Role Of Ghrelin Research Articles

GHSR signalling in perinatal phases is involved in liver metabolism at puberty.

Ghrelin has effects that range from the maturation of the central nervous system to the regulation of energy balance. The production of ghrelin increases significantly during the first weeks of life. Studies have addressed the metabolic effects of liver-expressed antimicrobial peptide 2 (LEAP2) in inhibiting the effects evoked by ghrelin, mainly in glucose homeostasis, insulin resistance, and lipid metabolism. Despite the known roles of ghrelin in the postnatal development, little is known about the long-term metabolic influences of modulation with the endogenous expressed growth hormone secretagogue receptor (GHSR) inverse agonist LEAP2. This study aimed to evaluate the contribution of GHSR signalling during perinatal phases, to neurodevelopment and energy metabolism in young animals, under inverse antagonism by LEAP2[1-14]. For this, two experimental models were used: (i) LEAP2[1-14] injections in female rats during the pregnancy. (ii) Postnatal modulation of GHSR with LEAP2[1-14] or MK677. Perinatal GHSR modulation by LEAP2[1-14] impacts glucose homeostasis in a sex and phase-dependent manner, despite no effects on body weight gain or food intake. Interestingly, liver PEPCK expression was remarkably impacted by LEAP2 injections. The observed results suggests that perinatal LEAP2 exposure can modulate liver metabolism and systemic glucose homeostasis. In addition, these results, although not expressive, may just be the beginning of the metabolic imbalance that will occur in adulthood.

Ghrelin/GHSR System in Depressive Disorder: Pathologic Roles and Therapeutic Implications.

Depression is the most common chronic mental illness and is characterized by low mood, insomnia, and affective disorders. However, its pathologic mechanisms remain unclear. Numerous studies have suggested that the ghrelin/GHSR system may be involved in the pathophysiologic process of depression. Ghrelin plays a dual role in experimental animals, increasing depressed behavior and decreasing anxiety. By combining several neuropeptides and traditional neurotransmitter systems to construct neural networks, this hormone modifies signals connected to depression. The present review focuses on the role of ghrelin in neuritogenesis, astrocyte protection, inflammatory factor production, and endocrine disruption in depression. Furthermore, ghrelin/GHSR can activate multiple signaling pathways, including cAMP/CREB/BDNF, PI3K/Akt, Jak2/STAT3, and p38-MAPK, to produce antidepressant effects, given which it is expected to become a potential therapeutic target for the treatment of depression.

Serum Ghrelin and Glucagon-like Peptide 1 Levels in Children with Prader-Willi and Bardet-Biedl Syndromes

Prader-Willi syndrome (PWS) and Bardet-Biedl syndrome (BBS) are causes of pediatric syndromic obesity. We aimed to investigate a possible role for ghrelin and glucagon-like peptide-1 (GLP-1) in the pathophysiology of PWS and BBS. The study included 12 children with PWS, 12 children with BBS, 13 pediatric obese controls (OC) and 12 pediatric lean controls (LC). Fasting serum ghrelin and GLP-1 levels were measured by ELISA. In the PWS group, no significant difference was detected for median ghrelin levels when compared with OC and LC, which were 0.96 (0.69-1.15), 0.92 (0.72-1.20) and 1.13 (0.84-1.29) ng/mL, respectively. Similarly, there was no difference in PWS median GLP-1 levels when compared with OC and LC; 1.86 (1.5-2.94), 2.24 (1.62-2.78) and 2.06 (1.8-3.41) ng/mL, respectively. In the BBS group, there was no difference in median ghrelin levels when compared with OC and LC; 1.05 (0.87-1.51), 0.92 (0.72-1.20) and 1.13 (0.84-1.29) ng/mL, respectively. Neither was there a significant difference in median GLP-1 levels; 2.46 (1.91-4.17), 2.24 (1.62-2.78) and 2.06 (1.8-3.41) ng/mL for BBS, OC and LC, respectively. There were no differences in median fasting ghrelin or GLP-1 levels when comparing patients with PWS and BBS with obese or lean peers. However, similar studies with larger series are needed.

Roles of ghrelin, hepcidin and HIF-2α in iron metabolism in iron deficiency anemia.

