FoxO1 in dopaminergic neurons regulates energy homeostasis and targets tyrosine hydroxylase.

TitleFoxO1 in dopaminergic neurons regulates energy homeostasis and targets tyrosine hydroxylase.
Publication TypeJournal Article
Year of Publication2016
AuthorsDoan KV, Kinyua AW, Yang DJoo, Ko CMann, Moh SHyun, Shong KEun, Kim H, Park S-K, Kim D-H, Kim I, Paik J-H, DePinho RA, Yoon SGi, Kim IYong, Seong JKyung, Choi Y-H, Kim KWoo
JournalNat Commun
Volume7
Pagination12733
Date Published2016 Sep 29
ISSN2041-1723
Abstract

Dopaminergic (DA) neurons are involved in the integration of neuronal and hormonal signals to regulate food consumption and energy balance. Forkhead transcriptional factor O1 (FoxO1) in the hypothalamus plays a crucial role in mediation of leptin and insulin function. However, the homoeostatic role of FoxO1 in DA system has not been investigated. Here we report that FoxO1 is highly expressed in DA neurons and mice lacking FoxO1 specifically in the DA neurons (FoxO1 KO) show markedly increased energy expenditure and interscapular brown adipose tissue (iBAT) thermogenesis accompanied by reduced fat mass and improved glucose/insulin homoeostasis. Moreover, FoxO1 KO mice exhibit an increased sucrose preference in concomitance with higher dopamine and norepinephrine levels. Finally, we found that FoxO1 directly targets and negatively regulates tyrosine hydroxylase (TH) expression, the rate-limiting enzyme of the catecholamine synthesis, delineating a mechanism for the KO phenotypes. Collectively, these results suggest that FoxO1 in DA neurons is an important transcriptional factor that directs the coordinated control of energy balance, thermogenesis and glucose homoeostasis.

DOI10.1038/ncomms12733
Alternate JournalNat Commun
PubMed ID27681312
PubMed Central IDPMC5056402
Grant ListR01 AG048284 / AG / NIA NIH HHS / United States
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Ji-Hye Paik, Ph.D.

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