Ghrelin Expression Research Articles

Influences of Serotonin Hydrochloride on Adiponectin, Ghrelin and KiSS1 Genes Expression.

Background: Serotonin and kisspeptin stimulates gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH) release while ghrelin and adiponectin inhibit them. In the present experimental study, the effects of central injection of serotonin were investigated on LH concentration, KiSS1, adiponectin, and ghrelin genes expression. Materials and Methods: Fifteen Wistar male rats in three groups received saline or serotonin hydrochloride via the third cerebral ventricle. Blood samples were collected via the tail vein. Serum LH concentration and relative gene expression were evaluated by radioimmunoassay and real-time polymerase chain reaction method, respectively. Results: Serotonin significantly increased the mean serum LH concentration and KiSS1 gene expression levels compared to the saline group. Serotonin significantly decreased the mean ghrelin and adiponectin genes expression levels compared to the saline group. Conclusion: The serotonergic pathway may have stimulatory effects on hypothalamic kisspeptin synthesis, partly via inhibiting hypothalamic ghrelin and adiponectin neural activity.

Influences of Serotonin Hydrochloride on Adiponectin, Ghrelin and KiSS1 Genes Expression

Background: Serotonin and kisspeptin stimulates gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH) release while ghrelin and adiponectin inhibit them. In the present experimental study, the effects of central injection of serotonin were investigated on LH concentration, KiSS1, adiponectin, and ghrelin genes expression. Materials and Methods: Fifteen Wistar male rats in three groups received saline or serotonin hydrochloride via the third cerebral ventricle. Blood samples were collected via the tail vein. Serum LH concentration and relative gene expression were evaluated by radioimmunoassay and real-time polymerase chain reaction method, respectively. Results: Serotonin significantly increased the mean serum LH concentration and KiSS1 gene expression levels compared to the saline group. Serotonin significantly decreased the mean ghrelin and adiponectin genes expression levels compared to the saline group. Conclusion: The serotonergic pathway may have stimulatory effects on hypothalamic kisspeptin synthesis, partly via inhibiting hypothalamic ghrelin and adiponectin neural activity.[GMJ.2020;9:e1767]

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.

Early overnutrition sensitizes the growth hormone axis to the impact of diet-induced obesity via sex-divergent mechanisms

In addition to its essential role in the physiological control of longitudinal growth, growth-hormone (GH) is endowed with relevant metabolic functions, including anabolic actions in muscle, lipolysis in adipose-tissue and glycemic modulation. Adult obesity is known to negatively impact GH-axis, thereby promoting a vicious circle that may contribute to the exacerbation of the metabolic complications of overweight. Yet, to what extent early-overnutrition sensitizes the somatotropic-axis to the deleterious effects of obesity remains largely unexplored. Using a rat-model of sequential exposure to obesogenic insults, namely postnatal-overfeeding during lactation and high-fat diet (HFD) after weaning, we evaluated in both sexes the individual and combined impact of these nutritional challenges upon key elements of the somatotropic-axis. While feeding HFD per se had a modest impact on the adult GH-axis, early overnutrition had durable effects on key elements of the somatotropic-system, which were sexually different, with a significant inhibition of pituitary gene expression of GH-releasing hormone-receptor (GHRH-R) and somatostatin receptor-5 (SST5) in males, but an increase in pituitary GHRH-R, SST2, SST5, GH secretagogue-receptor (GHS-R) and ghrelin expression in females. Notably, early-overnutrition sensitized the GH-axis to the deleterious impact of HFD, with a significant suppression of pituitary GH expression in both sexes and lowering of circulating GH levels in females. Yet, despite their similar metabolic perturbations, males and females displayed rather distinct alterations of key somatotropic-regulators/ mediators. Our data document a synergistic effect of postnatal-overnutrition on the detrimental impact of HFD-induced obesity on key elements of the adult GH-axis, which is conducted via mechanisms that are sexually-divergent.

High expression of ghrelin and obestatin prepropeptide in tumor tissues predicted adverse overall survival in gastric carcinoma patients.

