Knockdown of central ghrelin O-acyltransferase by vivo-morpholino reduces body mass of rats fed a high-fat diet

作者: Martin Wellman , Alfonso Abizaid

DOI: 10.1016/J.PEPTIDES.2015.05.007

关键词: Ghrelin O-acyltransferaseMetabolismBiologyEndocrinologyOrexigenicGhrelinMessenger RNAGene knockdownInternal medicineReceptorHypothalamus

摘要: The enzyme ghrelin O-acyltransferase (GOAT) activates the orexigenic peptide by transferring an acyl group from fatty acids to serine-3 residue of molecule. This allows bind its only known receptor, growth hormone secretagogue receptor type 1a (GHSR1a). While studies have examined hypothalamic transcriptional response GOAT metabolic challenge in mice, little has been rat hypothalamus. Furthermore, it not possible identify role central separate that periphery, since previous either knocked out system-wide or administered a inhibitor intraperitoneally. To determine if expression is modulated changes energy state, we subjected rats forty-eight hours food deprivation three weeks restriction and found mRNA increases significantly both hypothalamus stomach fundus challenges. We also GHSR1a deprivation, as well restriction. then conducted second study where continuously infused amorpholino antisense oligonucleotide into lateral ventricles knock-down centrally while animals were exposed high fat diet. Our results show receiving gained less weight, decreased their caloric efficiency when eating diet compared control animals. These data suggest plays modulating metabolism rats.

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