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The aim of this study was to investigate if the metabolic regulators sirtuins are affected in HD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Quantitative real\u2010time polymerase chain reactions were used to assess levels of <jats:italic>SIRT1\u20103<\/jats:italic> and downstream targets in <jats:italic>post mortem<\/jats:italic> brain tissue from HD patients and control cases as well as after selective hypothalamic expression of mutant huntingtin (HTT) using recombinant adeno\u2010associated viral vectors in mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We show that mRNA levels of the metabolic regulator SIRT1 are increased in the striatum and the cerebral cortex but not in the less affected cerebellum in <jats:italic>post mortem<\/jats:italic> HD brains. Levels of <jats:italic>SIRT2<\/jats:italic> are only increased in the striatum and <jats:italic>SIRT3<\/jats:italic> is not affected in HD. Interestingly, mRNA levels of <jats:italic>SIRT1<\/jats:italic> are selectively increased in the lateral hypothalamic area (LHA) and ventromedial hypothalamus (VMH) in HD. Further analyses of the LHA and VMH confirmed pathological changes in these regions including effects on SIRT1 downstream targets and reduced mRNA levels of orexin (hypocretin), prodynorphin and melanin\u2010concentrating hormone (<jats:italic>MCH<\/jats:italic>) in the LHA and of brain\u2010derived neurotrophic factor (<jats:italic>BDNF<\/jats:italic>) in the VMH. Analyses after selective hypothalamic expression of mutant HTT suggest that effects on BDNF, orexin, dynorphin and MCH are early and direct, whereas changes in SIRT1 require more widespread expression of mutant HTT.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We show that SIRT1 expression is increased in HD\u2010affected brain regions and that metabolic pathways are altered in the HD hypothalamus.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nan.12514","type":"journal-article","created":{"date-parts":[[2018,7,18]],"date-time":"2018-07-18T21:23:18Z","timestamp":1531948998000},"page":"361-379","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["<i>SIRT1<\/i> is increased in affected brain regions and hypothalamic metabolic pathways are altered in Huntington disease"],"prefix":"10.1111","volume":"45","author":[{"given":"B.","family":"Baldo","sequence":"first","affiliation":[{"name":"Translational Neuroendocrine Research Unit Department of Experimental Medical Science Lund University Lund Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Gabery","sequence":"additional","affiliation":[{"name":"Translational Neuroendocrine Research Unit Department of Experimental Medical Science Lund University Lund Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.","family":"Soylu\u2010Kucharz","sequence":"additional","affiliation":[{"name":"Translational Neuroendocrine Research Unit Department of Experimental Medical Science Lund University Lund Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R. 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