Background:Gastric cancer (GC) is the most prevailing digestive tract malignant tumor worldwide with high mortality and recurrence rates. However, its potential molecular mechanism and prognostic biomarkers are still not fully understood. We aim to screen novel prognostic biomarkers related to GC prognosis using comprehensive bioinformatic tools.Methods:Four gene expression microarray data were downloaded from the Gene Expression Omnibus (GEO) database (GSE26942, GSE33335, GSE63089, and GSE79973). Differentially expressed genes (DEGs) between gastric carcinoma and normal gastric tissue samples were identified by an integrated bioinformatic analysis. Gene Ontology (GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed using statistical software R. STRING and Cytoscape software were employed to construct protein–protein interaction (PPI) networks. Hub genes with a high score of connectivity identified from the PPI network were identified. Prognostic values of hub genes were evaluated in GSE15459 dataset. Hub genes related to GC overall survival were further validated in GEPIA (Gene Expression Profiling Interactive Analysis) online tool.Results:A total of 12 upregulated DEGs and 59 downregulated DEGs were identified when the 4 microarray data overlapped. Among them, 10 hub genes with a high score of connectivity were identified. High expression of ghrelin and obestatin prepropeptide (GHRL), BGN, TIMP metallopeptidase inhibitor 1, thrombospondin 2, secreted phosphoprotein 1, and low expression of CHGA were associated with a poor overall survival of gastric cancer (all log rank P < .05). After validation in GEPIA database, only GHRL was confirmed associated with a poor overall survival of gastric cancer (log rank P = .04).Conclusions:GHRL could be used as a novel biomarker for the prediction of a poor overall survival of gastric cancer, and could be a novel therapeutic target for gastric cancer treatment. However, future experimental studies are still required to validate these findings.

Ghrelin inhibits IKKβ/NF-κB activation and reduces pro-inflammatory cytokine production in pancreatic acinar AR42J cells treated with cerulein

BackgroundPrevious studies have provided conflicting results regarding whether the serum ghrelin concentration can reflect the severity of acute pancreatitis (AP). The present study examined the correlation between the serum ghrelin concentration and AP severity in animal models and investigated whether altered ghrelin expression in pancreatic acinar cells influences IKKβ/NF-κB signaling and pro-inflammatory cytokine production. MethodsMild or severe AP was induced in rats by intraperitoneal injection of cerulein or retrograde cholangiopancreatic duct injection of sodium taurocholate, respectively. After successful model induction, serum ghrelin, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) concentrations were determined by enzyme-linked immunosorbent assay, and IKKβ/NF-κB activation was assessed by immunohistochemistry. Subsequently, stable overexpression or knockdown of ghrelin in AR42J cells was achieved by lentiviral transfection. After transfected cells and control cells were treated with cerulein for 24 h, the TNF-α and IL-1β levels in the supernatants were determined by enzyme-linked immunosorbent assay, and the expression levels of p-p65, IKKβ, and p-IKKβ were detected by Western blotting. ResultsIn rat AP models, AP severity was correlated with increased IKKβ/NF-κB activation, pro-inflammatory cytokine production, and ghrelin secretion. The levels of pro-inflammatory cytokines TNF-α and IL-1β as well as IKKβ/NF-κB signaling activity were increased upon knockdown of ghrelin in the AP acinar cell model and decreased with ghrelin overexpression. ConclusionsSerum ghrelin is related to the severity of AP. Ghrelin may play a protective role in the pathogenesis of AP by inhibiting the pro-inflammatory cytokines and the activation of the IKKβ/NF-κB signaling pathway.

Ghrelin suppresses migration of macrophages via inhibition of ROCK2 under chronic intermittent hypoxia.

ObjectivesMigration of macrophages and atherosclerosis result in various diseases, including coronary heart disease. This study aimed to clarify the roles that ghrelin and Rho-associated coiled-coil-containing protein kinase 2 (ROCK2) play in migration of macrophages under chronic intermittent hypoxia (CIH).MethodsA rat model of CIH was constructed and changes in ghrelin and ROCK2 protein expression were measured by western blot assay. The migratory ability of macrophages was determined by the transwell assay. Hematoxylin and eosin staining was applied to detect the changes in intima-media thickness.ResultsWe found that CIH enhanced migration of macrophages, and this effect was attenuated by exogenous ghrelin. Additionally, the facilitative effect of CIH on migration of macrophages was strengthened or decreased by upregulation or downregulation of ROCK2, respectively. This phenomenon indicated that ROCK2 was involved in CIH-induced migration in macrophages. Furthermore, western blot and transwell assays showed that ghrelin inhibited CIH-induced migration via ROCK2 suppression in macrophages.ConclusionsIn summary, the present study shows that ghrelin inhibits CIH-induced migration via ROCK2 suppression in macrophages. Our research may help lead to identifying a new molecular mechanism for targeted therapy of atherosclerosis and its associated coronary artery diseases under intermittent hypoxia.

