{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T23:00:10Z","timestamp":1771628410435,"version":"3.50.1"},"reference-count":304,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,3,29]],"date-time":"2022-03-29T00:00:00Z","timestamp":1648512000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","doi-asserted-by":"publisher","award":["PD\/BD\/136863\/2018"],"award-info":[{"award-number":["PD\/BD\/136863\/2018"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","doi-asserted-by":"publisher","award":["CEECIND\/04266\/2017"],"award-info":[{"award-number":["CEECIND\/04266\/2017"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Accumulating evidence suggests the existence of a strong link between metabolic syndrome and neurodegeneration. Indeed, epidemiologic studies have described solid associations between metabolic syndrome and neurodegeneration, whereas animal models contributed for the clarification of the mechanistic underlying the complex relationships between these conditions, having the development of an insulin resistance state a pivotal role in this relationship. Herein, we review in a concise manner the association between metabolic syndrome and neurodegeneration. We start by providing concepts regarding the role of insulin and insulin signaling pathways as well as the pathophysiological mechanisms that are in the genesis of metabolic diseases. Then, we focus on the role of insulin in the brain, with special attention to its function in the regulation of brain glucose metabolism, feeding, and cognition. Moreover, we extensively report on the association between neurodegeneration and metabolic diseases, with a particular emphasis on the evidence observed in animal models of dysmetabolism induced by hypercaloric diets. We also debate on strategies to prevent and\/or delay neurodegeneration through the normalization of whole-body glucose homeostasis, particularly via the modulation of the carotid bodies, organs known to be key in connecting the periphery with the brain.<\/jats:p>","DOI":"10.3390\/nu14071425","type":"journal-article","created":{"date-parts":[[2022,3,29]],"date-time":"2022-03-29T21:41:30Z","timestamp":1648590090000},"page":"1425","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Dysmetabolism and Neurodegeneration: Trick or Treat?"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1811-5637","authenticated-orcid":false,"given":"Adriana","family":"Capucho","sequence":"first","affiliation":[{"name":"CEDOC, NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, Universidade NOVA de Lisboa, 1150-082 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2304-4121","authenticated-orcid":false,"given":"Ana","family":"Cheg\u00e3o","sequence":"additional","affiliation":[{"name":"CEDOC, NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, Universidade NOVA de Lisboa, 1150-082 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2161-459X","authenticated-orcid":false,"given":"F\u00e1tima","family":"Martins","sequence":"additional","affiliation":[{"name":"CEDOC, NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, Universidade NOVA de Lisboa, 1150-082 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8065-9259","authenticated-orcid":false,"given":"Hugo","family":"Vicente Miranda","sequence":"additional","affiliation":[{"name":"CEDOC, NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, Universidade NOVA de Lisboa, 1150-082 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5920-5700","authenticated-orcid":false,"given":"S\u00edlvia","family":"Conde","sequence":"additional","affiliation":[{"name":"CEDOC, NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, Universidade NOVA de Lisboa, 1150-082 Lisboa, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1016\/j.cell.2013.05.039","article-title":"The hallmarks of aging","volume":"153","author":"Blasco","year":"2013","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1126\/science.1257099","article-title":"The state of global health in 2014","volume":"345","author":"Murray","year":"2014","journal-title":"Science"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1973","DOI":"10.1001\/jama.2015.4260","article-title":"Prevalence of the Metabolic Syndrome in the United States, 2003\u20132012","volume":"313","author":"Aguilar","year":"2015","journal-title":"JAMA"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1093\/eurheartj\/ehu123","article-title":"Metabolically healthy obesity and the risk of cardiovascular disease and type 2 diabetes: The Whitehall II cohort study","volume":"36","author":"Hinnouho","year":"2014","journal-title":"Eur. 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