Search Results (556)

Eating disorders (EDs), including anorexia nervosa (AN), bulimia nervosa (BN), and binge-eating disorder (BED), are complex psychiatric conditions characterized by high morbidity and mortality. Increasing evidence suggests that beyond disorder-specific symptomatology, shared transdiagnostic mechanisms contribute to their onset and persistence. This narrative review synthesizes current data on neurobiological and nutritional factors implicated in EDs, with particular emphasis on trait–state interactions and starvation-induced neuroadaptations. Predisposing vulnerabilities such as heightened anxiety, cognitive rigidity, and perfectionism appear to interact with state-dependent biological alterations induced by malnutrition. Chronic dietary restriction is associated with measurable alterations in serotonergic and dopaminergic systems, altered reward processing, and persistent activation of the hypothalamic–pituitary–adrenal (HPA) axis. Experimental studies suggest that acute tryptophan depletion may transiently reduce anxiety in individuals with anorexia nervosa, suggesting that, in some individuals, food restriction may function as a biologically reinforced strategy of affect regulation. Furthermore, disturbances in leptin and ghrelin signaling, along with widespread micronutrient deficiencies—including zinc, iron, selenium, and B vitamins—may exacerbate cognitive inflexibility, mood instability, and impaired decision-making. These metabolic and endocrine adaptations may contribute to a self-perpetuating cycle in which starvation-induced neurochemical changes reinforce restrictive or dysregulated eating behaviors. Importantly, several of these mechanisms extend beyond anorexia nervosa and may represent common transdiagnostic processes across eating disorders and related mental health conditions, including anxiety, depression, and addictive behaviors. Recognition of these biological and nutritional factors has significant implications for treatment. Nutritional rehabilitation should be conceptualized not solely as weight restoration, but as a neurobiological recalibration of stress regulation, reward sensitivity, and affective processing systems. An integrative treatment approach that combines behavioral stabilization with attention to underlying neurobiological and relational mechanisms may offer a more comprehensive framework for long-term recovery. Full article

Endothelial cells have emerged as critical peripheral nutrient sensors that actively regulate systemic lipid metabolism rather than serving as passive conduits. Endothelial peroxisome proliferator-activated receptor γ maintains redox balance, supports nitric oxide-dependent perfusion, and preserves insulin sensitivity during high-fat feeding, while ghrelin signaling through endothelial GHS-R promotes triglyceride clearance and lipid uptake into white adipose tissue through an endothelial peroxisome proliferator-activated receptor γ-dependent program. These pathways reveal that the endothelium integrates hormonal and metabolic cues to tune lipid trafficking, vectorial fatty acid delivery, and depot-specific energy storage. The concept that the endothelial phenotype, rather than circulating lipid levels alone, determines organ-level lipid exposure reframes endothelial lipid sensing as a key regulator of whole-body metabolic homeostasis. Understanding how endocrine and transcriptional pathways shape endothelial lipid handling may reveal new therapeutic targets for the treatment of obesity, dyslipidemia, and related metabolic diseases. Full article

Exposure of healthy tissue to ionizing radiation (IR) occurs due to nuclear accidents and terrorism, as well as radiotherapy. The vascular endothelium is a key target of IR, and microvascular endothelial cells (ECs) are particularly vulnerable to radiation. IR induces EC activation leading to endothelial cell injury. Human ghrelin is a stomach-derived peptide with pleiotropic effects, including protection against inflammation. We hypothesize that human ghrelin improves survival in total body irradiation (TBI) and that ghrelin’s protective effect could be mediated by attenuating endothelial cell injury. To test this, mice were exposed to TBI and after 24 h were treated subcutaneously with human ghrelin once daily for 4 days and monitored for 30 days. The survival rate of the human ghrelin-treated group was significantly higher than that of the vehicle group. Subsequently, human ghrelin treatment showed an effective dose modification factor of 1.0681. On day 4 after TBI, human ghrelin significantly attenuated EC permeability in the lungs and improved tight junction protein ZO-1 expression. Human ghrelin also improved ZO-1 and Claudin5 expression in primary mouse lung vascular endothelial cells. Taken together, these results indicate that human ghrelin improves survival after TBI, and its survival benefit is in part due to the attenuation of EC permeability and microvascular barrier dysfunction. Full article