This study investigates the roles of HIF-2α, hepcidin, and ghrelin in iron deficiency anemia (IDA), the most widespread nutritional disorder globally. Fifty IDA patients (18-50years, BMI 19-25) and 40 healthy volunteers were studied. Hemoglobin, ferritin, hepcidin, HIF-2α, and ghrelin levels were analyzed. IDA patients showed lower hemoglobin, ferritin, hepcidin, and ghrelin levels than the control group, but HIF-2α levels were similar. Positive correlations were observed in both groups between hepcidin and HIF-2α (p < 0.001), hepcidin and ghrelin (p < 0.001), and HIF-2α and ghrelin (p < 0.001). Hemoglobin was correlated positively with HIF-2α, and ferritin was correlated positively with HIF-2α in the patient group. The study suggests that the low hepcidin levels in IDA patients enhance iron absorption. The lack of significant HIF-2α level differences may be due to the absence of chronic hypoxia in current hemoglobin levels of IDA patients. Moreover, the low ghrelin levels in patients and the correlations between ghrelin, hepcidin, and HIF-2α in both groups indicate their involvement in iron metabolism.

The role of ghrelin and leptin in the formation of morphological changes esophagus of patients with gastro-esophageal reflux disease against type 2 diabetes

Type 2 diabetes mellitus (T2DM) is associated today with a non-infectious epidemic. Every year, the number of people suffering from this disease only increases. The comorbidity of pathology, namely gastroesophageal reflux disease (GERD) against the background of type 2 diabetes mellitus, is increasingly observed. Pathogenetic mechanisms of the progression of the latter in the combined course with type 2 DM are not sufficiently studied today, and data on the effect of adipokines on the morphological pattern of the esophagus in patients with type 2 DM are emerging.&#x0D; The aim of this study is to study changes in the esophageal mucosa depending on the concentration of ghrelin and leptin in patients with comorbid GERD on the background of type 2 diabetes.&#x0D; Materials and methods of the research. 120 patients were recruited for the study and divided into 3 groups and a control group. The 1st group – 60 patients with a combined course of GERD and type 2 DM, the 2nd group – 20 patients with GERD, and the 3rd group – 20 patients with isolated type 2 DM. The control group - 20 practically healthy people of the appropriate age.&#x0D; The levels of ghrelin and leptin were determined by enzyme-linked immunosorbent assay (ELISA) on a Labline-90 analyzer (Austria).&#x0D; Endoscopic examination of the upper parts of the gastrointestinal tract (GI) with targeted biopsy was performed with an esophagogastroduodenoscope with end optics "Olympus GIF Q 150-03" (manufactured by Olympus Europa SE &amp; CO. KG, Japan).&#x0D; The degree of complexity and the presence of reflux esophagitis were determined according to the Los Angeles classification and grading system of esophagitis of the Japanese Society of Esophagitis (JSDE), modified in 1999 [1].&#x0D; Results. Correlation analysis of the relationship between ghrelin and leptin indicators showed a reliable, inverse, medium strength dependence (r = -0.5531; p&lt;0.05). Reliable maximum values of ghrelin were found in patients with non-erosive form of GERD, and minimum values of ghrelin were recorded in patients with reflux esophagitis stage C. When studying leptin indicators depending on the degree of esophagitis, the following data were obtained: the maximum values of leptin were found in patients with reflux - stage B esophagitis, and minimal - in patients with a non-erosive form of GERD. Regarding the reliability of the obtained data on leptin concentration, we did not find statistically significant differences in the studied groups (p&gt;0.05).&#x0D; Conclusions. According to the results of the conducted research, we can say that changes in the concentration of ghrelin have an important diagnostic value in the focus of GERD against the background of type 2 diabetes. Decreased ghrelin levels have been associated with erosive forms of GERD in the setting of type 2 diabetes, which can lead to a significant deterioration in the patient's lifestyle. According to the data obtained during the study on the influence of leptin levels on changes in the mucous membrane of the esophagus, it was found that morphological changes in the esophagus did not depend on the concentration of leptin in the studied groups

Ghrelin inhibits myocardial pyroptosis in diabetic cardiomyopathy by regulating ERS and NLRP3 inflammasome crosstalk through the PI3K/AKT pathway