Recognition of Invasive Prostate Cancer Using a GHRL Polypeptide Probe Targeting GHSR in a Mouse Model In Vivo.

Ghrelin (GHRL) is a polypeptide that can specifically bind to the growth hormone secretagogue receptor (GHSR). The expression of GHSR is significantly different in normal and prostate cancer (PC) tissues in humans. It is important to find an effective diagnostic method for the diagnosis and prognosis of invasive PC/neuroendocrine prostate cancer (NEPC). GHRL and GHSR mRNA levels were determined by a quantitative real-time polymerase chain reaction in PC tissues. The expression of GHRL and GHSR proteins was assessed by Western blot assay and immunohistochemistry. A GHRL polypeptide probe was synthesized by standard solid-phase polypeptide synthesis, and labeled with Alexa Fluor 660. Confocal microscopy was used to capture fluorescence images. Living imaging analysis showed tumor areas of different invasiveness in mice models. The levels of GHRL and GHSR copy number amplification and mRNA expression were increased in invasive PC/NEPC, and the protein expression levels of GHRL and GHSR were similarly increased in NEPC. The GHRL polypeptide probe could effectively bind to GHSR. In PC3 cells, it was found that the GHRL probe specifically binds to GHSR on the cell membrane and accumulates in the cells through internalization after binding. Live imaging in mice models showed that there were different signal intensities in tumor areas with different invasiveness. GHSR and GHRL might be used in molecular imaging diagnosis for invasive PC/NEPC in the future.

Low protein diet supplemented with crystalline amino acids suppressing appetite and apo-lipoprotein synthesis in laying hens

There are contrary reports in the application of low protein diet (LPD) in laying hens. The present study was conducted to explore the effects of LPD on the laying performance, hepatic lipogenesis, and expression of appetite-associated genes in laying hens. A total of 240 laying hens were randomly divided into two groups: one was fed diet contains 9.2 % crude protein (LPD) and the other received 16.5 % protein (Control). LPD decreased (P < 0.05) laying rate, egg weight, egg production, and feed intake, but increased the value of feed conversion ratio (FCR). LPD treatment decreased (P < 0.05) body weight (BW) and abdominal fat weight. The plasma concentrations of triglyceride (TG) and very low density lipoprotein (VLDL) were significantly reduced (P < 0.05) in LPD hens, while glucose were increased (P < 0.05). In hypothalamus, the expression levels of neuropeptide Y (NPY) was upregulated (P < 0.05) in LPD hens, while cocaine-and amphetamine-regulated transcript (CART) was suppressed (P < 0.05). The expression of ghrelin, agouti-gelated protein (AgRP), cholecystokinin (CCK), pro-opiomelanocortin (POMC), corticotropin-releasing hormone (CRH) and melanocortin receptor 4 (MCR-4) were not changed. The mRNA levels of ghrelin in the preventriculus was suppressed (P < 0.05), whereas the expression of CCK was increased (P < 0.05) in preventriculus and jejunum. In liver, LPD increased (P < 0.05) the expression of fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC), whereas had no influence (P> 0.05) on peroxisome proliferator-activated receptors α (PPAR-α), and sterol regulatory element binding proteins 1c (SREBP-1c). In contrast to the changed mRNA levels, the hepatic activities of FAS and malic enzyme (ME) were not influenced (P > 0.05) by LPD treatment. Adversely, the expression of apolipoprotein B (ApoB), apolipoprotein very-low density lipoportein (ApoVLDL) and carnitine palmitoyl transferase 1 (CPT1) were downregulated (P < 0.05) by LPD treatment. In abdominal fat tissue, the expression of FAS, ACC, CPT1, PPAR-γ, and SREBP-1c was not altered in LPD hens, compared to control hens. In conclusion, the down-regulated NPY expression in hypothalamus is associated with the suppressed feed consumption in hens provided with LPD. The result suggests that decreased apo-lipoprotein synthesis should be at least partially responsible for the inhibited yolk-precursor synthesis and in turn the decreased laying performance.