Background/Objectives: Fetal growth restriction (FGR) represents a model of adverse intrauterine programming associated with an increased risk of cardiometabolic disorders later in life. We examined the relationships between birth weight, catch-up growth, adipokine signaling, and early cardiometabolic risk in adolescents. Methods: This cross-sectional study included 80 term-born adolescents (40 FGR, 40 controls) matched for age and sex. Anthropometry, blood pressure, lipid profile, fasting glucose, adipokines (leptin, adiponectin), and ghrelin levels were assessed. Associations between birth weight, growth rate, adipokines, and cardiometabolic outcomes were analyzed. Results: Birth weight was not associated with adiposity, lipid profile, blood pressure, or glycemic status (p > 0.05). In contrast, catch-up growth in the FGR group was correlated with increased BMI (ρ = 0.680, p < 0.001), central adiposity (ρ = 0.714, p < 0.001), systolic blood pressure (ρ = 0.448, p = 0.0037) and diastolic blood pressure (ρ = 0.325, p = 0.0409). Mediation analyses showed that the current BMI largely explains the associations between catch-up growth and cardiometabolic risk, systolic blood pressure, and waist circumference (β = 2.832 kg/m² per 1-unit increase in ΔZ; p < 0.001). The hypertensive effect of catch-up growth was amplified in overweight/obese adolescents (β = 8.13 mmHg; p = 0.006). Catch-up growth was independently associated with higher leptin (β = 220 ng/L; p = 0.022) and a higher leptin/ghrelin ratio (β = 2.330; p = 0.034). Conclusions: Postnatal growth acceleration, rather than fetal size alone, drives early cardiometabolic susceptibility following FGR through adiposity-mediated and endocrine pathways. Full article

This study evaluates a non-invasive and feasible nutritional strategy as a realistic intervention to prevent or mitigate T2DM in one-year-old female Wistar rats. This strategy is based on replacing a commercial pâté (CP) with a functional one, either a silicon-enriched commercial pâté (Si-CP), a reduced-fat pâté formulated with a biopolymeric emulsion (BP), or a silicon-enriched and reduced-fat biopolymeric pâté (Si-BP). After consumption of a high-saturated fat high-cholesterol diet, CP rats exhibited elevated fecal excretion, fasting serum glucose, insulin, and LDL cholesterol, and altered islet morphology. Versus the CP group, the Si-CP consumption group exhibited significantly reduced fecal output (1.17 ± 0.02 vs. 2.09 ± 0.44) and serum insulin (12.06 ± 7.89 vs. 20.74 ± 7.44), triglycerides (47.51 ± 4.46 vs. 58.24 ± 9.97), LDL cholesterol (34.63 ± 5.14 vs. 42.20 ± 4.98), and ghrelin (32.49 ± 24.66 vs. 78.35 ± 22.85). Although BP rats also exhibited some positive effects, Si-BP animals presented the most promising results. Compared to the CP group, Si-BP consumption significantly reduced fecal excretion (1.44 ± 0.24) and serum glucose (129.1 ± 10.40 vs. 154.9 ± 15.76), insulin (9.49 ± 6.06), triglycerides (46.91 ± 5.13), and estradiol (528.2 ± 45.00 vs. 634.4 ± 98.87), preserved islet circularity (0.88 ± 0.02 vs. 0.82 ± 0.01), and significantly increased tibia length (4.09 ± 0.12 vs. 3.95 ± 0.09) and wet weight (0.65 ± 0.07 vs. 0.56 ± 0.06). This study demonstrates the antidiabetic effects of silicon from diatomaceous earth (4 mg Si/kg body/day) incorporated into pâté in middle-aged female rats. Replacing CP with a functional alternative improved the health status of diabetic female rats, supporting its potential as an effective nutritional adjuvant. Full article

