Search Results (820)

MAFLD progression is closely linked to a systemic failure of antioxidant defense systems. Se and Zn play crucial roles in maintaining redox balance in the liver. This study evaluated the effects of micronutrient-biofortified chickpea flours as functional ingredients for the prevention and management of MAFLD disturbances. Chickpea seeds were germinated with Na₂SeO₃, ZnSO₄, ZnSeO₃, or ZnSO₄ + Na₂SeO₃, processed into flours, and then subjected to gastrointestinal digestion to obtain biofortified-chickpea digests (BCD). SDS-PAGE and FTIR indicated treatment-dependent changes in the protein/peptide profile and in the structural organization of the digested matrix. Isoflavone content was higher in ZnSO₄-BCDs. The oleic acid-induced HepG2 cell model was used to emulate MAFLD conditions. Under preventive conditions, except for ZnSeO₃-BCD, all treatments reduce triglyceride accumulation from 17.1 to 38.6%. Non-biofortified (GC) chickpea flour and ZnSeO₃-BCD had greater effects on lipolysis and glycerol release. Overall, Se-BCD affected redox regulation 1.2–1.3-fold, suggesting potential improvement in lipid utilization. GC and ZnSO₄ + Na₂SeO₃ BCDs decreased triglyceride accumulation (21.1 and 20.5%, respectively) when evaluated post lipid exposure. In both experimental conditions, BCDs significantly reduced IL-6 levels by 25.1 to 34.7%, demonstrating their immunomodulatory potential. Biofortified chickpea flours exhibit complementary and coordinated biological activities against the main metabolic disturbances associated with MAFLD. Zn/Se-biofortification of chickpea is a valuable strategy for addressing micronutrient deficiencies and for producing functional ingredients to prevent or ameliorate MAFLD-associated disturbances and improve liver health. Full article

Glucagon-like peptide-1 (GLP-1) is an incretin hormone secreted in response to food intake that acts biologically by binding to GLP-1 receptors. The primary function of GLP-1 is to stimulate insulin secretion and inhibit glucagon secretion, which helps limit after-meal spikes in blood glucose. GLP-1 reduces intestinal contractility, slows down gastrointestinal motility and emptying, and also acts directly on the hypothalamus, thereby regulating appetite and food intake. Due to its metabolic effects, GLP-1 forms the basis of medications currently used to treat type 2 diabetes (T2DM) and obesity. However, it has also been observed that the use of GLP-1 agonists in the treatment of obesity or diabetes has a beneficial effect on comorbid respiratory conditions. This narrative review analyzes the scientific literature and describes the most recent information on the impact of GLP-1 receptor agonist (GLP-1 RA) therapies on the most common respiratory disorders—both the beneficial and undesirable effects. We discuss evidence that acute lung injury, COVID-19, pulmonary fibrosis, asthma, chronic obstructive pulmonary disease (COPD), and obstructive sleep apnea can benefit from therapies with various GLP-1 RAs. They can complement existing lung-targeted treatments, but as research progresses, they are likely to play an ever more important role in the treatment of respiratory diseases. Full article

