The expression of ghrelin O-acyltransferase (GOAT) in human tissues

Lim, Chung Thong; Kola, Blerina; Grossman, Ashley; Korbonits, Márta

doi:10.1507/endocrj.k11e-117

Cited by 86 publications

(65 citation statements)

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“…Human adipose tissue produces all the components of the ghrelin system, namely ghrelin, obestatin, GOAT, and the receptors of ghrelin-related peptides, GHS-R type 1a and G protein-coupled receptor 39 (GPR39) [8,21,29,30]. Our findings show for the first time that ghrelin and GOAT are co-produced in human visceral adipocytes and SVFC.…”

Section: Discussionmentioning

confidence: 60%

“…Although correlation does not imply causality, the association between GOAT and LDL-cholesterol may reflect an increased transport of ghrelin into the bloodstream, thereby contributing to the high levels of circulating acylated ghrelin in insulin resistance. Several nutritional and hormonal factors are involved in the regulation of the ghrelin/GOAT system [29,30]. Our data show that insulin and leptin suppressed ghrelin mRNA levels in human visceral fat cells.…”

Section: Discussionmentioning

confidence: 64%

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The ghrelin O-acyltransferase–ghrelin system reduces TNF-α-induced apoptosis and autophagy in human visceral adipocytes

et al. 2012

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Aims/hypothesis Proinflammatory and proapoptotic cytokines such as TNF-α are upregulated in human obesity. We evaluated the association between ghrelin isoforms (acylated and desacyl ghrelin) and TNF-α in obesity and obesity-associated type 2 diabetes, as well as the potential role of ghrelin in the control of apoptosis and autophagy in human adipocytes. Methods Plasma concentrations of the ghrelin isoforms and TNF-α were measured in 194 participants. Ghrelin and ghrelin O-acyltransferase (GOAT) levels were analysed by western-blot, immunohistochemistry and real-time PCR in 53 biopsies of human omental adipose tissue. We also determined the effect of acylated and desacyl ghrelin (10 to 1,000 pmol/l) on TNF-α-induced apoptosis and autophagy-related molecules in omental adipocytes. Results Circulating concentrations of acylated ghrelin and TNF-α were increased, whereas desacyl ghrelin levels were decreased in obesity-associated type 2 diabetes. Ghrelin and GOAT were produced in omental and subcutaneous adipose tissue. Visceral adipose tissue from obese patients with type 2 diabetes showed higher levels of GOAT, increased adipocyte apoptosis and increased expression of the autophagyrelated genes ATG5, BECN1 and ATG7. In differentiating Diabetologia (2012) human omental adipocytes, incubation with acylated and desacyl ghrelin reduced TNF-α-induced activation of caspase-8 and caspase-3, and cell death. In addition, acylated ghrelin reduced the basal expression of the autophagyrelated genes ATG5 and ATG7, while desacyl ghrelin inhibited the TNF-α-induced increase of ATG5, BECN1 and ATG7 expression. Conclusions/interpretation Apoptosis and autophagy are upregulated in human visceral adipose tissue of patients with type 2 diabetes. Acylated and desacyl ghrelin reduce TNF-α-induced apoptosis and autophagy in human visceral adipocytes.

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Section: Discussionmentioning

confidence: 60%

Section: Discussionmentioning

confidence: 64%

The ghrelin O-acyltransferase–ghrelin system reduces TNF-α-induced apoptosis and autophagy in human visceral adipocytes

et al. 2012

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“…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%

“…GOAT enzyme is able to process a range of fatty acids, being the most likely acyl donors for the acyl-coAs and, for this reason, GOAT has been postulated to be a putative transporter of acyl-coA from the cytosol to the ER lumen (Yang et al 2008b). GOAT mRNA is widely expressed in human tissues such as stomach, pancreas, skeletal muscle, heart, intestine, and bone (Lim et al 2011a), a tissue expression pattern that partially resembles that exhibited by ghrelin (Lim et al 2011a). Indeed, GOAT protein and mRNA transcripts exist in individual ghrelin-containing cells as is the case of gastric mucosal oxyntic cells (Sakata et al 2009).…”

