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Oxidative damage to human retinal pigment epithelial (RPE) cells is the main cause of age-related macular degeneration (AMD), in our previous work, we showed that ghrelin has an antioxidative effect on human lens epithelium (HLE) cells, however, the studies of using ghrelin in treating the degenerative diseases of the retina have rarely been reported. In this article, we assessed the effect of ghrelin on preventing oxidative stress induced by hydrogen peroxide (H2O2) in ARPE-19 cells and its mechanism. We observed that pretreatment with ghrelin protected ARPE-19 cells from H2O2-induced cell oxidative injuries and apoptosis responses. Furthermore, an oxidative stress-induced mouse model of AMD was established via injection of sodium iodate (NaIO3) to tail veins, and treatment with ghrelin preserved retinal function, and protected photoreceptors. Highlights: The first to report ghrelin' protective effect on H2O2-induced RPE cells. Treatment with ghrelin inhibits NaIO3-induced retinal cell apoptosis in vivo. Combined with in vitro and in vivo experiments, the results are comprehensive and reliable. [ABSTRACT FROM AUTHOR]

Background: To investigate the protective effect and mechanism of Ghrelin on Doxorubicin (Dox) hydrochloride induced heart failure (HF) and myocardial injury in rats. Methods: 45 rats were randomly divided into control group, HF group and Ghrelin group. Dox hydrochloride was injected intraperitoneally to establish the model of HF in rats of HF group and Ghrelin group. Rats in the Ghrelin group were given intraperitoneal injection of Ghrelin twice a day, and rats in the HF group and control group were given equal volume of normal saline for a total of 6 weeks. The changes of echocardiography, cardiac hemodynamics, myocardial histology and plasma inflammatory factors were observed. Results: After the Ghrelin intervention, compared with the HF group, the left ventricular end-diastolic diameter (LVDD) and left ventricular end-systolic diameter (LVSD) in the Ghrelin group was markedly reduced (P < 0.05), and left ventricular ejection fraction (LVEF) was significantly increased (P < 0.05). Compared with HF group, the left ventricular systolic pressure (LVSP), maximum rate of increase in left ventricular pressure (+ dP/dtmax) and maximum rate of decrease in left ventricular pressure (− dP/dtmax) of Ghrelin group was remarkedly increased (P < 0.05), left ventricular diastolic pressure (LVDP) decreased (P < 0.05). In the Ghrelin group, the degree and extent of cardiomyocyte degeneration and necrosis were remarkedly reduced compared with the HF group. The levels of TNF-α and iNOS in Ghrelin group were notably lower than those in HF group (P < 0.05), the IL-10 level increased markedly (P < 0.05). Conclusion: Ghrelin may reduce Dox-induced myocardial injury and improve cardiac function in rats by regulating inflammation and oxidative stress. [ABSTRACT FROM AUTHOR]

Objective This study was designed to compare basal concentrations of the gastrointestinal appetite modulators ghrelin, peptide tyrosine tyrosine (PYY), and glucagon-like peptide 1 (GLP-1) between obesity classes and obesity classes and controls. Methods The study included 49 healthy controls with body mass index (BMI) between 18.5 and 29.9 kg/m² and 62 individuals with obesity with BMI ≥30 kg/m². Basal ghrelin, PYY, and GLP-1 concentrations of the samples were analyzed by an enzyme-linked immunosorbent assay commercial kit (SunRed Human). Other biochemical parameters were measured by a clinical chemistry autoanalyzer (Beckman Coulter AU 5800) in the biochemistry laboratory. Results Compared with the control group, ghrelin, PYY, and GLP-1 levels were significantly lower in the obese group (P <.05). The PYY concentration was significantly different between obese groups (P <.05). The PYY and GLP-1 levels were significantly different between obesity class I and obesity class III. In addition, ghrelin levels were significantly different between obesity class II and obesity class III. Correlation analysis revealed a negative correlation between BMI and serum ghrelin, GLP-1, and PYY concentrations. Conclusion Low basal ghrelin, GLP-1, and PYY hormones in the obese group compared with the control group indicate impaired appetite regulation in this population. The significant difference in PYY levels between obese groups was associated with increasing obesity grade. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to explore how dietary macronutrient composition influences postprandial appetite hormone responses and subsequent energy intake. Methods: A total of 20 adults (mean [SEM], age 30 [1] years, BMI 27.8 [1.3] kg/m2, n = 8 with normal weight, n = 6 with overweight, n = 6 with obesity) consumed a low‐fat (LF) diet (10% fat, 75% carbohydrate) and a low‐carbohydrate (LC) diet (10% carbohydrate, 75% fat) for 2 weeks each in an inpatient randomized crossover design. At the end of each diet, participants consumed isocaloric macronutrient‐representative breakfast test meals, and 6‐h postprandial responses were measured. Ad libitum energy intake was measured for the rest of the day. Results: The LC meal resulted in greater mean postprandial plasma active glucagon‐like peptide‐1 (GLP‐1; LC: 6.44 [0.78] pg/mL, LF: 2.46 [0.26] pg/mL; p < 0.0001), total glucose‐dependent insulinotropic polypeptide (GIP; LC: 578 [60] pg/mL, LF: 319 [37] pg/mL; p = 0.0004), and peptide YY (PYY; LC: 65.6 [5.6] pg/mL, LF: 50.7 [3.8] pg/mL; p = 0.02), whereas total ghrelin (LC: 184 [25] pg/mL, LF: 261 [47] pg/mL; p = 0.0009), active ghrelin (LC: 91 [9] pg/mL, LF: 232 [28] pg/mL; p < 0.0001), and leptin (LC: 26.9 [6.5] ng/mL, LF: 35.2 [7.5] ng/mL; p = 0.01) were lower compared with LF. Participants ate more during LC at lunch (244 [85] kcal; p = 0.01) and dinner (193 [86] kcal; p = 0.04), increasing total subsequent energy intake for the day compared with LF (551 [103] kcal; p < 0.0001). Conclusions: In the short term, endogenous gut‐derived appetite hormones do not necessarily determine ad libitum energy intake. [ABSTRACT FROM AUTHOR]

Background: Cancer cachexia is characterized by the loss of body weight (BW) and anorexia. Anamorelin (ANAM) is a selective ghrelin receptor agonist with appetite-enhancing anabolic action. The ONO-7643-05 trial demonstrated that ANAM increased lean body mass and improved anorexia in a Japanese population. However, the clinical outcomes of patients on ANAM have not yet been reported. Patients and methods: We investigated the clinical outcomes of patients with unresectable, advanced, or recurrent gastrointestinal cancer (colorectal, gastric, or pancreatic cancer) who were treated with ANAM between April 2017 and August 2022. Cachexia was defined as the presence of anorexia and a loss of ≥ 5% of BW within 6 months. To evaluate the response to ANAM, the patients who had discontinued ANAM within 3 weeks were excluded. Response to ANAM was defined as maintenance of or increase in BW and improved appetite from baseline at every 3-week evaluation. We also collected data on the reasons for the discontinuation of ANAM and the correlation between clinical factors and ANAM response. Safety analysis of ANAM was performed for all patients who received ANAM. Results: Seventy-four patients were included in this study (49 males and 25 females), with a median age of 67.1 years (range, 36–83). The primary tumors were colorectal cancer in 27 (36.5%), gastric cancer in 20 (27.0%), and pancreatic cancer in 27 (36.5%). The Eastern Cooperative Oncology Group performance status was 0 in 10 (13.5%), 1 in 44 (59.5%), and ≥ 2 in 20 (27.0%). The number of previous chemotherapy regimens was 0 in 20 (27.0%), 1 in 22 (29.7%), and ≥ 2 in 32 (43.2%). ANAM was discontinued within 3 weeks in 28 patients for the following reasons: low-grade (grade 1 or 2) adverse events in 15 patients, ileus in three, grade 3 fatigue in one, progressive disease in one, censored follow-up in six, and unknown reasons in three. The proportion of ANAM responders was 63.6% (95% confidence interval, 47.8–77.6%). Among baseline characteristics, age ≥ 75 attenuated the ANAM response (p = 0.03). ANAM responders showed better disease control with chemotherapy than non-responders (75.0% vs. 37.5%, p = 0.02). Conclusions: ANAM may improve the outcomes of patients with gastrointestinal cancer cachexia in clinical practice. [ABSTRACT FROM AUTHOR]

