Erratum to “Failure of the feeding response to fasting in carnitine-deficient juvenile visceral steatosis (JVS) mice: Involvement of defective acyl-ghrelin secretion and enhanced corticotropin-releasing factor signaling in the hypothalamus”

We examined which factors suppress the rise of ghrelin secretion under hunger in 16-h-starved rats, and compared the responses of plasma ghrelin and leptin levels to various exogenous and endogenous stimuli in intact rats. Although an acute expansion of the stomach by infusion of 6 ml air or 3 ml water in rats starved for 16 h did not change the level of plasma acyl-ghrelin 3 ml corn starch solution, corn oil, or 20% ethanol significantly decreased it. Vagotomy inhibited suppression by nutrients but not by ethanol. Chronic infusion of ethanol into the stomach for 3 weeks in free-feeding rats caused widespread injury of the stomach mucosa, and increased both plasma ghrelin levels and the number of ghrelin cells. In intact rats, low temperature did not change ghrelin levels, but increased leptin levels. On the other hand, restriction stress decreased plasma ghrelin levels, but had the reverse effect on plasma leptin levels. Although insulin decreased and 20% glucose increased plasma glucose levels, they both decreased plasma ghrelin levels. Insulin elevated plasma leptin levels, but glucose had no effect. These results indicate that 1) acyl-ghrelin secretion from the stomach under fasting condition is suppressed by nutrients but not by mechanical expansion of the stomach; 2) high and low environmental temperature, stress, or administration of insulin reciprocally affect plasma levels of ghrelin and leptin; and 3) an increase of stomach ghrelin cell number and plasma ghrelin levels after chronic ethanol treatment may be involved in restoration of gastric mucosae.

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Role for central ghrelin in food intake and secretion profile of stomach ghrelin in rats

Journal of Endocrinology ◽

10.1677/joe.0.1740283 ◽

2002 ◽

Vol 174 (2) ◽

pp. 283-288 ◽

Cited By ~ 163

Author(s):

N Murakami ◽

T Hayashida ◽

T Kuroiwa ◽

K Nakahara ◽

T Ida ◽

...

Keyword(s):

Body Weight ◽

Food Intake ◽

Body Weight Gain ◽

Intestinal Hormones ◽

Amino Acid Peptide ◽

Secretion Profile ◽

Total Ghrelin ◽

Acyl Ghrelin ◽

Minimum Volumes ◽

Ghrelin Secretion

Ghrelin, a 28-amino-acid peptide, has recently been isolated from the rat stomach as an endogenous ligand for the GH secretagogue receptor. We have reported previously that central or peripheral administration of ghrelin stimulates food intake, and the secretion of GH and gastric acid in rats. In the present study, we investigated how much endogenous centrally released ghrelin is involved in the control of food intake and body weight gain. We also examined the profile of ghrelin secretion from the stomach by RIA using two kinds of anti-ghrelin antiserum, one raised against the N-terminal ([Cys(12)]-ghrelin[1-11]) region and one raised against the C-terminal ([Cys(0)]-ghrelin [13-28]) region of the peptide. The former antibody recognizes specifically ghrelin with n- octanoylated Ser 3 (acyl ghrelin), and does not recognize des-acyl ghrelin. The latter also recognizes des-acyl ghrelin (i.e. total ghrelin). Intracerebroventricular treatment with the anti-ghrelin antiserum against the N-terminal region twice a day for 5 days decreased significantly both daily food intake and body weight. Des-acyl ghrelin levels were significantly higher in the gastric vein than in the trunk. Either fasting for 12 h, administration of gastrin or cholecystokinin resulted in increase of both acyl and des-acyl ghrelin levels. The ghrelin levels exhibited a diurnal pattern, with the bimodal peaks occurring before dark and light periods. These two peaks were consistent with maximum and minimum volumes of gastric content respectively. These results suggest that (1) endogenous centrally released ghrelin participates in the regulation of food intake and body weight, (2) acyl ghrelin is secreted from the stomach, (3) intestinal hormones stimulate ghrelin release from the stomach, and (4) regulation of the diurnal rhythm of ghrelin is complex, since ghrelin secretion is augmented under conditions of both gastric emptying and filling.

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Influence of etanercept on leptin and ghrelin secretion in children with juvenile idiopathic arthritis

Journal of International Medical Research ◽

10.1177/0300060516688340 ◽

2017 ◽

Vol 45 (2) ◽

pp. 525-532 ◽

Cited By ~ 2

Author(s):

Izabela Maciejewska-Paszek ◽

Elżbieta Grochowska-Niedworok ◽

Andrzej Siwiec ◽

Anna Gruenpeter ◽

Lechosław Dul ◽

...

