Ghrelin and obestatin, two antagonist peptide hormones, are purportedly involved in stimulating appetite and controlling energy balance in humans. Serum ghrelin level is also associated with iron deficiency anemia (IDA), but no study has yet been made of the obestatin level in patients with IDA, even though both hormones are a single gene product. Therefore, the purpose of this investigation is to see whether there is a link between IDA and these two hormones among other hematological parameters in patients with IDA. To measure ghrelin and obestatin, human saliva and serum were collected from 30 women with IDA, aged 31.7 ± 10.7 years, and 30 control women, aged 30.2 ± 8.0 years, with repeated collection of samples over a period of 1 week and 1 month. Saliva and serum ghrelin levels were measured by ELISA. Serum hemoglobin, ferritin, hematocrit and total iron-binding capacity (TIBC) values were determined with an Olympus AU2700. Saliva and serum ghrelin and obestatin levels were significantly lower in the IDA group compared with controls; these levels increased slightly above baseline with iron treatment, but remained below the control values. Furthermore, and as expected, serum hemoglobin, ferritin, and hematocrit levels were significantly increased with iron treatment, while total iron-binding capacity decreased compared to baseline concentrations. The findings suggest that IDA might be linked to imbalance of circulating (serum) and non-circulating (saliva) ghrelin and obestatin levels. Decreased ghrelin and obestatin might destroy iron homeostasis through its effect on intestinal absorption. Measuring these hormone levels might be useful for monitoring the response to iron treatment. Also, serum and saliva levels for both hormones were well correlated. Thus, using saliva in place of serum for monitoring the two hormones should minimize inconvenience and patient discomfort.

Depression is the most common chronic mental illness and is characterized by low mood, insomnia, and affective disorders. However, the pathological mechanisms of depression 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 the experimental animals, increasing depressed behavior and decreasing anxiety. By combining several neuropeptides and traditional neurotransmitter systems to construct neural networks, it modifies signals connected to depression. The present review emphasizes the role of ghrelin in neuritogenesis, astrocyte protection, inflammatory factor production, and endocrine disruption in depression. Furthermore, ghrelin/GHSR can activate multiple signaling pathways to produce antidepressant effects, including cAMP/CREB/BDNF, PI3K/Akt, Jak2/STAT3, and p38-MAPK. Given the antidepressant effects of ghrelin/GHSR1a system, it is expected to become a potential therapeutic target for the treatment of depression.

Background and Objectives: Since the protective role of ghrelin against high glucose-induced retinal damage was not yet explored, we aimed to investigate the serum levels of total ghrelin (TG), its acylated (AG) and des-acylated (DAG) forms in diabetic retinopathy (DR) patients. Moreover, the correlation between serum ghrelin and neutrophil elastase (NE) levels, enhancing the risk of microhemorrhages, was investigated; Materials and Methods: Serum markers were determined by Enzyme-Linked Immunosorbent Assays in 12 non-diabetic subjects (CTRL), 15 diabetic patients without DR (Diabetic), 15 patients with non-proliferative (NPDR) and 15 patients with proliferative DR (PDR); Results: TG and AG serum levels were significantly decreased in NPDR (P < 0.01 vs Diabetic) and in PDR patients (P < 0.01 vs NPDR). AG serum levels were inversely associated with DR progression (r = -0.83,P < 0.01), serum neutrophils percentage (r = -0.74, P < 0.01) and serum NE levels (r = -0.73, P < 0.01). These were significantly increased in NPDR (P < 0.01 vs Diabetic) and PDR (P < 0.01 vs PDR) groups, positively correlating with DR progression (r = 0.86, P < 0.01). Conclusions: The reduction of circulating AG and its association with the increased risk of microhemorrhages could be considered a novel marker for DR progression.