Background: Gamma-aminobutyric acid (GABA), the principal inhibitory neurotransmitter in the central nervous system (CNS), is also a potent modulator of peripheral endocrine function. We previously demonstrated that dietary GABA supplementation improves growth and fatty acid metabolism in male mice while elevating pituitary growth hormone (GH). However, the mechanisms by which GABA regulates the somatotropic axis remain unclear. Methods: Adolescent mice (3–4 weeks old) were treated with or without GABA in drinking water. Cultured pituitaries and GH3 somatotroph-derived cells were exposed to GABA, Picrotoxin, or STO-609, and protein expression was analyzed by Western blot. Results: GABA treatment increased Pit-1 (POU1F1) protein levels among males in vivo (ctrl: 0.55 ± 0.11; GABA: 1.46 ± 0.16; p = 0.0034) and ex vivo (ctrl: 0.66 ± 0.03; GABA: 1.46 ± 0.14; p = 0.0013), as well as in GH3 cells (ctrl: 1.36 ± 0.12; GABA: 3.05 ± 0.12; p < 0.0001). GH expression was also increased by GABA treatment in ex vivo pituitaries (ctrl: 1.62 ± 0.06; GABA: 1.84 ± 0.01; p = 0.0115) and GH3 cells (ctrl: 0.34 ± 0.08; GABA: 1.35 ± 0.13; p = 0.0006). Mechanistically, GABA, via the GABA_A receptor (GABA_AR), enhanced CaMKK2 pathway activity, as evidenced by increased phosphorylation of CaMKIV (ctrl: 0.86 ± 0.07; GABA: 1.12 ± 0.07; p = 0.0378) and AKT (ctrl: 0.89 ± 0.08; GABA: 1.75 ± 0.23; p = 0.0122). Inhibition of GABA_ARs by picrotoxin (PTX) markedly reduced Pit-1 (GABA: 2.73 ± 0.29; GABA + PTX: 1.76 ± 0.21; p = 0.0351) and GH expression (GABA: 0.17 ± 0.02; GABA + PTX: 0.05 ± 0.02; p = 0.0052). Treatment with CaMKK2 inhibitor STO-609 reduced basal Pit-1 (ctrl: 1.76 ± 0.09; STO-609: 1.25 ± 0.12; p = 0.0157) and GH levels (ctrl: 1.18 ± 0.10; STO-609: 0.50 ± 0.04; p = 0.0006). Ghrelin receptor activation by anamorelin (ANA) increased Pit-1 (ctrl: 0.83 ± 0.8; ANA: 1.59 ± 0.28; p = 0.0425) and GH (ctrl: 0.27 ± 0.03; ANA: 0.66 ± 0.16; p = 0.0497) through a CaMKK2-independent pathway but required basal GABA_AR activity for maximal effect. Conclusions: These findings identify GABA as a modulator of somatotroph hormone expression through a CaMKK2/CaMKIV-dependent cascade and reveal a previously unrecognized interplay whereby the basal GABAergic tone promotes Pit-1 expression, thereby positively regulating ghrelin receptor signaling. This study provides new insights on the cellular mechanisms behind GABA-induced GH synthesis, which may reveal new strategies for modulating the somatotropic axis and help contextualize the variety of reported physiological and cognitive effects of GABA supplementation. Full article

Studies conducted in first-episode psychosis (FEP) patients have shown alterations in inflammation and metabolism. Our objective was to investigate potential treatment-related effects on these systems in Italian FEP patients undergoing either an experimental treatment consisting of a multi-element psychosocial intervention (EXP), including cognitive–behavioural therapy, or treatment as usual (TAU). A total of 191 FEP patients with first contact between April 2010 and March 2011 were clinically assessed at baseline and after 9 months of treatment, and the serum levels of 19 analytes were determined through single or multiplex enzyme-linked immunosorbent assays (ELISAs). A significant increase was observed in leptin levels and a significant decrease in Glucagon-Like Peptide-1 (GLP-1) levels during the treatment (time effect, p < 0.001 for both), with no significant interaction between time and treatment type. Although ghrelin levels changed significantly over time in the whole cohort (p = 0.008), a significant decrease was observed only in the EXP group (post hoc test: p = 0.001). None of the biomarkers measured at baseline showed a predictive effect on treatment efficacy, and no significant associations were identified between changes in clinical scores and changes in biomarker levels. These results suggest that early-phase psychosis treatments are associated with possible effects on metabolic regulation. Full article