Ghrelin suppresses insulin secretion in human islets and type 2 diabetes patients have diminished islet ghrelin cell number and lower plasma ghrelin levels

It is not known how ghrelin affects insulin secretion in human islets from patients with type 2 diabetes (T2D) or whether islet ghrelin expression or circulating ghrelin levels are altered in T2D. Here we sought out to identify the effect of ghrelin on insulin secretion in human islets and the impact of T2D on circulating ghrelin levels and on islet ghrelin cells.The effect of ghrelin on insulin secretion was assessed in human T2D and non-T2D islets. Ghrelin expression was assessed with RNA-sequencing (n = 191) and immunohistochemistry (n = 21). Plasma ghrelin was measured with ELISA in 40 T2D and 40 non-T2D subjects. Ghrelin exerted a glucose-dependent insulin-suppressing effect in islets from both T2D and non-T2D donors. Compared with non-T2D donors, T2D donors had reduced ghrelin mRNA expression and 75% less islet ghrelin cells, and ghrelin mRNA expression correlated negatively with HbA1c. T2D subjects had 25% lower fasting plasma ghrelin levels than matched controls.Thus, ghrelin has direct insulin-suppressing effects in human islets and T2D patients have lower fasting ghrelin levels, likely as a result of reduced number of islet ghrelin cells. These findings support inhibition of ghrelin signaling as a potential therapeutic avenue for stimulation of insulin secretion in T2D patients.

FGF21 Mimics a Fasting-Induced Metabolic State and Increases Appetite in Zebrafish

Fibroblast growth factor 21 (FGF21) is a member of the FGF superfamily that acts in an endocrine manner. FGF21 is a key regulator of energy balance and metabolism in mammals, and has emerged as a therapeutic potential for treating obesity and diabetes. Here, we report that mRNAs encoding FGF21 and its receptors are widely distributed within the zebrafish tissues and are importantly modulated by fasting (decreased in brain and liver, and increased in gut). FGF21 stimulates food intake in zebrafish, likely in part by modulating brain npy/agrp and nucb2/nesfatin-1 and gut ghrelin and cck mRNA expression. In accordance with this orexigenic role, the expression of FGF21 and its receptors were observed to increase preprandially and decrease post-feeding in the foregut and/or liver. Finally, we found important evidence in favor of a role for FGF21 in regulating glucose and lipid metabolism in the zebrafish liver in a way that mimics a fasting metabolic state.

Fasting Increases Iron Export by Modulating Ferroportin 1 Expression Through the Ghrelin/GHSR1α/MAPK Pathway in the Liver.

The liver is contributed to maintaining body iron homeostasis and controlling of body adaptation to fasting. Although previous studies implied a negative relationship between iron and ghrelin in both mice and humans, it remains to be explored whether fasting or ghrelin has a functional effect on iron homeostasis in the liver. In this study, we examined the roles of fasting and ghrelin in modulating the protein expression of Fpn1, transferrin receptor 1 (TfR1), and ferritin light chain (Ft-L), as well as the mRNA expression of ghrelin, hepcidin, ghrelin O-acyltransferase (GOAT), and growth hormone secretagogue receptor 1 alpha (GHSR1α) in mouse liver and cultured hepatocytes. Our in vivo results suggested that fasting significantly upregulated the mRNA expression of ghrelin, GOAT, and GHSR1α, as well as the protein levels of ghrelin, Fpn1, and Ft-L, but not TfR1, in mouse liver. Interestingly, mRNA expression of hepcidin did not change significantly after fasting. Meanwhile, in cultured hepatocytes, ghrelin significantly increased the protein expression of Fpn1 but not Ft-L and TfR1 and significantly enhanced ERK phosphorylation. Furthermore, the pretreatment of cultured hepatocytes with either a pERK inhibitor or a GHSR1α antagonist abolished the effects of ghrelin on Fpn1 expression and ERK phosphorylation. Our findings confirmed that fasting increases iron export in the liver by upregulating Fpn1 expression through the ghrelin/GHSR1α/MAPK signaling pathway.

