{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T16:40:08Z","timestamp":1789749608013,"version":"4.0.1"},"reference-count":101,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2022,11,5]],"date-time":"2022-11-05T00:00:00Z","timestamp":1667606400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Foundation for Applied Medical Research (FIMA)","award":["FPU18\/01458"],"award-info":[{"award-number":["FPU18\/01458"]}]},{"name":"Asociaci\u00f3n de Amigos de la Universidad de Navarra","award":["FPU18\/01458"],"award-info":[{"award-number":["FPU18\/01458"]}]},{"name":"Spanish Ministry of Universities","award":["FPU18\/01458"],"award-info":[{"award-number":["FPU18\/01458"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Obesity and aging are becoming increasingly prevalent across the globe. It has been established that aging is the major risk factor for Alzheimer\u2019s disease (AD), and it is becoming increasingly evident that obesity and the associated insulin resistance are also notably relevant risk factors. The biological plausibility of the link between high adiposity, insulin resistance, and dementia is central for understanding AD etiology, and to form bases for prevention efforts to decrease the disease burden. Several studies have demonstrated a strong association between short chain fatty acid receptor FFAR3 and insulin sensitivity. Interestingly, it has been recently established that FFAR3 mRNA levels are increased in early stages of the AD pathology, indicating that FFAR3 could play a key role in AD onset and progression. Indeed, in the present study we demonstrate that the ablation of the Ffar3 gene in Tg2576 mice prevents the development of cognitive deficiencies in advanced stages of the disease. Notably, this cognitive improvement is also maintained upon a severe metabolic challenge such as the exposure to high-fat diet (HFD) feeding. Moreover, FFAR3 deletion restores the brain hypermetabolism displayed by Tg2576 mice. Collectively, these data postulate FFAR3 as a potential novel target for AD.<\/jats:p>","DOI":"10.3390\/ijms232113591","type":"journal-article","created":{"date-parts":[[2022,11,8]],"date-time":"2022-11-08T11:56:36Z","timestamp":1667908596000},"page":"13591","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["The Cognitive Improvement and Alleviation of Brain Hypermetabolism Caused by FFAR3 Ablation in Tg2576 Mice Is Persistent under Diet-Induced Obesity"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7670-3237","authenticated-orcid":false,"given":"Maite","family":"Solas","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, University of Navarra, 31008 Pamplona, Spain"},{"name":"IdISNA, Navarra Institute for Health Research, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Zamarbide","sequence":"additional","affiliation":[{"name":"Neuroscience Program, Center for Applied Medical Research (CIMA), University of Navarra, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5328-2986","authenticated-orcid":false,"given":"Carlos G.","family":"Ardanaz","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, University of Navarra, 31008 Pamplona, Spain"},{"name":"IdISNA, Navarra Institute for Health Research, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3488-9579","authenticated-orcid":false,"given":"Mar\u00eda J.","family":"Ram\u00edrez","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, University of Navarra, 31008 Pamplona, Spain"},{"name":"IdISNA, Navarra Institute for Health Research, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1926-0972","authenticated-orcid":false,"given":"Alberto","family":"P\u00e9rez-Mediavilla","sequence":"additional","affiliation":[{"name":"IdISNA, Navarra Institute for Health Research, 31008 Pamplona, Spain"},{"name":"Neuroscience Program, Center for Applied Medical Research (CIMA), University of Navarra, 31008 Pamplona, Spain"},{"name":"Department of Biochemistry and Genetics, University of Navarra, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,5]]},"reference":[{"key":"ref_1","unstructured":"Alzheimer\u2019s Association (2022, September 29). 2022 Alzheimer\u2019s Disease Facts and Figures. 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