Background: Thyroid storm (TS), a life-threatening condition that can damage multiple organs, has limited therapeutic options. Hypercytokinemia is a suggested background, but the pathological condition is unclear and there are no appropriate animal models. We aimed to develop a TS mouse model by administration of triiodothyronine and lipopolysaccharide, and then to examine the effects of ghrelin on this model. Methods: We evaluated the use of serum IL-6 levels as a representative marker of hypercytokinemia in patients with TS. To establish the mouse model, preliminary experiments were conducted to determine the non-lethal doses of triiodothyronine and lipopolysaccharide when administered individually. As a TS model, C57BL/6 mice were administered with triiodothyronine 1.0 mg/kg (subcutaneously, once daily for seven consecutive days) and lipopolysaccharide 0.5 mg/kg (intraperitoneally, on day 7) to develop a lethal model with approximately 30% survival on day 8. We assessed the survival ratio, mouse sepsis scores and blood biomarkers (IL-6, metanephrine, alanine aminotransferase) and evaluated the effects of ghrelin 300 µg/kg on these parameters in TS model. Results: Serum IL-6 was increased in patients with TS compared with those with Graves' disease as the diseased control (18.2 vs. 2.85 pg/mL, P <.05, n = 4 each). The dosage for the murine TS model was triiodothyronine 1.0 mg/kg and lipopolysaccharide 0.5 mg/kg. The TS model group had increased mouse sepsis score, serum IL-6, metanephrine and alanine aminotransferase. In this model, the ghrelin improved the survival rate to 66.7% (P <.01, vs. 0% [saline-treated group]) as well as the mouse sepsis score, and it decreased the serum IL-6 and metanephrine. Conclusion: We established an animal model of TS that exhibits pathophysiological states similar to human TS with induction of serum IL-6 and other biomarkers by administration of T3 and LPS. The results suggest the potential effectiveness of ghrelin for TS in humans. [ABSTRACT FROM AUTHOR]

Ingestible electronics have the capacity to transform our ability to effectively diagnose and potentially treat a broad set of conditions. Current applications could be significantly enhanced by addressing poor electrode-tissue contact, lack of navigation, short dwell time, and limited battery life. Here we report the development of an ingestible, battery-free, and tissue-adhering robotic interface (IngRI) for non-invasive and chronic electrostimulation of the gut, which addresses challenges associated with contact, navigation, retention, and powering (C-N-R-P) faced by existing ingestibles. We show that near-field inductive coupling operating near 13.56 MHz was sufficient to power and modulate the IngRI to deliver therapeutically relevant electrostimulation, which can be further enhanced by a bio-inspired, hydrogel-enabled adhesive interface. In swine models, we demonstrated the electrical interaction of IngRI with the gastric mucosa by recording conductive signaling from the subcutaneous space. We further observed changes in plasma ghrelin levels, the "hunger hormone," while IngRI was activated in vivo, demonstrating its clinical potential in regulating appetite and treating other endocrine conditions. The results of this study suggest that concepts inspired by soft and wireless skin-interfacing electronic devices can be applied to ingestible electronics with potential clinical applications for evaluating and treating gastrointestinal conditions. Existing ingestible electronics suffer from poor tissue contact, short dwell time, and limited battery life. Here, the authors report an ingestible, battery- free, and tissue-adhering robotic interface for non-invasive and chronic electrostimulation of the gut. [ABSTRACT FROM AUTHOR]

Exercise training is a valuable tool for improving body weight and composition in overweight or obese adults, which leads to a negative energy balance. It is relevant to consider whether exercise can help people lose weight or prevent weight gain because any energy expended in exercise increases the severity of hunger and promotes food consumption. Over the past decade, the identification of the circulating peptide ghrelin, which alerts the brain to the body's nutritional state, has significantly expanded our understanding of this homeostatic mechanism that controls appetite and body weight. To shed more light on this issue, we decided to investigate the effects of resistance and endurance training on plasma ghrelin and leptin levels. In addition, we sought to understand the mechanisms by which acute and chronic exercise can regulate hunger. This review analyzes studies published in the last fifteen years that focused on changes suffered by ghrelin, leptin, or both after physical exercise in overweight or obese individuals. Most studies have shown a decrease in leptin levels and an increase in ghrelin levels in these cases. Exercise regimens that support weight maintenance need further investigation. [ABSTRACT FROM AUTHOR]

Obesity, a global health challenge, necessitates innovative approaches for effective management. Targeting gut peptides in the development of anti‐obesity pharmaceuticals has already demonstrated significant efficacy. Ghrelin, peptide YY (PYY), cholecystokinin (CCK), and amylin are crucial in appetite regulation offering promising targets for pharmacological interventions in obesity treatment using both peptide‐based and small molecule‐based pharmaceuticals. Ghrelin, a sole orexigenic gut peptide, has a potential for anti‐obesity therapies through various approaches, including endogenous ghrelin neutralization, ghrelin receptor antagonists, ghrelin O‐acyltransferase, and functional inhibitors. Anorexigenic gut peptides, peptide YY, cholecystokinin, and amylin, have exhibited appetite‐reducing effects in animal models and humans. Overcoming substantial obstacles is imperative for translating these findings into clinically effective pharmaceuticals. Peptide YY and cholecystokinin analogues, characterized by prolonged half‐life and resistance to proteolytic enzymes, present viable options. Positive allosteric modulators emerge as a novel approach for modulating the cholecystokinin pathway. Amylin is currently the most promising, with both amylin analogues and dual amylin and calcitonin receptor agonists (DACRAs) progressing to advanced stages of clinical trials. Despite persistent challenges, innovative pharmaceutical strategies provide a glimpse into the future of anti‐obesity therapies. [ABSTRACT FROM AUTHOR]

Background: Diabetes mellitus (DM) presents impediment to wound healing. While ultraviolet B (UVB) exposure showed therapeutic potential in various skin conditions, its capacity to mediate diabetic wound healing remains unclear. To investigate the efficacy of UVB on wound healing and its underlying basis. Materials and Methods: Male C57BL/6 mice were subjected to the high‐fat diet followed by streptozotocin administration to establish the diabetic model. Upon confirmation of diabetes, full‐thickness wounds were inflicted and the treatment group received UVB radiation at 50 mJ/cm2 for 5 min every alternate day for 2 weeks. Wound healing rate was then assessed, accompanied by evaluations of blood glucose, lipid profiles, CD31 expression, and concentrations of ghrelin and leptin. Concurrently, in vitro studies were executed to evaluate the protective role of ghrelin on human umbilical vein endothelial cells (HUVEC) under high glucose (HG) conditions. Results: Post UVB exposure, there was a marked acceleration in wound healing in DM mice without alterations in hyperglycemia and lipid profiles. Compared to non‐UVB‐exposed mice, the UVB group showed enhanced angiogenesis manifested by a surge in CD31 expression. This trend appeared to be in harmony with the elevated ghrelin levels. In vitro experiments indicated that ghrelin significantly enhanced the migratory pace and angiogenic properties of HUVEC under HG‐induced stress, potentially mediated by an upregulation in vascular endothelial growth factor expression. Conclusion: UVB exposure bolstered wound healing in diabetic mice, plausibly mediated through augmented angiogenesis induced by ghrelin secretion. Such findings underscore the vast potential of UVB‐induced ghrelin in therapeutic strategies targeting diabetic wound healing. [ABSTRACT FROM AUTHOR]

