Gastric Ghrelin Secretion Research Articles

The Problem of Appetite Loss After Major Abdominal Surgery: A Systematic Review.

Objective:To systematically review the problem of appetite loss after major abdominal surgery.Summary of Background Data:Appetite loss is a common problem after major abdominal surgery. Understanding of etiology and treatment options is limited.Methods:We searched Medline, Cochrane Central Register of Controlled Trials, and Web of Science for studies describing postoperative appetite loss. Data were extracted to clarify definition, etiology, measurement, surgical influence, pharmacological, and nonpharmacological treatment. PROSPERO registration ID: CRD42021224489.Results:Out of 6144 articles, we included 165 studies, 121 of which were also analyzed quantitatively. A total of 19.8% were randomized, controlled trials (n = 24) and 80.2% were nonrandomized studies (n = 97). The studies included 20,506 patients undergoing the following surgeries: esophageal (n = 33 studies), gastric (n = 48), small bowel (n = 6), colon (n = 27), rectal (n = 20), hepatobiliary (n = 6), and pancreatic (n = 13). Appetite was mostly measured with the Quality of Life Questionnaire of the European Organization for Research and Treatment of Cancer (EORTC QLQ C30, n = 54). In a meta-analysis of 4 randomized controlled trials gum chewing reduced time to first hunger by 21.2 hours among patients who had bowel surgery. Other reported treatment options with positive effects on appetite but lower levels of evidence include, among others, intravenous ghrelin administration, the oral Japanese herbal medicine Rikkunshito, oral mosapride citrate, multidisciplin-ary-counseling, and watching cooking shows. No studies investigated the effect of well-known appetite stimulants such as cannabinoids, steroids, or megestrol acetate on surgical patients.Conclusions:Appetite loss after major abdominal surgery is common and associated with increased morbidity and reduced quality of life. Recent studies demonstrate the influence of reduced gastric volume and ghrelin secretion, and increased satiety hormone secretion. There are various treatment options available including level IA evidence for postoperative gum chewing. In the future, surgical trials should include the assessment of appetite loss as a relevant outcome measure.

The regulation of gastric ghrelin secretion.

Ghrelin is a gastric hormone with multiple physiological functions, including the stimulation of food intake and adiposity. It is well established that circulating ghrelin levels are closely associated with feeding patterns, rising strongly before a meal and lowering upon food intake. However, the mechanisms underlying the modulation of ghrelin secretion are not fully understood. The purpose of this review is to discuss current knowledge on the circadian oscillation of circulating ghrelin levels, the neural mechanisms stimulating fasting ghrelin levels and peripheral mechanisms modulating postprandial ghrelin levels. Furthermore, the therapeutic potential of targeting the ghrelin pathway is discussed in the context of the treatment of various metabolic disorders, including obesity, type 2 diabetes, diabetic gastroparesis and Prader-Willi syndrome. Moreover, eating disorders including anorexia nervosa, bulimia nervosa and binge-eating disorder are also discussed.

The Effect of High-Fat Diet-Induced Obesity on the Expression of Nutrient Chemosensors in the Mouse Stomach and the Gastric Ghrelin Cell.

The stomach is the primary source of the orexigenic and adiposity-promoting hormone, ghrelin. There is emerging evidence on the nutrient-mediated modulation of gastric ghrelin secretion. However, limited information is available on gastric nutrient-sensing mechanisms in high-fat diet (HFD)-induced obesity. This study investigated the impact of HFD-induced obesity on the expression of nutrient chemosensors in mouse stomach, particularly ghrelin cells. Male C57BL/6 mice were fed either a standard laboratory diet (SLD) or HFD for 12 weeks. The expression of ghrelin, enzymes involved in ghrelin production (PC1/3, GOAT) and nutrient chemosensors (CD36, FFAR2&4, GPR93, CaSR, mGluR4 and T1R3) was determined by quantitative RT-PCR in the mouse corpus and antrum. Immunohistochemistry assessed the protein expression of CaSR and ghrelin in the corpus and antrum. Antral mRNA levels of CaSR and PC1/3 were increased in HFD compared to SLD mice, while mRNA levels of all other nutrient chemosensors examined remained unchanged. CaSR immunolabelling was observed in the gastric antrum only. Nearly 80% of antral ghrelin cells expressed CaSR, with a similar cell density and co-expression in SLD and HFD mice. In conclusion, HFD-induced obesity increased CaSR mRNA expression in mouse antrum. However, the high antral co-expression of CaSR and ghrelin was unaltered in HFD compared to SLD mice.

