Stimulate Food Intake Research Articles

Mitragynine and morphine produce dose-dependent bimodal action on food but not water intake in rats.

Kratom (Mitragyna speciosa), containing the primary alkaloid mitragynine, has emerged as an alternative self-treatment for opioid use disorder. Mitragynine binds numerous receptor types, including opioid receptors, which are known to modulate food consumption. However, the ability of acute mitragynine to modulate food consumption remains unknown. The current study assessed the effects of acute mitragynine or morphine administration on unconditioned food and water intake in 16 Sprague-Dawley rats. Food and water intake changes were monitored in response to morphine, mitragynine (1.78-56 mg/kg ip), saline, or vehicle controls for 12 h, starting at the onset of the dark cycle. Naltrexone pretreatment was used to examine pharmacological specificity. Both morphine and mitragynine demonstrated a biphasic food intake dose-effect, with low doses (5.6 mg/kg) increasing and high doses (56 mg/kg) decreasing food intake. All morphine doses reduced water intake; however, only the highest dose of mitragynine (56 mg/kg) reduced water intake. Naltrexone attenuated both stimulatory and inhibitory effects of morphine on food intake, but only the stimulatory effect of mitragynine. In conclusion, low doses of mitragynine stimulate food intake via opioid-related pathways, while high doses likely recruit other targets.NEW & NOTEWORTHY This study reveals that morphine and the kratom alkaloid mitragynine produce dose-dependent effects on feeding in rats. Low doses stimulate food intake via opioid pathways, while high doses decrease consumption through nonopioid mechanisms. Morphine potently suppresses water intake at all doses, whereas only high doses of mitragynine reduce drinking. These findings provide novel insights into the complex opioid and nonopioid mechanisms underlying the effects of mitragynine on ingestive behaviors.

UV Irradiation Increases Appetite and Prevents Body Weight Gain through the Upregulation of Norepinephrine in Mice

UV irradiation of the human skin downregulates lipid synthesis and adipokine production in subcutaneous fat. Recent evidence has suggested that UV exposure limits body weight gain in mouse models of obesity. However, the relationship between norepinephrine and UV irradiation has not been previously reported. Chronic UV exposure stimulated food intake but prevented body weight gain. Leptin, an appetite-suppressing hormone, was significantly reduced in the serum of the UV-irradiated mice. In contrast, UV irradiation induced browning of subcutaneous white adipose tissues without increasing physical activity. Notably, UV irradiation significantly increased norepinephrine levels, and the inhibition of norepinephrine production reversed the effects of chronic UV irradiation on food intake and body weight gain. In conclusion, chronic UV irradiation induces norepinephrine release, resulting in the stimulation of food intake due to the downregulation of leptin levels, but it prevents weight gain by inducing the browning process and elevating energy expenditure.

Motilin, a Novel Orexigenic Factor, Involved in Feeding Regulation in Yangtze Sturgeon (Acipenser dabryanus).

Motilin is a gastrointestinal hormone that is mainly produced in the duodenum of mammals, and it is responsible for regulating appetite. However, the role and expression of motilin are poorly understood during starvation and the weaning stage, which is of great importance in the seeding cultivation of fish. In this study, the sequences of Yangtze sturgeon (Acipenser dabryanus Motilin (AdMotilin)) motilin receptor (AdMotilinR) were cloned and characterized. The results of tissue expression showed that by contrast with mammals, AdMotilin mRNA was richly expressed in the brain, whereas AdMotilinR was highly expressed in the stomach, duodenum, and brain. Weaning from a natural diet of T. Limnodrilus to commercial feed significantly promoted the expression of AdMotilin in the brain during the period from day 1 to day 10, and after re-feeding with T. Limnodrilus the change in expression of AdMotilin was partially reversed. Similarly, it was revealed that fasting increased the expression of AdMotilin in the brain (3 h, 6 h) and duodenum (3 h), and the expression of AdMotilinR in the brain (1 h) in a time-dependent manner. Furthermore, it was observed that peripheral injection of motilin-NH2 increased food intake and the filling index of the digestive tract in the Yangtze sturgeon, which was accompanied by the changes of AdMotilinR and appetite factors expression in the brain (POMC, CART, AGRP, NPY and CCK) and stomach (CCK). These results indicate that motilin acts as an indicator of nutritional status, and also serves as a novel orexigenic factor that stimulates food intake in Acipenser dabryanus. This study lays a strong foundation for the application of motilin as a biomarker in the estimation of hunger in juvenile Acipenser dabryanu during the weaning phase, and enhances the understanding of the role of motilin as a novel regulator of feeding in fish.