Background: The source of rikkunshito (RKT) is thought to be Yixuezhengzhuan by Yu Tuan. RKT was originally designed for many patients to treat gastrointestinal symptoms such as abdominal bloating, discomfort, nausea, and anorexia. Key Findings: RKT consists of eight types of crude drugs. Clinical studies including randomized clinical trials (RCT) for patients with non‐erosive reflux disease (NERD) refractory to proton‐pump inhibitor (PPI) have demonstrated that RKT improves not only acid‐related dysmotility symptoms, but also extra‐esophageal symptoms, and with RCT trial for functional dyspepsia (FD), RKT can simultaneously treat gastrointestinal and psychological symptoms. Moreover, RKT was recently applied to the day‐to‐day conditions, post‐operative management, and chemotherapy in cancer patients. Preclinical studies have also reported that various pharmacological functions of RKT such as its protective effect on mucosal injuries and its prokinetic effect on gastrointestinal tract motility have been elucidated. RKT was considered to increase plasma ghrelin levels by the inhibition of 5‐HT2B and 5‐HT2C receptor activities, enhanced ghrelin‐mediated signaling, inhibited degradation of acylated ghrelin to suppress decreases in plasma ghrelin levels by inhibiting the rate of degradation of acyl ghrelin to des‐acyl ghrelin, and inhibited PDE III activity. The incidence of adverse events associated with RKT was only 1.2%, and almost all adverse drug reactions were non‐serious reactions. Conclusion: RKT is one of the very good candidates for beneficial medicines especially for patients presenting with intractable symptoms caused by gastrointestinal diseases such as disorders of gut–brain interaction or cancers. [ABSTRACT FROM AUTHOR]

Objectives: This study investigates the roles of HIF-2α, hepcidin, and ghrelin in iron deficiency anemia (IDA), the most widespread nutritional disorder globally. Material and methods: Fifty IDA patients (18–50 years, BMI 19–25) and 40 healthy volunteers were studied. Hemoglobin, ferritin, hepcidin, HIF-2α, and ghrelin levels were analyzed. Results: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

Background: Energy allocation between growth and reproduction determines puberty onset and fertility. In mammals, peripheral hormones such as leptin, insulin and ghrelin signal metabolic information to the higher centres controlling gonadotrophin-releasing hormone neurone activity. However, these observations could not be confirmed in lower vertebrates, suggesting that other factors may mediate the energetic trade-off between growth and reproduction. A bioinformatic and experimental study suggested co-regulation of the circadian clock, reproductive axis and growth-regulating genes in zebrafish. While loss-of-function of most of the identified co-regulated genes had no effect or only had mild effects on reproduction, no such information existed about the co-regulated somatostatin, well-known for its actions on growth and metabolism. Results: We show that somatostatin signalling is pivotal in regulating fecundity and metabolism. Knock-out of zebrafish somatostatin 1.1 (sst1.1) and somatostatin 1.2 (sst1.2) caused a 20–30% increase in embryonic primordial germ cells, and sst1.2−/− adults laid 40% more eggs than their wild-type siblings. The sst1.1−/− and sst1.2−/− mutants had divergent metabolic phenotypes: the former had 25% more pancreatic α-cells, were hyperglycaemic and glucose intolerant, and had increased adipocyte mass; the latter had 25% more pancreatic β-cells, improved glucose clearance and reduced adipocyte mass. Conclusions: We conclude that somatostatin signalling regulates energy metabolism and fecundity through anti-proliferative and modulatory actions on primordial germ cells, pancreatic insulin and glucagon cells and the hypothalamus. The ancient origin of the somatostatin system suggests it could act as a switch linking metabolism and reproduction across vertebrates. The results raise the possibility of applications in human and animal fertility. [ABSTRACT FROM AUTHOR]

Background: Apoprotein A-I (ApoA-I) and Apoprotein B (ApoB) have emerged as novel cardiovascular risk biomarkers influenced by feeding behavior. Hypothalamic appetite peptides regulate feeding behavior and impact lipoprotein levels, which effects vary in different weight states. This study explores the intricate relationship between body mass index (BMI), hypothalamic appetite peptides, and apolipoproteins with emphasis on the moderating role of body weight in the association between neuropeptide Y (NPY), ghrelin, orexin A (OXA), oxytocin in cerebrospinal fluid (CSF) and peripheral ApoA-I and ApoB. Methods: In this cross-sectional study, we included participants with a mean age of 31.77 ± 10.25 years, categorized into a normal weight (NW) (n = 73) and an overweight/obese (OW/OB) (n = 117) group based on BMI. NPY, ghrelin, OXA, and oxytocin levels in CSF were measured. Results: In the NW group, peripheral ApoA-I levels were higher, while ApoB levels were lower than in the OW/OB group (all p < 0.05). CSF NPY exhibited a positive correlation with peripheral ApoA-I in the NW group (r = 0.39, p = 0.001). Notably, participants with higher CSF NPY levels had higher peripheral ApoA-I levels in the NW group and lower peripheral ApoA-I levels in the OW/OB group, showing the significant moderating effect of BMI on this association (R2 = 0.144, β=-0.54, p < 0.001). The correlation between ghrelin, OXA and oxytocin in CSF and peripheral ApoB in both groups exhibited opposing trends (Ghrelin: r = -0.03 and r = 0.04; OXA: r = 0.23 and r=-0.01; Oxytocin: r=-0.09 and r = 0.04). Conclusion: This study provides hitherto undocumented evidence that BMI moderates the relationship between CSF NPY and peripheral ApoA-I levels. It also reveals the protective role of NPY in the NW population, contrasting with its risk factor role in the OW/OB population, which was associated with the at-risk for cardiovascular disease. [ABSTRACT FROM AUTHOR]

Objective: Ghrelin is an orexigenic peptide that becomes post-translationally modified. Natural autoantibodies to ghrelin (ghrelin-aAb) have been described in healthy subjects, in eating disorders and rheumatic diseases, with potential clinical relevance. Despite these important reports, the data base on the prevalence and physiological role is small and technical approaches for assessing ghrelin-aAb are few, encouraging respective research for improving knowledge on the potential endocrine significance. Methods: A novel immunoprecipitation assay was generated based on a fusion protein of human ghrelin with a reporter gene. Assay quality was verified with commercial antibodies. Assay characteristics and matrix effects were determined, including stability of natural ghrelin-aAb to freezing, signal linearity in dilution experiments, and comparison of different matrices. Three groups of serum samples were analyzed for ghrelin-aAb, comprising commercial sera from healthy subjects and patients with type 1 or type 2 diabetes mellitus. Results: The newly generated ghrelin-aAb assay proved sensitive, robust and reliable over a broad concentration range. Results from serum and plasma differed slightly. The signals from serum remained stable towards freezing and thawing, and in dilution experiments. Applying a mathematical criterion for outliers (P75 + 1.5-times IQR), an average prevalence of 11%–12% of positive samples was identified in the different human cohorts, with no significant sexor disease-related difference. General significance: A novel diagnostic autoantibody assay detected ghrelinaAb with a similar prevalence in diabetic patients and controls, suggesting that autoimmunity to ghrelin plays little role in diabetes mellitus, but may be of relevance in other diseases where ghrelin signaling is essential. [ABSTRACT FROM AUTHOR]

In this analysis, we aimed to investigate the effect of COVID-19 disease on eating behavior. A total of 55 right-handed adults, <50 years of age, without overweight or obesity, from two cross-sectional studies were included. The first one enrolled subjects between September 2018 and December 2019 (non-COVID-19 group). The second one included subjects enrolled between March 2022 and May 2023; for this analysis, 28 with a history of COVID-19 (COVID-19 group) were retained. Hunger, TFEQ-18, plasma ghrelin, neuropeptide Y (NPY) and resting-state fMRI were assessed during fasting. Intraregional neuronal synchronicity and connectivity were assessed by voxel-based regional homogeneity (ReHo) and degree of centrality (DC). Significantly higher ghrelin and NPY levels were observed in the COVID-19 group than in the non-COVID-19 group (ghrelin 197.5 pg/mL vs. 67.1 pg/mL, p < 0.001; NPY 128.0 pg/mL vs. 84.5 pg/mL, p = 0.005). The NPY levels positively correlated with the DC and ReHo in the left lingual (r = 0.67785 and r = 0.73604, respectively). Similar scores were noted for cognitive restraint, uncontrolled eating and emotional eating in both groups according to the TFEQ-18 questionnaire results (p > 0.05 for all). Our data showed increased levels of appetite-related hormones, correlated with activity in brain regions involved in appetite regulation, persisting long after COVID-19 infection. [ABSTRACT FROM AUTHOR]