Background: Rare sugar D-Allulose, a zero-calorie sweetener, markedly ameliorates obesity. It reportedly stimulates the release of endogenous glucagon-like peptide 1 (GLP-1) to activate vagal afferent and directly influences the neurons in hypothalamic arcuate nucleus (ARH), thus evoking vagal and central nervous routes. D-Allulose can now be produced substantially, being expected for diet therapy. Oral form GLP-1 receptor agonist (GLP-1RA), Oral semaglutide (O-Sema), without injection markedly ameliorates obesity. It evokes only central nervous route. Thus, these GLP-1-based substances utilize common/distinct routes, suggesting common/distinct effects on obesity and related disorders including sarcopenia. To address it, this study precisely compared their effects. Methods: O-Sema and D-Allulose were administered to diet-induced obese mice under identical conditions, equivalent doses, oral gavage, and food/water deprivation. Acute and sub-chronic effects on food intake, body weight and grip strength were measured. Results: Acutely, D-Allulose rapidly and O-Sema slowly reduced feeding. Sub-chronically, D-Allulose and O-Sema profoundly reduced food intake and weight in the early period (0–3 days) of treatment. The weight loss was diminished with O-Sema but maintained with D-Allulose in the late period (4–10 days) and after termination of treatment. D-Allulose and O-Sema increased muscle strength. Mechanistically, D-Allulose and semaglutide similarly activated anorexigenic leptin-responsive neurons while only D-Allulose significantly inhibited orexigenic ghrelin-responsive neurons in ARH. Conclusions: D-Allulose and O-Sema equally elicit weight reduction possibly via the central nervous route including ARH anorexigenic neuron activation. The weight loss is rebounded with O-Sema, while it is maintained with D-Allulose possibly via combined vagal afferent and central nervous routes including ARH orexigenic neuron inhibition. Their optimal use potentially provides precise control of obesity and related disorders. Full article

This study examined how different photoperiods affect net energy partitioning and explored the mechanisms via blood biochemistry, gut microbiota, and fecal metabolites. Twelve healthy crossbred pigs (47.7 ± 7.5 kg) were randomly allocated to two groups and subjected to a self-controlled crossover design. Following an 8-day baseline under a normal photoperiod (12L:12D, 12 h light:12 h dark), pigs were assigned to two photoperiod treatment groups: prolonged photoperiod (18L:6D, 18 h light:6 h dark; P group) and shortened photoperiod (6L:18D, 6 h light:18 h dark; S group). Measurements during the baseline (12L:12D) and treatment phases are designated as N1/P (for the P group) and N2/S (for the S group), respectively. The treatment periods were interspersed with the baseline 12L:12D photoperiod and repeated six times. It was observed that, compared to N2, shortened photoperiod (S) had significantly higher net energy deposition, net energy for protein deposition, and net energy for fat deposition (p < 0.05). Compared with N2, plasma low-density lipoprotein in short photoperiod decreased (p < 0.05), and gastric inhibitory peptides increased (p < 0.05). Compared to the prolonged photoperiod, the levels of ghrelin and apolipoprotein A-IV were higher in the shortened photoperiod (p < 0.05). A shortened photoperiod decreased fecal acetic acid compared to N2 (p < 0.05) and decreased propionic acids compared to P (p < 0.05). The significance test of differences between microbial groups showed that there were different microorganisms among the different groups. The results indicated that shortening the photoperiod significantly altered the energy allocation in growing pigs. Full article