Background: Cytarabine (Ara-C) remains the cornerstone of remission-induction and consolidation chemotherapy for acute myeloid leukemia (AML) and related hematological malignancies. Despite more than six decades of clinical use, its multi-organ toxicity continues to be managed almost exclusively through dose attenuation and supportive care, with no approved upstream pharmacological prevention strategy available. Objectives: This scoping review aimed to systematically map the breadth and nature of pharmacological agents tested in vivo for their capacity to mitigate cytarabine-induced multi-organ toxicity, to characterize their mechanisms of action and organ targets, and to identify evidence gaps and agents with translational potential. Methods: The review was designed and reported in accordance with the PRISMA-ScR checklist. A structured electronic search was conducted across PubMed/MEDLINE, Scopus, Cochrane Library and Embase, and Web of Science from database inception to 15 July 2025. Eligible studies were restricted to full-text, peer-reviewed, English-language research involving in vivo mammalian models administered cytarabine as the principal toxin, with at least one pharmacological co-intervention and at least one quantitative or histopathological organ-injury outcome. Results: From 5701 retrieved records, 36 eligible in vivo mammalian studies (spanning 1964–2024) were identified. Included studies addressed neurotoxicity (n = 6), gastrointestinal mucositis (n = 9), ocular toxicity (n = 3), hepatotoxicity (n = 3), bone marrow suppression (n = 4), chemotherapy-induced alopecia (n = 5), and reproductive and developmental toxicity (n = 4). Five recurring mechanistic strategies were identified across the heterogeneous agents tested: redox buffering (N-acetylcysteine, α-lipoic acid, rutin, swertiamarin, α-tocopherol), mitochondrial preservation (betanin, thymoquinone, vitamin D, sodium zinc dihydrolipoylhistidinate [DHLHZn]), tissue-microenvironment reprogramming (apraglutide, BADGE, plerixafor, short-chain fatty acids, β-glucan), molecular antagonism (deoxycytidine, dCMP), and immunomodulation (lienal peptide, IL-1β, AHCC). Conclusions: This scoping review provides the first systematic cartography of pharmacological mitigation strategies for cytarabine-induced multi-organ toxicity. Five mechanistic pathways converge across eight organ systems, with apraglutide and N-acetylcysteine representing the most clinically translatable candidates. Plerixafor and PPARγ blockade by BADGE constitute high-priority candidates for bone marrow niche protection, while the deoxycytidine antagonism principle warrants formal pharmacokinetic evaluation. The complete absence of cardiotoxicity mitigation data defines the most critical gap for future research. Full article

Over the last years, incretin receptor agonists—including glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1 RA) and the dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonist tirzepatide—have dramatically improved the management of type 2 diabetes, overweight and obesity. However, as the use of incretin receptor agonists continues to increase worldwide, micronutrient deficiencies—including iron deficiency—have emerged as newly recognized adverse effects of these drugs. The present article aims to discuss recent preliminary observational evidence on the potential relationship between incretin receptor agonist-based therapies and the development of iron deficiency and iron deficiency anemia (IDA), as well as the potential mechanisms by which incretin receptor agonists may affect iron homeostasis. Potential mechanisms and factors underlying the development of iron deficiency and IDA in patients treated with incretin receptor agonist-based therapies include inadequate dietary iron intake (due to incretin receptor agonist-mediated reduction in food intake and/or gastrointestinal adverse effects of incretin receptor agonists), low dietary variety, monotonous diets, and changes in food preferences, as well as impairment of intestinal iron absorption (due to delayed gastric emptying, reduced small intestinal motility and/or decreased gastric acid secretion caused by incretin receptor agonists). Moreover, vitamin B2 (riboflavin) deficiency and changes in gut microbiota composition are hypothetical mechanisms that may partly explain iron deficiency in patients treated with incretin receptor agonists, although these hypotheses require confirmation through mechanistic studies. Even though iron deficiency and IDA currently appear to be uncommon adverse effects of incretin receptor agonist-based therapies, clinicians should be aware of the possibility of their occurrence to ensure appropriate prevention and management of these nutritional complications. Nevertheless, future prospective studies are certainly needed to better establish the causal relationship between the initiation of incretin receptor agonist-based therapies and the development of iron deficiency/IDA, as well as the exact mechanisms underlying the potential development of these nutritional complications in patients treated with incretin receptor agonists. Meanwhile, the prescription of incretin receptor agonists should not be unjustifiably restricted by the possible and modest risk of iron deficiency and IDA in patients with one or more approved indications for therapeutic use of these agents. Since no established guidelines currently exist for the prevention and management of iron deficiency and IDA in patients treated with incretin receptor agonists, we herein propose practical strategies to address these possible nutritional complications of incretin receptor agonist-based therapies. These proposed strategies should only be regarded as practical clinical approaches deriving from the existing recommendations for the prevention and management of iron deficiency and IDA, although their cost-effectiveness for the prevention and management of incretin receptor agonist-associated iron deficiency/IDA should be appropriately assessed in future clinical trials. Full article