Drinking water to reduce alcohol craving? A randomized controlled study on the impact of ghrelin in mediating the effects of forced water intake in alcohol addiction

BackgroundRecent data suggest that ghrelin is involved in the pathophysiology of alcohol use disorders, affecting alcohol self-administration and craving. Gastric ghrelin secretion is reduced by stomach distension. We now tested the hypothesis whether the clinically well-known effects of high-volume water intake on craving reduction in alcoholism is mediated by acute changes in ghrelin secretion. MethodsIn this randomized human laboratory study, we included 23 alcohol-dependent male inpatient subjects who underwent alcohol cue exposure. Participants of the intervention group drank 1000ml of mineral water within 10min directly thereafter, compared to the participants of the control group who did not. Craving and plasma concentrations of acetylated ghrelin were measured ten times during the 120min following the alcohol cue exposure session. ResultsIn the intervention group, a significant decrease in acetylated ghrelin in plasma compared to the control group was observed. This decrease was correlated to a reduction in patients’ subjective level of craving. In the control group, no decrease of acetylated ghrelin in plasma and no association between alcohol craving and changes in plasma concentrations of acetylated ghrelin were observed. ConclusionsOur results present new evidence that the modulation in the ghrelin system by oral water intake mediates the effects of volume intake with craving reduction in alcohol use disorders. Hence, in addition to pharmacological interventions with ghrelin antagonists, the reduction of physiological ghrelin secretion might be a target for future interventions in the treatment of alcohol craving.

Changes in plasma ghrelin and leptin levels in patients with peptic ulcer and gastritis following eradication of Helicobacter pylori infection.

Background Helicobacter pylori (H. pylori) infection and eradication therapy have been known to influence gastric ghrelin and leptin secretion, which may lead to weight gain. However, the exact relationship between plasma ghrelin/leptin levels and H. pylori infection has remained controversial. The aim of this study was to investigate plasma ghrelin and leptin levels in H. pylori-positive and -negative patients, to compare the two levels of the hormones before and after H. pylori eradication, and to examine the correlation between body mass index (BMI) and active ghrelin or leptin levels, as well as that between atrophic pattern and active ghrelin or leptin levels.MethodsSeventy-two H. pylori-positive patients who underwent upper gastrointestinal endoscopy, 46 diagnosed as having peptic ulcer and 26 as atrophic gastritis, were enrolled. Control samples were obtained from 15 healthy H. pylori-negative volunteers. The extent of atrophic change of the gastric mucosa was assessed endoscopically. Body weight was measured and blood was collected before and 12 weeks after H. pylori eradication therapy. Blood samples were taken between 8 and 10 AM after an overnight fast.ResultsPlasma ghrelin levels were significantly lower in H. pylori-positive patients than in H. pylori-negative patients. In particular, plasma active ghrelin levels were significantly lower in patients with gastritis compared with patients with peptic ulcer. Plasma ghrelin levels decreased after H. pylori eradication in both peptic ulcer and gastritis patients, while plasma leptin levels increased only in peptic ulcer patients. Plasma leptin levels and BMI were positively correlated, and active ghrelin levels and atrophic pattern were weakly negatively correlated in peptic ulcer patients.Conclusion H. pylori infection and eradication therapy may affect circulating ghrelin/leptin levels. This finding suggests a relationship between gastric mucosal injury induced by H. pylori infection and changes in plasma ghrelin and leptin levels.