Aims Endoplasmic reticulum stress(ERS) can induce inflammation mediated by NLRP3 inflammatory bodies and link inflammation with oxidative stress in myocardial tissue. Ghrelin is an endogenous growth hormone-releasing peptide that has been proven to have multiple effects, such as regulating energy metabolism and inhibiting inflammation. However, the role of ghrelin in myocardial injury in diabetic rats and the mechanism have not been reported. Results We found that ghrelin could improve endoplasmic reticulum stress and inflammatory pyroptosis in the myocardial tissue of diabetic rats and reduce ERS and NLRP3 inflammasome crosstalk in H9C2 cardiomyocytes. Interestingly, ghrelin could activate the PI3K/AKT signalling pathway, playing a role in inhibiting endoplasmic reticulum stress and reducing the expression of pyroptosis-related proteins. However, these protective effects could be largely eliminated by LY294002. Conclusions In summary, we demonstrated that ghrelin inhibited myocardial pyroptosis in diabetic cardiomyopathy by regulating ERS and NLRP3 inflammasome crosstalk through the PI3K/AKT pathway. Our results provide new insights into the mechanism of diabetic myocardial injury induced by high glucose and high palmitic acid and ghrelin-mediated anti-inflammatory protection and provide potential therapeutic targets and strategies for diabetic cardiomyopathy.

Ghrelin is related to lower brain reward activation during touch.

The gut hormone ghrelin drives food motivation and increases food intake, but it is also involved in the anticipation of and response to rewards other than food. This pre-registered study investigated how naturally varying ghrelin concentrations affect the processing of touch as a social reward in humans. Sixty-seven volunteers received slow caressing touch (so-called CT-targeted touch) as a social reward and control touch on their shins during 3T functional imaging on two test days. On one occasion, participants were fasted, and on another, they received a meal. On each occasion, plasma ghrelin was measured at three time points. All touch was rated as more pleasant after the meal, but there was no association between ghrelin concentrations and pleasantness. CT-targeted touch was rated as the most pleasant and activated somatosensory and reward networks (whole brain). A region-of-interest in the right medial orbitofrontal cortex (mOFC) showed lower activation during all touches, the higher the ghrelin concentrations were. During CT-targeted touch, a larger satiety response (ghrelin decrease after the meal) was associated with higher mOFC activation, and this mOFC activation was associated with higher experienced pleasantness. Overall, higher ghrelin concentrations appear to be related to a lower reward value for touch. Ghrelin may reduce the value of social stimuli, such as touch, to promote food search and intake in a state of low energy. This suggests that the role of ghrelin goes beyond assigning value to food reward.

Role and molecular mechanism of ghrelin in degenerative musculoskeletal disorders.

Ghrelin is a brain-gut peptide, and the first 28-peptide that was found in the gastric mucosa. It has a growth hormone (GH)-releasing hormone-like effect and can potently promote the release of GH from pituitary GH cells; however, it is unable to stimulate GH synthesis. Therefore, ghrelin is believed to play a role in promoting bone growth and development. The correlation between ghrelin and some degenerative diseases of the musculoskeletal system has been reported recently, and ghrelin may be one of the factors influencing degenerative pathologies, such as osteoporosis, osteoarthritis, sarcopenia and intervertebral disc degeneration. With population ageing, the risk of health problems caused by degenerative diseases of the musculoskeletal system gradually increases. In this article, the roles of ghrelin in musculoskeletal disorders are summarized to reveal the potential effects of ghrelin as a key target in the treatment of related bone and muscle diseases and the need for further research.

Ghrelin is hungry hormone

The article provides data on the history of creation, study of the functions and role of the "hunger hormone" ghrelin in the human body and animals The regulatory effect of ghrelin on formation is described in detail appetite and eating behavior, the amount of its content in the blood under different conditions. Establishing the role of ghrelin in physiological processes is an important discovery. Actuality of theme. New data appear every year on the role of ghrelin in various processes. The conducted research is relevant and up-to-date. Main part. The role of ghrelin in conditions of chronic stress and depression, dysfunction is shown hypothalamus and obesity. Ghrelin is one of the main regulators of appetite and eating behavior. It plays an important role in the regulation of biochemical processes related to digestion, mainly by influencing the synthesis of various enzymes. The hormone is a powerful stimulator of gastric secretion and motility of the organs of the digestive system, including the gallbladder, which prevents bile stagnation and improves the function of other organs and systems. The work of scientists has opened another direction of the properties of ghrelin regarding its effect on the psyche. It becomes clear why some people who are in a state of stress or depression begin to overeat. According to the authors, ghrelin coordinates the body's overall behavioral response to stress and affects mood, stress and the level of energy consumption by the body. Conclusions. Therefore, ghrelin plays an essential role in the functioning of many organs and body systems. As an orexigenic hormone, it is one of the most important regulators of appetite and eating behavior, the level of which depends on the nature and mode of nutrition. Activating neurons of the hypothalamus leads to a positive energy balance due to stimulation of food consumption and increased utilization of fat