Non-alcoholic fatty liver disease (NAFLD), now increasingly termed metabolic dysfunction-associated steatotic liver disease (MASLD), is a growing cause of chronic liver disease with limited treatment options. Glucagon-like peptide-1 (GLP-1) receptor agonists, approved for type 2 diabetes and obesity, possess metabolic effects that may render them suitable for treating NAFLD and metabolic dysfunction-associated steatohepatitis (MASH). To evaluate the therapeutic effects of GLP-1 receptor agonists in adults with NAFLD, non-alcoholic steatohepatitis (NASH), MASLD, or MASH. PubMed, Scopus, Embase, and the Cochrane Library were systematically searched using keywords related to NAFLD and GLP-1 receptor agonists. Given heterogeneity in populations, designs, and outcomes, findings were synthesized narratively. The review is registered with PROSPERO (CRD420261337353). Twelve studies met the inclusion criteria. The most consistent outcome was a reduction in hepatic fat, seen with semaglutide, liraglutide, dulaglutide, and beinaglutide. Improvements in liver enzymes, particularly alanine aminotransferase, were less consistent and best regarded as supportive rather than definitive evidence of histological improvement. Histological benefits were strongest for steatohepatitis resolution in non-cirrhotic MASH. Fibrosis findings were mixed, with the greatest benefit in F2–F3 MASH and limited improvement in established cirrhosis. GLP-1 receptor agonists were generally well tolerated, with gastrointestinal symptoms the most common adverse effects. GLP-1 receptor agonists show promising liver-related benefits in NAFLD and MASH, particularly in obesity, type 2 diabetes, or earlier-stage disease. Their effects on advanced fibrosis and long-term outcomes remain uncertain, warranting larger, longer-term studies. Full article

The migrating myoelectric complex (MMC) is the electrical basis of fasting small intestinal motility. Although oxytocin (OT) regulates gastrointestinal functions through oxytocin receptors (OTRs), its effect on jejunal MMC activity during fasting remains unclear. This study investigated the effects of OT on jejunal MMC activity in fasted rats and evaluated the involvement of OTRs, glucagon-like peptide-1 receptors (GLP-1Rs), and nitric oxide (NO) pathways. Bipolar electrodes were implanted at three jejunal sites in adult male Sprague Dawley rats for MMC recordings. After recovery and 18 h fasting, OT was administered intraperitoneally (4–32 µg/kg) following one hour of basal recording. To assess mechanisms, rats were pretreated with the OTR antagonist atosiban (2 mg/kg), the GLP-1R antagonist exendin (9–39) (200 µg/kg), or the nitric oxide synthase inhibitor NG-nitro-L-arginine (L-NNA; 5 mg/kg) before OT (16 µg/kg). Oxytocin dose-dependently reduced spike frequency and MMC cycle number (p < 0.05–0.001 vs. vehicle). Atosiban completely reversed these effects (p < 0.001 vs. OT), while exendin (9–39) partially attenuated them (p < 0.01–0.001 vs. OT). L-NNA showed no significant effect. These findings indicate that OT inhibits jejunal MMC activity via OTR-dependent mechanisms with partial involvement of GLP-1R signaling but not NO pathways. Full article

Porcine blood meal is a protein and iron-rich animal by-product, but its use in companion animal diets is often limited by poor solubility and variable digestibility caused by thermal processing. This study evaluated whether enzymatic hydrolysis could improve the physicochemical properties, digestibility, iron-related characteristics, and antioxidant capacity of porcine blood meal for potential use in canine diets. Porcine blood meal was hydrolyzed using alcalase or pepsin under controlled conditions, and the resulting hydrolysates were characterized by degree of hydrolysis, electrophoretic peptide profiles, techno-functional properties, in vitro digestibility using a simulated canine gastrointestinal model, heme and non-heme iron fractions, and antioxidant activities. Alcalase treatment produced a higher degree of hydrolysis and more extensive peptide fragmentation than pepsin. Consistent with these structural changes, the alcalase hydrolysate exhibited significantly higher in vitro apparent digestibility. Enzymatic hydrolysis increased extractable heme iron while reducing ferrozine-reactive non-heme iron, suggesting changes in iron binding forms after proteolysis. Hydrolyzed samples also showed enhanced radical scavenging activity and ferric-reducing capacity, whereas superoxide dismutase (SOD)-like activity decreased following hydrolysis. These findings indicate that controlled enzymatic hydrolysis, particularly with alcalase, could improve apparent digestibility and non-enzymatic antioxidant capacity of porcine blood meal, supporting its potential as an iron-containing ingredient in canine diets. Further in vivo studies would be required to confirm iron availability and nutritional efficacy. Full article