Mo1883 Mechanism for Inhibition of Gastric Ghrelin Secretion by Brain Urocortin 1

Mo1883 Mechanism for Inhibition of Gastric Ghrelin Secretion by Brain Urocortin 1

Pathophysiological mechanisms linking obesity and esophageal adenocarcinoma.

In recent decades there has been a dramatic rise in the incidence of esophageal adenocarcinoma (EAC) in the developed world. Over approximately the same period there has also been an increase in the prevalence of obesity. Obesity, especially visceral obesity, is an important independent risk factor for the development of gastro-esophageal reflux disease, Barrett's esophagus and EAC. Although the simplest explanation is that this mediated by the mechanical effects of abdominal obesity promoting gastro-esophageal reflux, the epidemiological data suggest that the EAC-promoting effects are independent of reflux. Several, not mutually exclusive, mechanisms have been implicated, which may have different effects at various points along the reflux-Barrett's-cancer pathway. These mechanisms include a reduction in the prevalence of Helicobacter pylori infection enhancing gastric acidity and possibly appetite by increasing gastric ghrelin secretion, induction of both low-grade systemic inflammation by factors secreted by adipose tissue and the metabolic syndrome with insulin-resistance. Obesity is associated with enhanced secretion of leptin and decreased secretion of adiponectin from adipose tissue and both increased leptin and decreased adiponectin have been shown to be independent risk factors for progression to EAC. Leptin and adiponectin have a set of mutually antagonistic actions on Barrett's cells which appear to influence the progression of malignant behaviour. At present no drugs are of proven benefit to prevent obesity associated EAC. Roux-en-Y reconstruction is the preferred bariatric surgical option for weight loss in patients with reflux. Statins and aspirin may have chemopreventative effects and are indicated for their circulatory benefits.

The Gastric CB1 Receptor Modulates Ghrelin Production through the mTOR Pathway to Regulate Food Intake

Over the years, the knowledge regarding the relevance of the cannabinoid system to the regulation of metabolism has grown steadily. A central interaction between the cannabinoid system and ghrelin has been suggested to regulate food intake. Although the stomach is the main source of ghrelin and CB1 receptor expression in the stomach has been described, little information is available regarding the possible interaction between the gastric cannabinoid and ghrelin systems in the integrated control of energy homeostasis. The main objective of the present work was to assess the functional interaction between these two systems in terms of food intake using a combination of in vivo and in vitro approaches. The present work demonstrates that the peripheral blockade of the CB1 receptor by rimonabant treatment decreased food intake but only in food-deprived animals. This anorexigenic effect is likely a consequence of decreases in gastric ghrelin secretion induced by the activation of the mTOR/S6K1 intracellular pathway in the stomach following treatment with rimonabant. In support of this supposition, animals in which the mTOR/S6K1 intracellular pathway was blocked by chronic rapamycin treatment, rimonabant had no effect on ghrelin secretion. Vagal communication may also be involved because rimonabant treatment was no longer effective when administered to animals that had undergone surgical vagotomy. In conclusion, to the best of our knowledge, the present work is the first to describe a CB1 receptor-mediated mechanism that influences gastric ghrelin secretion and food intake through the mTOR pathway.

Effect of H. pylori and its Eradication on Gastric Ghrelin Secretion

Effect of H. pylori and its Eradication on Gastric Ghrelin Secretion

Early alterations in plasma ghrelin levels in offspring of calorie-restricted rats during gestation may be linked to lower sympathetic drive to the stomach

Serum ghrelin concentration is generally reduced in obesity. We aimed to assess whether this alteration is present in rats predisposed to obesity because of moderate undernutrition during gestation, and to explore whether this could be related with alterations in stomach sympathetic innervation, which is involved in gastric ghrelin secretion. Offspring of control and 20% gestational calorie-restricted dams (CR) exposed to normal-fat-diet from weaning onward were studied. Circulating ghrelin levels were measured at 25 days and 4 months of age. Morphometry, number of ghrelin-positive (ghrelin+) cells, ghrelin mRNA and protein levels, and tyrosine hydroxylase (TH) protein levels in stomach were determined at 25 days. Adult CR male animals, but not females, exhibited greater body-weight (BW) than their controls, but both males and females showed lower circulating ghrelin levels. This alteration in ghrelin levels was already present at 25 days, prior to any difference in BW. At this juvenile age, no differences in gastric morphometry, number of ghrelin+ cells or ghrelin mRNA/protein levels were found between control and CR animals, however, CR animals showed lower TH stomach content. These results suggest that circulating ghrelin concentration is early altered in rats prenatally programmed to develop obesity. This does not seem to be associated with lower ghrelin production capacity but with specific alterations in sympathetic drive to the stomach.