Objectives: Our objective was to evaluate the acute effect of L-leucine supplementation and high-intensity sprint exercise on appetite-controlling neuropeptides and their association with the subjective perception of appetite (SPA), satiety (SPS), food intake, and inflammatory response in overweight participants. Methods: In a double-masked, randomized, counterbalanced, and crossover design, 12 sedentary overweight adult men performed four experiments: (1) exercise and L-leucine (EX-Leu), (2) exercise and placebo (EX-PLA), (3) L-leucine without exercise (SED-Leu), and (4) placebo without exercise (SED-PLA). The supplementation consisted of three daily doses of 70 mg/kg body weight of L-leucine or placebo (on the day of exercise and one day after). During the experiments, we recorded the food intake, SPA, and SPS, and evaluated the neuropeptides (GLP-1, PYY, CCK, and ghrelin) and cytokines (IL1-beta, IL-6, IL-10, and TNF-α) in peripheral blood. The acute exercise trial consisted of four sets of 30 sec cycle ergometer sprint exercises. Results: EX-Leu, EX-PLA, and SED-Leu decreased SPA, compared to SED-PLA; only EX-PLA improved SPS; EX-PLA and EX-Leu reduced food intake. GLP-1 decreased in the EX-PLA trial compared to SED-Leu. IL-6 and IL1-β levels increased in the EX-Leu trial compared to SED-PLA. An anti-inflammatory profile was identified in the EX-PLA trial compared to the other trials. Both neuropeptides (increased) and cytokines (a pro-inflammatory profile) were associated with changes in SPA, SPS, and food intake. Conclusions: The acute inflammatory balance induced by EX-Leu seems to improve appetite control. Sprint exercise had a consistent acute anorexic effect, while isolated L-leucine decreased SPA, but their impact on SPS and food intake is not clear (FAPESP grants: 2020/09936-2 and 2021/03601-1). Full article

Ghrelin is a regulator of appetite and growth hormone secretion, rising during fasting and decreasing after food intake. Children born small for gestational age (SGA) who undergo postnatal catch-up growth are at increased risk of obesity and metabolic disturbances, which may be related to impaired ghrelin regulation. This study assessed fasting and post-glucose ghrelin responses during an oral glucose tolerance test (OGTT) in prepubertal SGA children in relation to obesity and metabolic syndrome components. Ninety-eight children aged 5–9 years were included. Anthropometry, blood pressure, fasting lipids, glucose, insulin, and ghrelin were measured; BMI SDS and HOMA-IR were calculated. Ghrelin concentrations were assessed at baseline and 120 min after glucose ingestion. Ghrelin levels declined significantly during OGTT. Obese SGA children showed lower fasting and post-load ghrelin levels and a smaller decline compared with non-obese peers. Fasting and post-load ghrelin correlated inversely with BMI SDS, waist circumference, and insulin levels. In regression analyses, fasting ghrelin and its suppression were independently associated with HOMA-IR, whereas post-load ghrelin was determined by post-load insulin. These findings indicate that ghrelin dynamics in SGA children are more closely related to insulin sensitivity than adiposity and are blunted in the presence of obesity. Full article

Thermoregulatory dysfunction is a major pathophysiological consequence of aging, affecting many elderly individuals. Growth hormone secretagogue receptor (GHSR) regulates energy homeostasis and immune function. We previously showed that global GHSR deletion improves thermogenic adaptation of brown adipose tissue (BAT) in aging, but the responsible cell type remained unclear. GHSR is expressed in macrophages, and its expression in macrophages increases with aging. Here, we studied myeloid-specific Ghsr-deleted male mice (LysM-Cre; Ghsr^f/f denoted as “KO”) to assess their metabolic and immune responses to cold stress at young and old ages. Old mice showed impaired thermogenesis, marked by reduced core body temperature under 4 °C cold exposure, a blunted cold-induced increase in glucose levels, reduced BAT mass, and increased infiltration of pro-inflammatory CD38⁺ macrophages in BAT. In contrast, KO mice exhibited enhanced cold tolerance in both young and old mice. Notably, aged KO mice showed preserved BAT mass and a pronounced shift in resident macrophages toward an anti-inflammatory state. Consistently, aged KO mice showed reduced pro-inflammatory markers (Ccl2, Nos2) and increased expression of the thermogenic gene Ppargc1a and UCP1 protein under cold exposure. Together, these findings demonstrate that macrophage GHSR drives age-associated pro-inflammatory remodeling of BAT, and that its deletion promotes an immune environment favorable for thermogenic activation. Thus, targeting macrophage GHSR may offer a new therapeutic strategy to restore thermogenesis and enhance thermal resilience in aging. Full article

