Search Results (354)

This study investigates whether, in a mouse model under ad libitum feeding conditions, substituting a wheat-flour-based diet with a rice-flour-based diet influences body-weight- and glucose-related outcomes. Using female KK-A^y mice, we compared diets containing wheat or rice flour. After seven weeks, the rice-flour-based diet was associated with significantly lower body weight (8.5% lower) and improved glucose tolerance compared with the wheat-flour-based diet; however, no significant improvement in insulin sensitivity was observed. Gene expression analysis revealed that Ucp3 mRNA expression in skeletal muscle was significantly higher in the rice-flour-based diet group than in the wheat-flour-based diet group, whereas no significant differences were observed in the expression of genes encoding enzymes involved in pyruvate oxidation and the TCA cycle. These results suggest that the lower body weight and improved glucose tolerance observed in the rice-flour-based diet group may be associated with increased skeletal muscle Ucp3 mRNA expression; however, whether this increase reflects altered UCP3 protein activity or energy expenditure remains unclear and requires further functional validation. Overall, substituting the wheat-flour-based diet with the rice-flour-based diet was associated with lower body weight and improved glucose tolerance in this model. Full article

Type 2 diabetes mellitus (T2DM) is characterized by skeletal muscle insulin resistance, which contributes to systemic metabolic dysregulation and diabetic myopathy (DM), a complication involving the loss of muscle mass and contractile function. Although hypoxic exercise has demonstrated metabolic benefits in chronic diseases, its efficacy against DM remains unclear. We hypothesized that hypoxic exercise would be more effective than normoxic exercise in ameliorating diabetic myopathy-associated skeletal muscle abnormalities. Accordingly, adult zebrafish underwent an 8-week high-glucose intervention combining high-glucose feeding and glucose immersion to establish a T2DM-associated diabetic myopathy model and were subsequently subjected to 5 weeks of normoxic or hypoxic exercise (28.8 cm/s, corresponding to 70% of critical swimming speed (Ucrit) determined under normoxic conditions, 2 h/day, 5 days/week) to compare their effects on skeletal muscle outcomes. Hypoxic exercise produced greater improvements in glucose tolerance and locomotor performance than normoxic exercise, while the effects on skeletal muscle morphological and atrophy-related indices varied across outcomes. Both normoxic exercise and intermittent hypoxic exposure altered the abundance of mitochondrial quality-control-related proteins in the skeletal muscle of zebrafish with diabetic myopathy, whereas hypoxic exercise produced more pronounced changes in several of these proteins. Moreover, hypoxic exercise more markedly increased the abundance of mitochondrial respiratory-chain proteins than aerobic exercise or intermittent hypoxic exposure alone. Marked reactive oxygen species (ROS) accumulation was observed in the skeletal muscle of zebrafish with diabetic myopathy. Both aerobic and hypoxic exercise effectively reduced excessive ROS production, with hypoxic exercise producing the greater effect. Analysis of Foxo3a and its phosphorylation showed that p-Foxo3a expression decreased most prominently in the T2DM hypoxia exercise (DHE) group, indicating that hypoxic exercise is associated with modulation of Hif1a/Foxo3a-related signaling. Hypoxic exercise was associated with greater Hif1a protein abundance and lower Foxo3a Ser253 phosphorylation than normoxic exercise, accompanied by improved mitochondrial quality control and reduced ROS accumulation. In conclusion, hypoxic exercise ameliorated diabetic skeletal myopathy and was accompanied by modulation of Hif1a/Foxo3a-related signaling, more favorable mitochondrial morphology, altered abundance of mitochondrial quality-control-related and respiratory-chain proteins, and reduced dihydroethidium-detectable oxidative signals. Full article