Keyword(s):

Juvenile Idiopathic Arthritis ◽

Conventional Treatment ◽

Cross Sectional Study ◽

Control Groups ◽

Cross Sectional ◽

Total Ghrelin ◽

Low Bmi ◽

Acyl Ghrelin ◽

And Control ◽

Ghrelin Secretion

Objective To assess possible changes in leptin and ghrelin secretion due to etanercept in juvenile idiopathic arthritis (JIA). Methods 50 patients with JIA and 16 age-matched controls were enrolled into this prospective, cross-sectional study. Serum leptin, total and acyl ghrelin were measured in addition to white blood cell (WBC) and lymphocyte counts. Results 25 patients received etanercept and 25 conventional therapies (including methotrexate) for JIA. There was no difference between treatment and control groups in leptin or ghrelin levels and no evidence of a relationship between leptin and ghrelin in patients with JIA. In all children with JIA there was a correlation between leptin and body mass index (BMI). However, compared with children in the conventional treatment group, children in the etanercept group showed a positive correlation between total ghrelin and BMI and those with a low BMI showed a negative correlation between acyl ghrelin and BMI. Conclusion No differences in leptin and ghrelin concentrations were found when patients with JIA and controls were compared or when patients who received etanercept were compared with those who received conventional treatment for JIA.

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Jejunal administration of glucose enhances acyl ghrelin suppression in obese humans

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00082.2016 ◽

2016 ◽

Vol 311 (1) ◽

pp. E252-E259 ◽

Cited By ~ 7

Author(s):

Robyn A. Tamboli ◽

Reem M. Sidani ◽

Anna E. Garcia ◽

Joseph Antoun ◽

James M. Isbell ◽

...

Keyword(s):

Plasma Glucose ◽

Surgical Stress ◽

Proximal Jejunum ◽

Gi Tract ◽

Glucose Administration ◽

Glucose Levels ◽

Direct Exposure ◽

Obese Subjects ◽

Acyl Ghrelin ◽

Ghrelin Secretion

Ghrelin is a gastric hormone that stimulates hunger and worsens glucose metabolism. Circulating ghrelin is decreased after Roux-en-Y gastric bypass (RYGB) surgery; however, the mechanism(s) underlying this change is unknown. We tested the hypothesis that jejunal nutrient exposure plays a significant role in ghrelin suppression after RYGB. Feeding tubes were placed in the stomach or jejunum in 13 obese subjects to simulate pre-RYGB or post-RYGB glucose exposure to the gastrointestinal (GI) tract, respectively, without the confounding effects of caloric restriction, weight loss, and surgical stress. On separate study days, the plasma glucose curves obtained with either gastric or jejunal administration of glucose were replicated with intravenous (iv) infusions of glucose. These “isoglycemic clamps” enabled us to determine the contribution of the GI tract and postabsorptive plasma glucose to acyl ghrelin suppression. Plasma acyl ghrelin levels were suppressed to a greater degree with jejunal glucose administration compared with gastric glucose administration ( P < 0.05). Jejunal administration of glucose also resulted in a greater suppression of acyl ghrelin than the corresponding isoglycemic glucose infusion ( P ≤ 0.01). However, gastric and isoglycemic iv glucose infusions resulted in similar degrees of acyl ghrelin suppression ( P > 0.05). Direct exposure of the proximal jejunum to glucose increases acyl ghrelin suppression independent of circulating glucose levels. The enhanced suppression of acyl ghrelin after RYGB may be due to a nutrient-initiated signal in the jejunum that regulates ghrelin secretion.

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Pursuing the Mechanisms Underlying Alcohol-Induced Changes in the Ghrelin System: New Insights from Preclinical and Clinical Investigations

10.1101/2020.07.30.228494 ◽

2020 ◽

Author(s):

Mehdi Farokhnia ◽

Sara L Deschaine ◽

Adriana Gregory-Flores ◽

Lia J Zallar ◽

Zhi-Bing You ◽

...

Keyword(s):