A new ghrelin receptor antagonist agrelax participates in the control of emotional-explorative behavior and anxiety in rats

BACKGROUND: Currently, no study has investigated on the role of ghrelin in the reinforcing system and emotional behavior. Previously, we examined the properties of GHSR1A antagonist [D-Lys3]-GHRP-6 to reduce negative emotional states caused by stress.&#x0D; AIM: To study the involvement of a new peptide antagonist of the GHSR1A receptor agrelax in the control of emotionalexploratory behavior and anxiety in rats.&#x0D; MATERIALS AND METHODS: Experiments were performed on 42 male Wistar rats. The behavior of rats was observed; agrelax 1 g/mL (or water) with a volume of 20 L (10 l in each nostril) was administered intranasally. A battery of behavioral tests was used: an elevated plus maze, an open field, a marble test, an intruderresident test, and an anxiety-phobic state assessment (FS).&#x0D; RESULTS: In the elevated plus maze test, the time spent in the light arm and the number of hangings from the open arm increased in the test animals compared with animals that did not receive the drug (p 0.05). After the administration of agrelax, the number of balloons buried and the number of elevations supported by the wall of the chamber in the marble test decreased compared with that in animals that did not receive the drug (p 0.05). In the open field, agrelax-infected rats showed a decrease in the number of sniffs (p 0.01). In the FS test after the agrelax administration, the time of descent from the platform decreased compared with the control (p 0.05). In the intruderresident test, individual behavior (p 0.01) and protective behavior (p 0.05) decreased after agrelax administration.&#x0D; CONCLUSION: A new peptide antagonist of the GHSR1A receptor agrelax is involved in the control of emotionalexploratory behavior in rats. Agrelax reduced anxiety levels and exploratory activity. The results provide grounds for the development of new approaches to the treatment of phobic spectrum disorders using drugs that modulate ghrelin regulation.

Roles of Ghrelin and Leptin in Body Mass Regulation under Food Restriction Based on the AMPK Pathway in the Red-Backed Vole, Eothenomys miletus, from Kunming and Dali Regions.

The phenotype plasticity of animals' physiological characteristics is an important survival strategy to cope with environmental changes, especially the change in climate factors. Small mammals that inhabit seasonally changing environments often face the stress of food shortage in winter. This study measured and compared the thermogenic characteristics and related physiological indicators in the adenosine-5'-monophosphate-activated protein kinase (AMPK) pathway in Eothenomys miletus between Kunming (KM, n = 18) and Dali (DL, n = 18) under food restriction and refeeding. The results showed that food restriction and the region have significant effects on body mass, the resting metabolic rate (RMR), hypothalamic neuropeptide gene expression, ghrelin levels in the stomach and serum, serum leptin level and the activity of AMPK, and malonyl CoA and carnitine palmitoyltransferase 1 (CPT-1) activity. Food restriction reduced the body mass, the gene expression of neuropeptide proopiomelanocortin (POMC), cocaine- and amphetamine-regulated transcription peptide (CART), and leptin level. However, the ghrelin concentration and AMPK activity increased. After refeeding, there was no difference in these physiological indexes between the food restriction and control groups. Moreover, the physiological indicators also showed regional differences, such as the body mass, POMC and CART gene expression, ghrelin concentration in the stomach and serum, and AMPK activity in DL changed more significantly. All these results showed that food restriction reduces energy metabolism in E. miletus. After refeeding, most of the relevant physiological indicators can return to the control level, indicating that E. miletus has strong phenotypic plasticity. Ghrelin, leptin, and the AMPK pathway play an important role in the energy metabolism of E. miletus under food restriction. Moreover, regional differences in physiological indicators under food restriction may be related to the different temperatures or food resources in different regions.

