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Open Access Green as soon as Postprint is submitted to ZB.
Current understanding of the hypothalamic ghrelin pathways inducing appetite and adiposity.
Trends Neurosci. 40, 167-180 (2017)
Ghrelin is a multifaceted regulator of metabolism. Ghrelin regulates energy balance in the short term via induction of appetite and in the long term via increased body weight and adiposity. Recently, several central pathways modulating the metabolic actions of ghrelin were unmasked, and it was shown to act through different hypothalamic nuclei to induce feeding. Ghrelin also modulates glucose homeostasis, but the central mechanisms responsible for this action have not been studied in detail. Although ghrelin also acts through extrahypothalamic areas to promote feeding, this review specifically dissects hypothalamic control of ghrelin's orexigenic and adipogenic actions and presents current understanding of the intracellular ghrelin orexigenic pathways, including their dependence on other relevant systems implicated in energy balance. The lack of ghrelin in adulthood has no effect on feeding or body weight. Ghrelin- or ghrelin receptor-deficient mice fed a high-fat diet after weaning and neuronal deletion of ghrelin receptor are diet-induced resistant. Ghrelin inhibition before weaning caused increased adiposity and feeding.Energy sensors controlling neuronal function and plasticity are located in the hypothalamus and ghrelin acts through these energy sensors to modulate feeding.The orexigenic but not the adipogenic action of ghrelin is impaired in obese animals.Mutations in the ghrelin receptor that prevented its binding to beta-arrestin did not influence ghrelin orexigenic action but increased its effects on adiposity and insulin resistance.Ghrelin's actions on energy and glucose homeostasis are of clinical relevance: ghrelin agonists show beneficial effects in patients with cancer cachexia; and an agonist of des-acyl ghrelin improves insulin sensitivity in humans.
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Publication type
Article: Journal article
Document type
Review
Keywords
Adiposity ; Fatty Acids ; Feeding ; Ghrelin ; Ghrelin Receptor ; Hypothalamus
ISSN (print) / ISBN
0166-2236
e-ISSN
1878-108X
Journal
Trends in Neurosciences
Quellenangaben
Volume: 40,
Issue: 3,
Pages: 167-180
Publisher
Elsevier
Publishing Place
Amsterdam [u.a.]
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Diabetes and Obesity (IDO)