Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comment
. 2020 Sep 1;130(9):4540-4542.
doi: 10.1172/JCI140585.

Coordination of metabolism, arousal, and reward by orexin/hypocretin neurons

Natalie J Michael  1 , Joel K Elmquist  2
Affiliations
Comment

Coordination of metabolism, arousal, and reward by orexin/hypocretin neurons

Natalie J Michael et al. J Clin Invest. .

Abstract

Orexin/hypocretin neurons located in the lateral hypothalamus play a critical role in the maintenance of arousal and contribute to the regulation of multiple homeostatic and behavioral processes. In this issue of the JCI, Tan and Hang et al. report that feeding a high-fat diet to mice compromised the function of the orexin system, leading to impairments in reward-seeking and active coping mechanisms. The researchers observed changes at the cellular and circuit levels suggesting that reduced excitability of orexin neurons affects behavior through induction of a hypoarousal state.

PubMed Disclaimer

Conflict of interest statement

Conflict of interest: The authors have declared that no conflict of interest exists.

Figures

Figure 1
Figure 1. Obesity-induced cellular and circuit level changes in the orexin system are associated with maladaptive behavioral responses.
Chronic HFF alters glutamatergic inputs to orexin/hypocretin neurons (Ox/Hcrt), thereby increasing overall inhibitory tone and inducing a state of hypoarousal. Altered cellular activity of orexin neurons influences the activity of downstream neural networks in the lateral hypothalamus and hippocampus and decreases reward-seeking and coping behaviors. Chemogenetic activation of orexin neurons reverses changes in network activity and corrects the behavioral consequences of HFF (14). GluR, glutamate receptor; D1R, dopamine 1 receptor; hM3Dq, chemogenic receptor.
See this image and copyright information in PMC

Comment on

References

    1. Schwartz MW, et al. Central nervous system control of food intake. Nature. 2000;404(6778):661–671. doi: 10.1038/35007534. - DOI - PubMed
    1. Vgontzas AN, Bixler EO, Tan TL, Kantner D, Martin LF, Kales A. Obesity without sleep apnea is associated with daytime sleepiness. Arch Intern Med. 1998;158(12):1333–1337. doi: 10.1001/archinte.158.12.1333. - DOI - PubMed
    1. Sharma S, Fulton S. Diet-induced obesity promotes depressive-like behaviour that is associated with neural adaptations in brain reward circuitry. Int J Obes (Lond) 2013;37(3):382–389. doi: 10.1038/ijo.2012.48. - DOI - PubMed
    1. de Lecea L, et al. The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity. Proc Natl Acad Sci U S A. 1998;95(1):322–327. doi: 10.1073/pnas.95.1.322. - DOI - PMC - PubMed
    1. Sakurai T, et al. Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell. 1998;92(4):573–585. doi: 10.1016/S0092-8674(00)80949-6. - DOI - PubMed