Plasma Concentrations of Gut Hormones Acyl Ghrelin and Peptide YY and Subsequent Risk of Colorectal Cancer and Molecular Tumor Subtypes.

The findings of this study do not support a major role for the metabolic gut hormones ghrelin and PYY in colorectal cancer development but suggest the possibility of an involvement for ghrelin in specific tumor subtypes. Elucidating subtype-specific risk factors and mechanisms of carcinogenesis may have implications for precision prevention.

Circulating ghrelin changes as a biomarker of the stress response and craving in abstinent smokers

RationaleThere has been growing interest in the role of ghrelin in stress and addiction. Ghrelin regulates central reward mechanisms by mediating the mesolimbic dopaminergic system. Stress also induces neurophysiological activations related to drug reward. However, the extent to which psychosocial stress is associated with changes in ghrelin levels has not been tested in individuals with nicotine dependency undergoing withdrawal, a condition known to induce stress-like symptoms. ObjectivesWe investigated the association of stress-induced ghrelin, craving, and smoking lapse. MethodsThirty-six smokers attended a laboratory session that included acute stress tasks during the initial phase of quitting. Self-report measures and biochemical samples were collected for the assessment of smoking status. Blood samples for the measurement of ghrelin and self-report measures of craving were collected multiple times throughout the session ResultsMultivariate analysis of variance controlling for gender found a significant main effect of sampling time and lapse group (p < 0.05). Ghrelin levels significantly increased over the pre-stress and post-stress periods (ps < 0.001), suggesting a delayed stress response. Those who lapsed during the study had higher ghrelin levels than those who were able to successfully abstain. A ghrelin stress response was calculated and a significant association was found between this response and craving, which changed across time points (ps < 0.008). ConclusionsThe results of this study demonstrate that ghrelin is sensitive to acute manipulation of stress and that there is potential usefulness for ghrelin as a marker of stress, craving, and smoking lapse.

Effects of Short-term Fasting on Ghrelin/GH/IGF-1 Axis in Healthy Humans: The Role of Ghrelin in the Thrifty Phenotype.

A greater decrease in 24-hour energy expenditure (24hEE) during short-term fasting is indicative of a thrifty phenotype. As ghrelin and the growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis are implicated in the regulation of energy intake and metabolism, we investigated whether ghrelin, GH, and IGF-1 concentrations mediate the fasting-induced decrease in 24hEE that characterizes thriftiness. In 47 healthy individuals, 24hEE was measured in a whole-room indirect calorimeter both during 24-hour eucaloric and fasting conditions. Plasma total ghrelin, GH, and IGF-1 concentrations were measured by enzyme-linked immunosorbent assay after an overnight fast the morning before and after each 24-hour session. During 24-hour fasting, on average 24hEE decreased by 8.0% (P < .001), GH increased by ~5-fold (P < .001), whereas ghrelin (mean +23 pg/mL) and IGF-1 were unchanged (both P ≥ .19) despite a large interindividual variability in ghrelin change (SD 150 pg/mL). Greater fasting-induced increase in ghrelin was associated with a greater decrease in 24hEE during 24-hour fasting (r = -0.42, P = .003), such that individuals who increased ghrelin by 200 pg/mL showed an average decrease in 24hEE by 55 kcal/day. Short-term fasting induced selective changes in the ghrelin/GH/IGF-1 axis, specifically a ghrelin-independent GH hypersecretion that did not translate into increased IGF-1 concentrations. Greater increase in ghrelin after 24-hour fasting was associated with greater decrease in 24hEE, indicating ghrelin as a novel biomarker of increased energy efficiency of the thrifty phenotype.