Coconut kernel fiber (CKF) is a by-product of coconut oil processing; it is rich in protein and serves as a potential source of bioactive peptides. In this study, from the enzymatic hydrolysis products of CKF (CKFH), a low-molecular-weight CKFH component (LW-CKFH, 1–3 kDa), exhibiting 74.49% α-glucosidase inhibition and restoring glucose metabolism in IR-HepG2 cells to 71.37% of normal levels. In a type 2 diabetes (T2DM) mouse model, LW-CKFH alleviated insulin resistance and enhanced insulin sensitivity by repairing liver damage, thereby improving glucose and lipid metabolism and reducing inflammation; its effects on improving insulin resistance and sensitivity reached 75.43% and 75.47% of the efficacy of metformin, respectively. Molecular docking analysis identified FDLPAR, LPFPRPAGPR, and ANVFNPR as key active peptides responsible for inhibiting α-glucosidase activity. Furthermore, LW-CKFH exhibited good gastrointestinal digestibility and processing stability, while significantly reducing the glucose release rate from bread (>50%), indicating its suitability for the development of hypoglycemic or low-GI functional foods. LW-CKFH was particularly suitable as a functional ingredient for fruits, vegetables, grains, and dairy products to develop low-GI or hypoglycemic foods. This study provides new insights into the high-value utilization of the coconut processing by-product CKF. Full article

Marine-derived collagen peptides exhibit potent intestinal barrier protection; however, their gastrointestinal fate and molecular targets remain unclear, limiting their practical applications. This study investigated the digestive stability and transepithelial transport of GPSGPQGSR, a mucoprotective peptide from Alaska pollock (Gadus chalcogrammus) skin, using simulated gastrointestinal digestion, a Caco-2 cell transport model, and an UPLC-QTOF-MS/MS. The results showed that GPSGPQGSR was a digestion-resistant peptide that reached the intestinal epithelium intact. Although brush border membrane enzymes partially hydrolysed the peptide, 42.16% of intact GPSGPQGSR remained in the luminal compartment after 2 h of incubation. No intact peptide was detected in the basolateral compartment. Molecular docking and 100 ns molecular dynamics simulations identified TLR2 (−14.936 kcal/mol) and PAR2 (−10.154 kcal/mol) as high-affinity extracellular targets of GPSGPQGSR, with stable peptide–receptor interactions and extensive hydrogen bonding networks between the peptide and each receptor (RMSD of 1.8 Å and 2.2 Å, respectively). Pharmacological blockade of TLR2 or PAR2 abolished the protective effects of GPSGPQGSR. These findings demonstrate that GPSGPQGSR acts as a digestion-resistant extracellular signalling peptide that reaches the intestinal epithelium intact and protects barrier function through apical TLR2 and PAR2, providing a mechanistic basis for the rational development of marine collagen peptides for improving intestinal health. Full article

The emergence of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and dual incretin-based therapies has fundamentally transformed obesity pharmacotherapy, enabling magnitudes of non-surgical weight loss that were previously unattainable. Yet, the clinical success of these treatments cannot be measured in kilograms alone. Total body weight is a composite, tissue-nonspecific endpoint that fails to distinguish between adipose reduction and losses in skeletal muscle mass, strength, and physical function—compartments of direct relevance to metabolic health, functional independence, and long-term resilience. This narrative review builds on and extends existing conceptualizations of weight loss quality by proposing a clinically oriented, multidimensional framework of high-quality weight loss. Within this framework, preferential adiposity reduction is achieved while preserving skeletal muscle mass, neuromuscular function, dietary adequacy, and cardiometabolic health. We examine the physiological and clinical consequences of lean tissue loss during pharmacological energy restriction, with specific attention to phenotypes at greatest risk (i.e., older adults, individuals with sarcopenic obesity, and those with type 2 diabetes). We then evaluate the evidence supporting precision protein nutrition, dietary fiber adequacy, and gastrointestinal tolerability management as nutritional countermeasures, followed by a mechanistic and clinical analysis of resistance training as the primary exercise strategy for preserving lean mass and function. Finally, we discuss body composition monitoring, integrated multidisciplinary care, and unresolved research gaps. The future of obesity treatment lies not in greater weight loss per se, but in achieving better weight loss—defined as metabolically favorable, functionally responsible, and clinically sustainable. Bone health is treated as a further dimension of high-quality weight loss, since pharmacologically driven energy restriction can adversely affect areal bone mineral density and microarchitecture, and adequate protein intake combined with mechanical loading is required to preserve skeletal integrity alongside lean mass. Full article