Section: Ghrelin-o-acyl-transferasementioning

confidence: 99%

“…However, the precise role of the ghrelin system in the physiology of the adrenal gland has not been fully elucidated. Specifically, it has been shown that some ghrelin gene-derived hormones, GOAT, and GHSRs are expressed in the cortex and/or the medulla of human and rat adrenal glands (Barreiro et al 2002, Andreis et al 2003, Tortorella et al 2003, Raghay et al 2008, Rucinski et al 2009, Lim et al 2011a. Indeed, the GHSR seems to be more abundant in the adrenal zona glomerulosa, the cambium layer involved in the maintenance of adrenal cortex growth (Tortorella et al 2003).…”

Section: Posterior Pituitary Hormonesmentioning

confidence: 99%

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Ghrelin gene products, receptors, and GOAT enzyme: biological and pathophysiological insight

Gahete

Rincón-Fernández

Villa-Osaba

et al. 2013

Journal of Endocrinology

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Ghrelin is a 28-amino acid acylated hormone, highly expressed in the stomach, which binds to its cognate receptor (GHSR1a) to regulate a plethora of relevant biological processes, including food intake, energy balance, hormonal secretions, learning, inflammation, etc. However, ghrelin is, in fact, the most notorious component of a complex, intricate regulatory system comprised of a growing number of alternative peptides (e.g. obestatin, unacylated ghrelin, and In1-ghrelin, etc.), known (GHSRs) and, necessarily unknown receptors, as well as modifying enzymes (e.g. ghrelin-O-acyl-transferase), which interact among them as well as with other regulatory systems in order to tightly modulate key (patho)-physiological processes. This multiplicity of functions and versatility of the ghrelin system arise from a dual, genetic and functional, complexity. Importantly, a growing body of evidence suggests that dysregulation in some of the components of the ghrelin system can lead to or influence the development and/or progression of highly concerning pathologies such as endocrine-related tumors, inflammatory/cardiovascular diseases, and neurodegeneration, wherein these altered components could be used as diagnostic, prognostic, or therapeutic targets. In this context, the aim of this review is to integrate and comprehensively analyze the multiple components and functions of the ghrelin system described to date in order to define and understand its biological and (patho)-physiological significance.

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Brain Mapping of Ghrelin O‐Acyltransferase in Goldfish (Carassius Auratus): Novel Roles for the Ghrelinergic System in Fish?

Blanco

Sánchez-Bretaño

Delgado

et al. 2016

The Anatomical Record

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Ghrelin O-acyltransferase (GOAT) is the enzyme responsible for acylation of ghrelin, a gut-brain hormone with important roles in many physiological functions in vertebrates. Many aspects of GOAT remain to be elucidated, especially in fish, and particularly its anatomical distribution within the different brain areas has never been reported to date. The present study aimed to characterize the brain mapping of GOAT using RT-qPCR and immunohistochemistry in a teleost, the goldfish (Carassius auratus). Results show that goat transcripts are expressed in different brain areas of the goldfish, with the highest levels in the vagal lobe. Using immunohistochemistry, we also report the presence of GOAT immunoreactive cells in different encephalic areas, including the telencephalon, some hypothalamic nuclei, pineal gland, optic tectum and cerebellum, although they are especially abundant in the hindbrain. Particularly, an important signal is observed in the vagal lobe and some fiber tracts of the brainstem, such as the medial longitudinal fasciculus, Mauthneri fasciculus, secondary gustatory tract and spinothalamic tract. Most of the forebrain areas where GOAT is detected, particularly the hypothalamic nuclei, also express the ghs-r1a ghrelin receptor and other appetite-regulating hormones (e.g., orexin and NPY), supporting the role of ghrelin as a modulator of food intake and energy balance in fish. Present results are the first report on the presence of GOAT in the brain using imaging techniques. The high presence of GOAT in the hindbrain is a novelty, and point to possible new functions for the ghrelinergic system in fish. Anat Rec, 299:748-758, 2016. V C 2016 Wiley Periodicals, Inc.

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The expression of ghrelin O-acyltransferase (GOAT) in human tissues

Cited by 86 publications

References 15 publications

The ghrelin O-acyltransferase–ghrelin system reduces TNF-α-induced apoptosis and autophagy in human visceral adipocytes

The ghrelin O-acyltransferase–ghrelin system reduces TNF-α-induced apoptosis and autophagy in human visceral adipocytes

Ghrelin gene products, receptors, and GOAT enzyme: biological and pathophysiological insight

Brain Mapping of Ghrelin O‐Acyltransferase in Goldfish (Carassius Auratus): Novel Roles for the Ghrelinergic System in Fish?

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