Document Detail

Transthyretin knockouts are a new mouse model for increased neuropeptide Y.
MedLine Citation:
PMID:  16263939     Owner:  NLM     Status:  MEDLINE    
Transthyretin (TTR) has access to the brain and nerve through the blood and cerebrospinal fluid. To investigate TTR function in nervous system homeostasis, differential gene expression in wild-type (WT) and TTR knockout (KO) mice was assessed. Peptidylglycine alpha-amidating monooxygenase (PAM), the rate-limiting 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-depressant. Our findings demonstrate that TTR KOs are a model for increased NPY and that TTR plays a role in nervous system physiology.
Ana Filipa Nunes; Maria João Saraiva; Mónica Mendes Sousa
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2005-11-01
Journal Detail:
Title:  FASEB journal : official publication of the Federation of American Societies for Experimental Biology     Volume:  20     ISSN:  1530-6860     ISO Abbreviation:  FASEB J.     Publication Date:  2006 Jan 
Date Detail:
Created Date:  2006-01-05     Completed Date:  2006-03-23     Revised Date:  2012-02-15    
Medline Journal Info:
Nlm Unique ID:  8804484     Medline TA:  FASEB J     Country:  United States    
Other Details:
Languages:  eng     Pagination:  166-8     Citation Subset:  IM    
Molecular Neurobiology, Instituto de Biologia Molecular e Celular-IBMC, Porto, Portugal.
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MeSH Terms
Cells, Cultured
Dietary Carbohydrates
Gene Deletion*
Gene Expression Profiling
Gene Expression Regulation
Lipoprotein Lipase / genetics,  metabolism
Mice, Knockout
Mice, Transgenic
Mixed Function Oxygenases / metabolism
Models, Animal*
Multienzyme Complexes / metabolism
Neurons / metabolism
Neuropeptide Y / metabolism*
Prealbumin / deficiency*,  genetics*,  metabolism
Substance P / metabolism
Reg. No./Substance:
0/Dietary Carbohydrates; 0/Multienzyme Complexes; 0/Neuropeptide Y; 0/Prealbumin; 33507-63-0/Substance P; EC 1.-/Mixed Function Oxygenases; EC monooxygenase; EC Lipase

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