Ghrelin mediated cardioprotection using in vitro models of oxidative stress

Ghrelin is commonly known as the ‘hunger hormone’ due to its role in stimulating food intake in humans. However, the roles of ghrelin extend beyond regulating hunger. Our aim was to investigate the ability of ghrelin to protect against hydrogen peroxide (H2O2), a reactive oxygen species commonly associated with cardiac injury. An in vitro model of oxidative stress was developed using H2O2 injured H9c2 cells. Despite lentiviral ghrelin overexpression, H9c2 cell viability and mitochondrial function were not protected following H2O2 injury. We found that H9c2 cells lack expression of the preproghrelin cleavage enzyme prohormone convertase 1 (encoded by PCSK1), required to convert ghrelin to its active form. In contrast, we found that primary rat cardiomyocytes do express PCSK1 and were protected from H2O2 injury by lentiviral ghrelin overexpression. In conclusion, we have shown that ghrelin expression can protect primary rat cardiomyocytes against H2O2, though this effect was not observed in other cell types tested.

Food, nutrition and the dining experience in aged care settings: Findings of a nationwide survey.

Previous research on food, nutrition and dining practices in Australian residential aged care (RAC) homes has been based on a limited sample of single-home or multiple-home providers, but a nationwide study has not been conducted. The aim of this study was to provide a preliminary overview of current food, nutrition and dining practices across Australian RAC facilities using a nationwide survey. A survey was distributed to Australian RAC homes in August-September 2020, as part of the National Congress on Food, Nutrition and the Dining Experience in Aged Care (February 2021). The survey, administered via an online portal, consisted of 38 semistructured questions including yes/no or multiple-choice responses, free text, frequency scales and number entry. Six key topics were explored, including 'food service system and environment', 'catering style', 'menu planning and evaluation', 'nutrition planning and requirements', 'nutrition-related screening and assessment' and 'training and additional information', which were informed by the Australian Government Department of Health and reflected the interests of the Congress. The final sample included 292 respondents (204 individual homes and 88 multiple-home proprietors) representing 1152 homes and 125,393 residents, encompassing approximately 43% of RAC homes (of a possible 2671) and 57% of residents (of a possible 219,965) in Australia. Survey respondents representing RAC homes included service managers, catering managers, Chief Executive Officers, cooks, chefs, dietitians or staff from other roles within homes. A number of potential areas of need were identified, included increasing the autonomy of residents to select the foods they desire, increasing the variety and choice (including timing) of meals, enhancing the dining environments in homes to stimulate food intake and increasing staff training and the number of trained chefs in homes, so that meals are prepared which address diverse nutritional needs of residents. This study provides insight into the food service and mealtime practices of over a third of Australian RAC homes. The findings of this survey may help to identify key targets for intervention to improve the food, nutrition and quality of life of aged care residents.

Exploring the short-term impact of swapping consumption from standard protein snacks to higher protein snacks on energy intake in social drinkers: Is protein worth a nudge?

