Transthyretin knockouts are a new mouse model for increased neuropeptide Y

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 α‐amidating monooxygenase (PAM), the rat...

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Bibliographic Details
Published in:The FASEB journal 2006-01, Vol.20 (1), p.166-168
Main Authors: Nunes, Ana Filipa, Saraiva, Maria João, Sousa, Mónica Mendes
Format: Article
Language:English
Subjects:
Animals
Cells, Cultured
depression
Dietary Carbohydrates
Female
Gene Deletion
Gene Expression Profiling
Gene Expression Regulation
lipoprotein lipase
Lipoprotein Lipase - genetics
Lipoprotein Lipase - metabolism
Male
Mice
Mice, Knockout
Mice, Transgenic
Mixed Function Oxygenases - metabolism
Models, Animal
Multienzyme Complexes - metabolism
Neurons - metabolism
Neuropeptide Y - metabolism
peptidylglycine α‐amidating monooxygenase
peripheral nerve
Prealbumin - deficiency
Prealbumin - genetics
Prealbumin - metabolism
Substance P - metabolism
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Summary: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 α‐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.
ISSN:0892-6638
1530-6860
DOI:10.1096/fj.05-4106fje