Abstract
The neural basis for fasting activation of the hypothalamic-pituitary adrenal axis
Physiology (Bethesda, Md.), Vol.38(S1)
05/01/2023
DOI: 10.1152/physiol.2023.38.s1.5726127
Abstract
Fasting initiates a multitude of adaptations to allow survival. Activation of the hypothalamic-pituitary-adrenal (HPA) axis and subsequent release of glucocorticoid hormones is a key response that mobilizes fuel stores to meet energy demands. Despite the importance of the HPA axis response, the neural mechanisms that drive its activation during energy deficit are unknown. Here, we show that hypothalamic agouti-related peptide (AgRP)-expressing neurons trigger and are essential for fasting-induced HPA axis activation. AgRP neurons stimulate activity of the HPA axis via projections to the paraventricular hypothalamus (PVH), where, in a mechanism not previously described for AgRP neurons, they presynaptically inhibit the terminals of tonically active GABAergic afferents from the bed nucleus of the stria terminalis (BNST) that otherwise restrain activity of corticotrophin-releasing hormone (CRH)-expressing neurons. This disinhibition of PVH-Crh neurons requires GABA (γ-aminobutyric acid)/GABA-B receptor signaling and potently activates the HPA axis. Importantly, stimulation of the HPA axis by AgRP neurons is independent of their induction of hunger, showing that these canonical ‘hunger neurons’ drive multiple parallel adaptations to the fasted state. Together our findings identify the neural basis for fasting-induced HPA axis activation and uncover a unique means by which AgRP neurons activate downstream neurons – via presynaptic inhibition of GABAergic afferents. Given the potency of this disinhibition of tonically active BNST afferents, other activators of the HPA axis such as psychological stress may work via a similar mechanism. NIH R01DK096010, NIH R00HL144923, AHA 935362 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Details
- Title: Subtitle
- The neural basis for fasting activation of the hypothalamic-pituitary adrenal axis
- Creators
- Jon Resch - University of IowaAmelia Douglass - Beth Israel Deaconess Medical CenterJoseph Madara - Beth Israel Deaconess Medical CenterHakan Kucukdereli - Beth Israel Deaconess Medical CenterOfer Yizhar - Weizmann Institute of ScienceAbhinav Grama - Harvard University PressMasahito Yamagata - Harvard University PressZongfang Yang - Beth Israel Deaconess Medical CenterBradford Lowell - Beth Israel Deaconess Medical Center
- Resource Type
- Abstract
- Publication Details
- Physiology (Bethesda, Md.), Vol.38(S1)
- Publisher
- American Physiological Society
- DOI
- 10.1152/physiol.2023.38.s1.5726127
- ISSN
- 1548-9213
- eISSN
- 1548-9221
- Language
- English
- Date published
- 05/01/2023
- Academic Unit
- Fraternal Order of Eagles Diabetes Research Center; Iowa Neuroscience Institute; Neuroscience and Pharmacology
- Record Identifier
- 9984528117602771
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