Apelin is a postnatal peptide implicated in gastrointestinal maturation, yet its combined effects on mucosa, enteric plexuses, and gut-derived appetite signals are not well defined. We investigated the impact of chronic intragastric apelin-13 on the stomach and small intestine of unweaned rats. Twelve Wistar pups of both sexes received apelin-13 (100 nmol/kg body weight, twice daily) or saline from postnatal day 10 for 14 days. After euthanasia, gastric and small-intestinal samples were processed for histomorphometry, neurofilament immunohistochemistry of myenteric and submucosal plexuses, and quantitative staining for ghrelin and leptin. Apelin-13 increased gastric mucosal thickness and pit and gland height, enlarged zymogen cells, and reduced muscularis propria thickness, while leaving submucosa and parietal cell area unchanged. In the small intestine, apelin produced a clear proximal-distal gradient, with enhanced villus-mucosa indices proximally and reduced indices in mid-to-distal jejunum, alongside broader crypt remodeling. Enterocyte and goblet cell dimensions changed in parallel with these regional shifts. Myenteric and submucosal ganglia were also remodeled in a segment-dependent manner. Ghrelin immunoreactivity increased in most regions, whereas leptin showed opposite proximal and distal responses. Overall, early-life luminal apelin-13 reshapes gastric and intestinal architecture and local hormone expression. Full article

Antiretroviral drugs are associated with increased body weight and metabolic disorders. Fat gain and insulin resistance are commonly associated with abdominal obesity in people with HIV (PWH). There is currently an open ongoing discussion about how antiretroviral therapy affects body weight and its significance in hunger–satiety circuit alteration. Until now, the impact of the drug on this circuit has not been explored. This study aimed to assess the hormones involved in appetite and satiety regulation in the serum and hypothalamus after efavirenz (EFV) administration in mice. EFV (10 mg/kg) and distilled water (1.5 μL/kg) (control group) were orally administered for 36 days to CD1 mice. Body weight and food intake were determined throughout treatment. At the end of the treatment, the metabolic profile (glucose, triglycerides, cholesterol) was assessed, and leptin, soluble receptor of leptin (sOB-R), and ghrelin were measured in serum; moreover, we evaluated the expression of growth hormone secretagogue receptor 1a (GHS-R1a), neuropeptide Y receptor 1 (NPYR1), and leptin in the hypothalamus, and a sucrose preference test (SPT) was conducted. Outcomes showed an increase in serum ghrelin and the expression of GHS-R1a and NPYR1 receptors in the hypothalamus, coinciding with an increase in appetite and preference for sucrose in mice in the EFV group. Furthermore, serum leptin, sOB-R, and the free leptin index (FLI) showed that hunger is not related to a lack of satiety. Despite increased food intake, a reduction in body weight was observed, and triglyceride and cholesterol levels were increased. According to our findings, mice treated with EFV showed a decrease in body weight, despite increased food intake resulting from appetite stimulation, which is caused by specific compounds, hormones, and neural signals acting on the brain’s hunger centres, primarily in the hypothalamus, promoting eating behaviours. However, further studies are necessary to investigate the mechanisms of EFV’s effects on energy expenditure. Full article

Aquaculture has been established as a sustainable alternative to traditional fisheries, which face challenges such as overexploitation and environmental degradation. However, disease outbreaks, often caused by poor farming conditions, pollution, and environmental stress, remain a major concern, leading to economic losses and increasing the risk of antibiotic resistance due to the overuse of antibiotics. Therefore, it is crucial to seek new strategies that improve fish health and well-being, preventing drug resistance and promoting sustainable practices. GHRP-6, a synthetic growth hormone-releasing peptide that mimics ghrelin, has shown potential immunostimulatory properties and feed efficiency in fish. In this study, we evaluated the effects of orally administered GHRP-6 in an oil-based formulation on juvenile tilapia (Oreochromis sp.) challenged or unchallenged with Pseudomonas aeruginosa. We assessed its influence on immune gene expression and digestive enzyme activity. The results demonstrated that GHRP-6 treatment significantly enhanced growth performance (weight and length), reduced in vivo bacterial load after infection, and modulated key genes related to innate and adaptive immunity in the gills, intestine and head kidney. In addition, our results demonstrated, for the first time, a direct link between a growth hormone secretagogue in fish and the modulation of specific enzyme activity in the gut following a bacterial challenge. These findings highlight the potential of GHRP-6 as a dietary immunomodulator and growth promoter in fish farming, offering a promising strategy to reduce antibiotic usage and promote more sustainable aquaculture practices. Full article