Ghrelin, Ghrelin O-Acyltransferase, and Carbohydrate Metabolism During Pregnancy in Calorie-Restricted Mice

Trivedi, Arjun; Babic, Sandra; Heiman, Mark L.; Gibson, William T.; Chanoine, Jean‐Pierre

doi:10.1055/s-0042-116117

Cited by 9 publications

(10 citation statements)

References 57 publications

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“…Ghrelin exists in two forms: acylated ghrelin (AG) and unacylated ghrelin. O -acyltransferase (GOAT) transfers an acyl group from the fatty acids to the serine-3 residue of ghrelin and, thus, stimulates GH secretion and food intake [ 4 , 5 ]. GOAT activates ghrelin depending on an esterification reaction, and blockade of GOAT activity induces less food intake and weight gain [ 4 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

Ghrelin, a gastrointestinal hormone, regulates energy balance and lipid metabolism

et al. 2018

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Ghrelin, an acylated peptide hormone of 28 amino acids, is an endogenous ligand of the released growth hormone secretagogue receptor (GHSR). Ghrelin has been isolated from human and rat stomach and is also detected in the hypothalamic arcuate nucleus. Ghrelin receptor is primarily located in the neuropeptide Y and agouti-related protein neurons. Many previous studies have shown that ghrelin and GHSR are involved in the regulation of energy homeostasis, and its administration can increase food intake and body weight gain. AMP-activated protein kinase is activated by ghrelin in the hypothalamus, which contributes to lower intracellular long-chain fatty acid level. Ghrelin appears to modulate the response to food cues via a neural network involved in the regulation of feeding and in the appetitive response to food cues. It also increases the response of brain areas involved in visual processing, attention, and memory to food pictures. Ghrelin is also an important factor linking the central nervous system with peripheral tissues that regulate lipid metabolism. It promotes adiposity by the activation of hypothalamic orexigenic neurons and stimulates the expression of fat storage-related proteins in adipocytes. Meanwhile, ghrelin exerts direct peripheral effects on lipid metabolism, including increase in white adipose tissue mass, stimulation of lipogenesis in the liver, and taste sensitivity modulation.

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Section: Introductionmentioning

confidence: 99%

Ghrelin, a gastrointestinal hormone, regulates energy balance and lipid metabolism

et al. 2018

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“…A recent study found that AG could regulate GOAT expression in the stomach[ 8 ] and that the widespread expression of GOAT corresponded to the widespread distribution of ghrelin expression, e.g ., in the pancreas, stomach and hypothalamus[ 8 , 9 ]. Multiple studies have demonstrated that both ghrelin and GOAT play important roles in the regulation of obesity, blood glucose and insulin[ 5 , 10 , 11 ]. However, it is not clear whether the ghrelin/GOAT axis in the hypothalamus ( via autocrine/paracrine signaling) is involved in the maintenance of blood glucose concentrations and energy homeostasis by restricting food intake after SG.…”

Section: Introductionmentioning

confidence: 99%

Changes of Ghrelin/GOAT axis and mTOR pathway in the hypothalamus after sleeve gastrectomy in obese type-2 diabetes rats

Wang

Tang

Rao

et al. 2017

WJG

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AIMTo examine the changes of the ghrelin/ghrelin O-acyltransferase (GOAT) axis and the mammalian target of rapamycin (mTOR) pathway in the hypothalamus after sleeve gastrectomy.METHODSA total of 30 obese type-2 diabetes Sprague-Dawley (SD) rats, 6 wk of age, fed with high-sugar and high-fat fodder for 2 mo plus intraperitoneal injection of streptozotocin were randomly divided into three groups: non-operation group (S0 group, n = 10), sham operation group (Sh group, n = 10) and sleeve gastrectomy group (SG group, n = 10). Data of body mass, food intake, oral glucose tolerance test (OGTT), acylated ghrelin (AG) and total ghrelin (TG) were collected and measured at the first day (when the rats were 6 wk old), preoperative day 3 and postoperative week 8. The mRNA expression of preproghrelin, GOAT and neuropeptide Y (NPY), and protein expression of ghrelin, GOAT, GHSR and the mTOR pathway (p-Akt, p-mTOR and p-S6) were measured in the hypothalamus.RESULTSSG can significantly improve metabolic symptoms by reducing body mass and food intake. The obese rats showed lower serum TG levels and no change in AG, but the ratio of AG/TG was increased. When compared with the S0 and Sh groups, the SG group showed decreased TG (1482.03 ± 26.55, 1481.49 ± 23.30 and 1206.63 ± 52.02 ng/L, respectively, P < 0.05), but unchanged AG (153.06 ± 13.74, 155.37 ± 19.30 and 144.44 ± 16.689 ng/L, respectively, P > 0.05). As a result, the ratio of AG/TG further increased in the SG group (0.103 ± 0.009, 0.105 ± 0.013 and 0.12 ± 0.016, respectively, P < 0.05). When compared with the S0 group, SG suppressed mRNA and protein levels of preproghrelin (0.63 ± 0.12 vs 0.5 ± 0.11, P < 0.05) and GOAT (0.96 ± 0.09 vs 0.87 ± 0.08, P < 0.05), but did not change NPY mRNA expression (0.61 ± 0.04 vs 0.65 ± 0.07, P > 0.05) in the hypothalamus. The protein levels of p-Akt, p-mTOR and p-S6 were higher in the SG group, which indicated that the hypothalamic mTOR pathway was activated after SG at the postoperative week 8.CONCLUSIONThe reduction of ghrelin expression and activation of the mTOR pathway might have opposite effects on food intake, as SG improves obesity and T2DM.

