The pathogenesis of anorexia nervosa (AN) has been hypothesized to involve several biological systems. However, reliable biomarkers for AN have yet to be established. This study was aimed to identify statistically significant and clinically meaningful peripheral biomarkers associated with AN. A systematic literature search was conducted to identify studies published in English from inception until 30 June 2022. We conducted two-level random-effects meta-analyses to examine the difference between AN and comparison groups across 52 distinct biomarkers and found that acylated ghrelin, adrenocorticotropic hormone (ACTH), carboxy-terminal collagen crosslinks (CTX), cholesterol, cortisol, des-acyl ghrelin, ghrelin, growth hormone (GH), obestatin, and soluble leptin receptor levels were significantly higher in cases of AN compared with those in non-AN controls. Conversely, C-reactive protein (CRP), CD3 positive, CD8, creatinine, estradiol, follicle-stimulating hormone (FSH), free thyroxine, free triiodothyronine, glucose, insulin, insulin-like growth factor 1 (IGF-1), leptin, luteinizing hormone, lymphocyte, and prolactin levels were significantly lower in AN compared with those in non-AN controls. Our findings indicate that peripheral biomarkers may be linked to the pathophysiology of AN, such as processes of adaptation to starvation. Scientific investigation into peripheral biomarkers may ultimately yield breakthroughs in personalized clinical care for AN.

Atherosclerosis, a leading cause of peripheral artery disease (PAD), is driven by lipid accumulation and chronic inflammation within arterial walls. Objectives: This study investigates the expression of ghrelin, an anti-inflammatory peptide hormone, in plaque morphology and inflammation in patients with PAD, highlighting its potential role in age-related vascular diseases and metabolic syndrome. Methods: The analysis specifically focused on the immunohistochemical expression of ghrelin in atherosclerotic plaques and perivascular adipose tissue (PVAT) from 28 PAD patients. Detailed immunohistochemical staining was performed to identify ghrelin within these tissues, comparing its presence in various plaque types and assessing its association with markers of inflammation and macrophage polarization. Results: Significant results showed a higher prevalence of calcification in fibro-lipid plaques (63.1%) compared to fibrous plaques, with a notable difference in inflammatory infiltration between the two plaque types (p = 0.027). Complicated plaques exhibited increased ghrelin expression, suggesting a modulatory effect on inflammatory processes, although this did not reach statistical significance. The correlation between ghrelin levels and macrophage presence, especially the pro-inflammatory M1 phenotype, indicates ghrelin\'s involvement in the inflammatory dynamics of atherosclerosis. Conclusions: The findings propose that ghrelin may influence plaque stability and vascular inflammation, pointing to its therapeutic potential in managing atherosclerosis. The study underlines the necessity for further research to clarify ghrelin\'s impact on vascular health, particularly in the context of metabolic syndrome and age-related vascular alterations.

Mammalian hibernators survive prolonged periods of cold and resource scarcity by temporarily modulating normal physiological functions, but the mechanisms underlying these adaptations are poorly understood. The hibernation cycle of thirteen-lined ground squirrels (Ictidomys tridecemlineatus) lasts for 5-7 months and comprises weeks of hypometabolic, hypothermic torpor interspersed with 24-48-h periods of an active-like interbout arousal (IBA) state. We show that ground squirrels, who endure the entire hibernation season without food, have negligible hunger during IBAs. These squirrels exhibit reversible inhibition of the hypothalamic feeding center, such that hypothalamic arcuate nucleus neurons exhibit reduced sensitivity to the orexigenic and anorexigenic effects of ghrelin and leptin, respectively. However, hypothalamic infusion of thyroid hormone during an IBA is sufficient to rescue hibernation anorexia. Our results reveal that thyroid hormone deficiency underlies hibernation anorexia and demonstrate the functional flexibility of the hypothalamic feeding center.

BACKGROUND: Coffee consumption has demonstrated an effect on the regulation of appetite, causing less hunger and/or greater satiety; however, its effects are not well known in woman with overweight or obesity. Therefore, this study aimed to evaluate the effect of coffee consumption on hunger, satiety, sensory specific desire (SSD), and dietary intake in women with overweight or obesity.
METHODS: A randomized crossover clinical trial was realized in 3 sessions: in the first session a clinical history, anthropometric measurements and body composition analysis were performed; in sessions 2 and 3 the participants randomly consumed 240mL of coffee with 6mg/caffeine/kg of weight or 240mL of water along with a standardized breakfast. At fasting and every 30min after breakfast for the next 3h, appetite sensations and SSD were recorded using visual analog scales. Blood samples were taken at fasting, 30 and 180min after breakfast. Dietary intake was recorded in the rest of the intervention days.
RESULTS: In the coffee intervention there was an increased desire for sweet foods, higher fructose intake during the rest of the day, and higher triglyceride levels than with the water intervention. No differences were detected in ghrelin or cholecystokinin.
CONCLUSIONS: Coffee consumption may lead to higher triglycerides and higher intake of simple sugars, mainly fructose, through changes in the SSD.
BACKGROUND: https://clinicaltrials.gov/NCT05774119.

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.