Postprandial inhibition of gastric ghrelin secretion by long-chain fatty acid through GPR120 in isolated gastric ghrelin cells and mice

Ghrelin is a gastric peptide hormone that controls appetite and energy homeostasis. Plasma ghrelin levels rise before a meal and fall quickly thereafter. Elucidation of the regulation of ghrelin secretion has been hampered by the difficulty of directly interrogating ghrelin cells diffusely scattered within the complex gastric mucosa. Therefore, we generated transgenic mice with ghrelin cell expression of green fluorescent protein (GFP) to enable characterization of ghrelin secretion in a pure population of isolated gastric ghrelin-expressing GFP (Ghr-GFP) cells. Using quantitative RT-PCR and immunofluorescence staining, we detected a high level of expression of the long-chain fatty acid (LCFA) receptor GPR120, while the other LCFA receptor, GPR40, was undetectable. In short-term-cultured pure Ghr-GFP cells, the LCFAs docosadienoic acid, linolenic acid, and palmitoleic acid significantly suppressed ghrelin secretion. The physiological mechanism of LCFA inhibition on ghrelin secretion was studied in mice. Serum ghrelin levels were transiently suppressed after gastric gavage of LCFA-rich lipid in mice with pylorus ligation, indicating that the ghrelin cell may directly sense increased gastric LCFA derived from ingested intraluminal lipids. Meal-induced increase in gastric mucosal LCFA was assessed by measuring the transcripts of markers for tissue uptake of LCFA, lipoprotein lipase (LPL), fatty acid translocase (CD36), glycosylphosphatidylinositol-anchored HDL-binding protein 1, and nuclear fatty acid receptor peroxisome proliferator-activated receptor-γ. Quantitative RT-PCR studies indicate significantly increased mRNA levels of lipoprotein lipase, glycosylphosphatidylinositol-anchored HDL-binding protein 1, and peroxisome proliferator-activated receptor-γ in postprandial gastric mucosa. These results suggest that meal-related increases in gastric mucosal LCFA interact with GPR120 on ghrelin cells to inhibit ghrelin secretion.

Enhanced Gastric Ghrelin Production and Secretion in Rats with Gastric Outlet Obstruction

Ghrelin has distinct effects on gastrointestinal motility through the vagus nerve and gastric excitatory neural plexus. The objectives of this study were to investigate the dynamics of ghrelin and expression of neuromuscular markers in a newly established surgically manipulated rat model of gastric outlet obstruction (GOO), akin to the pyloric stricture associated with duodenal ulcer, advanced gastric cancer, and other conditions, in the clinical setting. The rats were divided into two groups, a control group (sham operation) and the GOO group (proximal duodenal stricture). The animals were sacrificed 2 weeks after the operation. Plasma and gastric ghrelin were measured by radioimmunoassay. mRNA expression in the stomach of neural choline acetyltransferase (ChAT), c-kit, and membrane-bound stem cell factor (SCF) were analyzed by quantitative RT-PCR. In addition, gastric mRNA expression of the aforementioned were also evaluated 60 min after intraperitoneal administration of a synthetic GHS-R1a antagonist ([D: -Lys3] GHRP-6 6.0 mg/kg). Mechanical GOO induced increases of fasting plasma ghrelin levels and hyperplasia of the gastric muscle layers, with enhanced expression of the gastric neuromuscular markers. Administration of [D: -Lys3] GHRP-6 normalized the enhanced expression of c-kit and SCF. GOO stimulates ghrelin dynamics and then enhances the mechanistic expression of gastric cellular communication network molecules between nerves and smooth muscle cells.