Background: Anxiety disorders are one of the most common mental disorders. Ghrelin is a critical orexigenic brain-gut peptide that regulates food intake and metabolism. Recently, the ghrelin system has attracted more attention for its crucial roles in psychiatric disorders, including depression and anxiety. However, the underlying neural mechanisms involved have not been fully investigated. Methods: In the present study, the effect and underlying mechanism of ghrelin signaling in the nucleus accumbens (NAc) core on anxiety-like behaviors were examined in normal and acute stress rats, by using immunofluorescence, qRT-PCR, neuropharmacology, molecular manipulation and behavioral tests. Results: We reported that injection of ghrelin into the NAc core caused significant anxiolytic effects. Ghrelin receptor growth hormone secretagogue receptor (GHSR) is highly localized and expressed in the NAc core neurons. Antagonism of GHSR blocked the ghrelin-induced anxiolytic effects. Moreover, molecular knockdown of GHSR induced anxiogenic effects. Furthermore, injection of ghrelin or overexpression of GHSR in the NAc core reduced acute restraint stress-induced anxiogenic effects. Conclusions: This study demonstrates that ghrelin and its receptor GHSR in the NAc core are actively involved in modulating anxiety induced by acute stress, and raises an opportunity to treat anxiety disorders by targeting ghrelin signaling system. [ABSTRACT FROM AUTHOR]

Aim: The study aim was to determine and compare daytime/night-time differences of serum melatonin, leptin and ghrelin in women with metabolic syndrome in their division by groups based on homeostasis model assessment of insulin resistance (HOMA-IR). Material and methods: 57 women with metabolic syndrome were studied: 30 with HOMA-IR ≥ 2.5 and 27 with HOMA-IR < 2.5. In all women measurements of waist circumference took place and indices of body mass and HOMA-IR were calculated. Venous blood was collected at 03:00 and 08:00 to determine the melatonin, leptin and ghrelin levels. Routine hematological and biochemistry parameters and insulin were studied from the blood collected at 08:00. Results: At 03:00 women with HOMA-IR ≥ 2.5 had higher melatonin (P = 0.023) and leptin (p = 0.050) and lower ghrelin (p = 0.014). At 08:00 both groups did not differ in their values of melatonin, leptin and ghrelin (p < 0.05). Women with HOMA-IR ≥ 2.5 have a smaller night-time/daytime difference of melatonin compared to women with HOMA-IR < 2.5 (6.53 ± 11.28 pg/ml vs 54.43 ± 15.76 pg/ml, р = 0.0151). The two groups did not differ in night-time/daytime difference of leptin (р = 0.0557) and ghrelin (Р = 0.0686). In the women with HOMA-IR < 2.5 ghrelin measured at 03:00 is higher than 08:00 (р = 0.006); no difference between the daytime and night-time values of melatonin (р = 0.069) and leptin (R = 0.496) is present. In the woman with HOMA-IR ≥ 2.5 no differences between the daytime and night-time concentrations of studied parameters is present. Conclusion: In women with metabolic syndrome and proven insulin resistance the daytime/night-time rhythm of secretion of melatonin and ghrelin is impaired. The established non-significant difference between the daytime and nigh-time leptin suggests that adipose tissue is not the only determiner of serum leptin concentration. In women without laboratory data of insulin resistance, a reversed daytime/night-time rhythm of melatonin is present, while the secretion of ghrelin and leptin is close to physiological secretion, with an underlined daytime/night-time rhythm of ghrelin and lack of a similar rhythm in leptin. In a practical aspect, not only the one-time measured concentration of these hormones but also the rhythm of their secretion should be considered. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) comprises subtypes with distinct symptom profiles. For example, patients with melancholic and atypical MDD differ in the direction of appetite and body weight changes as well as mood reactivity. Despite reported links to altered energy metabolism, the role of circulating neuropeptides from the gut in modulating such symptoms remains largely elusive. We collected data from 103 participants, including 52 patients with MDD and 51 healthy control participants (HCP). After an overnight fast, we measured plasma levels of (acyl and des-acyl) ghrelin and participants reported their current metabolic and mood states using visual analog scales (VAS). Furthermore, they completed symptom-related questionnaires (i.e., STAI-T). Patients with atypical versus melancholic MDD reported less negative affect (p = 0.025). Higher levels of acyl ghrelin (corrected for BMI) were associated with improved mood (p = 0.012), specifically in patients with MDD. These associations of ghrelin were not mood-item specific and exceeded correlations with trait markers of negative affectivity. In contrast to associations with mood state, higher levels of ghrelin were not associated with increased hunger per se or changes in appetite in patients with MDD. The study is limited by the cross-sectional design without an intervention. Our results reveal potentially mood-enhancing effects of ghrelin in fasting individuals that exceed associations with metabolic state ratings. These associations with circulating neuropeptides might help explain anti-depressive effects of fasting interventions and could complement conventional treatments in patients with melancholic MDD. [Display omitted] • Gut hormones have the potential to modulate mood and appetite disturbances. • Acyl ghrelin is associated with an elevated mood state, specifically in depression. • Acyl ghrelin is associated with a general mood factor rather than specific items. • Acyl ghrelin is more strongly associated with state (vs trait) negative affect. • Ghrelin might help explain anti-depressive effects of fasting interventions. [ABSTRACT FROM AUTHOR]

Background: The commercial availability of anamorelin, Japan's first therapeutic agent for cancer cachexia in 2021, led to an investigation into its prescription patterns at Toyama University Hospital. Objective: We aimed to analyze anamorelin prescription trends and outcomes among cancer cachexia patients. Methods: A retrospective study from July 2021 to December 2022 examined 88 cases, assessing demographics, cancer types, prescription locations, and meal intake changes. Results: Anamorelin usage was predominant during chemotherapy, especially for pancreatic cancer in outpatient settings. Approximately 30% experienced increased meal intake. Chemotherapy-initiated cases had a longer median duration (55 days) compared with best supportive care only cases (12 days). Conclusion: Anamorelin demonstrated significant prescription patterns, particularly during chemotherapy for pancreatic cancer in outpatient settings, suggesting potential efficacy enhancements when administered with chemotherapy in cancer cachexia management. The study underscores the importance of tailored approaches to optimize anamorelin's therapeutic benefits. [ABSTRACT FROM AUTHOR]

Background: Sleep can be affected in patients with chronic spontaneous urticaria (CSU). The mechanisms of sleep regulation remain poorly understood. Orexin-A, a neuroexcitatory peptide, plays a role in coordinating sleep-wake states. Ghrelin and leptin are involved in sleep regulation through the orexin system. Objective: The effects of orexin-A, ghrelin, and leptin on sleep quality in patients with CSU have not been investigated. We aimed to determine the effects of CSU on sleep quality and the association between serum orexin-A, ghrelin, and leptin levels, and sleep quality in patients with CSU. Methods: Thirty-three patients with CSU and 34 sex- and age-matched controls were included in the study. Serum orexin-A, leptin, and ghrelin levels, and the Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale (ESS) scores were measured in patients with CSU and in the controls; also used were the chronic urticaria quality-of-life questionnaire score and the urticaria activity score used for 7 consecutive days. Results: Median (minimum-maximum) orexin-A, leptin, and ghrelin levels in patients were 385 pg/mL (90–495 pg/mL), 3.1 ng/mL (0–21.2 ng/mL), and 701.8 pg/mL (101.9–827.7 pg/mL), respectively. Median serum orexin-A and leptin levels were higher in the patients compared with the controls (p < 0.001 and p = 0.012, respectively), whereas the median serum ghrelin levels were similar to the controls (p = 0.616). The serum orexin-A level was positively correlated with ghrelin (r = 0.298, p = 0.014), PSQI sleep quality (r = 0.356, p = 0.003), and ESS (r = 0.357, p = 0.003). Conclusion: Serum orexin-A is associated with sleep quality in patients with CSU. Further studies are needed to elucidate the role of ghrelin and leptin on sleep quality in patients with CSU. [ABSTRACT FROM AUTHOR]