Breast cancer (BC) is the most frequently diagnosed cancer and a leading cause of cancer-related mortality among women globally. Resistin, omentin and ghrelin, adipokines involved in inflammation and metabolic regulation, have been implicated in cancer development, yet their associations with BC remain unclear. This systematic review and meta-analysis aimed to elucidate the relationships between resistin, omentin, and ghrelin concentrations and BC, while exploring potential moderators such as body mass index (BMI) and menopausal status. A comprehensive search of electronic databases up to 13 May 2024 identified studies comparing resistin and omentin, but not ghrelin, concentrations in BC patients and healthy controls. Standardized mean differences (SMDs) were calculated using random-effects models, and meta-regression and subgroup analyses were performed to investigate sources of heterogeneity. Analysis of 11 studies showed that BC patients exhibited significantly higher resistin concentrations compared to controls, with a pooled SMD of 2.05 (95 % CI 1.24 to 2.86, p < 0.001). Meta-regression indicated that BMI significantly moderated the resistin-BC association (p = 0.003). In contrast, omentin concentrations presented a complex picture, with a pooled SMD of -0.27 (95 % CI -1.39 to 0.84, I^2 = 96.2 %, p < 0.001), indicating substantial heterogeneity and inconclusive results, whereas only one study investigated ghrelin. Our findings support a significant association between elevated resistin concentrations and BC, suggesting a potential role of resistin in BC pathophysiology. The data on omentin and ghrelin remain inconclusive, warranting further investigation. Future research should focus on large, longitudinal studies with standardized methodologies to validate these findings and clarify the role of adipokines in BC.

Longer-term pecan consumption has shown appetite-regulating effects as a part of a free-living diet, yet the physiologic appetite responses to a single pecan-containing meal are unclear. The purpose of this study was to compare the acute physiologic, subjective, and direct appetite responses of a pecan-containing meal to an energy- and macronutrient-matched control meal. This was an acute meal challenge study utilizing a double-blinded randomized crossover design with two periods. Participants were young, healthy adults (BMI: 22.9 ± 3.3 kg/m2, age: 22 ± 3 y) who consumed a meal containing either 68 g of pecans (PEC; 795 kcal) or an energy- and macronutrient-matched control meal (CON; 794 kcal) on separate testing days. At both testing visits, five postprandial blood draws, and visual analog scale (VAS) questionnaires (in-lab) were used to determine differences in peptide YY (PYY), ghrelin, and subjective appetite over a 4-h postprandial period. Participants also completed VAS questionnaires (at-home) and food records for the rest of the day after leaving the testing visits. Thirty-one out of thirty-two randomized participants completed the study. There was a greater overall postprandial PYY response (p < 0.001), and a greater suppression of postprandial ghrelin after time point 120 min (p < 0.001), with the PEC vs. CON meal. Further, there was a greater increase in subjective fullness (p = 0.001), and suppression of at-home overall appetite (p = 0.02), from time 240-780 min post-meal with PEC vs. CON meals. There were no differences in self-reported EI between meals or any other VAS measure. In conclusion, a pecan-containing breakfast shake produced more favorable physiologic and subjective improvements in appetite compared to an energy- and macronutrient-matched control meal. This trial is registered at clinicaltrials.gov (NCT05230212).

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.

The mechanisms contributing to alcohol use disorder (AUD) are complex and the orexigenic peptide ghrelin, which enhances alcohol reward, is implied as a crucial modulator. The major proportion of circulating ghrelin is however the non-octanoylated form of ghrelin, des-acyl ghrelin (DAG), whose role in reward processes is unknown. As recent studies show that DAG decreases food intake, we hypothesize that DAG attenuates alcohol-related responses in animal models. Acute and repeated DAG treatment dose-dependently decreased alcohol drinking in male and female rats. In these alcohol-consuming male rats, repeated DAG treatment causes higher levels of dopamine metabolites in the ventral tegmental area, an area central to reward processing. The role of DAG in reward processing is further supported as DAG prevents alcohol-induced locomotor stimulation, reward in the conditioned place preference paradigm, and dopamine release in the nucleus accumbens in male rodents. On the contrary, DAG does not alter the memory of alcohol reward or affect neurotransmission in the hippocampus, an area central to memory. Further, circulating DAG levels are positively correlated with alcohol drinking in female but not male rats. Studies were conducted in attempts to identify tentative targets of DAG, which currently are unknown. Data from these recombinant cell system revealed that DAG does not bind to either of the monoamine transporters, 5HT2A, CB1, or µ-opioid receptors. Collectively, our data show that DAG attenuates alcohol-related responses in rodents, an effect opposite to that of ghrelin, and contributes towards a deeper insight into behaviors regulated by the ghrelinergic signaling pathway.

OBJECTIVE: The aim of this study was to evaluate the relationship between levels of leptin, growth hormone (GH), and ghrelin in the bloodstream and fibromyalgia.
METHODS: We conducted a meta-analysis to compare the serum/plasma levels of leptin, GH, and ghrelin in individuals with fibromyalgia, as compared to healthy controls. The analysis included sixteen articles, which provided data from 697 fibromyalgia patients and 560 controls.
RESULTS: The meta-analysis found that there was no significant difference in leptin levels between fibromyalgia patients and controls overall (SMD = 0.324, 95% CI = -0.264 to 0.913, P = 0.281). However, when subgroup analysis was done based on geographically different populations, it showed a positive association between high leptin levels and fibromyalgia in European populations (SMD = 1.131, 95% CI = 0.197 to 2.064, P = 0.018), while no significant association was found in Latin American populations (SMD = -0.160, 95% CI = -0.847 to 0.528, P = 0.649). As for GH levels, there was no significant difference between fibromyalgia patients and controls overall (SMD = -0.903, 95% CI = -2.036 to 0.231, P = 0.119). However, when subgroup analysis was done based on geographically different populations, it revealed a significant decrease in GH levels in European populations with fibromyalgia (SMD = -2.341, 95% CI = -3.664 to -1.017, P = 0.001), while no significant association was found in North American populations. Lastly, the analysis of ghrelin levels showed no significant association with fibromyalgia overall (SMD = -0.661, 95% CI = -1.382 to 0.059, P = 0.072).
CONCLUSIONS: This meta-analysis shows that patients with fibromyalgia in Europeans have significantly higher levels of circulating leptin and GH. However, no significant association was found between ghrelin levels and fibromyalgia.