18.97.14.88
18.97.14.88
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Central dopaminergic system regulates energy balance and BAT function
( Ki Woo Kim )
UCI I410-ECN-0102-2021-500-000701578
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Dopaminergic (DA) neurons are involved in integration of neuronal and hormonal signals to regulate food consumption and energy balance. Forkhead transcription factor O1 (FoxO1) in the hypothalamus plays a crucial role in mediation of leptin and insulin function. However, the homeostatic 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 KODAT) show markedly increased energy expenditure and interscapular brown adipose tissue (iBAT) thermogenesis accompanied by reduced fat mass and improved glucose/insulin homeostasis. Moreover, FoxO1 KODAT mice present higher reward value for sucrose in concomitance with increased dopamine and norepinephrine levels. Finally, we found that FoxO1 directly targets and negatively regulates tyrosine hydroxylase (TH) expression, the rate-limiting enzyme of the catecholamines synthesis, delineating a mechanism for the KO phenotypes. Collectively, these results suggest that the FoxO1 in DA neurons directs transcriptional programs that are important in the coordinated control of energy balance, thermogenesis, and glucose homeostasis.

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