Does Helicobacter pylori infection protect against esophageal diseases in Asia?

The speculations on the protective role of Helicobacter pylori against gastroesophageal reflux disease (GERD) originated from epidemiological observations. These studies have shown that the rising trend of GERD is coincident with declining prevalence of H. pylori and peptic ulcer disease in Asia. Furthermore, most case-control and population-based studies suggest a negative association between H. pylori infection and GERD. It is generally believed that the preponderance of cagA+ and vacA+ virulent strains and proinflammatory interleukin-1 beta polymorphism increase the risk of hypochlohydria and protects against the development of GERD in Asian population. Recovery of gastric acid secretion and emergence of reflux esophagitis has been reported after H. pylori eradication in patients with corpus gastritis and atrophic gastritis. Recent studies have also reported that H. pylori eradication leads to recovery of ghrelin secreting cells in the gastric corpus and a rise in plasma ghrelin levels, which may contribute to obesity through its appetite-stimulating action and predispose to GERD. The prevalence of H. pylori infection is generally lower in younger Asians who enjoy improved socioeconomic status and sanitation compared with their older counterparts. The Asian population is probably facing a rising generation with high gastric acid and ghrelin secretion rates. These physiological changes may contribute to increased dietary calorie intake, obesity and increased prevalence of GERD.

Inhibition of Gastric Ghrelin Secretion by Urocortin 1

G A A b st ra ct s cortex (pcc), mediodorsal thalamus (mdThal), M1, and vermis. In the rectal distention studies, results were found in the right and left aIns, left pIns, posterior thalamus (pulvinar), rOFC , M1, ACC, and PCC . Contrasting gastric with rectal distention demonstrated that gastric distention produced greater activation in the hippocampus (Hip), mdThal and cerebellar vermis. Conclusion: Brain activity in response to both rectal and gastric distention was shown in regions typically associated with emotional (amygdala, ACC, PCC, OFC), decision making (dlpfc, ofc, hippocampus), motor action (M1), and visceral sensation (insula, thalamus). However, gastric distention may induce greater activity within limbic (mdThal, Hip) and cerebellar emotional (vermis) circuitries. The greater brain response to gastric stimulation may have been due to distinct peripheral innervation pathways, as well as the different emotional valences placed on epigastric versus lower GI sensations. Future studies should investigate potential differences in functional GI disease populations, and compare these results to other GI related sensations such as nausea.

Macronutrients act directly on the stomach to regulate gastric ghrelin release

Ghrelin is a gastric secreted hormone deeply implicated in meal initiation and body weight regulation. This peptide is a peripheral orexigenic hormone with a nutritional status-dependent regulation showing a pre-pandrial rise and post-prandial fall pattern. A wide variety of studies have tested the effect of meal different nutrient composition over stomach mucosa ghrelin content and plasmatic ghrelin levels; nevertheless, few and non-conclusive data exist about the direct action of macronutrients on the stomach in order to regulate ghrelin secretion. The recent identification of taste receptors or chemoreceptors in the stomach mucosa would reinforce this paradigm. To investigate the individual effect of different macronutrients (l-glutamine, lipids, and glucose) over gastric ghrelin secretion by using an in vitro gastric explants model. L-glutamine and intralipid emulsion act locally in the stomach decreasing ghrelin secretion, while no effect was found after glucose exposure. These results show for the first time that macronutrients, and specially amino acids and lipids, act directly in the stomach in order to regulate gastric ghrelin release. Consequently, the chemosensory capacity of the stomach, until now restricted to the oral cavity or intestine, is demonstrated.

