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Ghrelin induces clock gene expression in the liver of goldfish in vitro via protein kinase C and protein kinase A pathways



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Sánchez Bretaño, Aída and Blanco, Ayelen M. and Alonso Gómez, Ángel Luis and Delgado Saavedra, María Jesús and Kah, Olivier and Isorna Alonso, Esther (2017) Ghrelin induces clock gene expression in the liver of goldfish in vitro via protein kinase C and protein kinase A pathways. Journal of Experimental Biology, 220 . pp. 1295-1306. ISSN 0022-0949


Official URL: http://jeb.biologists.org/


The liver is the most important link between the circadian system and metabolism. As a food-entrainable oscillator, the hepatic clock needs to be entrained by food-related signals. The objective of the present study was to investigate the possible role of ghrelin (an orexigenic peptide mainly synthesized in the gastrointestinal tract) as an endogenous synchronizer of the liver oscillator in teleosts. To achieve this aim, we first examined the presence of ghrelin receptors in the liver of goldfish. Then, the ghrelin regulation of clock gene expression in the goldfish liver was studied. Finally, the possible involvement of the phospholipase C/protein kinase C (PLC/PKC) and adenylate cyclase/protein kinase A (AC/PKA) intracellular signalling pathways was investigated. Ghrelin receptor transcripts, ghs-r1a, are present in the majority of goldfish hepatic cells. Ghrelin induced the mRNA expression of the positive (gbmal1a, gclock1a) and negative (gper genes) elements of the main loop of the molecular clock machinery, as well as grev-erbα (auxiliary loop) in cultured liver. These effects were blocked, at least in part, by a ghrelin antagonist. Incubation of liver with a PLC inhibitor (U73122), a PKC activator (phorbol 12-myristate 13-acetate) and a PKC inhibitor (chelerythrine chloride) demonstrated that the PLC/PKC pathway mediates such ghrelin actions. Experiments with an AC activator (forskolin) and a PKA inhibitor (H89) showed that grev-erbα regulation could be due to activation of PKA. Taken together, the present results show for the first time in vertebrates a direct action of ghrelin on hepatic clock genes and support a role for this hormone as a temporal messenger in the entrainment of liver circadian functions.

Item Type:Article
Uncontrolled Keywords:Orexigenic peptides, Circadian system, Protein kinase C,Protein kinase A, Hepatic clock, Teleos
Subjects:Medical sciences > Biology
Medical sciences > Biology > Animal physiology
Medical sciences > Biology > Fishes
ID Code:44335
Deposited On:23 Aug 2017 09:58
Last Modified:23 Aug 2017 10:37

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