TY - JOUR

T1 - Biased Ghrelin Receptor Signaling and the Dopaminergic System as Potential Targets for Metabolic and Psychological Symptoms of Anorexia Nervosa

AU - Khelifa, Mariam S.

AU - Skov, Louise J.

AU - Holst, Birgitte

N1 - Publisher Copyright: © Copyright © 2021 Khelifa, Skov and Holst.

PY - 2021

Y1 - 2021

N2 - Anorexia Nervosa (AN) is a complex disease that impairs the metabolic, mental and physiological health of affected individuals in a severe and sometimes lethal way. Many of the common symptoms in AN patients, such as reduced food intake, anxiety, impaired gut motility or overexercising are connected to both the orexigenic gut hormone ghrelin and the dopaminergic system. Targeting the ghrelin receptor (GhrR) to treat AN seems a promising possibility in current research. However, GhrR signaling is highly complex. First, the GhrR can activate four known intracellular pathways Gαq, Gαi/o, Gα12/13 and the recruitment of β-arrestin. Biased signaling provides the possibility to activate or inhibit only one or a subset of the intracellular pathways of a pleiotropic receptor. This allows specific targeting of physiological functions without adverse effects. Currently little is known on how biased signaling could specifically modulate GhrR effects. Second, GhrR signaling has been shown to be interconnected with the dopaminergic system, particularly in the context of AN symptoms. This review highlights that a biased agonist for the GhrR may be a promising target for the treatment of AN, however extensive and systematic translational studies are still needed and the connection to the dopaminergic system has to be taken into account.

AB - Anorexia Nervosa (AN) is a complex disease that impairs the metabolic, mental and physiological health of affected individuals in a severe and sometimes lethal way. Many of the common symptoms in AN patients, such as reduced food intake, anxiety, impaired gut motility or overexercising are connected to both the orexigenic gut hormone ghrelin and the dopaminergic system. Targeting the ghrelin receptor (GhrR) to treat AN seems a promising possibility in current research. However, GhrR signaling is highly complex. First, the GhrR can activate four known intracellular pathways Gαq, Gαi/o, Gα12/13 and the recruitment of β-arrestin. Biased signaling provides the possibility to activate or inhibit only one or a subset of the intracellular pathways of a pleiotropic receptor. This allows specific targeting of physiological functions without adverse effects. Currently little is known on how biased signaling could specifically modulate GhrR effects. Second, GhrR signaling has been shown to be interconnected with the dopaminergic system, particularly in the context of AN symptoms. This review highlights that a biased agonist for the GhrR may be a promising target for the treatment of AN, however extensive and systematic translational studies are still needed and the connection to the dopaminergic system has to be taken into account.

KW - anorexia nervosa

KW - anxiety

KW - biased signaling

KW - dopamine

KW - food intake

KW - ghrelin

KW - gut motility

KW - locomotion

UR - http://www.scopus.com/inward/record.url?scp=85116900527&partnerID=8YFLogxK

U2 - 10.3389/fendo.2021.734547

DO - 10.3389/fendo.2021.734547

M3 - Review

C2 - 34646236

AN - SCOPUS:85116900527

VL - 12

JO - Frontiers in Endocrinology

JF - Frontiers in Endocrinology

SN - 1664-2392

M1 - 734547

ER -