Gastric Mucosa ◽

Ex Vivo ◽

Sucrose Solution ◽

Ethanol Administration ◽

Post Mortem ◽

Wild Type ◽

Ghrelin Receptor ◽

Acyl Ghrelin ◽

Ghrelin Secretion

Ghrelin is a gastric-derived peptide hormone with demonstrated impact on alcohol intake and craving, but the reverse side of this bidirectional link, i.e., the effects of alcohol on the ghrelin system, remains to be fully established. To characterize the downstream effects of alcohol on the ghrelin system, we examined the following: (1) plasma ghrelin levels across four human laboratory alcohol administration experiments with non-treatment seeking, heavy-drinking participants, (2) expression of ghrelin, ghrelin receptor, and ghrelin-O-acyltransferase (GOAT) genes (GHRL, GHSR, and MBOAT4, respectively) in human post-mortem brain tissue from individuals with alcohol use disorder (AUD) vs. controls, (3) plasma ghrelin levels in Ghsr knockout and wild-type rats following intraperitoneal (i.p.) ethanol administration, (4) effect of ethanol on ghrelin secretion from gastric mucosa cells ex vivo and GOAT enzymatic activity in vitro, and (5) plasma ghrelin levels in rats following i.p. ethanol administration vs. an iso-caloric sucrose solution. Peripheral acyl- and total ghrelin levels significantly decreased following acute ethanol administration in humans. No difference in GHRL, GHSR, and MBOAT4 mRNA expression in the brain was observed between AUD vs. control post-mortem samples. In rats, acyl-ghrelin levels significantly decreased following i.p. ethanol administration in both genotype groups (Ghsr knockout and wild-type), while des-acyl-ghrelin was not affected by ethanol. No effect of ethanol was observed ex vivo on ghrelin secretion from gastric mucosa cells or in vitro on GOAT acylation activity. Lastly, we observed different effects of i.p. ethanol and sucrose solution on acyl- and des-acyl-ghrelin in rats despite administering amounts with equivalent caloric value. Ethanol acutely decreases peripheral ghrelin concentrations in humans and rats, and our findings suggest that this effect does not occur through interaction with ghrelin-secreting gastric mucosal cells, the ghrelin receptor, or the GOAT enzyme. Moreover, this effect does not appear to be proportional to caloric load. Our findings, therefore, suggest that ethanol does not suppress circulating ghrelin through direct interaction with the ghrelin system, or in proportion to the caloric value of alcohol, and may differentially affect ghrelin acylation and ghrelin peptide secretion.

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The intestinal lymph fistula model—a novel approach to study ghrelin secretion

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00367.2009 ◽

2010 ◽

Vol 298 (3) ◽

pp. G474-G480 ◽

Cited By ~ 8

Author(s):

Jenny Tong ◽

Matthias H. Tschöp ◽

Benedikt A. Aulinger ◽

Harold W. Davis ◽

Qing Yang ◽

...

Keyword(s):

Sprague Dawley ◽

Intestinal Lymph ◽

Mesenteric Lymph ◽

Novel Approach ◽

Sprague Dawley Rats ◽

Before And After ◽

Total Ghrelin ◽

Lymph Duct ◽

Acyl Ghrelin ◽

Ghrelin Secretion

The orexigenic hormone ghrelin is secreted from the stomach and has been implicated in the regulation of energy and glucose homeostasis. We hypothesized that ghrelin, like other gastrointestinal (GI) hormones, is present in intestinal lymph, and sampling this compartment would provide advantages for studying ghrelin secretion in rodents. Blood and lymph were sampled from catheters in the jugular vein and mesenteric lymph duct before and after intraduodenal (ID) administration of isocaloric Ensure, dextrin, or Liposyn meals or an equal volume of saline in conscious Sprague-Dawley rats. Total ghrelin levels were measured using an established radioimmunoassay. Acyl and des-acyl ghrelin were measured using two-site ELISA. Fasting ghrelin levels in lymph were significantly higher than in plasma (means ± SE: 3,307.9 ± 272.9 vs. 2,127.1 ± 115.0 pg/ml, P = 0.004). Postingestive acyl and des-acyl ghrelin levels were also significantly higher, whereas the ratio of acyl:des-acyl ghrelin was similar in lymph and plasma (0.91 ± 0.28 vs. 1.20 ± 0.36, P = 0.76). The principle enzymes responsible for deacylation of ghrelin were lower in lymph than in plasma. Following ID Ensure, maximum ghrelin suppression occurred at 2 h in lymph compared with at 1 h in plasma. The return of suppressed ghrelin levels to baseline was also delayed in lymph. Similarly, dextrin also induced significant suppression of ghrelin (two-way ANOVA: P = 0.02), whereas Liposyn did not ( P = 0.32). On the basis of these findings, it appears that intestinal lymph, which includes drainage from the interstitium of the GI mucosa, is enriched in ghrelin. Despite reduced deacylating activity in lymph, there is not a disproportionate amount of acyl ghrelin in this pool. The postprandial dynamics of ghrelin are slower in lymph than plasma, but the magnitude of change is greater. Assessing ghrelin levels in the lymph may be advantageous for studying its secretion and concentrations in the gastric mucosa.

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Decreased plasma ghrelin contributes to anorexia following novelty stress

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00121.2011 ◽

2011 ◽

Vol 301 (4) ◽

pp. E685-E696 ◽

Cited By ~ 48

Author(s):

Yayoi Saegusa ◽

Hiroshi Takeda ◽

Shuichi Muto ◽

Koji Nakagawa ◽

Shunsuke Ohnishi ◽

...