Background: Obesity is a metabolic disorder characterized by excessive lipid accumulation, disrupted fatty acid homeostasis, and gut microbiota dysbiosis. Zanthoxylum bungeanum essential oil (ZBO) is a natural plant volatile oil with diverse bioactivities, but its anti-obesity effects and potential associations remain unclear. Methods: HFD-induced obese (DIO) mice were evaluated to determine the effects of ZBO. Physiological parameters, glucose tolerance, and serum biochemical markers were assessed. Potential correlates were explored using a multi-omics approach, including integrated serum untargeted metabolomics, 16S rRNA gene sequencing, and RT-qPCR analysis of key genes involved in lipid metabolism in the liver and white adipose tissue. Results: ZBO significantly mitigated HFD-induced body weight gain, visceral adiposity, hepatic steatosis, dyslipidemia, and glucose intolerance. Metabolomics indicated that ZBO administration was associated with alterations in the serum metabolic landscape, particularly in pathways related to fatty acid metabolism and AMPK/PPAR-α signaling. Consistently, ZBO treatment was associated with upregulated mRNA expression of lipid-oxidizing genes (AMPK, PPAR-α, CPT1) and downregulated lipogenic genes (SREBP-1c, ACC, FAS, SCD1, LPL). 16S rRNA sequencing suggested that ZBO was associated with increased gut microbial diversity, decreased the Firmicutes/Bacteroidota ratio, and enriched beneficial taxa (e.g., Ligilactobacillus, Alistipes) while suppressing pro-inflammatory genera. Correlation analysis established robust associations between ZBO-modulated microbes and key fatty acid metabolites, particularly acylcarnitines and AMPK/PPAR-α-related intermediates. Conclusions: Collectively, these multi-omics data suggest that ZBO administration is associated with remodeling of the gut microbiota and correlated changes in fatty acid metabolic pathways. These findings provide preliminary preclinical evidence supporting further investigation of ZBO in the context of dietary strategies for alleviating HFD-induced obesity. Full article

Allergies and diabetes mellitus are highly prevalent, frequently co-occurring diseases. Antihistamines, the first-line treatment for allergies, block H1 receptors but also exhibit anti-inflammatory and antioxidant properties that may improve glucose metabolism. This systematic review examined the evidence for the potential antidiabetic effects of commonly used first- and second-generation antihistamines. A comprehensive search of the PubMed database (1978–May 2026) yielded 17 eligible in vivo, in vitro, clinical, and in silico studies. Most reports indicated that antihistamines improve glucose tolerance, insulin sensitivity, and insulin secretion. Proposed mechanisms include enhanced insulin release, mast cell stabilization, attenuation of immune-mediated responses, reduced nephron alteration, and improved incretin signalling. Although substantial heterogeneity in study designs limits direct comparisons, current evidence suggests a beneficial role of antihistamines in modulating glucose metabolism, particularly for patients managing both allergies and diabetes. These findings highlight the potential for drug repurposing. However, further well-designed clinical trials are required to ensure reproducibility, successful animal-to-human translation, and overall safety before clinical implementation. Full article

Obesity is a multifactorial disorder with increasing global prevalence, highlighting the importance of identifying early-life factors that may influence long-term metabolic outcomes. While metformin is widely used to improve metabolic dysfunction in adulthood, whether neonatal exposure to this drug modifies adult responses to subsequent dietary challenges remains poorly understood. This exploratory study evaluated whether intraperitoneal metformin administration during the neonatal period alters adult metabolic responses to hyperlipidic diet (HL) exposure in Wistar rats. Following weaning and sex determination, male offspring (n = 80) were included in the study and distributed among four experimental groups, i.e., saline–normolipidic (SAL-NL), saline–high-fat (SAL-HL), metformin–normolipidic (MET-NL), and metformin–high-fat (MET-HL), with 20 animals per group. From postnatal days 1 to 12, animals received daily intraperitoneal saline or metformin (100 mg/kg/day). From days 60 to 90, animals were fed normolipidic or hyperlipidic diets. Body mass, food intake, glucose tolerance (GTT), and insulin tolerance (ITT) were assessed. Neonatal metformin exposure was associated with reduced body mass gain in MET-HL animals compared to SAL-HL, while food intake differed according to dietary condition. Metformin-treated animals also exhibited improved insulin sensitivity, reflected by higher kITT values, while no significant differences were observed in glucose tolerance. These preliminary findings suggest that neonatal metformin administration may influence adult metabolic responses to dietary challenge. Further studies are required to elucidate the mechanisms and long-term implications of this early-life intervention. Full article

