{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T20:04:57Z","timestamp":1793736297625,"version":"4.6.1"},"reference-count":158,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,5,6]],"date-time":"2022-05-06T00:00:00Z","timestamp":1651795200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"PAIDI CTS-151 Junta de Andalucia, Spain","id":[{"id":"https:\/\/ror.org\/01jem9c82","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Obesity is a growing worldwide health problem, affecting many people due to excessive saturated fat consumption, lack of exercise, or a sedentary lifestyle. Leptin is an adipokine secreted by adipose tissue that increases in obesity and has central actions not only at the hypothalamic level but also in other regions and nuclei of the central nervous system (CNS) such as the cerebral cortex and hippocampus. These regions express the long form of leptin receptor LepRb, which is the unique leptin receptor capable of transmitting complete leptin signaling, and are the first regions to be affected by chronic neurocognitive deficits, such as mild cognitive impairment (MCI) and Alzheimer\u2019s Disease (AD). In this review, we discuss different leptin resistance mechanisms that could be implicated in increasing the risk of developing AD, as leptin resistance is frequently associated with obesity, which is a chronic low-grade inflammatory state, and obesity is considered a risk factor for AD. Key players of leptin resistance are SOCS3, PTP1B, and TCPTP whose signalling is related to inflammation and could be worsened in AD. However, some data are controversial, and it is necessary to further investigate the underlying mechanisms of the AD-causing pathological processes and how altered leptin signalling affects such processes.<\/jats:p>","DOI":"10.3390\/ijms23095202","type":"journal-article","created":{"date-parts":[[2022,5,6]],"date-time":"2022-05-06T14:49:38Z","timestamp":1651848578000},"page":"5202","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":191,"title":["Obesity as a Risk Factor for Dementia and Alzheimer\u2019s Disease: The Role of Leptin"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9021-0228","authenticated-orcid":false,"given":"Juan Antonio","family":"Flores-Cordero","sequence":"first","affiliation":[{"name":"Department of Medical Biochemistry and Molecular Biology and Immunology, Medical School, Virgen Macarena University Hospital, University of Seville, Av. S\u00e1nchez Pizjuan 4, 41009 Sevilla, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5660-735X","authenticated-orcid":false,"given":"Antonio","family":"P\u00e9rez-P\u00e9rez","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Molecular Biology and Immunology, Medical School, Virgen Macarena University Hospital, University of Seville, Av. S\u00e1nchez Pizjuan 4, 41009 Sevilla, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6956-7740","authenticated-orcid":false,"given":"Carlos","family":"Jim\u00e9nez-Cortegana","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Molecular Biology and Immunology, Medical School, Virgen Macarena University Hospital, University of Seville, Av. S\u00e1nchez Pizjuan 4, 41009 Sevilla, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gonzalo","family":"Alba","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Molecular Biology and Immunology, Medical School, Virgen Macarena University Hospital, University of Seville, Av. S\u00e1nchez Pizjuan 4, 41009 Sevilla, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfonso","family":"Flores-Barrag\u00e1n","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Molecular Biology and Immunology, Medical School, Virgen Macarena University Hospital, University of Seville, Av. S\u00e1nchez Pizjuan 4, 41009 Sevilla, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8638-8680","authenticated-orcid":false,"given":"V\u00edctor","family":"S\u00e1nchez-Margalet","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Molecular Biology and Immunology, Medical School, Virgen Macarena University Hospital, University of Seville, Av. S\u00e1nchez Pizjuan 4, 41009 Sevilla, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1192\/bjb.2019.77","article-title":"Mild cognitive impairment: Narrative review of taxonomies and systematic review of their prediction of incident Alzheimer\u2019s disease dementia","volume":"44","author":"Bradfield","year":"2020","journal-title":"BJPsych Bull."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"101720","DOI":"10.1016\/j.pneurobio.2019.101720","article-title":"Microglia, neurodegeneration and loss of neuroendocrine control","volume":"184","author":"Chowen","year":"2020","journal-title":"Prog. 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