GHS-R1a signaling in the DMH and VMH contributes to food anticipatory activity
M Merkestein1, M A van Gestel1, E M van der Zwaal1
1Rudolf Magnus Institute of Neuroscience, Department of Neuroscience and Pharmacology, University Medical Center Utrecht, Utrecht, The Netherlands.
Background:
Rats that have restricted access to food at a fixed time point of the circadian phase display high levels of food anticipatory activity (FAA). The orexigenic hormone ghrelin has been implicated in the regulation of FAA. However, it is not known via which brain area ghrelin exerts this effect. Growth hormone secretagogue receptor 1a (GHS-R1a) is highly expressed in the hypothalamus, including the dorsomedial hypothalamus (DMH) and the ventromedial hypothalamus (VMH). These two hypothalamic areas have been reported to play a role in FAA.
Aim Of The Study:
To examine the role of GHS-R1a signaling in the DMH and VMH in FAA.
Design:
Adeno-associated virus expressing a shRNA directed against GHS-R1a was used to establish local knockdown of GHS-R1a in the DMH and VMH in rats. Rats were subsequently subjected to a restricted feeding schedule (RFS).
Results:
Under ad libitum conditions, knockdown of GHS-R1a in the VMH increased food intake and body weight gain. In addition, GHS-R1a knockdown in VMH and DMH reduced body temperature and running wheel activity (RWA). When rats were subjected to a RFS, the main effect of GHS-R1a knockdown in both DMH and VMH was a decrease in RWA and an attenuation of body weight loss. Rats with knockdown of GHS-R1a in DMH and VMH showed a delay in onset of FAA. In addition, GHS-R1a knockdown in DMH resulted in a reduction of FAA amplitude.
Conclusion:
This is the first study to investigate the effect of local hypothalamic knockdown of GHS-R1a on FAA. Our results implicate hypothalamic GHS-R1a signaling in the regulation of FAA. Nevertheless, some FAA remained, suggesting that a distributed network of brain areas and signaling pathways is involved in the development of FAA.
Related Concept Videos
Regulation of Food Intake
Neural Regulation
Hedgehog Signaling Pathway
Primary Motives: Hunger and Thirst
Hunger arises when the brain detects changes in the body's nutrient levels, including glucose, lipids, amino acids, and hormones such as ghrelin and leptin. The hypothalamus plays a central role in hunger regulation. The lateral hypothalamus acts...
Hormonal Regulation
Cephalic Phase of Digestion