Background/Objectives: Ciliary neurotrophic factor (CNTF), a pleiotropic cytokine with central and peripheral actions, has been implicated in obesity, insulin resistance, and aging, yet its role in skeletal muscle and cardiometabolic health remains unclear. This study examined skeletal muscle CNTF mRNA expression in relation to adiposity and glucose tolerance in older adults and assessed the effects of six-month weight loss (WL) and aerobic exercise training (AEX) interventions on its expression. Methods: Sixty-seven adults (age, 60.75 ± 7.58) underwent a vastus lateralis muscle biopsy, VO₂max testing, dual-energy X-ray absorptiometry (DXA) scan, a resting metabolic rate (RMR) and substrate oxidation assessment, and a 3-h oral glucose tolerance test with glucose and insulin area under the curve (AUC) calculation. A subset completed 6 months of either a WL program (n = 21) or a supervised 3 times per week AEX intervention (n = 20). Results: At baseline, skeletal muscle CNTF expression was inversely associated with RMR, fat oxidation, 3-h glucose AUC, and insulin AUC, but not with BMI, percent body fat, or VO₂max. WL reduced body weight, fat mass, glucose AUC, insulin AUC, and basal muscle CNTF expression, whereas AEX increased VO₂max and reduced fat mass without altering body weight, glucose AUC, insulin AUC, or basal CNTF. Insulin-stimulated CNTF expression increased after both WL and AEX, and the intervention-induced change in glucose disposal (M) was positively associated with the change in insulin-stimulated CNTF. Conclusions: In older adults, skeletal muscle CNTF is associated with glucose intolerance but is not associated with body composition or aerobic fitness. Improvements in insulin sensitivity are associated with increases in muscle CNTF during hyperinsulinemia. Further work is needed to determine the mechanism for muscle CNTF change during hyperinsulinemia after weight loss and exercise training, and its role in glucose metabolism and obesity in older adults. Full article

Background: Impaired glucose tolerance (IGT) is the principal prediabetic stage preceding type 2 diabetes mellitus (T2D), yet islet-specific biomarkers capable of tracking progressive molecular changes from normal glucose tolerance (NGT) through IGT to T2D remain unestablished. We sought to identify a multi-gene biomarker panel with monotonically increasing expression and causal support across the full glycemic continuum. Methods: Two human islet transcriptomic datasets (GSE76895, GSE164416; n = 181: NGT 50, IGT 56, T2D 75) were integrated following ComBat batch correction. Candidate biomarkers were identified at the intersection of limma differential expression and weighted gene co-expression network analysis (WGCNA), then refined through a five-algorithm machine learning consensus (LASSO, random forest, XGBoost, SVM-RFE, elastic net). Progressive expression was assessed by the Jonckheere–Terpstra (J–T) trend test. Two-sample Mendelian randomization (MR) with eQTLGen cis-eQTL instruments, Steiger directionality testing, and Bayesian colocalization provided causal inference. A diagnostic model was internally validated via 1000-iteration bootstrap resampling. Cell-type specificity was verified using single-cell RNA sequencing (GSE200044; 127,919 cells). Results: A 12-gene biomarker panel (ALDOB, DKK3, PCOLCE2, KCNE4, INHBA, IRF8, ITGB2, LAPTM5, MYOF, RAMP3, RUNX2, S100A4) was identified, with all members passing Bonferroni-corrected J–T trend testing across the NGT–IGT–T2D axis (p ≤ 2.4 × 10⁻³). Notably, a direct IGT-versus-NGT transcriptome-wide comparison (11,948 genes) yielded no significant DEGs after FDR correction, indicating that prediabetic islet signals are subtle and detectable only through progressive trend analysis on preselected candidates. Nevertheless, the mean IGT-stage effect size of the 12 hub genes reached 41.9% of the T2D value, with KCNE4 achieving 94.0% (nominal p = 1.75 × 10⁻⁴), identifying it as the earliest-altered biomarker. Two-sample MR using whole-blood eQTLs suggested protective effects of genetically proxied MYOF (OR 0.999, FDR = 1.68 × 10⁻⁴) and RUNX2 (OR 0.998, FDR = 1.68 × 10⁻⁴) on T2D risk, with Steiger testing supporting an expression-to-disease direction (p < 10⁻³⁶). However, Bayesian colocalization indicated independent causal variants at both loci (PP.H3 > 0.76, PP.H4 < 0.001), substantially weakening the causal interpretation and suggesting that the MR associations may reflect linkage disequilibrium rather than shared causal biology. The panel achieved a bootstrap-corrected AUC of 0.833 (apparent 0.879) with PR-AUC of 0.951. Single-cell validation confirmed upregulation of 7 hub genes in β cells and revealed cell-type-specific patterns invisible in bulk data, including bidirectional INHBA regulation between β and α cells and progressive α-cell proportion expansion (28.97% → 46.41%). Pathway enrichment converged on three mechanistic axes: extracellular matrix remodeling, immune activation, and autoimmune-like responses, with direct enrichment of the type 1 diabetes pathway (hsa04940). Conclusions: This study establishes a 12-gene progressive islet biomarker panel spanning the NGT–IGT–T2D continuum, supported by machine learning robustness, genetic causal evidence, diagnostic modeling, and single-cell biological validation. KCNE4 emerges as a candidate early-warning biomarker for prediabetes, while MYOF and RUNX2 represent causally supported compensatory targets, collectively providing a multilayered foundation for T2D risk stratification and precision intervention. From a clinical perspective, the identification of progressive islet biomarkers at the prediabetic stage provides molecular support for early lifestyle intervention, reinforcing that timely detection and behavioral modification remain the most effective strategies to prevent T2D progression. Full article

