{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T17:28:08Z","timestamp":1769880488992,"version":"3.49.0"},"reference-count":48,"publisher":"Bioscientifica","issue":"1","content-domain":{"domain":["jme.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,1,1]]},"abstract":"<jats:p>ATXN2 gene, encoding for ataxin-2, is located in a trait <jats:italic>locus<\/jats:italic> for obesity. <jats:italic>Atxn2<\/jats:italic> knockout (KO) mice are obese and insulin resistant; however, the cause for this phenotype is still unknown. Moreover, several findings suggest ataxin-2 as a metabolic regulator, but the role of this protein in the hypothalamus was never studied before. The aim of this work was to understand if ataxin-2 modulation in the hypothalamus could play a role in metabolic regulation. Ataxin-2 was overexpressed\/re-established in the hypothalamus of C57Bl6\/<jats:italic>Atxn2<\/jats:italic> KO mice fed either a chow or a high-fat diet (HFD). This delivery was achieved through stereotaxic injection of lentiviral vectors encoding for ataxin-2. We show, for the first time, that HFD decreases ataxin-2 levels in mouse hypothalamus and liver. Specific hypothalamic ataxin-2 overexpression prevents HFD-induced obesity and insulin resistance. Ataxin-2 re-establishment in <jats:italic>Atxn2<\/jats:italic> KO mice improved metabolic dysfunction without changing body weight. Furthermore, we observed altered clock gene expression in <jats:italic>Atxn2<\/jats:italic> KO that might be causative of metabolic dysfunction. Interestingly, ataxin-2 hypothalamic re-establishment rescued these circadian alterations. Thus, ataxin-2 in the hypothalamus is a determinant for weight, insulin sensitivity and clock gene expression. Ataxin-2\u2019s potential role in the circadian clock, through the regulation of clock genes, might be a relevant mechanism to regulate metabolism. Overall, this work shows hypothalamic ataxin-2 as a new player in metabolism regulation, which might contribute to the development of new strategies for metabolic disorders.<\/jats:p>","DOI":"10.1530\/jme-21-0272","type":"journal-article","created":{"date-parts":[[2022,9,14]],"date-time":"2022-09-14T15:17:11Z","timestamp":1663168631000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-6","source":"Crossref","is-referenced-by-count":10,"title":["Ataxin-2 in the hypothalamus at the crossroads between metabolism and clock genes"],"prefix":"10.1530","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6124-0428","authenticated-orcid":true,"given":"Sara","family":"Carmo-Silva","sequence":"first","affiliation":[{"name":"CNC-UC \u2013 Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal"},{"name":"CIBB \u2013 Center for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, Portugal"},{"name":"MIA \u2013 Multidisciplinary Institute of Ageing, University of Coimbra, Coimbra, Portugal"}]},{"given":"Marisa","family":"Ferreira-Marques","sequence":"additional","affiliation":[{"name":"CNC-UC \u2013 Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal"},{"name":"CIBB \u2013 Center for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, Portugal"},{"name":"Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal"}]},{"given":"Cl\u00e9vio","family":"N\u00f3brega","sequence":"additional","affiliation":[{"name":"CNC-UC \u2013 Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal"},{"name":"ABC-RI, Algarve Biomedical Center Research Institute, Faro, Portugal"},{"name":"Faculdade de Medicina e Ci\u00eancias Biom\u00e9dicas, Universidade do Algarve, Faro, Portugal"}]},{"given":"Mariana","family":"Botelho","sequence":"additional","affiliation":[{"name":"CNC-UC \u2013 Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal"}]},{"given":"Daniela","family":"Costa","sequence":"additional","affiliation":[{"name":"CNC-UC \u2013 Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal"},{"name":"CIBB \u2013 Center for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, Portugal"},{"name":"Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal"}]},{"given":"C\u00e9lia A","family":"Aveleira","sequence":"additional","affiliation":[{"name":"CNC-UC \u2013 Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal"},{"name":"CIBB \u2013 Center for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, Portugal"},{"name":"MIA \u2013 Multidisciplinary Institute of Ageing, University of Coimbra, Coimbra, Portugal"}]},{"given":"Stefan M","family":"Pulst","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Utah, Salt Lake City, Utah, USA"}]},{"given":"Lu\u00eds","family":"Pereira de Almeida","sequence":"additional","affiliation":[{"name":"CNC-UC \u2013 Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal"},{"name":"CIBB \u2013 Center for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, Portugal"},{"name":"Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8020-9266","authenticated-orcid":true,"given":"Claudia","family":"Cavadas","sequence":"additional","affiliation":[{"name":"CNC-UC \u2013 Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal"},{"name":"CIBB \u2013 Center for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, Portugal"},{"name":"Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal"}]}],"member":"416","reference":[{"key":"bib1","series-title":"Journal of Neurology","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1007\/s00415-008-0690-4","article-title":"Spinocerebellar ataxia type 2 (SCA2) in an Egyptian family presenting with polyphagia and marked CAG expansion in infancy","volume":"255","author":"Abdel-Aleem","year":"2008","unstructured":"Abdel-Aleem AZaki MS2008Spinocerebellar ataxia type 2 (SCA2) in an Egyptian family presenting with polyphagia and marked CAG expansion in infancy. 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