To characterize the metabolic actions of D-Pinitol, a dietary inositol, in male Wistar rats, we analysed its oral pharmacokinetics and its effects on a) the secretion of hormones regulating metabolism (insulin, glucagon, IGF-1, ghrelin, leptin and adiponectin), b) insulin signaling in the liver and c) the expression of glycolytic and neoglucogenesis enzymes. Oral D-Pinitol administration (100 or 500 mg/Kg) resulted in its rapid absorption and distribution to plasma and liver compartments. Its administration reduced insulinemia and HOMA-IR, while maintaining glycaemia thanks to increased glucagon activity. In the liver, D-Pinitol reduced the key glycolytic enzyme pyruvate kinase and decreased the phosphorylation of the enzymes AKT and GSK-3. These observations were associate with an increase in ghrelin concentrations, a known inhibitor of insulin secretion. The profile of D-Pinitol suggests its potential use as a pancreatic protector decreasing insulin secretion through ghrelin upregulation while sustaining glycaemia through liver-based mechanisms of glycolysis control.

Introduction: Leptin and ghrelin are two hormones that play a role in weight homeostasis. Leptin, which is produced primarily by adipocytes and is dependent on body fat mass, suppresses appetite and increases energy expenditure. Conversely, ghrelin is the “hunger hormone”, it stimulates appetite and promotes fat storage. Bariatric surgery significantly alters the levels and activity of these hormones, contributing to weight loss and metabolic improvements. Clarifying the interplay between bariatric surgery, weight loss, physical exercise, leptin, and ghrelin is essential for developing comprehensive strategies for optimizing long-term outcomes for candidates for bariatric surgery, especially sarcopenic patients. Methods: This was a randomized controlled study with two groups (n=22). The patients in both groups have obesity and sarcopenia. A Roux-en-Ygastric bypass (RYGB) procedure was performed in all patients. The intervention group participated in a structured exercise program three times per week beginning one month after surgery and lasting 16 weeks. Patient assessment was performed before surgery (baseline) and after completion of the exercise program. The control group received the usual standard of care and was assessed similarly. Results: After surgery, weight, BMI and lean mass decreased significantly in both groups from baseline to the second assessment. Leptin was not significantly different from baseline to the second assessment in the physical exercise group but was significantly lower in the control group (p=0.05). Ghrelin increased over time in both groups, but the differences were not significant. When we associated leptin (the dependent variable) with weight (the independent variable), we found that lower weight was associated with lower leptin levels. A similar relationship was also observed between leptin and sarcopenia parameters (muscle strength and mass), as well as with bone health parameters (bone mineral density and t-score). Higher ghrelin levels were significantly associated with higher t-scores and z-score (p<0.05). Conclusion: Exercise has been shown to have a significant effect on leptin and ghrelin levels after bariatric surgery. By incorporating regular physical activity into their lifestyle, bariatric patients can optimize their weight loss outcomes and improve their overall health. After the physical exercise protocol, patients in the intervention group revealed more established leptin levels, which may indicate a protected pattern concerning decreased leptin levels. An unfavorable profile was evidenced, according to which greater weight loss, sarcopenia, and osteoporosis were associated with lower leptin levels.

Dietary approach is essential to obesity control, but the effectiveness of changes in meal frequency (MF) as strategies for loss and maintenance of body mass remain unclear. This study aimed to evaluate the influence of MF on a hypocaloric diet on weight loss, active ghrelin levels and metabolic indicators of women with obesity. This is a randomized, parallel clinical trial, including forty women, randomized in two groups, both following a hypocaloric diet, according to MF (G1 – six meals/day; G2 – three meals/day). Dietary, laboratory, anthropometric and body composition indicators were assessed, as well as energy expenditure (EE), before and after the 90 days of intervention. After intervention, both groups decreased body weight, body mass index (BMI), waist circumference, fat mass (FM), insulin and HOMA-IR. G1 increased insulin sensitivity and G2 reduced triglyceride and FM and increased fat-free mass (FFM). MF increased ghrelin levels. There were no differences in EE variables. Hypocaloric diet with different MF promoted a reduction in total weight, BMI, WC and FM and an improvement in glycidic metabolism. However, the accomplishment of the three meals/day increased the FFM and active ghrelin and reduced triglyceride, while six meals/day was more beneficial in increasing insulin sensitivity.

