2010
DOI: 10.1016/j.mce.2009.12.023
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Metabolic regulation of ghrelin O-acyl transferase (GOAT) expression in the mouse hypothalamus, pituitary, and stomach

Abstract: Ghrelin acts as an endocrine link connecting physiological processes regulating food intake, body composition, growth, and energy balance. Ghrelin is the only peptide known to undergo octanoylation. The enzyme mediating this process, ghrelin O-acyltransferase (GOAT), is expressed in the gastrointestinal tract (GI; primary source of circulating ghrelin) as well as other tissues. The present study demonstrates that stomach GOAT mRNA levels correlate with circulating acylatedghrelin levels in fasted and diet-indu… Show more

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Cited by 114 publications
(128 citation statements)
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“…Our results also show that insulin increases GOAT transcript levels in human fat cells. The existing literature on the effect of insulin on GOAT is scarce and controversial, with insulin inhibiting GOAT in INS-1 pancreatic cells, but lacking effect in murine primary pituitary cells [40,41]. Here, we have also shown that acylated ghrelin promotes ghrelin production and acylation in human adipocytes, a finding in agreement with previously published data on murine primary pituitary cells [41], while desacyl ghrelin acts as a repressor of ghrelin transcription.…”
Section: Discussionsupporting
confidence: 92%
See 1 more Smart Citation
“…Our results also show that insulin increases GOAT transcript levels in human fat cells. The existing literature on the effect of insulin on GOAT is scarce and controversial, with insulin inhibiting GOAT in INS-1 pancreatic cells, but lacking effect in murine primary pituitary cells [40,41]. Here, we have also shown that acylated ghrelin promotes ghrelin production and acylation in human adipocytes, a finding in agreement with previously published data on murine primary pituitary cells [41], while desacyl ghrelin acts as a repressor of ghrelin transcription.…”
Section: Discussionsupporting
confidence: 92%
“…The existing literature on the effect of insulin on GOAT is scarce and controversial, with insulin inhibiting GOAT in INS-1 pancreatic cells, but lacking effect in murine primary pituitary cells [40,41]. Here, we have also shown that acylated ghrelin promotes ghrelin production and acylation in human adipocytes, a finding in agreement with previously published data on murine primary pituitary cells [41], while desacyl ghrelin acts as a repressor of ghrelin transcription. In this sense, Mboat4 knockout mice, which lack acylated ghrelin, but otherwise exhibit physiological levels of desacyl ghrelin, showed a decreased body weight without changes in fat mass when fed a high-fat diet [42], which may be explained by the negative regulatory effect of desacyl ghrelin on GHRL evidenced in the present study.…”
Section: Discussionsupporting
confidence: 92%
“…Collectively, these data support the contention that the reduction of circulating ghrelin levels in rats induced by peripheral administration of somatostatin (18,55,57) or sst 2 agonist (present study) and by endogenous somatostatin released by urethane or likely by abdominal surgery involves the activation of sst 2 receptors expressed on gastric X/A-like cells. Of interest, recent in vitro studies in mouse primary pituitary cell cultures showed that somatostatin inhibits GOAT mRNA expression monitored after 24-h incubation and, conversely, somatostatin knockout mice displayed high GOAT mRNA expression (23). Therefore, it can be speculated that the observed reduced gastric GOAT protein expression induced by abdominal surgery may also be related to the increased somatostatin signaling under these conditions.…”
Section: Discussionmentioning
confidence: 99%
“…However, it has been demonstrated that native ghrelin is also expressed at the pituitary gland (Korbonits et al 2001), suggesting the existence of a paracrine and/or autocrine regulation by locally produced ghrelin (Luque et al 2006). This idea is further reinforced by the fact that GOAT is also expressed in the hypothalamus and pituitary gland (Gahete et al 2010a, Lim et al 2011a). In addition, alternative ghrelin gene-derived variants, such as human In1-ghrelin or murine In2-ghrelin, have been also found to be present and regulated under different physiological conditions in the pituitary gland , Gahete et al 2011a, which further supports the idea of the existence of a complex regulation of pituitary function by the ghrelin system.…”
Section: Endocrine Actionsmentioning
confidence: 99%