The growth hormone secretagogue receptor (GHSR), primarily known as the receptor for the hunger hormone ghrelin, potently controls food intake, yet the specific Ghsr-expressing cells mediating the orexigenic effects of this receptor remain incompletely characterized. Since Ghsr is expressed in gamma-aminobutyric acid (GABA)–producing neurons, we sought to investigate whether the selective expression of Ghsr in a subset of GABA neurons is sufficient to mediate GHSR's effects on feeding. First, we crossed mice that express a tamoxifen-dependent Cre recombinase in the subset of GABA neurons that express glutamic acid decarboxylase 2 (Gad2) enzyme (Gad2-CreER mice) with reporter mice, and found that ghrelin mainly targets a subset of Gad2 -expressing neurons located in the hypothalamic arcuate nucleus (ARH) and that is predominantly segregated from Agouti-related protein (AgRP)–expressing neurons. Analysis of various single-cell RNA-sequencing datasets further corroborated that the primary subset of cells coexpressing Gad2 and Ghsr in the mouse brain are non-AgRP ARH neurons. Next, we crossed Gad2-CreER mice with reactivable GHSR-deficient mice to generate mice expressing Ghsr only in Gad2 -expressing neurons (Gad2-GHSR mice). We found that ghrelin treatment induced the expression of the marker of transcriptional activation c-Fos in the ARH of Gad2-GHSR mice, yet failed to induce food intake. In contrast, food deprivation–induced refeeding was higher in Gad2-GHSR mice than in GHSR-deficient mice and similar to wild-type mice, suggesting that ghrelin-independent roles of GHSR in a subset of GABA neurons is sufficient for eliciting full compensatory hyperphagia in mice. [ABSTRACT FROM AUTHOR]

The effect of dietary macronutrients on fasting and postprandial responses was examined. Thirty-six healthy dogs were fed a high-carbohydrate (HiCHO) food once daily for 5 weeks, followed by randomization to either a high-protein, low-carbohydrate (PROT_LoCHO) or high-fat, low-carbohydrate (FAT_LoCHO) food for 5 weeks, then crossed over to the other LoCHO food for 5 weeks. Plasma samples were obtained at the end of each feeding period at timepoints before (0 h) and 2 h post-feeding. Apparent total circulating energy availability was assessed as a summation of the energetic contributions of measured glucose, β-hydroxybutyrate, triglycerides (TGs), non-esterified fatty acids (NEFAs), and fatty acids not from TGs or NEFAs. In both the fed and fasted states, there were increases in circulating apparent total energy availability after feeding the FAT_LoCHO food compared with the HiCHO or PROT_LoCHO foods. Changes from the postabsorptive to postprandial points in catabolic, anabolic, and signaling lipids all exhibited food effects. Consumption of either LoCHO food led to lower leptin/ghrelin ratios in the fasted state relative to the HiCHO food. The FAT_LoCHO food led to the highest postprandial levels of the incretins gastric inhibitory peptide and glucagon-like peptide-1, yet the lowest increases in insulin relative to the other foods. These findings provide information on how macronutrients can influence dietary energy processing and metabolic health. [ABSTRACT FROM AUTHOR]

Background and Objectives: In this study, the effects of a six-week training program and various diets on subfatin, asprosin, irisin, leptin, ghrelin and the lipid profile were investigated in overweight women. Materials and Methods: A total of 78 women voluntarily participated in the study. Groups: The study was divided into eight groups: Healthy Control, Obese Control, Obese + Vegetarian, Obese + Ketogenic, Obese + Intermittent Fasting, Obese + Exercise + Vegetarian, Obese + Exercise + Ketogenic and Obese + Exercise + Intermittent Fasting. While there was no intervention in the healthy and obese control groups, the other groups followed predetermined exercise and diet programs for 6 weeks. Blood samples were taken from the participants in the research group twice (before and after the interventions). An autoanalyzer was used to determine the lipid profile in the blood samples taken, and the ELISA method was used to analyze other parameters. Results: Overall, a significant difference was found in the values of weight, BMI, subfatin, ghrelin, leptin, cholesterol, triglyceride, HDL and LDL as a result of the exercise and diet interventions (p < 0.05). There was no significant difference in asprosin and irisin values (p > 0.05). Conclusions: In conclusion, regular exercise and dietary interventions in obese women can regulate lipid profile, ghrelin, leptin and asprosin levels, and increasing irisin with exercise can activate lipid metabolism and support positive changes in lean mass. [ABSTRACT FROM AUTHOR]

Abstract Oxidative damage to human retinal pigment epithelial (RPE) cells is the main cause of age-related macular degeneration (AMD), in our previous work, we showed that ghrelin has an antioxidative effect on human lens epithelium (HLE) cells, however, the studies of using ghrelin in treating the degenerative diseases of the retina have rarely been reported. In this article, we assessed the effect of ghrelin on preventing oxidative stress induced by hydrogen peroxide (H2O2) in ARPE-19 cells and its mechanism. We observed that pretreatment with ghrelin protected ARPE-19 cells from H2O2-induced cell oxidative injuries and apoptosis responses. Furthermore, an oxidative stress-induced mouse model of AMD was established via injection of sodium iodate (NaIO3) to tail veins, and treatment with ghrelin preserved retinal function, and protected photoreceptors.

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.

Abstract Background Anxiety disorders are one of the most common mental disorders. Ghrelin is a critical orexigenic brain-gut peptide that regulates food intake and metabolism. Recently, the ghrelin system has attracted more attention for its crucial roles in psychiatric disorders, including depression and anxiety. However, the underlying neural mechanisms involved have not been fully investigated. Methods In the present study, the effect and underlying mechanism of ghrelin signaling in the nucleus accumbens (NAc) core on anxiety-like behaviors were examined in normal and acute stress rats, by using immunofluorescence, qRT-PCR, neuropharmacology, molecular manipulation and behavioral tests. Results We reported that injection of ghrelin into the NAc core caused significant anxiolytic effects. Ghrelin receptor growth hormone secretagogue receptor (GHSR) is highly localized and expressed in the NAc core neurons. Antagonism of GHSR blocked the ghrelin-induced anxiolytic effects. Moreover, molecular knockdown of GHSR induced anxiogenic effects. Furthermore, injection of ghrelin or overexpression of GHSR in the NAc core reduced acute restraint stress-induced anxiogenic effects. Conclusions This study demonstrates that ghrelin and its receptor GHSR in the NAc core are actively involved in modulating anxiety induced by acute stress, and raises an opportunity to treat anxiety disorders by targeting ghrelin signaling system.

Background: Chewing Khat (Catha edulis) releases cathine and cathinone, which may reduce appetite via an unknown mechanism. This study investigated the peripheral and central effects of fresh leaves and buds of Catha edulis water extract (CEWE) on appetite biomarkers, gene expression, and body weight, using in vivo, ex vivo, and in silico models. Methods: Rats of both sexes were orally administered CEWE at different doses and durations in three different experiments. Liquid chromatography-mass spectroscopy (LC-MS)-MS was used to detect cathinone and cathine in the murine blood. The effect of Khat on serotonin receptors was studied in isolated rat fundus samples. Docking of the two Khat ligands was performed on G (The 5-hydroxytryptamine-type 2C receptor (5-HT2C) in an agonist-bound active conformation) and H (5-HT2C in an antagonist-bound inactive conformation) proteins to determine which ligands are most likely to act as agonists or antagonists. Results: Significant differences (P < 0.05) in body weight were observed between the CEWE-treated groups and the controls over eight weeks. However, the plasma leptin and ghrelin levels did not change significantly (P > 0.05). The expression of the ghrelin and leptin genes was also unaffected, but the expression of the 5-hydroxytryptamine (5-HT) gene decreased (P < 0.05) with CEWE treatment. CEWE antagonizes 5-HT receptors in isolated rat fundus samples. Docking findings indicated that the khat ligands bound to 5-HT2C receptors. Cathine and cathinone levels in rat plasma were measured. Conclusion: Khat extract may suppress appetite by antagonizing the 5-HT receptors. Further research is required to understand its mechanism and potential applications. [ABSTRACT FROM AUTHOR]

Abstract Fetal alcohol spectrum disorders (FASD) are a severe developmental condition resulting from exposure to alcohol during pregnancy. The aim of this study was to examine the concentrations of hormones involved in appetite regulation—ghrelin, leptin, and putative peptide YY-3 (PYY)—in the serum of individuals with FASD. Additionally, we investigated the relationship between these hormone levels and clinical indicators. We conducted an enzyme-linked immunosorbent assay on samples collected from 62 FASD patients and 23 individuals without the condition. Our results revealed a significant decrease in leptin levels among FASD patients compared to the control group (5.124 vs. 6.838 ng/mL, p = 0.002). We revealed no statistically significant differences in the levels of other hormones studied (ghrelin and PYY). Comparisons of hormone levels were also conducted in three subgroups: FAS, neurobehavioral disorders associated with prenatal alcohol exposure and FASD risk, as well as by sex. Assignment to FASD subgroups indicated changes only for leptin. Sex had no effect on the levels of hormones. Moreover, the levels of leptin showed a negative correlation with cortisol levels and a positive correlation with BMI and proopiomelanocortin. Alterations in appetite regulation can contribute to the improper development of children with FASD, which might be another factor that should be taken into consideration in the proper treatment of patients.