Drinking alcoholic beverages stimulates food intake and contributes to the passive overconsumption of dietary energy. As protein is the most satiating of all the macronutrients, increased levels in snacks taken with alcohol have the potential to minimize excess energy consumption. We hypothesized that swapping consumption from retail-available standard protein (SP) snacks to higher protein (HP) snack foods would increase satiety and reduce acute food energy intake in social drinkers. A randomized single-blind crossover trial with 19 healthy participants aged 19-31 years was conducted. Participants attended two separate testing sessions, where they ingested white wine (30 g alcohol) and were offered adlibitum access to either HP snacks with a protein-fortified dip or SP snacks with a dip. There were no significant differences in mean food mass, food energy intake, or subjective appetite ratings between the high and SP snacks (all p > .05). Mean protein intake was significantly increased with HP snacks compared with standard snacks (p < .001). Plasma glucose median incremental area under the curve and mean peak were significantly higher with the SP snacks (all p < .05) but remained within the reference range. This study demonstrated that consumption of a higher amount of protein after a moderate alcohol dose does not result in a change in food mass and energy intake or promote satiety in healthy young adults. The potential for a simple swap to different snack types is unlikely to bring substantial benefits to social drinkers and reduce passive energy consumption.

SAT654 Regulation Of The Melanocortin-4 Receptor (mc4r) By Attractin Like Protein 1 (alp1)

Abstract Disclosure: P. Buscaglia: None. J. Sebag: None. The Melanocortin-4 Receptor (MC4R) plays a central role in the regulation of energy homeostasis. Mutations in MC4R are responsible for up to 6% of early onset obesity in humans and deletion of MC4R in mice results in severe obesity due to hyperphagia. MC4R is a GPCR expressed in different region of the brains including the paraventricular nucleus of the hypothalamus. Stimulation of MC4R by its agonist αMSH and inhibition by its endogenous inverse agonist AGRP result in inhibition or stimulation of food intake respectively. MC4R is known to interact with two single transmembrane proteins, the Melanocortin Receptor Accessory Protein 2 (MRAP2) and Attractin Like Protein 1 (ALP1). Whereas MRAP2 has been shown to promote MC4R signaling in vitro and in vivo, the pharmacological and physiological relevance of ALP1 for MC4R signaling and actions is not known. To determine if ALP1 alters MC4R signaling, we measured αMSH-stimulated cAMP production in cells transfected with MC4R alone or with either ALP1 or MRAP2. We found that ALP1 increases MC4R signaling to a larger extent than MRAP2. We also showed that ALP1 inhibits β-arrestin recruitment to MC4R, thus likely preventing desensitization of the receptor. To assess the physiological importance of ALP1, we generated an ALP1Flox mouse and bred it to MC4RCRE mice. Deletion of ALP1 in MC4R neurons resulted in increased body weight compared to MC4RCRE control on standard diet. This increase in body weight was further exacerbated when animals were fed a high fat diet. In conclusion our results suggest that ALP1 regulates MC4R signaling and that deletion of ALP1 from MC4R neurons causes weight gain that may be due to decreased MC4R activity. Presentation: Saturday, June 17, 2023

Kappa opioid receptor activation increases thermogenic energy expenditure which drives increased feeding

Opioid receptors, including the kappa opioid receptor (KOR), exert control over thermoregulation and feeding behavior. Notably, activation of KOR stimulates food intake, leading to postulation that KOR signaling plays a central role in managing energy intake. KOR has also been proposed as a target for treating obesity. Herein, we report studies examining how roles for KOR signaling in regulating thermogenesis, feeding, and energy balance may be interrelated using pharmacological interventions, genetic tools, quantitative thermal imaging, and metabolic profiling. Our findings demonstrate that activation of KOR in the central nervous system causes increased energy expenditure via brown adipose tissue activation. Importantly, pharmacologic, or genetic inhibition of brown adipose tissue thermogenesis prevented the elevated food intake triggered by KOR activation. Furthermore, our data reveal that KOR-mediated thermogenesis elevation is reversibly disrupted by chronic high-fat diet, implicating KOR signaling as a potential mediator in high-fat diet-induced weight gain.