Several studies suggests that ghrelin (GHRL) has neurobiological effects that extend beyond control of food intake. Our previous results confirmed that GHRL modulates the secretory activity of the pineal gland (PG) through nocturnal melatonin (MEL) secretion in sheep, the seasonally reproductive animals. Here we investigated the effects of GHRL (10 ng/ml) on the expression of enzymes limiting synthesis of MEL, including tryptophan 5-hydroxylase 1 (TPH1), serotonin N-acetyltransferase (AA-NAT) and its phosphorylated form p31T-AA-NAT in sheep PG explants (n = 72) during the 4-hour incubation in a gas-liquid interface, at a short (SD) and long (LD) photoperiods. After each hour of incubation selected explants were frozen in liquid nitrogen and stored at -80°C for subsequent analysis (real-time PCR, western-blotting, ELISA). Results show that GHRL regulates nightly MEL secretion in a TPH1-independent manner. The factor modulating GHRL activity was photoperiod. During SD photoperiod GHRL significantly reduced the expression of p31T-AA-NAT, AA-NAT and inhibited MEL secretion from PG explants. Whereas, during LD photoperiod no effect of GHRL on MEL secretion and expression of examined enzymes was noted. Studies indicate that GHRL directly affects PG under in vitro conditions and causes MEL secretion in animals which exhibit seasonality in reproductive and metabolic processes.

The aim of the present study was to evaluate the effects on the presence and distribution of oxyntopeptic cells (OPs) and enteroendocrine cells (EECs) expressing GHR, NPY and SOM in the gastric mucosa of European seabass and seabream of dietary levels of bioactive peptides (BPs) obtained from salmon processing by-products (in silico approach). In this study, 27 seabass and 27 seabreams were divided into three experimental groups: a control group (CTR) fed a control diet and two groups fed different levels of BP to replace fishmeal: 5% BP (BP5%) and 10% BP (BP10%). The stomach of each fish was sampled and processed for immunohistochemistry. Some SOM, NPY and GHR-IR cells exhibited alternating “open type” and “closed type” EECs morphologies. In seabream gastric mucosa, the BP10% group (16.8 ± 7.5) showed a significant change in NPY-IR cell number compared to CTR (CTR 8.5 ± 4.8) and BP5% (BP10% vs. CTR P ≤ 0.01; BP10% vs. BP5% P ≤ 0.05). In seabream, SOM-IR cells in the BP 10% diet (16.8 ± 3.5) differed from those in CTR (12.5 ± 5) (CTR vs. BP 10% P ≤ 0.05) and BP 5% (12.9 ± 2.5) (BP 5% vs. BP 10% P ≤ 0.01). In seabass, EEC SOM-IR cells increased at 10 % BP (5.3 ± 0.7) compared to 5 % BP (4.4 ± 0.8) (5 % BP vs. 10 % BP P ≤ 0.05). The results obtained suggest that salmon BPs have a promising impact as circulating ingredients for seabass and seabream.

Polycystic ovary syndrome (PCOS) is an insulin resistant state, compensated by hyperinsulinemia. More than 50% of the women with PCOS are obese, and/or have metabolic syndrome. Weight loss improves both metabolic and reproductive outcomes. Not only the energy content, but also the nutrient composition of a diet may be important. This article will present a series of studies from our research comparing effects of dietary protein vs. simple-carbohydrates (CHO). Results of the acute challenge studies demonstrate that simple-CHO intake causes reactive hypoglycemia in one third of the women with PCOS, especially among obese and insulin resistant individuals. Symptoms of hypoglycemia are associated with secretion of cortisol and adrenal androgens. Simple-CHO suppresses the hunger signal ghrelin for a shorter period. During weight loss, women who receive protein supplementation achieve larger amounts of weight- and fat-mass losses. Amino acid compositions of the protein supplements do not affect the improvements in weight and insulin resistance. It is plausible that simple-CHO intake leads to weight gain, or interferes with weight-loss, by causing reactive hypoglycemia, triggering adrenal steroid secretion, and leading to snacking. Since obese women with PCOS are more susceptible to reactive hypoglycemia, a vicious cycle establishes. Restriction of simple-CHO may break this cycle.