Obesity-associated metabolic disorders are characterized by impaired glucose and lipid metabolism, insulin resistance, and adipose tissue dysfunction. Interferon regulatory factor 1 (IRF1) is a transcription factor primarily involved in immune regulation; however, its role in adipocyte metabolic regulation remains incompletely understood. In this study, adipocyte-specific Irf1 knockout (Irf1 AKO) mice were generated using the Cre/loxP system and subjected to either a regular chow diet or a high-fat diet (HFD). Metabolic phenotyping, insulin signaling analysis, mitochondrial homeostasis-related assessment, and in vitro adipocyte experiments were performed. Adipocyte-specific IRF1 deficiency improved insulin-stimulated AKT phosphorylation in white adipose tissues and enhanced glucose tolerance and insulin sensitivity under HFD conditions. These metabolic improvements were accompanied by reduced oxygen consumption, energy expenditure, heat production, β3-adrenergic-induced lipolytic response, and cold tolerance. At the molecular level, IRF1 deficiency was associated with reduced TOMM20 expression, decreased mtDNA content, downregulation of oxidative phosphorylation-related genes, and reduced ATP levels in adipose tissues, suggesting altered mitochondrial homeostasis. In 3T3-L1 adipocytes, IRF1 knockdown increased insulin-stimulated AKT activation, glucose uptake, and lipid accumulation, whereas IRF1 overexpression showed opposite trends. Collectively, these findings suggest that adipocyte IRF1 is associated with insulin signaling, lipid metabolic remodeling, and mitochondrial homeostasis, and highlight a potential dissociation between improved insulin responsiveness and reduced energy expenditure in diet-induced obesity. Full article

Objectives: This study clarified sex-specific short- and long-term impacts of maternal excessive palm oil (plant-derived saturated) and lard (animal-derived saturated fat) intake on offspring reproductive health and underlying mechanisms. Methods: Female mice were randomized to control, palm oil, or lard diets during gestation and lactation. Offspring received a control diet post-weaning until adulthood, followed by an optional 16-week HFD rechallenge. Gonadal weight and organ index, sperm quality, ovarian follicle number, serum sex hormones, metabolic phenotypes (serum lipid profiles, glucose and insulin tolerance), oxidative stress, apoptosis, proliferation, and transcriptomic profiles were detected at weaning, early and late adulthood. Results: In males, excessive maternal lard intake significantly induces sperm malformation and reduces seminiferous tubule diameter and spermatogenic epithelium thickness upon HFD rechallenge during adulthood, with no changes in oxidative stress, proliferation, and apoptosis. Transcriptomics identified Slc24a5 upregulation as a potential correlate through metal ion transmembrane transporter activity and cellular calcium ion homeostasis. Under normal adult diets, reduced sperm motility resulting from maternal excess lard may be mediated by apoptosis, whereas that induced by maternal high palm oil likely arises from suppressed proliferation and thinner spermatogenic epithelium. GO analysis revealed palm oil-specific Ugt1a5 upregulation associated with altered steroid hormone metabolism. In females, maternal palm oil intake reduced primordial follicles and increased atresia, with sequencing predicted to involve Nedd4 downregulation; lard intake elevated ovarian oxidative stress and atresia only upon HFD rechallenge, with Lamc3 upregulation predicted as a putative regulatory factor. Conclusions: Maternal excessive intake of saturated fat exerts offspring reproductive damage in a sex-specific and source-dependent manner with distinct mechanisms. This work provides novel insights into fat source-dependent and sex-specific effects of nutritional interventions during pregnancy and lactation. Full article