Effects of Various LED Light Spectra on Growth, Gonadal Development, and Growth-/Reproduction-Related Hormones in the Juvenile Red Spotted Grouper, Epinephelus akaara.

The light spectrum is a key environmental cue involved in growth and reproduction in teleosts. This study investigated the effects of exposure on juvenile red spotted grouper exposed to white (control), red (590 nm), blue (480 nm), and green (520 nm) light-emitting diodes (LEDs) (12 h light:12 h dark) for two months. The body weight (BW), total length (TL), condition factor (CF), weight gain rate (WGR), gonadosomatic index (GSI), and hepatosomatic index (HSI) were assessed. Gonadal development was observed. The gene expression of growth-related hormones, such as growth hormone (GH), pre-pro-somatostatin-I (PSS-I), neuropeptide Y (NPY), and CCK, and of reproduction-related hormones, such as Kiss1, Kiss2, GPR54, sbGnRH, FSHβ, and LHβ, was analyzed. The results showed that the fish in the white LED group exhibited the best BW, TL, CF, WGR, and HSI after one or two months. The fish exposed to white LEDs showed the best growth after two months, but no significant differences in GH levels were detected. Contrarily, the expression levels of the PSS-I significantly increased (p < 0.05) in fish from the white group, suggesting the complex regulation of GH production and the limited effects of PSS-I on the inhibition of GH synthesis and somatic growth. The significantly increased NPY levels in the four LED groups (p < 0.05) indicated that these four LED spectra were effective in stimulating food intake and energy homeostasis. After two months, the gonads developed from chromatin nucleolar-stage oocytes to perinucleolar-stage oocytes in the four LED groups. The gene expression of Kiss2 and GPR54 in the four LED groups and of sbGnRH in the white and blue LED groups significantly increased when compared to that in the initial group (p < 0.05), while there were no significant differences in FSHβ and LHβ expression in the four LED groups. These results suggest that FSH and LH may not play important roles in gonadal development in juvenile red spotted grouper that are exposed to these four LED spectra.

CaMK1D signalling in AgRP neurons promotes ghrelin-mediated food intake.

Hypothalamic AgRP/NPY neurons are key players in the control of feeding behaviour. Ghrelin, a major orexigenic hormone, activates AgRP/NPY neurons to stimulate food intake and adiposity. However, cell-autonomous ghrelin-dependent signalling mechanisms in AgRP/NPY neurons remain poorly defined. Here we show that calcium/calmodulin-dependent protein kinase ID (CaMK1D), a genetic hot spot in type 2 diabetes, is activated upon ghrelin stimulation and acts in AgRP/NPY neurons to mediate ghrelin-dependent food intake. Global Camk1d-knockout male mice are resistant to ghrelin, gain less body weight and are protected against high-fat-diet-induced obesity. Deletion of Camk1d in AgRP/NPY, but not in POMC, neurons is sufficient to recapitulate above phenotypes. In response to ghrelin, lack of CaMK1D attenuates phosphorylation of CREB and CREB-dependent expression of the orexigenic neuropeptides AgRP/NPY in fibre projections to the paraventricular nucleus (PVN). Hence, CaMK1D links ghrelin action to transcriptional control of orexigenic neuropeptide availability in AgRP neurons.