1425-P: Effect of Ghrelin on Glucose Tolerance after Sleeve Gastrectomy

Introduction: Ghrelin is an appetite-stimulating peptide hormone secreted from the gastric mucosa in the fasting state that decreases in response to food intake. After sleeve gastrectomy (SG) , plasma levels of ghrelin decrease dramatically, whether this may influence glucose tolerance is unknown. We therefore investigated the effects of physiological ghrelin infusions on glucose tolerance in individuals with obesity before and after SG. Methods: Nine morbidly obese individuals with normal glucose tolerance, scheduled for SG, were enrolled. Four-hour standard mixed-meal tests with concomitant patient-blinded infusions of either acyl-ghrelin (1 pmol/kg/min) or placebo (saline) were performed in randomized order before and 3 months after surgery. All values are mean ± SEM. Results: Before SG, fasting plasma glucose was unaffected by ghrelin infusion, whereas both peak (7.93 ± 0.3 mmol/L versus 6.98 ± 0.2, p&amp;lt;0.001) and total area under the curve (tAUC) of plasma glucose concentrations (1874 ± 61 mmol/L*min versus 1702 ± 42, p=0.03) increased significantly during ghrelin infusion versus placebo. After SG, fasting plasma glucose was again unaffected by ghrelin infusion, whereas peak of plasma glucose increased (8.65 ± 0.5 mmol/L versus 7.92 ± 0.3 mmol/L, p=0.04) and tAUC of plasma glucose tended to increase (1817 ± 73 mmol/L*min versus 1636 ± 44 mmol/l*min, p=0.054) during ghrelin infusions versus placebo. The increase in tAUC during ghrelin infusion versus placebo was 10% before surgery and 11% after SG (p=0.98) . Conclusion: Ghrelin infusions increased postprandial plasma glucose concentrations in obese individuals both before and following SG, suggesting a role of ghrelin in the regulation of postprandial glucose metabolism. This response appears to be maintained following SG and the low levels of ghrelin after SG may thus contribute to the improved glucose control after the operation. Disclosure N.Hedbäck: None. S.Madsbad: None. M.Dichman: None. C.Dirksen: None. K.N.Bojsen-moller: None. N.B.Jørgensen: Advisory Panel; Novo Nordisk A/S, Research Support; Boehringer Ingelheim International GmbH, Speaker's Bureau; Novo Nordisk A/S, Stock/Shareholder; Eli Lilly and Company, Novo Nordisk A/S. M.G.Hindsø: Research Support; Novo Nordisk Foundation. V.B.Kristiansen: None. J.J.Holst: Advisory Panel; Novo Nordisk, Board Member; Antag Therapeutics, Bainan Biotech. M.S.Svane: None. Funding European Research Council (Grant 695069-BYPASSWITHOUTSURGERY) Novo Nordisk Foundation

Energetic demands of lactation produce an increase in the expression of growth hormone secretagogue receptor in the hypothalamus and ventral tegmental area of the rat despite a reduction in circulating ghrelin.

Lactating rats show changes in the secretion of hormones and brain signals that promote hyperphagia and facilitate the production of milk. Little is known, however, about the role of ghrelin in the mechanisms sustaining lactational hyperphagia. Here, we used Wistar female rats that underwent surgery to sever the galactophores to prevent milk delivery (GC rats) and decrease the energetic drain of milk delivery. We compared plasma acyl-ghrelin concentrations and growth hormone secretagogue receptor (GHSR) mRNA expression in different brain regions of GC rats with those of sham operated lactating and nonlactating rats. Additional lactating and nonlactating rats were implanted with cannulae aimed at the lateral ventricles and were used to compare feeding responses to central ghrelin or GHSR antagonist infusions to those of nonlactating rats receiving similar infusions on day 14-16 postpartum (pp). Results show lower plasma acyl-ghrelin concentrations on day 15 pp sham operated lactating rats compared to GC or nonlactating rats. These changes occur in association with increased GHSR mRNA expression in the hypothalamic arcuate nucleus (ARC) and ventral tegmental area (VTA) of sham operated lactating rats. Despite lactational hyperphagia, infusions of ghrelin (0.25 or 1μg) resulted in similar increases in food intake in lactating and nonlactating rats. In addition, infusions of the GHSR antagonist JMV3002 (4μg in 1μl of vehicle) produced greater suppression of food intake in lactating rats than in nonlactating rats. These data suggest that, despite lower plasma ghrelin, the energetic drain of lactation increases sensitivity to the orexigenic effects of ghrelin in brain regions important for food intake and energy balance, and these events are associated with lactational hyperphagia.