Introduction: Obesity is a chronic, multifactorial disease associated with significant metabolic and cardiovascular complications. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as effective pharmacological options for weight management, demonstrating clinically relevant weight loss in controlled trials. However, real-world evidence is essential to assess their effectiveness and safety under routine clinical conditions and to verify if trial results are reproducible in diverse populations. Objective: We aimed to evaluate the effectiveness and safety of GLP-1RAs in terms of weight loss in real-world clinical practice and to compare outcomes among different available agents, focusing on their impact on obesity management. Method: A cross-sectional, observational pilot study was conducted in Spain. Adult patients receiving GLP-1RAs for at least four weeks were included. Data collected included sociodemographic variables, treatment characteristics, anthropometric measurements, and adverse effects. Weight loss outcomes were analyzed using descriptive statistics, ANOVA for inter-drug comparisons, and multivariate ANCOVA to adjust for confounders. This pilot study also validated the protocol for a subsequent nationwide multicenter study. Results: A total of 32 patients (62.5% women; mean age 58.2 years) were analyzed. Mean weight loss was 2.97 kg (3.17%). Significant differences between drugs were observed (p = 0.005), with semaglutide 2.4 mg (Wegovy^®) showing the greatest weight reduction (11.0 kg). Patients without diabetes achieved significantly greater weight loss than those with diabetes (5.0 vs. 0.8 kg; p = 0.021). Treatments were well tolerated, with 53.1% reporting no adverse effects; most side effects were mild gastrointestinal symptoms. Conclusions: GLP-1RAs are effective and well-tolerated for obesity treatment in real-world clinical practice, although weight loss is more modest than in pivotal clinical trials. Differences between agents were observed after multivariate adjustment, although these findings should be interpreted cautiously given the exploratory pilot design and limited sample size. These findings support the need for individualized treatment strategies in obesity care. This pilot study successfully validated the methodology for an ongoing nationwide investigation. Full article

The calcitonin gene-related peptide (CGRP) is a 37-amino acid neuropeptide belonging to the calcitonin family, discovered as a product of alternative splicing of the calcitonin gene. CGRP has emerged as a pleiotropic signaling molecule with widespread distribution in the central and peripheral nervous systems, particularly within primary sensory neurons. This narrative review synthesizes current knowledge on the CGRP system, integrating recent advances in its molecular structure, gene organization, and post-translational processing with high-resolution structural insights into its heterodimeric receptor complex (CLR-RAMP1) obtained through cryo-electron microscopy. We also include long-term safety data on anti-CGRP monoclonal antibodies, emerging cardiovascular risk signals, and novel therapeutic applications in vestibular migraine and pediatric populations. The intracellular signaling cascades activated by CGRP, including the canonical cAMP-PKA pathway, MAP kinase activation, and context-dependent calcium signaling, are discussed in relation to its diverse physiological functions. These encompass vasodilation, nociception modulation, neurogenic inflammation, gastrointestinal motility, bone metabolism, tissue regeneration, and energy homeostasis. The central role of CGRP in migraine pathophysiology is examined to understand the development of targeted therapies. The current pharmacological landscape is reviewed, including the evolution of small-molecule CGRP receptor antagonists (gepants) through three generations and the four approved monoclonal antibodies targeting CGRP or its receptor, with comparative analysis of their efficacy, safety profiles, and clinical positioning. Beyond migraine, emerging and predominantly preclinical roles of the CGRP system are discussed in chronic pain, osteoarthritis, cardiovascular diseases, sepsis, cancer (particularly bone metastases and tumor microenvironment immunomodulation), and neurodegenerative disorders such as Alzheimer’s disease. In these areas, the available evidence remains heterogeneous and, in most cases, is not yet sufficient to support clinical translation. Finally, future directions are discussed, including the development of stable CGRP analogs, allosteric modulators, and the potential expansion of therapeutic applications into oncology, intensive care medicine, and neuroprotection. Full article