Characterization of Ghrelin O-acyltransferase mRNA in channel catfish

Food intake is regulated by the reaction between hypothalamic neurotransmitters and peripheral signals. Ghrelin, known as a hunger hormone, stimulates food intake. Ghrelin O-acyltransferase (GOAT) catalyzes the acylation of medium-chain fatty acids to ghrelin to modify ghrelin activity. GOAT is found in all vertebrates, including fish, and is critical for modifying the activity of ghrelin. We hypothesized that GOAT is critical for regulating food intake because it modifies the activity of ghrelin in channel catfish. However, very little is known about GOAT in channel catfish, including the tissue distribution of its mRNA. We identified the nucleotide sequence that corresponds to the GOAT mRNA in GenBank. The sequencing alignment analysis showed that the sequence similarity between channel catfish GOAT mRNA and those of other fish species was high (&gt;65%) in the region that corresponded to the open reading frame of the channel catfish GOAT mRNA. Examination of the tissue distribution of GOAT mRNA, including the brain, liver, muscle, kidneys, spleen, heart, and small and large intestines, revealed that GOAT mRNA expression was detectable in the brain, small intestine, and muscles. We are currently verifying the results of tissue distribution analysis using quantitative real-time PCR. We are also examining the relationship between changes in food intake and the expression of GOAT mRNA in the brain and muscle using real-time PCR. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Soy-fortelin: A ghrelin sensitivity-enhancing peptide that stimulates food intake in aged mice.

Ghrelin sensitivity is known to decrease with aging in mice and humans, and the decrease contributes to anorexia with aging. In this study, we discovered novel ghrelin sensitivity-enhancing peptides. Ghrelin sensitivity was evaluated by examining whether dipeptide samples enhanced the calcium response to ghrelin in the growth hormone secretagogue receptor-transfected cell line. First, dipeptides were screened using a 336-dipeptide library and we revealed that Ser-Tyr (SY) potentiated ghrelin sensitivity in particular. Based on the structure-activity relationship determined using the dipeptide library and comprehensive analysis of peptides in the chymotrypsin digest of soy β-conglycinin (β-CG), which enhanced ghrelin sensitivity, candidate peptides were narrowed down. Among the chemosynthesized peptides, we discovered that an undecapeptide, SLVNNDDRDSY, corresponding to β-CGα(267-277), stimulated ghrelin sensitivity in vitro. This peptide enhanced the orexigenic activity of ghrelin in C57BL/6 mice and stimulated food intake. Thus, we demonstrated that SLVNNDDRDSY stimulated ghrelin sensitivity in vitro and in vivo and named it "soy-fortelin". Moreover, orally administered soy-fortelin had a similar but smaller effect in the young C57BL/6 mice, whereas it strongly stimulated food intake in 2-year-old aged mice that exhibited high blood ghrelin levels and low ghrelin sensitivity. In conclusion, we discovered soy-fortelin as a novel peptide that enhances ghrelin sensitivity in vivo and in vitro and increases food intake in young and aged ghrelin-resistant mice. Soy-fortelin is the first food-derived peptide reported to enhance ghrelin sensitivity.

TET3 epigenetically controls feeding and stress response behaviors via AGRP neurons.

The TET family of dioxygenases promote DNA demethylation by oxidizing 5-methylcytosine to 5-hydroxymethylcytosine (5hmC). Hypothalamic agouti-related peptide–expressing (AGRP-expressing) neurons play an essential role in driving feeding, while also modulating nonfeeding behaviors. Besides AGRP, these neurons produce neuropeptide Y (NPY) and the neurotransmitter GABA, which act in concert to stimulate food intake and decrease energy expenditure. Notably, AGRP, NPY, and GABA can also elicit anxiolytic effects. Here, we report that in adult mouse AGRP neurons, CRISPR-mediated genetic ablation of Tet3, not previously known to be involved in central control of appetite and metabolism, induced hyperphagia, obesity, and diabetes, in addition to a reduction of stress-like behaviors. TET3 deficiency activated AGRP neurons, simultaneously upregulated the expression of Agrp, Npy, and the vesicular GABA transporter Slc32a1, and impeded leptin signaling. In particular, we uncovered a dynamic association of TET3 with the Agrp promoter in response to leptin signaling, which induced 5hmC modification that was associated with a chromatin-modifying complex leading to transcription inhibition, and this regulation occurred in both the mouse models and human cells. Our results unmasked TET3 as a critical central regulator of appetite and energy metabolism and revealed its unexpected dual role in the control of feeding and other complex behaviors through AGRP neurons.

Acylation, a Conductor of Ghrelin Function in Brain Health and Disease.