ORIGINAL ARTICLE: Dysregulation of plasma ghrelin in alcoholic cirrhosis

SummaryObjective Abnormalities in circulating ghrelin have been reported in chronic liver disease. This study assessed the response of anabolic peptides ghrelin, growth hormone (GH) and insulin‐like growth factor 1 (IGF‐1) in patients with alcoholic cirrhosis and healthy subjects to oral glucose. In a previous study, using oral glucose we identified loss of ghrelin regulation in nonalcoholic steato‐hepatitis.Patients/Design/Measurements Fourteen patients with alcoholic cirrhosis were compared with 11 healthy subjects. Patients with cirrhosis were studied when adjudged clinically stable in hospital. After an overnight fast, they ingested 100‐g glucose dissolved in 250 ml of water. Blood was sampled before and every 20 minutes after ingestion for 120 minutes. Plasma acylated and des‐acyl ghrelin, GH, IGF‐1 and insulin were assayed by ELISA.Results Expressed as median (95% CI): 120‐minutes integrated acylated ghrelin was 26 (19–66) in controls compared to 170 (129–252) pg/ml per hour in patients with cirrhosis; P < 0·001. Both groups exhibited a normal postglucose plasma total ghrelin profile. Among patients with cirrhosis (compared to controls), growth hormone was increased 15‐fold and IGF‐1 decreased 4‐fold. Acylated ghrelin correlated with GH (Spearman r = 0·69, P = 0·0015) in control subjects but not in patients with cirrhosis.Conclusions Acylated ghrelin is markedly increased in alcoholic cirrhosis, with apparent preservation of normal postprandial mechanisms of gastric ghrelin secretion. GH is also increased; however, its correlation with acylated ghrelin (confirmed in healthy subjects) is absent in patients with cirrhosis. Despite increased ghrelin and GH, patients with alcoholic cirrhosis remain anorexic and catabolic suggesting potential tissue resistance to the actions of these anabolic peptides.

Age, sex, and lactating status regulate ghrelin secretion and GOAT mRNA levels from isolated rat stomach

Ghrelin is a stomach derivate peptide involved in energy homeostasis regulation, and ghrelin O-acyltransferase (GOAT) is the enzyme responsible for ghrelin acylation. Puberty is a period characterized by profound changes in the metabolic requirements and notable variations of sexual hormone levels. On the other hand, the weaning process is a fundamental modification of the diet, which implicates several adaptations of the gastrointestinal tract physiology. Until now the direct secretion of ghrelin by the stomach in these conditions, without interferences from other organs, has never been studied. The main objective of this article was to investigate how the stomach modulates ghrelin production and secretion as well as GOAT expression on these periods of life. Gastric ghrelin secretion is regulated through postnatal life in an independent way of gastric expression and circulating levels of this hormone. The present work shows a strong regulation of gastric ghrelin secretion by estrogens. The weaning strongly regulates gastric ghrelin secretion. Animals subjected to delayed weaning present a lower body weight than the corresponding controls. For the first time, it is shown that a noticeable decrease in circulating levels of testosterone and estrogens is associated with delay of weaning. GOAT mRNA levels in the stomach are strongly regulated by age, breastfeeding, and testosterone. In conclusion, the stomach itself regulates ghrelin and GOAT production to adapt the organism to the metabolic requirements demanded through each stage of life.

The influence of the eradication of Helicobacter pylori on gastric ghrelin, appetite, and body mass index in patients with peptic ulcer disease

Helicobacter pylori (H. pylori) infection has been known to influence the gastric leptin and ghrelin secretion, for which the exact pathogenic role has not been documented yet. This study was designed to investigate the influence of H. pylori eradication on plasma or gastric levels of ghrelin, body mass index (BMI), and resultant levels of appetite in patients with peptic ulcer disease. Twenty-two patients with H. pylori-associated active duodenal or gastric ulcer were treated with 7 weeks of antisecretory medication followed with 7 days of eradication regimen. The plasma and tissue ghrelin levels, tumor necrosis factor-alpha (TNF-alpha) mRNA, BMI, and appetite scale were checked before and after treatment. An additional endoscopic examination was conducted in 10 patients taking both ulcer treatment and H. pylori eradication. Gastric ghrelin mRNA expression was significantly increased after either ulcer healing or H. pylori eradication, whereas gastric TNF-alpha mRNA expression was decreased after ulcer treatment and H. pylori eradication. In parallel with these changes, the visual analog scales for hunger and prospective food consumption were significantly increased after ulcer healing and H. pylori eradication. An increase in BMI was not statistically related to ulcer healing and H. pylori eradication therapy. In the subgroup analysis of 10 patients performed with additional endoscopic examination, ulcer treatment was associated with increased plasma ghrelin level and tissue ghrelin expression irrelevant to H. pylori eradication. Restored tissue levels of ghrelin and improved status of appetite was achieved with gastric ulcer healing and H. pylori eradication.