Endogenous bioactive lipids are complex signaling mediators actively involved in a plethora of pathophysiological processes, including energy homeostasis and fibrosis. Energy homeostasis is a stable internal state resulting from a dynamic balance between energy expenditure and storage. Dysregulated energy balance can contribute to fibrosis, exhibiting key metabolic effects on insulin sensitivity, glucose tolerance, lipid accumulation and metabolism, as well as on energy expenditure, ultimately leading to metabolic disorders. In this context, three major classes of endogenous lipid mediators derived from polyunsaturated fatty acids (PUFAs)—eicosanoids, specialized pro-resolving mediators, and endocannabinoids—represent a key signaling network involved in the regulation of energy metabolism. Hence, alterations in their metabolism and signaling are often associated with fibrosis and other related molecular changes. Here, we provide a comprehensive overview of the role of the above-mentioned lipid classes in energy homeostasis and fibrosis by reviewing the available literature spanning nearly four decades, with a primary focus on studies published over the past 20 years. Full article

Obesity is a chronic metabolic disorder closely associated with dyslipidemia, insulin resistance, low-grade inflammation, and gut microbiota dysbiosis. Mulberry leaves are rich in bioactive proteins, but whether mulberry leaf albumin-type protein can improve diet-induced obesity remains unclear. In this study, ultrafiltered mulberry leaf albumin-type protein (UMP) was prepared and its anti-obesity effects were evaluated in high-fat diet (HFD)-fed C57BL/6J mice. UMP contained 87.12 ± 0.52 g/100 g protein, 2.52 ± 0.00 g/100 g polyphenols, and 8.21 ± 1.49 g/100 g polysaccharides, with two major albumin-type protein bands of approximately 14 and 52 kDa. Structural analysis showed that UMP was mainly composed of β-turns and α-helices. In HFD-fed mice, daily administration of UMP for 16 weeks reduced body weight gain by 3.85 g and 5.63 g in the low- and high-dose groups, respectively, without affecting food intake. Biochemical assays, glucose and insulin tolerance tests, and histological analysis showed that UMP improved insulin responsiveness, alleviated serum dyslipidemia, reduced hepatic lipid accumulation, and decreased circulating alanine aminotransferase, aspartate aminotransferase, and lipopolysaccharide levels. Histological analysis and nuclear magnetic resonance-based short-chain fatty acid quantification further showed that UMP protected colonic morphology and increased colonic short-chain fatty acid levels. Gut microbiota analysis showed that UMP restored microbial diversity, reduced the Firmicutes/Bacteroidota ratio, and enriched potentially beneficial genera, including Ileibacterium and norank_f_Muribaculaceae. Fecal biochemical assays suggested that UMP promoted fecal free fatty acid excretion and partially improved bile acid-related metabolic alterations. Untargeted serum metabolomics revealed that UMP reshaped metabolic pathways related to lipid turnover, bile acid signaling, glucose utilization, and glucuronidation. Correlation analysis linked UMP-enriched bacterial taxa with key metabolites involved in fatty acid and energy metabolism. Together, these findings indicate that UMP attenuates HFD-induced obesity through coordinated regulation of gut microbiota, intestinal metabolites, and systemic metabolic homeostasis. UMP may therefore represent a promising functional dietary protein for the prevention of obesity-related metabolic disorders. Full article

