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Junta de Andaluc\u00eda","award":["P18-TP-5194"],"award-info":[{"award-number":["P18-TP-5194"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Increasing evidence links metabolic disorders with neurodegenerative processes including Alzheimer\u2019s disease (AD). Late AD is associated with amyloid (A\u03b2) plaque accumulation, neuroinflammation, and central insulin resistance. Here, a humanized AD model, the 5xFAD mouse model, was used to further explore food intake, energy expenditure, neuroinflammation, and neuroendocrine signaling in the hypothalamus. Experiments were performed on 6-month-old male and female full transgenic (Tg5xFAD\/5xFAD), heterozygous (Tg5xFAD\/-), and non-transgenic (Non-Tg) littermates. Although histological analysis showed absence of A\u03b2 plaques in the hypothalamus of 5xFAD mice, this brain region displayed increased protein levels of GFAP and IBA1 in both Tg5xFAD\/- and Tg5xFAD\/5xFAD mice and increased expression of IL-1\u03b2 in Tg5xFAD\/5xFAD mice, suggesting neuroinflammation. This condition was accompanied by decreased body weight, food intake, and energy expenditure in both Tg5xFAD\/- and Tg5xFAD\/5xFAD mice. Negative energy balance was associated with altered circulating levels of insulin, GLP-1, GIP, ghrelin, and resistin; decreased insulin and leptin hypothalamic signaling; dysregulation in main metabolic sensors (phosphorylated IRS1, STAT5, AMPK, mTOR, ERK2); and neuropeptides controlling energy balance (NPY, AgRP, orexin, MCH). These results suggest that glial activation and metabolic dysfunctions in the hypothalamus of a mouse model of AD likely result in negative energy balance, which may contribute to AD pathogenesis development.<\/jats:p>","DOI":"10.3390\/ijms22105365","type":"journal-article","created":{"date-parts":[[2021,5,20]],"date-time":"2021-05-20T06:13:45Z","timestamp":1621491225000},"page":"5365","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["A Negative Energy Balance Is Associated with Metabolic Dysfunctions in the Hypothalamus of a Humanized Preclinical Model of Alzheimer\u2019s Disease, the 5XFAD Mouse"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7716-9056","authenticated-orcid":false,"given":"Antonio J.","family":"L\u00f3pez-Gambero","sequence":"first","affiliation":[{"name":"Instituto de investigaci\u00f3n Biom\u00e9dica de M\u00e1laga-IBIMA, 29010 M\u00e1laga, Spain"},{"name":"UGC Salud Mental, Hospital Regional Universitario de M\u00e1laga, 29010 M\u00e1laga, Spain"},{"name":"Departamento de Biolog\u00eda Celular, Gen\u00e9tica y Fisiolog\u00eda, Campus de Teatinos s\/n, Universidad de M\u00e1laga, Andalucia Tech, 29071 M\u00e1laga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9545-0976","authenticated-orcid":false,"given":"Cristina","family":"Rosell-Valle","sequence":"additional","affiliation":[{"name":"Instituto de investigaci\u00f3n Biom\u00e9dica de M\u00e1laga-IBIMA, 29010 M\u00e1laga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0342-1287","authenticated-orcid":false,"given":"Dina","family":"Medina-Vera","sequence":"additional","affiliation":[{"name":"Instituto de investigaci\u00f3n Biom\u00e9dica de M\u00e1laga-IBIMA, 29010 M\u00e1laga, Spain"},{"name":"UGC Salud Mental, Hospital Regional Universitario de M\u00e1laga, 29010 M\u00e1laga, Spain"},{"name":"Departamento de Biolog\u00eda Celular, Gen\u00e9tica y Fisiolog\u00eda, Campus de Teatinos s\/n, Universidad de M\u00e1laga, Andalucia Tech, 29071 M\u00e1laga, Spain"},{"name":"Facultad de Medicina, Campus de Teatinos s\/n, Universidad de M\u00e1laga, Andalucia Tech, 29071 M\u00e1laga, Spain"},{"name":"UGC Coraz\u00f3n, Hospital Universitario Virgen de la Victoria, 29010 M\u00e1laga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3089-0983","authenticated-orcid":false,"given":"Juan Antonio","family":"Navarro","sequence":"additional","affiliation":[{"name":"Instituto de investigaci\u00f3n Biom\u00e9dica de M\u00e1laga-IBIMA, 29010 M\u00e1laga, Spain"},{"name":"UGC Salud Mental, Hospital Regional Universitario de M\u00e1laga, 29010 M\u00e1laga, Spain"},{"name":"Facultad de Medicina, Campus de Teatinos s\/n, Universidad de M\u00e1laga, Andalucia Tech, 29071 M\u00e1laga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Vargas","sequence":"additional","affiliation":[{"name":"Instituto de investigaci\u00f3n Biom\u00e9dica de M\u00e1laga-IBIMA, 29010 M\u00e1laga, Spain"},{"name":"UGC Salud Mental, Hospital Regional Universitario de M\u00e1laga, 29010 M\u00e1laga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Rivera","sequence":"additional","affiliation":[{"name":"Instituto de investigaci\u00f3n Biom\u00e9dica de M\u00e1laga-IBIMA, 29010 M\u00e1laga, Spain"},{"name":"UGC Salud Mental, Hospital Regional Universitario de M\u00e1laga, 29010 M\u00e1laga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3505-0481","authenticated-orcid":false,"given":"Carlos","family":"Sanjuan","sequence":"additional","affiliation":[{"name":"EURONUTRA S.L, Parque Tecnol\u00f3gico de Andaluc\u00eda, 29590 Campanillas, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4516-5795","authenticated-orcid":false,"given":"Fernando","family":"Rodr\u00edguez de Fonseca","sequence":"additional","affiliation":[{"name":"Instituto de investigaci\u00f3n Biom\u00e9dica de M\u00e1laga-IBIMA, 29010 M\u00e1laga, Spain"},{"name":"UGC Salud Mental, Hospital Regional Universitario de M\u00e1laga, 29010 M\u00e1laga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5254-9802","authenticated-orcid":false,"given":"Juan","family":"Su\u00e1rez","sequence":"additional","affiliation":[{"name":"Instituto de investigaci\u00f3n Biom\u00e9dica de M\u00e1laga-IBIMA, 29010 M\u00e1laga, Spain"},{"name":"Facultad de Medicina, Campus de Teatinos s\/n, Universidad de M\u00e1laga, Andalucia Tech, 29071 M\u00e1laga, Spain"},{"name":"Departamento de Anatom\u00eda Humana, Medicina Legal e Historia de la Ciencia, Universidad de M\u00e1laga, 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