Objective To study the effect of ghrelin gene knockout on the postsynaptic potential of dopaminergic neurons in the substantia nigra of mice. Methods Substantia nigra tissue was taken from 10-week-old ghrelin-/- male mice (ghrelin-/- group) and their male wild-type (WT) littermates (WT group). RNA-seq technique was used to screen differently expressed genes (DEGs). KEGG pathway enrichment analysis was performed for the neuronal synaptic activity-associated signaling pathways which DEGs might be involved in. Quantitative real-time PCR (RT-qPCR) was used for validation of the identified DEGs, and western blotting was used for protein expression of neuronal synaptic activity-related genes. Results Compared with the WT group, the ghrelin-/- group had significant changes in the expression levels of 23 genes in the synaptic signaling pathway of dopaminergic neurons. Specifically, Ionotropic glutamate receptors α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid type subunit 3 (GluA3) and glycogen synthase kinase3-β (GSK-3β) regulated α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor and N-methyl-D-aspartic acid receptor on the postsynaptic membrane of neurons, respectively. GluA3 and GSK-3β genes were significantly downregulated in the substantia nigra tissue of mice in the ghrelin-/- group. RT-qPCR results showed that compared to the WT group, the ghrelin-/- group had significant downregulation of the mRNA expression levels of GluA3 and GSK-3β in the substantia nigra tissue of mice (t =2.408,2.740,P

Introduction: The aim of our study was to investigate the effects of ghrelin receptor antagonist [D-Lys-3]-GHRP-6 on impulsivity and compulsivity in a model of gambling addiction in adult rats after maternal deprivation MD in early ontogenesis. Materials and Methods: The cubs were deprived of their mother daily for 3 h from days 2 to 12 postnatal. Adult Wistar rats were trained in a three-arm maze for 21 days. Two seeds were fed in arm 1 with reinforcement mode FR1. In arm 2, three seeds were presented with reinforcement mode FR2; in arms 3, 4 seeds were presented with reinforcement mode FR3 (i.e., only every 3rdrun to the feeder was reinforced with food). The animals were also examined to quantify their status of compulsive behavior in a marble test. The rat was placed in the cage with sawdust and glass beads for 30 min, after which, the number of balls covered with sawdust by more than 2/3 was counted. Results: In the MD group, the number of entrances to arm 3 increased 1.5-fold, indicating the selection of a larger reinforcement value at its low probability. The number of entrances to arm 1 (reward with high probability (100%) but with the lowest food reinforcement) decreased compared to the control group. The intranasal administration of the selective GHSR1A receptor antagonist [D-Lys (3)]-GHRP-6 (1 mg/mL) to animals MD led to significant (p

Abstract Background Laparoscopic sleeve gastrectomy combined with fundoplication (LSGFD) can significantly control body weight and achieve effective anti-reflux effects. The aim of this study is to investigate the correlation between the alteration in Ghrelin levels and weight loss following SGFD, and to compare Ghrelin levels, weight loss and metabolic improvements between SG and SGFD, with the objective of contributing to the existing body of knowledge on SGFD technique in the management of patients with obesity and gastroesophageal reflux disease (GERD). Methods A retrospective analysis was conducted on the clinical data of 115 obese patients who underwent bariatric surgery between March 2023 and June 2023 at the Department of Minimally Invasivew Surgery, Hernia and Abdominal Wall Surgery, People’s Hospital of Xinjiang Uygur Autonomous Region. The subjects were divided into two groups based on surgical methods: sleeve gastrectomy group (SG group, 93 cases) and sleeve gastrectomy combined with fundoplication group (SGFD group, 22 cases). Clinical data, such as ghrelin levels before and after the operation, were compared between the two groups, and the correlation between changes in ghrelin levels and weight loss effectiveness after the operation was analyzed. Results: Three months after the operation, there was no significant difference in body mass, BMI, EWL%, fasting blood glucose, triglyceride, cholesterol, and uric acid levels between the SG and SGFD groups (P > 0.05). However, the SGFD group exhibited a significant decrease in body weight, BMI, and uric acid levels compared to preoperative levels (P 0.05). Logistic regression analysis indicated that ghrelin levels three months after the operation were influential in postoperative weight loss. Conclusion The reduction of plasma Ghrelin level in patients after SGFD is not as obvious as that in patients after SG, but it can make obese patients get the same good weight loss and metabolic improvement as patients after SG. Ghrelin level at the third month after operation is the influencing factor of postoperative weight loss.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. DISCUSSION AND CONCLUSION: 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.

AIM: To observe the effect of ghrelin, a growth hormone-releasing peptide, on retinal angiogenesis in vitro under high glucose (HG) stress and to explore the possible mechanism of autophagy. METHODS: Human retinal microvascular endothelial cells (HRMECs) were treated with high concentration of glucose alone or in combination with ghrelin. The cell migration, tube formation and the expression of the autophagy-related proteins LC3-II/I, Beclin-1, p62, phosphorylated AKT (p-AKT)/AKT and phosphorylated mammalian target of rapamycin (p-mTOR)/mTOR were detected. Then, to clarify the correlation between ghrelin effect and autophagy, AKT inhibitor VIII was adopted to treat HRMECs, and cell migration, tube formation as well as the protein expressions of LC3-II/I, Beclin-1 and p62 were observed. RESULTS: Under HG stress, ghrelin inhibited migration and tube formation of HRMECs. Ghrelin inhibited the increases in the protein levels of LC3-II/I, Beclin-1 and the decreases in the protein levels of p62, p-AKT/AKT and p-mTOR/mTOR induced by HG stress. Moreover, under the action of AKT/mTOR pathway inhibitors, the effects of ghrelin on migration and tube formation were both reduced. In addition, the expression of LC3-II/I and Beclin-1 were significantly up-regulated and the expression of p62 was down-regulated. CONCLUSION: Retinal angiogenesis under in vitro HG stress can be inhibited by ghrelin through activating AKT/mTOR pathway to inhibit autophagy.

ABSTRACT: The purpose of this study was to investigate if consumption of a high-protein, low-carbohydrate breakfast (PRO) leads to a lower subsequent ad libitum energy intake at lunch and the rest of the day compared with ingestion of an isocaloric low-protein, high-carbohydrate breakfast (CHO) or no breakfast (CON). The study was designed as a randomized controlled 3-period crossover study. Thirty young (18–30 yr) females with overweight to obesity (body mass index >25 kg/m2) in random order completed 3 separate experimental days where they consumed either a PRO, CHO, or CON breakfast test meal followed by an ad libitum lunch meal 3 h after breakfast. Participants were allocated to a sequence group by their inclusion number. The PRO and CHO breakfasts were matched in dietary fiber and fat content. Energy intake at lunch was calculated and dietary records were obtained for the rest of the day to calculate the total daily energy intake and macronutrient intake. Ratings of appetite sensations between meals and palatability of the test meals were assessed using visual analog scale sheets in intervals ranging from 10 to 30 min. In addition, blood samples were obtained at multiple time points separated by 10 to 60 min intervals between breakfast and lunch and were analyzed for appetite-regulating gut hormones, insulin, and glucose. Finally, performance in a cognitive concentration test was tested 150 min after breakfast. Compared with CHO and CON, the area under the curves for satiety, fullness, and satisfaction in the 3 h after breakfast were significantly higher after PRO, whereas the areas under the curve for hunger, desire to eat, and prospective eating were significantly lower after PRO. The appetite-regulating gut hormones cholecystokinin, glucagon-like peptide-1, and ghrelin in the hours after breakfast, energy intake during the ad libitum lunch meal, and the total daily energy intake did not differ significantly between PRO, CHO, and CON. However, the cognitive concentration test score was 3.5 percentage points higher for PRO, but not CHO, versus CON. A dairy-based high-protein, low-carbohydrate breakfast increased satiety sensation in the hours after breakfast but did not reduce total daily energy intake compared with an isocaloric low-protein, high-carbohydrate breakfast or omitting breakfast. However, performance in a cognitive concentration test before lunch was enhanced after the high-protein, low-carbohydrate breakfast, but not the low-protein, high-carbohydrate breakfast, compared with omitting breakfast.

