FoxO1 in dopaminergic neurons regulates energy homeostasis and targets tyrosine hydroxylase

Khanh V. Doan, Ann W. Kinyua, Dong Joo Yang, Chang Mann Ko, Sang Hyun Moh, Ko Eun Shong, Hail Kim, Sang Kyu Park, Dong Hoon Kim, Inki Kim, Ji Hye Paik, Ronald A. Depinho, Seul Gi Yoon, Il Yong Kim, Je Kyung Seong, Yun Hee Choi, Ki Woo Kim

Research output: Contribution to journalArticle

14 Citations (Scopus)

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 DAT) 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 DAT 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.

Original languageEnglish
Article number12733
JournalNature communications
Volume7
DOIs
Publication statusPublished - 2016 Sep 29

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homeostasis
tyrosine
Dopaminergic Neurons
Tyrosine 3-Monooxygenase
neurons
Neurons
Homeostasis
insulin
Thermogenesis
Energy balance
glucose
mice
norepinephrine
hypothalamus
catecholamine
adipose tissues
Insulin
Glucose
dopamine
mediation

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Doan, Khanh V. ; Kinyua, Ann W. ; Yang, Dong Joo ; Ko, Chang Mann ; Moh, Sang Hyun ; Shong, Ko Eun ; Kim, Hail ; Park, Sang Kyu ; Kim, Dong Hoon ; Kim, Inki ; Paik, Ji Hye ; Depinho, Ronald A. ; Yoon, Seul Gi ; Kim, Il Yong ; Seong, Je Kyung ; Choi, Yun Hee ; Kim, Ki Woo. / FoxO1 in dopaminergic neurons regulates energy homeostasis and targets tyrosine hydroxylase. In: Nature communications. 2016 ; Vol. 7.
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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 DAT) 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 DAT 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.",
author = "Doan, {Khanh V.} and Kinyua, {Ann W.} and Yang, {Dong Joo} and Ko, {Chang Mann} and Moh, {Sang Hyun} and Shong, {Ko Eun} and Hail Kim and Park, {Sang Kyu} and Kim, {Dong Hoon} and Inki Kim and Paik, {Ji Hye} and Depinho, {Ronald A.} and Yoon, {Seul Gi} and Kim, {Il Yong} and Seong, {Je Kyung} and Choi, {Yun Hee} and Kim, {Ki Woo}",
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Doan, KV, Kinyua, AW, Yang, DJ, Ko, CM, Moh, SH, Shong, KE, Kim, H, Park, SK, Kim, DH, Kim, I, Paik, JH, Depinho, RA, Yoon, SG, Kim, IY, Seong, JK, Choi, YH & Kim, KW 2016, 'FoxO1 in dopaminergic neurons regulates energy homeostasis and targets tyrosine hydroxylase', Nature communications, vol. 7, 12733. https://doi.org/10.1038/ncomms12733

FoxO1 in dopaminergic neurons regulates energy homeostasis and targets tyrosine hydroxylase. / Doan, Khanh V.; Kinyua, Ann W.; Yang, Dong Joo; Ko, Chang Mann; Moh, Sang Hyun; Shong, Ko Eun; Kim, Hail; Park, Sang Kyu; Kim, Dong Hoon; Kim, Inki; Paik, Ji Hye; Depinho, Ronald A.; Yoon, Seul Gi; Kim, Il Yong; Seong, Je Kyung; Choi, Yun Hee; Kim, Ki Woo.

In: Nature communications, Vol. 7, 12733, 29.09.2016.

Research output: Contribution to journalArticle

TY - JOUR

T1 - FoxO1 in dopaminergic neurons regulates energy homeostasis and targets tyrosine hydroxylase

AU - Doan, Khanh V.

AU - Kinyua, Ann W.

AU - Yang, Dong Joo

AU - Ko, Chang Mann

AU - Moh, Sang Hyun

AU - Shong, Ko Eun

AU - Kim, Hail

AU - Park, Sang Kyu

AU - Kim, Dong Hoon

AU - Kim, Inki

AU - Paik, Ji Hye

AU - Depinho, Ronald A.

AU - Yoon, Seul Gi

AU - Kim, Il Yong

AU - Seong, Je Kyung

AU - Choi, Yun Hee

AU - Kim, Ki Woo

PY - 2016/9/29

Y1 - 2016/9/29

N2 - 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 DAT) 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 DAT 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.

AB - 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 DAT) 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 DAT 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.

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