Ghrelin antagonist regulates metabolic hormone receptorsin the hypothalamus of ewes

Abstract This study evaluates the effects of ghrelin antagonist on mRNA abundance for metabolic hormone receptors in feed-restricted ewes. Ewes were randomly assigned to one of three treatments; Control (CO): feed above maintenance energy intake requirements and daily subcutaneous saline infusion; Feed restriction (FR): feed restricted and daily subcutaneous saline infusion; Ghrelin antagonist (GA): feed restricted and daily subcutaneous of 7.5 μg/kg of d -Lys3-GHRP-6. Blood was sampled on days 1, 4, 9, and 13, relative to the start of the experiment, to quantify plasma glucose, NEFA and ghrelin concentrations. At day 13, the hypothalamus was collected to evaluate relative mRNA expression. The CO ewes had lesser plasma NEFA concentration compared with FR and GA ewes. There was a treatment by time interaction for plasma glucose concentration, all treatment started with similar plasma glucose concentration, but at day 13 CO ewes had a greater plasma concentration than FR and GA. Relative mRNA expression for glucagon receptor in GA ewes tended to be lesser compared with CO and FR treated ewes. There were no differences in insulin receptor mRNA relative expression between the groups. Ghrelin receptor mRNA relative expression tended to be greater in the GA compared with the CO treated ewes. There was no effect of GA on leptin receptors. However, there was a tendency toward greater relative expression of leptin receptor mRNA in the FR compared with the CO ewes. Relative expression of adiponectin receptor mRNA was lesser in the GA compared with CO and FR ewes. Cortisol receptor relative mRNA expression was greater in the FR compared with the CO ewes. Restricting dietary intake of ewes change mRNA relative expression of cortisol and leptin receptors in the hypothalamus of ewes. These variations are countered with ghrelin antagonist. Ghrelin antagonist modifies the mRNA relative expression of ghrelin, glucagon and adiponectin receptors. These results suggest that ghrelin could regulates metabolic hormone activity by modifying the relative expression of their receptors mRNA.

Nutritional programming improves dietary plant protein utilization in zebrafish Danio rerio.

Nutritional Programming (NP) has been shown to counteract the negative effects of dietary plant protein (PP) by introducing PP at an early age towards enhancement of PP utilization during later life stages. This study explored the effect of NP and its induction time on growth, expression of appetite-stimulating hormones, and any morphological changes in the gut possibly responsible for improved dietary PP utilization. At 3 days post-hatch (dph) zebrafish were distributed into 12 (3 L) tanks, 100 larvae per tank. This study included four groups: 1) The control (NP-FM) group received fishmeal (FM)-based diet from 13–36 dph and was challenged with PP-based diet during 36–66 dph; 2) The NP-PP group received NP with dietary PP in larval stage via live food enrichment during 3–13 dph followed by FM diet during 13–36 dph and PP diet during 36–66 dph; 3) The T-NP group received NP between 13–23 dph through PP diet followed by FM diet during 23–36 dph and PP diet during 36–66 dph; and 4) The PP group received PP diet from 13–66 dph. During the PP challenge the T-NP group achieved the highest weight gain compared to control and PP. Ghrelin expression in the brain was higher in T-NP compared to NP-FM and NP-PP, while in the gut it was reduced in both NP-PP and T-NP groups. Cholecystokinin expression showed an opposite trend to ghrelin. The brain neuropeptide Y expression was lower in NP-PP compared to PP but not different with NP-FM and T-NP groups. The highest villus length to width ratio in the middle intestine was found in T-NP compared to all other groups. The study suggests that NP induced during juvenile stages improves zebrafish growth and affects digestive hormone regulation and morphology of the intestinal lining–possible mechanisms behind the improved PP utilization in pre-adult zebrafish stages.

The effects of feeding obese rats with bee bread on leptin and ghrelin expression

The effects of feeding obese rats with bee bread on leptin and ghrelin expression

Plasma levels of acylated ghrelin in patients with insulinoma and expression of ghrelin and its receptor in insulinomas