Obesity, which develops especially in childhood and adolescence, is an important health problem at all ages. Hormones that stimulate the hypothalamus about the body's energy stores prevent eating and keep body weight within certain physiological limits. Investigating obesity and the hormones associated with obesity is very important in this context. We believe that the functions of obesity-associated hormones that have been identified to date can guide further studies. In this review, obesity-related hormones and their mechanisms of action are discussed.

In this study, we investigated the effect of Capsaicin (CAP) on leptin and ghrelin expression in diabetic kidneys by immunohistochemical method. The subjects were separated into 5 groups: control, sham, diabetes, CAP, and D+CAP. Streptozotocin (45 mg/kg, single dose) was administered to each rat in the diabetes and D+CAP groups intraperitoneally. Rats with blood glucose levels of 200 mg/dL or higher were considered diabetic. Capsaicin (1 mg/kg) was administered subcutaneously to the rats in the CAP and D+CAP groups every day for 2 weeks. H&E, PAS, and Crossman"s Triple staining were performed to examine the histology of the kidney. Leptin and ghrelin in the kidney were examined by immunohistochemical method. Histological examination revealed normal kidney tissue in the control, sham, and CAP groups. The diabetes group showed the glomerulus with scattered and narrowing of the Bowman"s capsule. While leptin immunoreactivity was most intense in the diabetes group, it was observed the weakest in the CAP and D+CAP groups. While strong ghrelin immunoreactivity was seen in the control and sham groups, mild immunoreactivity was seen in the CAP group, and weak immunoreactivity was seen in the diabetes and D+CAP groups. In this study, we concluded that the application of CAP could prevent loss of appetite by reducing the leptin expression during diabetes, but could not protect ghrelin from adverse effects of diabetes.

Food intake behavior is under the tight control of the central nervous system. Most studies to date focus on the contribution of neurons to this behavior. However, although previously overlooked, astrocytes have recently been implicated to play a key role in feeding control. Most of the recent literature has focused on astrocytic contribution in the hypothalamus or the dorsal vagal complex. The contribution of astrocytes located in the lateral parabrachial nucleus (lPBN) to feeding behavior control remains poorly understood. Thus, here, we first investigated whether activation of lPBN astrocytes affects feeding behavior in male and female rats using chemogenetic activation. Astrocytic activation in the lPBN led to profound anorexia in both sexes, under both adlibitum feeding schedule and after a fasting challenge. Astrocytes have a key contribution to glutamate homeostasis and can themselves release glutamate. Moreover, lPBN glutamate signaling is a key contributor to potent anorexia, which can be induced by lPBN activation. Thus, here, we determined whether glutamate signaling is necessary for lPBN astrocyte activation-induced anorexia, and found that pharmacological N-methyl D-aspartate (NMDA) receptor blockade attenuated the food intake reduction resulting from lPBN astrocyte activation. Since astrocytes have been shown to contribute to feeding control by modulating the feeding effect of peripheral feeding signals, we further investigated whether lPBN astrocyte activation is capable of modulating the anorexic effect of the gut/brain hormone, glucagon like peptide -1, as well as the orexigenic effect of the stomach hormone - ghrelin, and found that the feeding effect of both signals is modulated by lPBN astrocytic activation. Lastly, we found that lPBN astrocyte activation-induced anorexia is affected by a diet-induced obesity challenge, in a sex-divergent manner. Collectively, current findings uncover a novel role for lPBN astrocytes in feeding behavior control. [ABSTRACT FROM AUTHOR]

Ischemia–reperfusion (IR) injury is primarily characterized by the restoration of blood flow perfusion and oxygen supply to ischemic tissue and organs, but it paradoxically leads to tissue injury aggravation. IR injury is a challenging pathophysiological process that is difficult to avoid clinically and frequently occurs during organ transplantation, surgery, shock resuscitation, and other processes. The major causes of IR injury include increased levels of free radicals, calcium overload, oxidative stress, and excessive inflammatory response. Ghrelin is a newly discovered brain‐intestinal peptide with anti‐inflammatory and antiapoptotic effects that improve blood supply. The role and mechanism of ghrelin in intestinal ischemia–reperfusion (IIR) injury remain unclear. We hypothesized that ghrelin could attenuate IIR‐induced oxidative stress and apoptosis. To investigate this, we established IIR by using a non‐invasive arterial clip to clamp the root of the superior mesenteric artery (SMA) in mice. Ghrelin was injected intraperitoneally at a dose of 50 μg/kg 20 min before IIR surgery, and [D‐Lys3]‐GHRP‐6 was injected intraperitoneally at a dose of 12 nmol/kg 20 min before ghrelin injection. We mimicked the IIR process with hypoxia‐reoxygenation (HR) in Caco‐2 cells, which are similar to intestinal epithelial cells in structure and biochemistry. Our results showed that ghrelin inhibited IIR/HR‐induced oxidative stress and apoptosis by activating GHSR‐1α. Moreover, it was found that ghrelin activated the GHSR‐1α/Sirt1/FOXO1 signaling pathway. We further inhibited Sirt1 and found that Sirt1 was critical for ghrelin‐mediated mitigation of IIR/HR injury. Overall, our data suggest that pretreatment with ghrelin reduces oxidative stress and apoptosis to attenuate IIR/HR injury by binding with GHSR‐1α to further activate Sirt1. [ABSTRACT FROM AUTHOR]

Liver-expressed antimicrobial peptide-2 (LEAP-2) has mutual antagonism with ghrelin, which evokes food intake under a freely fed state. Nevertheless, the impact of LEAP-2 on ghrelin under time-restricted feeding (TRF), which has benefits in the context of metabolic disease, is still unknown. This study aims to explore the impact of central administration of LEAP-2 on the ingestion behavior of rats, which was evaluated using their cumulative food intake in the TRF state. Before intracerebroventricular (ICV) administration of O-n-octanoylated ghrelin (0.1 nmol/rat), as a food-stimulatory model, the rats received various doses of LEAP-2 (0.3, 1, 3 nmol/rat, ICV). Cumulative food intake was recorded at 1, 2, 4, 8, 12, and 24 h after ICV injection under 12 h freely fed and TRF states in a light phase. In 12 h freely fed and TRF states, central administration of ghrelin alone induced feeding behavior. Pre-treatment with LEAP-2 (1 and 3 nmol/rat, ICV) suppressed ghrelin-induced food intake in a dose-dependent manner in a 12 h freely fed state instead of a TRF state, which may have disturbed the balance of ghrelin and LEAP-2. This study provides neuroendocrine-based evidence that may explain why TRF sometimes fails in fighting obesity/metabolic dysfunction-associated steatotic liver disease in clinics. [ABSTRACT FROM AUTHOR]