Acyl-ghrelin (AG) is an orexigenic hormone that has a unique octanoyl modification on its third serine residue. It is often referred to as the “hunger hormone” due to its involvement in stimulating food intake and regulating energy homeostasis. The discovery of the enzyme ghrelin-O-acyltransferase (GOAT), which catalyses ghrelin acylation, provided further insights into the relevance of this lipidation process for the activation of the growth hormone secretagogue receptor (GHS-R) by acyl-ghrelin. Although acyl-ghrelin is predominantly linked with octanoic acid, a range of saturated fatty acids can also bind to ghrelin possibly leading to specific functions. Sources of ghrelin acylation include beta-oxidation of longer chain fatty acids, with contributions from fatty acid synthesis, the diet, and the microbiome. In addition, both acyl-ghrelin and unacyl-ghrelin (UAG) have feedback effects on lipid metabolism which in turn modulate their levels. Recently we showed that whilst acyl-ghrelin promotes adult hippocampal neurogenesis and enhances memory function, UAG inhibits these processes. As a result, we postulated that the circulating acyl-ghrelin:unacyl-ghrelin (AG:UAG) ratio might be an important regulator of neurogenesis and cognition. In this review, we discuss emerging evidence behind the relevance of ghrelin acylation in the context of brain physiology and pathology, as well as the current challenges of identifying the provenance of the acyl moiety.

LEAP2 reduces postprandial glucose excursions and ad libitum food intake in healthy men

SummaryThe gastric hormone ghrelin stimulates food intake and increases plasma glucose through activation of the growth hormone secretagogue receptor (GHSR). Liver-expressed antimicrobial peptide 2 (LEAP2) has been proposed to inhibit actions of ghrelin through inverse effects on GHSR activity. Here, we investigate the effects of exogenous LEAP2 on postprandial glucose metabolism and ad libitum food intake in a randomized, double-blind, placebo-controlled, crossover trial of 20 healthy men. We report that LEAP2 infusion lowers postprandial plasma glucose and growth hormone concentrations and decreases food intake during an ad libitum meal test. In wild-type mice, plasma glucose and food intake are reduced by LEAP2 dosing, but not in GHSR-null mice, pointing to GHSR as a potential mediator of LEAP2’s glucoregulatory and appetite-suppressing effects in mice.

DOCK4 regulates ghrelin production in gastric X/A-like cells.

Ghrelin, a gastric hormone, provides a hunger signal to the central nervous system to stimulate food intake. Ghrelin also modulates neuroinflammatory and apoptotic processes. Dedicator of cytokinesis 4 (DOCK4), a guanine nucleotide exchange factor (GEF), isinvolvedinthe regulationofneuronal polarization and axon regeneration. However, the effect of DOCK4 on ghrelin production has not been explored. The expression of DOCK4 in human and mouse stomach was examined by immunohistochemical staining. The synthesis and secretion of ghrelin in Dock4 null mice were evaluated by real-time quantitative PCR, Western blot and ELISA. The effects of DOCK4 on ghrelin production in mHypoE-42 cells were measured by real-time quantitative PCR and Western blot. We showed that DOCK4 was expressed in both human and mouse gastric ghrelin cells. The mRNA and protein levels of gastric ghrelin, as well as ghrelin secretion, were remarkably diminished in Dock4 null mice. Furthermore, we showed that overexpression of Dock4 significantly stimulated ghrelin expression, while siRNA knockdown of endogenous Dock4 resulted in a marked decrease of ghrelin in mHypoE-N42 cells. Our results identify DOCK4 as a critical regulator for ghrelin production in gastric X/A-like cells.

The Statin Target Hmgcr Regulates Energy Metabolism and Food Intake through Central Mechanisms.