BackgroundInsulinoma is a subtype of pancreatic neuroendocrine tumors. Many patients with insulinoma are obese due to frequent food intake. Ghrelin is associated with obesity and blood levels of insulin. It is not clear if plasma levels of ghrelin in insulinoma patients correlate with hyperinsulinemia and obesity. Expression of ghrelin and its receptor has not been well demonstrated in insulinoma.ObjectiveTo study if plasma levels of ghrelin is associated with obesity and hyperinsulinemia or hyperproinsulinemia in patients with insulinoma, and to detect the expression of ghrelin and its receptor in insulinoma.MethodsPlasma levels of acylated ghrelin, insulin, and proinsulin were measured in 37 patients with insulinoma and 25 controls by ELISA. Expression of ghrelin and its receptor GHS-R1A was examined in 20 insulinoma and paired pancreatic specimens by immunostaining. P ≤ 0.05 was considered significant.ResultsThe plasma levels of acylated ghrelin in patients with insulinoma were significantly lower than that in the controls (median 15 pg/ml vs. 19 pg/ml, respectively, P = 0.016). The reduced plasma levels of acylated ghrelin in patients were significantly correlated with obesity, hyperinsulinemia, and hyperproinsulinemia (P = 0.029 and P = 0.028, respectively). Expression of ghrelin and its receptor GHS-R1A was shown in the majority of insulinoma specimens. The expression of GHS-R1A was positively correlated with ghrelin expression in insulinoma (P = 0.014).ConclusionsPlasma levels of acylated ghrelin decreased in patients with insulinoma, probably due to the hyperinsulinemia and obesity in the patients. Expression of both ghrelin and its receptor is common in insulinoma.

In vivo and in vitro effects of Salsola collina on gastrointestinal motility in rats.

Objective(s): Salsola collina is widely distributed along the Bohai coast and consumed as an edible plant by native residents. We have found surprisingly that S. collina extracts promoted gastrointestinal motility in mice previously. In the present study, effects of S. collina on gastrointestinal motility in rats and its underlying mechanism were explored.Materials and Methods: In vivo, different fraction extracts from S. collina were prepared and the effects on gastric emptying and small intestinal propulsion in normal rats were measured. Plasma ghrelin (GRL), motilin (MTL), gastrin (GAS) and vasoactive intestinal peptide (VIP) and expressions of GRL receptor (GHSR), MTL receptor (MTLR), VIP receptor 2 (VIPR2) in the duodenum were also detected. In vitro, gastric antrum strips were prepared and activities of different extracts on gastric smooth muscle contractions were evaluated.Results:Results showed that the ethyl acetate extract (EAE) was the most effective fraction to promote gastric emptying and intestinal propulsion, showing a dose-dependent manner. EAE increased plasma GRL and GAS, elevated GHSR expression and restrained VIPR2 expression in the duodenum. In vitro, EAE promoted contraction of normal gastric antrum strips as well as relaxed strips induced by atropine.Conclusion:These data indicate that EAE has a significant prokinetic activity via a mechanism that mainly involves in modulating plasma GRL and GAS, expressions of GSHR and VIPR2 in the duodenum and activating M-cholinergic receptor. Our study provides a pharmacological basis for the use of S. collina extract in treating gastrointestinal motility disorders.

Abstract No. 688 Bariatric arterial embolization with radiopaque microspheres suppresses ghrelin expression and weight gain in swine

To evaluate the embolization effect of calibrated radiopaque microspheres on ghrelin production and weight change in a swine model. Eight healthy growing swine (∼23 kg) were randomized to receive either bariatric artery embolization (BAE) with 100-200 μm radiopaque microspheres (Boston Scientific) (n = 5) or saline (n = 3) in the left gastroepiploic artery and right gastric artery under x-ray guidance. Weight and fasting blood samples were obtained at baseline and weekly for 8 weeks. Cone beam CT (CBCT) images of the stomachs were acquired immediately after embolization, at 8 weeks prior to sacrifice and postmortem to examine the imaging visibility and persistence of the embolic microspheres. Biopsies of the fundus were taken during endoscopic examination at ∼1 week after embolization. Ulcers were scored from 0 to 3. Plasma ghrelin levels were assessed using a radioimmunoassay. The ghrelin-expressing cell densities in the stomach were assessed by immunohistochemical staining and analyzed using the Wilcoxon rank sum test. Radiopaque microspheres were visible on x-ray and CBCT during the procedure and the radiopacity persisted for 8 weeks after BAE. BAE pigs showed a significant reduction of the percentage of weight gain relative to controls (42.3% ± 5.7 vs. 51.6% ± 2.9, P = 0.04). The ghrelin-expressing cell densities of fundal biopsies were similar between embolized animals and controls. Yet, both fundal ghrelin-expressing cell densities (16.1 ± 6.7 vs. 23.6 ± 12.6, P = 0.04) and plasma ghrelin levels (1709 ± 172 vs. 4343 ± 1555, P <0.01) of embolized animals were significantly lower than those of controls at week 8. All BAE animals developed superficial ulcers (score 1: n = 4, score 2: n = 2) that healed by week 8 after embolization. Radiopaque microspheres enabled direct visualization of embolics delivery and deposition during and post embolization procedure. The suppression of fundal and systemic plasma ghrelin levels as well as the percentage of weight gain in combination with mild mucosal damage suggests that the calibrated 100-200 μm radiopaque microspheres may be the optimal embolics for effective weight management via BAE.

