: Both obese groups exhibited significant visceral adiposity and hyperlipidemia. The ZDF-HG group was further characterized by glucose intolerance, hepatic insulin resistance, and reduced \u03b2-cell function. Behavioral results showed that while obesity decreased motor activity, hyperglycemia significantly exacerbated the loss of both short- and long-term recognition memory. Histologically, obesity was associated with decreased neuronal density in the hippocampal DG and CA1 regions. Furthermore, hippocampal ROS was significantly elevated in the ZDF-HG group, and glutathione reductase activity was reduced in both obese phenotypes. Conclusions: The findings demonstrate that obesity initiates hippocampal neurodegeneration and motor decline, and that hyperglycemia severely impairs recognition memory. These results emphasize the critical interplay between metabolic dysfunction and cognitive decline, highlighting the necessity of managing both obesity and T2D to prevent early neurodegenerative changes.<\/jats:p>","DOI":"10.3390\/metabo16020107","type":"journal-article","created":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T09:00:58Z","timestamp":1770109258000},"page":"107","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Synergistic Effects of Obesity and Hyperglycemia on Hippocampal Neurodegenerative Decline Disrupt the Neural Circuitry Regulating Motivation in Zucker Diabetic Fatty Rats"],"prefix":"10.3390","volume":"16","author":[{"given":"Martha Patricia","family":"Islas-Islas","sequence":"first","affiliation":[{"name":"Laboratorio de Neuroplasticidad y Metabolismo, Instituto de Fisiolog\u00eda, Benem\u00e9rita Universidad Aut\u00f3noma de Puebla, 14 Sur 6301, Ciudad Universitaria, Puebla C.P. 72560, Mexico"},{"name":"Doctorado en Ciencias Biol\u00f3gicas, Centro de Tlaxcala de Biolog\u00eda de la Conducta, Universidad Aut\u00f3noma de Tlaxcala, Tlaxcala C.P. 90000, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleida Monserrat","family":"Coss-Orozco","sequence":"additional","affiliation":[{"name":"Laboratorio de Neuroplasticidad y Metabolismo, Instituto de Fisiolog\u00eda, Benem\u00e9rita Universidad Aut\u00f3noma de Puebla, 14 Sur 6301, Ciudad Universitaria, Puebla C.P. 72560, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4500-0648","authenticated-orcid":false,"given":"Diana","family":"Moroni-Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n en Reproducci\u00f3n Animal, Cinvestav-Universidad Aut\u00f3noma de Tlaxcala, AP 62, Tlaxcala C.P. 90000, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erick","family":"Flores-Cholula","sequence":"additional","affiliation":[{"name":"Laboratorio de Metabol\u00f3mica y Enfermedades Cr\u00f3nico-Degenerativas, Instituto de Fisiolog\u00eda, Benem\u00e9rita Universidad Aut\u00f3noma de Puebla, 14 Sur 6301, Ciudad Universitaria, Puebla C.P. 72560, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9685-4710","authenticated-orcid":false,"given":"Jos\u00e9 Everardo","family":"Avelino-Cruz","sequence":"additional","affiliation":[{"name":"Laboratorio de Cardiolog\u00eda Molecular, Instituto de Fisiolog\u00eda, Benem\u00e9rita Universidad Aut\u00f3noma de Puebla, 14 Sur 6301, Ciudad Universitaria, Puebla C.P. 72560, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8712-2400","authenticated-orcid":false,"given":"Julio Cesar","family":"Morales-Medina","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n en Reproducci\u00f3n Animal, Cinvestav-Universidad Aut\u00f3noma de Tlaxcala, AP 62, Tlaxcala C.P. 90000, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4092-6636","authenticated-orcid":false,"given":"Alfonso","family":"Diaz","sequence":"additional","affiliation":[{"name":"Laboratorio de Neuroqu\u00edmica y Conducta, Instituto de Fisiolog\u00eda, Benem\u00e9rita Universidad Aut\u00f3noma de Puebla, 14 Sur 6301, Ciudad Universitaria, Puebla C.P. 72560, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5536-458X","authenticated-orcid":false,"given":"Fabi\u00e1n","family":"Galindo-Ram\u00edrez","sequence":"additional","affiliation":[{"name":"Laboratorio de C\u00e1ncer y Comunicaci\u00f3n Celular, Instituto de Fisiolog\u00eda, Benem\u00e9rita Universidad Aut\u00f3noma de Puebla, 14 Sur 6301, Ciudad Universitaria, Puebla C.P. 72560, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5679-1671","authenticated-orcid":false,"given":"Samuel","family":"Trevi\u00f1o","sequence":"additional","affiliation":[{"name":"Laboratorio de Metabol\u00f3mica y Enfermedades Cr\u00f3nico-Degenerativas, Instituto de Fisiolog\u00eda, Benem\u00e9rita Universidad Aut\u00f3noma de Puebla, 14 Sur 6301, Ciudad Universitaria, Puebla C.P. 72560, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2712-5714","authenticated-orcid":false,"given":"Rub\u00e9n Antonio","family":"V\u00e1zquez-Roque","sequence":"additional","affiliation":[{"name":"Laboratorio de Neuroplasticidad y Metabolismo, Instituto de Fisiolog\u00eda, Benem\u00e9rita Universidad Aut\u00f3noma de Puebla, 14 Sur 6301, Ciudad Universitaria, Puebla C.P. 72560, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,3]]},"reference":[{"key":"ref_1","unstructured":"(2024, January 20). 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