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To investigate TTR function in nervous system homeostasis, differential gene expression in wild\u2010type (WT) and TTR knockout (KO) mice was assessed. Peptidylglycine \u03b1\u2010amidating monooxygenase (PAM), the rate\u2010limiting enzyme in neuropeptide maturation, is overexpressed in the peripheral (PNS) and central nervous system (CNS) of TTR KOs that, consequently, display increased neuropeptide Y (NPY) levels. NPY acts on energy homeostasis by increasing white adipose tissue lipoprotein lipase (LPL) and decreasing thermogenesis; accordingly, we show increased LPL expression and activity in white adipose tissue, PNS, and CNS as well as decreased body temperature in TTR KOs. Associated to increased NPY levels, TTR KOs display increased carbohydrate consumption and preference. In neuronal cells, absence of TTR is related to increased PAM activity, NPY levels and LPL expression, reinforcing that TTR is involved in neuropeptide maturation and that increased NPY correlates with LPL overexpression in the nervous system. Furthermore, we provide molecular insights to the reduced depressive behavior of TTR KOs, as NPY is anti\u2010depressant. Our findings demonstrate that TTR KOs are a model for increased NPY and that TTR plays a role in nervous system physiology.<\/jats:p>","DOI":"10.1096\/fj.05-4106fje","type":"journal-article","created":{"date-parts":[[2005,11,1]],"date-time":"2005-11-01T20:33:40Z","timestamp":1130877220000},"page":"166-168","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["Transthyretin knockouts are a new mouse model for increased neuropeptide Y"],"prefix":"10.1096","volume":"20","author":[{"given":"Ana Filipa","family":"Nunes","sequence":"first","affiliation":[{"name":"Molecular Neurobiology Instituto de Biologia Molecular e Celular\u2010IBMC  Porto Portugal"},{"name":"ICBAS University of Porto  Portugal"}]},{"given":"Maria Jo\u00e3o","family":"Saraiva","sequence":"additional","affiliation":[{"name":"Molecular Neurobiology Instituto de Biologia Molecular e Celular\u2010IBMC  Porto Portugal"},{"name":"ICBAS University of Porto  Portugal"}]},{"given":"M\u00f3nica Mendes","family":"Sousa","sequence":"additional","affiliation":[{"name":"Molecular Neurobiology Instituto de Biologia Molecular e Celular\u2010IBMC  Porto Portugal"}]}],"member":"311","published-online":{"date-parts":[[2005,11]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)93118-2"},{"key":"e_1_2_6_3_1","author":"Soprano D. 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