Background/Objectives: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have transformed type 2 diabetes mellitus (T2DM) and obesity care, with clinical trials demonstrating weight loss exceeding 15%. However, real-world effectiveness lags trial efficacy, largely owing to high discontinuation rates. We characterize the global persistence gap and propose a framework integrating Medical Nutrition Therapy (MNT) to improve adherence. Methods: We conducted a narrative review of real-world evidence from North America, Europe, Asia, and Latin America, synthesized with physiological, nutritional, and behavioral data to distinguish established contributors to discontinuation from strategies that remain partly extrapolated from related populations. Results: Global persistence varies widely: from approximately 75–80% at 12 months in reimbursed T2DM cohorts (Sweden, Denmark) to below 10% in obesity-focused or high out-of-pocket-cost settings (Poland, Colombia), with intermediate rates in the United States and United Kingdom; in several cohorts, persistence falls below 15% by 24 months. The primary drivers are gastrointestinal intolerance and economic barriers. Meal size, dietary composition, and gastric-emptying effects influence gastrointestinal tolerability; inadequate protein intake during rapid weight loss raises concern for lean mass loss. Conclusions: Pharmacotherapy alone is unlikely to sustain long-term obesity management. Narrowing the persistence gap will require an integrated care model in which structured nutritional support—targeting protein intake, micronutrient density, and gastric-sparing feeding—is systematically offered rather than treated as an optional adjunct, while recognizing that most supporting evidence is extrapolated from primary trials in obesity and cardiometabolic disease rather than derived from GLP-1–specific randomized trials. Full article

Background: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonists have transformed obesity treatment, producing substantial weight loss during active therapy. However, real-world effectiveness may be limited by gastrointestinal adverse events, reduced dietary intake, fat-free mass loss as part of total weight reduction, and weight regain after discontinuation. Methods: This narrative review synthesizes current pharmacological, nutritional, gastrointestinal, body-composition, and implementation evidence to propose an evidence-informed nutrition-first framework for patients receiving incretin-based therapy for obesity. Results: We translate pharmacologic mechanisms into practical dietary strategies, including protein prioritization, structured meal patterns, hydration and fiber management, symptom-targeted interventions, resistance-training support, and maintenance planning. Because direct trials of structured nutrition interventions in GLP-1RA- or dual incretin-treated populations remain limited, several recommendations are extrapolated from the broader obesity, caloric restriction, body-composition, gastrointestinal, and expert-consensus literature. Conclusions: Integrating structured nutrition care into pharmacotherapy pathways may help address meal-related symptom burden, support protein and fluid adequacy, identify patients at higher nutritional or body-composition risk, and prepare patients for long-term weight-management behaviors. Embedding practical nutrition management within multidisciplinary obesity care may help translate pharmacologic efficacy into durable, patient-centered outcomes. Full article

Animal models are essential for elucidating human disease mechanisms and advancing translational research. Here, we used a well-established rat tail-suspension model to investigate the pathophysiological changes associated with simulated microgravity-induced functional dyspepsia (FD) and to evaluate its utility for preclinical to clinical translation. Thirty male Wistar rats were randomly assigned to control, simulated weightlessness using hindlimb unloading (HU), and domperidone groups. The HU model was induced by 21-day tail suspension, a widely accepted ground-based platform for simulating microgravity. Behavioral tests (sucrose preference, novelty-suppressed feeding), gastrointestinal motility measurements (gastric emptying, intestinal propulsion), and serum brain–gut peptide levels were assessed. Gastric and hypothalamic gene expression was analyzed by qRT-PCR. The model successfully recapitulated key FD phenotypes, including anxiety/depression-like behaviors, reduced gastric emptying and intestinal propulsion, and systemic brain–gut peptide imbalance—characterized by decreased excitatory peptides [substance P (SP), gastrin (GAS), motilin (MTL), ghrelin] and increased inhibitory peptides [vasoactive intestinal peptide (VIP), cholecystokinin (CCK), calcitonin gene-related peptide (CGRP), nesfatin-1] in serum. Consistent transcriptional dysregulation was observed in gastric and hypothalamic tissues. Hippocampal brain-derived neurotrophic factor (BDNF) was decreased, and colon 5-hydroxytryptamine (5-HT) increased, with no organic gastric lesions. Domperidone treatment significantly ameliorated behavioral abnormalities and gastrointestinal dysmotility, partially reversed brain–gut peptide imbalances at both protein and transcriptional levels, and restored hippocampal BDNF. These findings demonstrate that the rat tail-suspension model provides a reproducible platform for studying microgravity-induced FD, implicating brain–gut axis dysregulation. Domperidone’s therapeutic effects highlight the model’s utility for evaluating countermeasures against spaceflight-associated digestive dysfunction. Full article