FoxO1 in Dopaminergic Neurons Regulates Energy Homeostasis and Targets Tyrosine Hydroxylase

Overview

Journal Nat Commun

Specialty Biology

Date 2016 Sep 30

PMID 27681312

Citations 26

Authors

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

Affiliations

Soon will be listed here.

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.

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