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“…pituitary ghrelin expression in pregnant and non-pregnant mice reported previously (Trivedi et al 2017). However, the 1.5-fold greater density of ghrelin-positive cells in the stomach antrum of pregnant than non-pregnant mice sampled at ZT13 (study one) suggests a greater capacity to secrete ghrelin, although this was not seen at ZT23 (study two).…”

Section: Journal Of Endocrinologymentioning

confidence: 74%

“…Intravenous administration of exogenous acyl-ghrelin induces GH pulses in humans and rodents (Kojima et al 1999, Arvat et al 2001, while mice deficient in ghrelin or Mboat4 have lower amplitude GH pulses than littermate controls (Hassouna et al 2014, Xie et al 2015. Acyl-ghrelin, but not des-acyl ghrelin, also acts centrally to stimulate food intake (Nakazato et al 2001, Neary et al 2006, and acyl-ghrelin plays an important role in metabolic adaptations to maintain circulating glucose in response to calorie restriction, particularly in pregnancy (Trivedi et al 2017). Although ghrelin and Mboat4 are predominantly expressed in the stomach (Kojima et al 1999), ghrelin, Mboat4 and GHSR expression are also detected in the human (Gnanapavan et al 2002, González-Domínguez et al 2016 and rodent (Gualillo et al 2001, Nonoshita et al 2010 placenta.…”

Section: Introductionmentioning

confidence: 99%

Pregnancy, but not dietary octanoic acid supplementation, stimulates the ghrelin-pituitary growth hormone axis in mice

Kaur

Mühlhäusler

Sim

et al. 2020

Journal of Endocrinology

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Circulating growth hormone (GH) concentrations increase during pregnancy in mice and remain pituitary-derived. Whether abundance or activation of the GH secretagogue ghrelin increase during pregnancy, or in response to dietary octanoic acid supplementation, is unclear. We therefore measured circulating GH profiles in late pregnant C57BL/6J mice and in aged-matched non-pregnant females fed with standard laboratory chow supplemented with 5% octanoic or palmitic (control) acid (n = 4–13/group). Serum total and acyl-ghrelin concentrations, stomach and placenta ghrelin mRNA and protein expression, Pcsk1 (encoding prohormone convertase 1/3) and Mboat4 (membrane bound O-acyl transferase 4) mRNA were determined at zeitgeber (ZT) 13 and ZT23. Total and basal GH secretion were higher in late pregnant than non-pregnant mice (P < 0.001), regardless of diet. At ZT13, serum concentrations of total ghrelin (P = 0.004), but not acyl-ghrelin, and the density of ghrelin-positive cells in the gastric antrum (P = 0.019) were higher, and gastric Mboat4 and Pcsk1 mRNA expression were lower in pregnant than non-pregnant mice at ZT23. In the placenta, ghrelin protein was localised mostly to labyrinthine trophoblast cells. Serum acyl-, but not total, ghrelin was lower at mid-pregnancy than in non-pregnant mice, but not different at early or late pregnancy. In conclusion, dietary supplementation with 5% octanoic acid did not increase activation of ghrelin in female mice. Our results further suggest that increases in maternal GH secretion throughout murine pregnancy are not due to circulating acyl-ghrelin acting at the pituitary. Nevertheless, time-dependent increased circulating total ghrelin could potentially increase ghrelin action in tissues that express the acylating enzyme and receptor.

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Ghrelin, Ghrelin O-Acyltransferase, and Carbohydrate Metabolism During Pregnancy in Calorie-Restricted Mice

Cited by 9 publications

References 57 publications

Ghrelin, a gastrointestinal hormone, regulates energy balance and lipid metabolism

Ghrelin, a gastrointestinal hormone, regulates energy balance and lipid metabolism

Changes of Ghrelin/GOAT axis and mTOR pathway in the hypothalamus after sleeve gastrectomy in obese type-2 diabetes rats

Pregnancy, but not dietary octanoic acid supplementation, stimulates the ghrelin-pituitary growth hormone axis in mice

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