Perivascular Adipose Tissue Inflammation: The Anti-Inflammatory Role of Ghrelin in Atherosclerosis Progression

Perivascular adipose tissue (PVAT) and its adipokines engage in bidirectional crosstalk with the vascular wall. Atherosclerosis disrupts this interaction through inflammation, rupture-prone plaques, and subsequent thrombosis. The cardioprotective effects of ghrelin are in contradiction to its adipogenic properties. The concurrent research of anti-/pro-atherogenic mechanisms of ghrelin and PVAT-derived adipokines provides a better understanding of atherosclerosis progression in metabolic disorders. In-depth coverage of the characteristic features of PVAT concerning vascular dysfunction, with a survey of ghrelin-induced anti-inflammatory effects on adipose tissue macrophage infiltration and the inhibitory activity of ghrelin on the proinflammatory adipokine secretion, show that the impact of ghrelin on the endothelial function should be studied in relation to PVAT.

The role of ghrelin and leptin in feeding behavior: Genetic and molecular evidence

Feeding behavior is integrated within a wide variety of eating behaviors, which depend on psychosocial, biological and environmental factors. These types of behavior can cause nutrition-related diseases such as obesity, which affects more than 650 million people worldwide. Ghrelin and leptin are key hormones that regulate appetite, food intake and energy metabolism. Research in genetics suggests that genetic variants of both hormones are associated with complex forms of eating behavior, such as a preference for palatable food, making individuals susceptible to the modern obesogenic environment. This review analyses the scientific evidence around polymorphisms in the ghrelin and leptin genes and their association with eating behavior. The understanding of these mechanisms is relevant since it could impact on the objectives of pharmacological or behavioral interventions for their treatment.

Ghrelin Gene Deletion Alters Pulsatile Growth Hormone Secretion in Adult Female Mice.

Using preproghrelin-deficient mice (Ghrl-/-), we previously observed that preproghrelin modulates pulsatile growth hormone (GH) secretion in post-pubertal male mice. However, the role of ghrelin and its derived peptides in the regulation of growth parameters or feeding in females is unknown. We measured pulsatile GH secretion, growth, metabolic parameters and feeding behavior in adult Ghrl-/- and Ghrl+/+ male and female mice. We also assessed GH release from pituitary explants and hypothalamic growth hormone-releasing hormone (GHRH) expression and immunoreactivity. Body weight and body fat mass, linear growth, spontaneous food intake and food intake following a 48-h fast, GH pituitary contents and GH release from pituitary explants ex vivo, fasting glucose and glucose tolerance were not different among adult Ghrl-/- and Ghrl+/+ male or female mice. In vivo, pulsatile GH secretion was decreased, while approximate entropy, that quantified orderliness of secretion, was increased in adult Ghrl-/- females only, defining more irregular GH pattern. The number of neurons immunoreactive for GHRH visualized in the hypothalamic arcuate nucleus was increased in adult Ghrl-/- females, as compared to Ghrl+/+ females, whereas the expression of GHRH was not different amongst groups. Thus, these results point to sex-specific effects of preproghrelin gene deletion on pulsatile GH secretion, but not feeding, growth or metabolic parameters, in adult mice.

Leptin, ghrelin, & insulin levels and food intake in premenstrual syndrome: A case-control study

ObjectivesThe objective of this study was to evaluate the relationship between food intake and serum levels of leptin and ghrelin in the luteal (LP) and follicular (FP) phases of the MC (menstrual cycle) in participants with and without PMS (premenstrual syndrome). MethodsThis was a case-control study with healthy participants aged 20–45 years with regular menstrual cycles (24–35 days) with and without PMS. After the Daily Record of Severity of Problems (DRSP) was filled out for two months (PMS diagnosis), a nutritional assessment was carried out based on twelve food intake records (for two menstrual cycles) to quantify food intake. Results: Of the 69 participants analyzed, 35 experienced PMS and 34 did not experience PMS. For participants with PMS, calorie and carbohydrate intake was higher during LP than in FP (p = 0.004 and p = 0.003, respectively), whereas these changes were not observed in participants without PMS (p > 0.05). There were interactions between the groups and the MC phases (LP and FP) for the intake of calories (p = 0.028) and carbohydrates (p = 0.001). There was a marginal negative relationship between the levels of ghrelin and calorie intake in FP (rS = −0.314, p = 0.066) in the PMS group and a negative relationship between the levels of ghrelin and leptin in LP (rS = −0.490, p = 0.004) in the group without PMS. ConclusionsThese results indicated a higher calorie and carbohydrate intake during LP in participants with PMS, in addition to the hypothesis that the roles of ghrelin and leptin in energy regulation may be different in participants with PMS compared to those without PMS.