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In this regard, a large body of evidence indicates a pivotal role of disturbed autophagic flux in the pathogenesis of obesity-associated neuropsychiatric deficits.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>This work was designed to evaluate the effects of the glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide, which is increasingly utilized for the management of chronic obesity, on the depressive\/cognitive deficits in the high-fat diet (HFD) rat model of obesity with an emphasis on its hippocampal mechanistic backgrounds.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The effects of chronic liraglutide administration (subcutaneous; 300\u00a0\u00b5g\/kg\/day for 28 days) were investigated on depressive-like phenotypes, cognitive deficits, and hippocampal phosphatidylinositol 3-kinase (PI3K)\/protein kinase B (Akt)\/mechanistic target of rapamycin (mTOR)-regulated autophagy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Chronic liraglutide treatment amended the HFD-induced depressive-like phenotype (in the sucrose preference and the forced swimming tests) and cognitive deficits (in the Morris water maze test). Moreover, liraglutide enhanced the hippocampal expression of brain-derived neurotrophic factor (BDNF), PI3K, Akt, p-Akt, and p-mTOR and downregulated the expression of the autophagic markers (Beclin-1, LC3) and the inflammatory markers (TNF-\u03b1, IL-6) with amelioration of HFD-induced hippocampal neurodegeneration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This work highlights the antidepressant and pro-cognitive properties of liraglutide in HFD-exposed rats, which could be mediated through amelioration of the disrupted PI3K\/Akt\/mTOR signaling activity with a possible impedance of the exaggerated autophagy-mediated neurodegenerative cascades. Indeed, this study highlights that liraglutide is not only effective in weight control, but its effects also extend to managing obesity-related psychiatric disorders.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00213-025-06834-7","type":"journal-article","created":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T02:44:16Z","timestamp":1750128256000},"page":"2801-2816","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Liraglutide improves depressive and cognitive deficits in a high-fat diet rat model of obesity: the role of hippocampal autophagy and the PI3K\/Akt\/mTOR pathway"],"prefix":"10.1007","volume":"242","author":[{"given":"Yosra M.","family":"Magdy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherif A.","family":"Kamar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7161-8121","authenticated-orcid":false,"given":"Mohamed Z.","family":"Habib","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hagar Yousry","family":"Rady","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed R.","family":"Rabei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Khedr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,6,17]]},"reference":[{"key":"6834_CR1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3897\/pharmacia.71.e113659","volume":"71","author":"RK Abdullah","year":"2024","unstructured":"Abdullah RK, Issa RA, Abu-Samak M, Mohammad BA, Abbas MA, Awwad SH (2024) Nephroprotective effects of Equisetum ramosissimum L. extract in streptozotocin-induced diabetic rats. 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