Effect of hawthorn seed extract on the gastrointestinal function of rats with diabetic gastroparesis

Diabetic gastroparesis (DGP) is a common chronic complication of diabetes mellitus. Its pathogenesis is related to many factors. Hawthorn seeds are the seeds of Crataegus pinnatifida Bunge, which has many chemical constituents and pharmacological properties. In this study, we investigated the therapeutic effect and potential mechanism of ethyl acetate extract from hawthorn seeds (HSEAE) on DGP rats. We measured their body weight, blood sugar, gastric emptying rate, and intestinal propulsion rate, as well as the effects of HSEAE on superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) in gastric homogenate. The levels of ghrelin in rat plasma were determined by radioimmunoassay, while those of motilin (MTL) and gastrin (GAS) were determined by enzyme-linked immunosorbent assay. Western blot was used to detect the expression of c-kit, ghrelin, and neuronal nitric oxide synthase (nNOS) in the rats’ stomachs, and immunohistochemistry was used to detect changes in interstitial cells of Cajal (ICC). The results showed that different doses of HSEAE effectively promoted the gastric emptying and small intestinal propulsion (P < 0.05 or P < 0.01). In addition, HSEAE increased SOD and GSH-Px in the rats’ stomachs while decreasing MDA, and increased plasma ghrelin while decreasing MTL and GAS (P < 0.05 or P < 0.01). The expression of c-kit, ghrelin, and nNOS proteins and the number of ICCs in the rats’ stomachs also significantly increased (P < 0.05 or P < 0.01). Our experiments showed that HSEAE improved gastrointestinal motility in DGP rats, and its potential mechanism might be involved in the inhibition of oxidative stress injury induced by hyperglycemia, upregulating n-NOS, c-kit expression, and ICCs in their stomachs and regulating gastrointestinal hormones.

The Effects of Low-Dose and High-Dose Decoctions of Fructus aurantii in a Rat Model of Functional Dyspepsia.

BackgroundFructus aurantii is a flavonoid derived from Citrus aurantium (bitter orange) that is used in traditional Chinese medicine (TCM) to treat gastric motility disorders. This study aimed to investigate the effects of low-dose and high-dose decoctions of Fructus aurantii in a rat model of functional dyspepsia (FD).Material/MethodsSprague-Dawley rats (n=90) were divided into nine study groups: the control group, the FD model group, the domperidone-treated (Domp) group, the low-dose raw Fructus aurantii (FA-L) group, the high-dose raw Fructus aurantii (FA-H) group, the low-dose Fructus aurantii with stir-fried wheat bran (Bran-L) group, the high-dose Fructus aurantii with stir-fried wheat bran (Bran-H) group, the low-dose Fructus aurantii with stir-fried wheat bran and honey (Honey-L) group, and the high-dose Fructus aurantii with stir-fried wheat bran and honey (Honey-H) group. The FD rat model was established by semi-starvation, followed by tail damping, stimulation, and forced exercise with fatigue. Change in weight, rate of gastric emptying and intestinal propulsion, and serum levels of leptin, motilin, vasoactive intestinal peptide (VIP), gastrin, calcitonin gene-related peptide (CGRP), ghrelin, and cholecystokinin were compared between the groups.ResultsIn the FD model group, weight, rate of gastric emptying and intestinal propulsion significantly decreased, the expression of leptin, VIP and CGRP increased, and expression of motilin, gastrin, ghrelin, and cholecystokinin significantly decreased. Treatment with low-dose Fructus aurantii with stir-fried wheat bran significantly reversed these effects.ConclusionsIn the rat model of FD, low-dose Fructus aurantii with stir-fried wheat bran increased gastrointestinal motility and gastrointestinal hormone levels.