Keyword(s):

Food Intake ◽

Early Stage ◽

Ghrelin Level ◽

Corticotropin Releasing Factor ◽

Intracerebroventricular Injection ◽

Appetite Loss ◽

Ghrelin Concentration ◽

Novel Environment ◽

Ghrelin Secretion

We hypothesized that anorexia induced by novelty stress caused by exposure to a novel environment may be due to activation of corticotropin-releasing factor (CRF) and subsequently mediated by decreasing peripheral ghrelin concentration via serotonin (5-HT) and melanocortin-4 receptors (MC4R). Each mouse was transferred from group-housed cages to individual cages to establish the novelty stress. We observed the effect of changes in feeding behavior in a novel environment using the method of transferring group-housed mice to individual cages. We investigated the effect of an intracerebroventricular injection of antagonists/agonists of CRF1/2 receptors (CRF1/2Rs), 5-HT1B/2C receptors (5-HT1B/2CR), and MC4R to clarify the role of each receptor on the decrease in food intake. Plasma ghrelin levels were also measured. The novelty stress caused a reduction in food intake that was abolished by administering a CRF1R antagonist. Three hours after the novelty stress, appetite reduction was associated with reduced levels of neuropeptide Y/agouti-related peptide mRNA, increased levels of proopiomelanocortin mRNA in the hypothalamus, and a decrease in plasma ghrelin level. Administering a CRF1R antagonist, a 5-HT1B/2CR antagonist, an MC4R antagonist, exogenous ghrelin, and an enhancer of ghrelin secretion, rikkunshito, resolved the reduction in food intake 3 h after the novelty stress by enhancing circulating ghrelin concentrations. We showed that anorexia during a novelty stress is a process in which CRF1R is activated at the early stage of appetite loss and is subsequently activated by a 5-HT1B/2CR and MC4R stimulus, leading to decreased peripheral ghrelin concentrations.

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Abdominal surgery inhibits circulating acyl ghrelin and ghrelin-O-acyltransferase levels in rats: role of the somatostatin receptor subtype 2

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00018.2011 ◽

2011 ◽

Vol 301 (2) ◽

pp. G239-G248 ◽

Cited By ~ 22

Author(s):

Andreas Stengel ◽

Miriam Goebel-Stengel ◽

Lixin Wang ◽

Almaas Shaikh ◽

Nils W. G. Lambrecht ◽

...

Keyword(s):

Abdominal Surgery ◽

Time Course ◽

Somatostatin Receptor ◽

Receptor Subtype ◽

Oxyntic Mucosa ◽

Acyl Ghrelin ◽

Gastric Ileus ◽

Somatostatin Receptor Subtype 2 ◽

Ghrelin Secretion

Clinical studies are evaluating the efficacy of synthetic ghrelin agonists in postoperative ileus management. However, the control of ghrelin secretion under conditions of postoperative gastric ileus is largely unknown. Peripheral somatostatin inhibits ghrelin secretion in animals and humans. We investigated the time course of ghrelin changes postsurgery in fasted rats and whether somatostatin receptor subtype 2 (sst2) signaling is involved. Abdominal surgery (laparotomy and 1-min cecal palpation) induced a rapid and long-lasting decrease in plasma acyl ghrelin levels as shown by the 64, 67, and 59% reduction at 0.5, 2, and 5 h postsurgery, respectively, compared with sham (anesthesia alone for 10 min, P < 0.05). Levels were partly recovered at 7 h and fully restored at 24 h. The percentage of acyl ghrelin reduction was significantly higher than that of desacyl ghrelin at 2 h postsurgery and not at any other time point. This was associated with a 48 and 23% decrease in gastric and plasma ghrelin- O-acyltransferase protein concentrations, respectively ( P < 0.001). Ghrelin-positive cells in the oxyntic mucosa expressed sst2a receptor and the sst2 agonist S-346-011 inhibited fasting acyl ghrelin levels by 64 and 77% at 0.5 and 2 h, respectively. The sst2 antagonist S-406-028 prevented the abdominal surgery-induced decreased circulating acyl ghrelin but not the delayed gastric emptying assessed 0.5 h postinjection. These data show that activation of sst2 receptor located on gastric X/A-like cells plays a key role in the rapid inhibition of circulating acyl ghrelin induced by abdominal surgery while not being primarily involved in the early phase of postoperative gastric ileus.

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Acyl-Ghrelin Secretion Declines over a 37.5-H Fast in Healthy Young Men.

10.1210/endo-meetings.2010.part2.p11.p2-506 ◽

2010 ◽

pp. P2-506-P2-506

Author(s):

R Nass ◽

BD Gaylinn ◽

J Liu ◽

SS Pezzoli ◽

MO Thorner

Keyword(s):

Young Men ◽

Acyl Ghrelin ◽

Ghrelin Secretion

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