Background: Laparoscopic sleeve gastrectomy combined with fundoplication (LSGFD) can significantly control body weight and achieve effective anti-reflux effects. The aim of this study is to investigate the correlation between the alteration in Ghrelin levels and weight loss following SGFD, and to compare Ghrelin levels, weight loss and metabolic improvements between SG and SGFD, with the objective of contributing to the existing body of knowledge on SGFD technique in the management of patients with obesity and gastroesophageal reflux disease (GERD). Methods: A retrospective analysis was conducted on the clinical data of 115 obese patients who underwent bariatric surgery between March 2023 and June 2023 at the Department of Minimally Invasivew Surgery, Hernia and Abdominal Wall Surgery, People's Hospital of Xinjiang Uygur Autonomous Region. The subjects were divided into two groups based on surgical methods: sleeve gastrectomy group (SG group, 93 cases) and sleeve gastrectomy combined with fundoplication group (SGFD group, 22 cases). Clinical data, such as ghrelin levels before and after the operation, were compared between the two groups, and the correlation between changes in ghrelin levels and weight loss effectiveness after the operation was analyzed. Results: Three months after the operation, there was no significant difference in body mass, BMI, EWL%, fasting blood glucose, triglyceride, cholesterol, and uric acid levels between the SG and SGFD groups (P > 0.05). However, the SGFD group exhibited a significant decrease in body weight, BMI, and uric acid levels compared to preoperative levels (P < 0.05), while the decrease in ghrelin levels was not statistically significant (P > 0.05). Logistic regression analysis indicated that ghrelin levels three months after the operation were influential in postoperative weight loss. Conclusion: The reduction of plasma Ghrelin level in patients after SGFD is not as obvious as that in patients after SG, but it can make obese patients get the same good weight loss and metabolic improvement as patients after SG. Ghrelin level at the third month after operation is the influencing factor of postoperative weight loss. [ABSTRACT FROM AUTHOR]

Triacylglycerols (TAGs) are a major fat component in human milk. Since gastric lipase produces 1,2-diacylglycerol from TAGs, we focused on the bioactivity of human milk-derived diacylglycerols in stomach cells. Ghrelin is produced in the stomach and acts as an important regulator of growth hormone secretion and energy homeostasis. In this study, we showed that 1-oleoyl-2-palmitoylglycerol (OP) increased ghrelin secretion, whereas 1,3-dioleoyl-2-palmitoylglycerol (OPO), a major component of human milk TAGs, did not increase ghrelin secretion in the ghrelin-secreting cell line, MGN3-1. Therefore, diacylglycerol OP may directly contribute to the regulation of ghrelin secretion. We also found that 2-palmitoylglycerol and 1- and 2-oleoylglycerol increased ghrelin secretion. Finally, we demonstrated that intracellular cAMP levels and preproghrelin and ghrelin O-acyl transferase expression levels were enhanced by OP treatment in MGN3-1 cells. This may represent an example of a novel mother-infant interaction mediated by fat components derived from human breast milk. [ABSTRACT FROM AUTHOR]

Genome-wide association studies (GWAS) have successfully revealed numerous susceptibility loci for obesity. The PREDATORR study (2014) shows that in Romania, 346% of adults aged 20–79 y/o are overweight, and 31.4% are obese with a high risk of cardiometabolic complications, a number that puts almost 67% of Romania's population in the abnormal weight group. Our study aims to investigate the current status of the genetic foundation in metabolic disease associated with obesity, applied to a pilot group of patients specifically examining the impact of known polymorphisms and their haplotype of six food intake-regulating genes, namely leptin (LEP), leptin receptor (LEP-R), serotonin receptor (5HTR2A), ghrelin (GHRL), neuropeptide Y (NPY), and fat-mass and obesity-associated protein (FTO) with the following polymorphisms: LEP A-2548G, LEPR A-223G, 5HTR2A G-1439A, GHRL G-72T, NPY T-29063C, FTO A-T, and body mass index (BMI). A notable link between the LEP-2548 rs7799039 gene's AG genotype and the risk of obesity was observed, particularly pronounced in males aged 40–49, with an approximately seven-fold increased likelihood of obesity. The 5HTR2A rs6311 AA genotype was associated with a higher BMI, which was not statistically significant. The FTO rs9939609 gene's AA genotype emerged as a significant predictor of obesity risk. Besides these significant findings, no substantial associations were observed with the LEPR, 5HTR2A, GHRL, and NPY genes. Haplotype association analysis showed a suggestive indication of GRGMLA (rs7799039, rs1137101, rs6311, rs696217, rs16139, rs9939609 sequence) haplotype with a susceptibility effect towards obesity predisposition. Linkage disequilibrium (LD) analysis showed statistically significant associations between LEP and LEPR gene (p = 0.04), LEP and GHRL gene (p = 0.0047), and GHRL and FTO gene (p = 0.03). Our study, to the best of our knowledge, is one of the very few on the Romanian population, and aims to be a starting point for further research on the targeted interventional strategies to reduce cardiometabolic risks. [ABSTRACT FROM AUTHOR]

Unacylated ghrelin (UAG), the unacylated form of ghrelin, accounts for 80%–90% of its circulation. Accumulated studies have pointed out that UAG may be used to treat metabolic disorders. This study aimed to investigate the effect of intestinal perfusion of UAG on metabolically associated fatty liver disease (MAFLD) induced by a high-fat diet and its possible mechanisms. Neuronal retrograde tracking combined with immunofluorescence, central administration of a glucagon-like peptide-1 receptor (GLP-1R) antagonist, and hepatic vagotomy was performed to reveal its possible mechanism involving a central glucagon-like peptide-1 (GLP-1) pathway. The results showed that intestinal perfusion of UAG significantly reduced serum lipids, aminotransferases, and food intake in MAFLD rats. Steatosis and lipid accumulation in the liver were significantly alleviated, and lipid metabolism-related enzymes in the liver were regulated. UAG upregulated the expression of GLP-1 receptor (GLP-1R) in the paraventricular nucleus (PVN) and GLP-1 in the nucleus tractus solitarii (NTS), as well as activated GLP-1 neurons in the NTS. Furthermore, GLP-1 fibers projected from NTS to PVN were activated by the intestinal perfusion of UAG. However, hepatic vagotomy and GLP-1R antagonists delivered into PVN before intestinal perfusion of UAG partially attenuated its alleviation of MAFLD. In conclusion, intestinal perfusion of UAG showed a therapeutic effect on MAFLD, which might be related to its activation of the GLP-1 neuronal pathway from NTS to PVN. The present results provide a new strategy for the treatment of MAFLD. NEW & NOTEWORTHY: Intestinal perfusion of UAG, the unacylated form of ghrelin, has shown promising potential for treating MAFLD. This study unveils a potential mechanism involving the central GLP-1 pathway, with UAG upregulating GLP-1R expression and activating GLP-1 neurons in specific brain regions. These findings propose a novel therapeutic strategy for MAFLD treatment through UAG and its modulation of the GLP-1 neuronal pathway. [ABSTRACT FROM AUTHOR]

Exposure to high altitude might cause the body to adapt with negative energy and fluid balance that compromise body composition and physical performance. In this field study involving 12 healthy adults, sex-balanced, and aged 29 ± 4 years with a body mass index of 21.6 ± 1.8 kg/m2, we investigated the effects of a 4-day trekking up to 4556 m a.s.l. on Monte Rosa (Alps, Italy). The food intake was recorded using food diaries and nutrient averages were calculated. The bio-impedance analysis was performed at low and high altitudes, and a wearable biosensor (Swemax) was used to track hydro-saline losses in two participants. Daily total energy intake was 3348 ± 386 kcal for males and 2804 ± 415 kcal for females (13%–14% protein, 35% fat, 44%–46% carbohydrates). Although there was a significant body weight loss (65.0 ± 9.3 vs. 64.2 ± 9.10 kg, p < 0.001, d = 1.398), no significant changes in body composition parameter were found but a trend in the increase of the bioelectrical phase angle in males (p = 0.059, d = −0.991). Body water percentage significantly changed (p = 0.026, η2p = 0.440), but the absolute water did not, suggesting that the weight loss was not due to water loss. Salivary and urinary osmolality did not change. A reduction in sweat rate at higher altitudes was observed in both participants. Interestingly, salivary leptin increased (p = 0.014, η2p = 0.510), and salivary ghrelin decreased (p = 0.036, η2p = 0.403). Therefore, the 4-day trekking at altitude of hypoxia exposure induced changes in satiety and appetite hormones. High altitude expeditions require more specific nutritional guidance, and using multiplex analysis could help in monitoring fluid balance and body composition. [ABSTRACT FROM AUTHOR]