Dietary supplementation with zinc oxide stimulates ghrelin secretion from the stomach of young pigs

Dietary supplementation with zinc is known to enhance food intake and growth in young children. However, the underlying mechanisms remain largely unknown. Ghrelin, a peptide derived mainly from stomach, plays an important role in food-intake regulation. The present study was conducted with the piglet model to test the hypothesis that zinc may increase gastric ghrelin secretion. In Experiment 1 (Exp. 1) , thirty-six 28-day-old weaned pigs were assigned to two groups (18 pigs/group), receiving four-week supplementation of 0 or 2000 mg/kg Zn (as ZnO) to the basal diet containing 100 mg/kg Zn. In Experiment (Exp. 2), sixteen 28-day-old piglets were assigned to the same treatments ( n=8/group) as in Exp. 1, except that they were pair-fed an equal amount of diet. At the end of the experiments, blood, stomach and duodenum samples were obtained for biochemical analysis, including assays of ghrelin protein and insulin-like growth factor-I (IGF-I) in plasma, as well as quantification of ghrelin and IGF-I mRNA levels in the duodenum and gastric mucosa. Further, gastric mucosal cells from unsupplemented piglets were cultured with 0–0.5 mM ZnO for 2–24 h for assays of ghrelin production and gene expression. Dietary Zn supplementation increased plasma concentrations of ghrelin, IGF-I and cholecystokinin; IGF-I gene expression in the duodenum as well as food intake and piglet growth (Exp. 1). The effects of ZnO on plasma levels of ghrelin, intestinal IGF-I expression and piglet growth were independent of food intake. Addition of ZnO to culture medium enhanced ghrelin production from gastric mucosal cells without affecting ghrelin mRNA levels. Collectively, our results indicate that ZnO stimulates ghrelin secretion from the stomach at the post-transcriptional level. This novel finding aids in elucidating the cellular and molecular mechanism for a role of zinc in promoting food intake and growth of young children.

Ghrelin secretion is not reduced by increased fat mass during diet-induced obesity

Ghrelin is a stomach hormone that stimulates growth hormone (GH) secretion, adiposity, and food intake. Gastric ghrelin production and secretion are regulated by caloric intake; ghrelin secretion increases during fasting, decreases with refeeding, and is reduced by diet-induced obesity. The aim of the present study was to test the hypotheses that 1) an increase in body adiposity will play an inhibitory role in the reduction of gastric ghrelin synthesis and secretion during chronic ingestion of a high-fat (HF) diet and 2) chronic ingestion of an HF diet will suppress the rise in circulating ghrelin levels in response to acute fasting. Adult male Sprague-Dawley rats were fed a standard AIN-76A (approximately 5-12% of calories from fat) or an HF (approximately 45% of calories from fat) diet. The effect of increased adiposity on gastric ghrelin homeostasis was assessed by comparison of stomach ghrelin production and plasma ghrelin levels in obese and nonobese rats fed the HF diet. HF diet-fed, nonobese rats were generated by administration of triiodothyronine to lower body fat accumulation. Our findings indicate that an increased fat mass per se does not exert an inhibitory effect on ghrelin homeostasis during ingestion of the HF diet. Additionally, the magnitude of change in plasma ghrelin in response to fasting was not blunted, indicating that a presumed, endogenous signal for activation of ingestive behavior remains intact, despite excess stored calories in HF-fed rats.