The statin drug target, 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), is strongly linked to body mass index (BMI), yet how HMGCR influences BMI is not understood. In mammals, studies of peripheral HMGCR have not clearly identified a role in BMI maintenance and, despite considerable central nervous system expression, a function for central HMGCR has not been determined. Similar to mammals, Hmgcr is highly expressed in the Drosophila melanogaster brain. Therefore, genetic and pharmacological studies were performed to identify how central Hmgcr regulates Drosophila energy metabolism and feeding behavior. We found that inhibiting Hmgcr, in insulin-producing cells of the Drosophila pars intercerebralis (PI), the fly hypothalamic equivalent, significantly reduces the expression of insulin-like peptides, severely decreasing insulin signaling. In fact, reducing Hmgcr expression throughout development causes decreased body size, increased lipid storage, hyperglycemia, and hyperphagia. Furthermore, the Hmgcr induced hyperphagia phenotype requires a conserved insulin-regulated α-glucosidase, target of brain insulin (tobi). In rats and mice, acute inhibition of hypothalamic Hmgcr activity stimulates food intake. This study presents evidence of how central Hmgcr regulation of metabolism and food intake could influence BMI.

Social Modeling of Virtual Healthy Food Intake

People tend to adapt the amount of their food intake to that of others around them. This so-called social modeling of eating has been extensively studied over the past decades. The current study complements these experiments and aims to investigate social modeling of healthy food intake using a video paradigm in which a virtual model consumed either a small or a large portion of apple. In addition, it was tested whether modeling effects of a virtual female confederate were equally strong in male and female participants. Thirty participants (13 female, 17 male) completed the low norm condition in which a virtual model consumed 30 g of apple. Another 30 participants (17 female, 13 male) were allocated to the high norm condition in which a virtual model consumed 100 g of apple. Participants completed an irrelevant task, after which their own intake of apple was measured. Average intake in the low norm condition was 3 g, average intake in the high norm condition was 26 g (p &amp;lt; 0.001). In conclusion, participants adapted their intake to that of the virtual model. This effect was found irrespective of gender; female and male participants equally adapted their intake to that of a female virtual model. Stimulating food intake via a virtual model in people who have difficulty to meet dietary requirements or inhibiting food intake in people who tend to consume too much would be interesting new steps in the development of healthcare applications.

Effects of Exogenous Ghrelin on Feeding, Drinking and Growth Hormone Secretion in African Ostrich Chicks

Background: Ghrelin is widely distributed in an animal’s body, playing important biological roles. In mammals, Ghrelin can stimulate food intake and weight gain, but in poultry, it inhibits food intake and drinking. We aimed to determine the effect of Ghrelin on feeding, drinking, body weight and growth hormone (GH) content of African ostrich chicks. Methods: Sixteen 40-day-old African ostrich chicks were randomly divided into four groups and injected intravenously with saline (control) or Ghrelin (10, 50 and 100 µg/kg) for 7 days. The feeding, drinking and growth hormone (GH) levels using measurement method and radioimmunoassay were determined. Result: The results show that exogenous Ghrelin increased the feed intake rate, the drinking rate and the secretion of GH in the ostriches.

Advances in the Development of Nonpeptide Small Molecules Targeting Ghrelin Receptor.

Ghrelin is an octanoylated peptide acting by the activation of the growth hormone secretagogue receptor, namely, GHS-R1a. The involvement of ghrelin in several physiological processes, including stimulation of food intake, gastric emptying, body energy balance, glucose homeostasis, reduction of insulin secretion, and lipogenesis validates the considerable interest in GHS-R1a as a promising target for the treatment of numerous disorders. Over the years, several GHS-R1a ligands have been identified and some of them have been extensively studied in clinical trials. The recently resolved structures of GHS-R1a bound to ghrelin or potent ligands have provided useful information for the design of new GHS-R1a drugs. This perspective is focused on the development of recent nonpeptide small molecules acting as GHS-R1a agonists, antagonists, and inverse agonists, bearing classical or new molecular scaffolds, as well as on radiolabeled GHS-R1a ligands developed for imaging. Moreover, the pharmacological effects of the most studied ligands have been discussed.