Sustained consumption of Western-style diets (WDs), rich in fat and cholesterol, challenges metabolic homeostasis and results in organ-specific alterations, notably hepatic lipid accumulation and adipose tissue dysfunction. Medicinal mushrooms such as Ganoderma lucidum have gained attention for their biological activities; however, the extent to which nutritionally realistic dietary intake of G. lucidum modulates tissue-specific metabolic adaptation under obesogenic conditions remains poorly defined. This exploratory study aimed to evaluate how dietary supplementation with a Ganoderma lucidum extract (GLE) modulates metabolic and organ-specific responses in a WD-fed preclinical mouse model. Forty-seven male C57BL/6J mice were assigned to five groups receiving a control diet (CTR), a cholesterol-enriched WD, or the WD supplemented with increasing concentrations of GLE (0.7%, 1.4%, or 2.8%). Over thirteen weeks, body mass and food and water intake were monitored weekly. Afterwards, mice were euthanized, and tissue and blood samples were collected for further analysis. Fasting glucose was lower in WD+2.8% GLE than in CTR, although no GLE-supplemented group differed significantly from WD and glucose tolerance was unchanged. All GLE-supplemented groups had a lower hepatic genetic damage index than WD. WD+1.4% GLE showed a higher frequency of localized periportal hepatic vacuolar changes than WD, whereas WD+2.8% GLE had lower relative liver weight. GLE supplementation was also associated with depot-specific variation in the occurrence of multilocular adipocytes with a beige-like appearance, without significant changes in final body mass or adiposity. In this preclinical model, subchronic dietary GLE was associated with selected tissue-specific differences, most consistently lower hepatic DNA damage and depot-specific variation in multilocular adipocyte morphology, without consistent systemic metabolic improvements. Full article

Background: Glucagon-like peptide-1 receptor agonists and dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 (GIP/GLP-1) receptor agonists have substantially improved the management of obesity and cardiometabolic disease, providing significant benefits on weight reduction, glycemic control, and cardiovascular outcomes. Despite these advances, gastrointestinal (GI) adverse events remain a major cause of dose reduction, treatment interruption, and poor long-term adherence. Increasing evidence suggests that interactions between incretin-based therapies and the intestinal microenvironment may contribute to GI tolerability and influence treatment persistence. Methods: We conducted a narrative review of the literature examining the relationship between incretin-based therapies, gut microbiota, intestinal barrier function, and microbial metabolites. Evidence from randomized clinical trials, observational studies, systematic reviews, and mechanistic investigations was evaluated to explore potential gut-directed supportive strategies during incretin-based treatment. Results: Preclinical and mechanistic evidence suggests possible bidirectional interactions between incretin pharmacology and the intestinal microenvironment, whereas direct human evidence remains limited and inconsistent. Alterations in gastrointestinal motility induced by GLP-1 receptor agonists could theoretically influence microbial composition and fermentation dynamics, although human studies have not consistently demonstrated significant microbiota changes. Based on these observations, we propose the Incretin–Microbiota Tolerance Axis (IMTA) as a conceptual framework linking gut homeostasis, GI tolerability, and treatment adherence. Among potential supportive interventions, partially hydrolyzed guar gum (PHGG) may promote SCFA-producing microbiota and improve bowel function, whereas simethicone may provide symptomatic relief of gas-related discomfort during dose escalation. SCFA-supportive nutritional approaches may further contribute to maintenance of intestinal homeostasis. Conclusions: Optimization of the intestinal microenvironment may represent a complementary strategy to improve GI tolerability and support long-term adherence during incretin-based therapy. Although the IMTA framework is supported by biological plausibility and emerging evidence, prospective clinical studies are required to determine whether microbiota-targeted interventions improve treatment persistence and cardiometabolic outcomes in patients receiving GLP-1 receptor agonists or dual GIP/GLP-1 receptor agonists. Full article

Magnesium is an essential mineral involved in numerous physiological and neurobiological processes. However, the biological effects of distinct Mg forms remain insufficiently characterized. This study compared the systemic and neurobiological effects of a multi-form Mg supplement (Magnesium Breakthrough™, Mg BT™, BIOptimizers, Reno, NV, USA) with commonly used single-form Mg compounds in a rat model. Sixty-day-old male Wistar rats were assigned to a control group or to groups receiving Mg BT™ or individual Mg compounds (oxide, citrate or glycinate). Treatments were administered by gastric gavage for 30 days at 50 mg/kg/day of elemental Mg. A comprehensive panel of endpoints was evaluated, including Mg distribution in biological fluids and tissues, metabolic markers, glucose tolerance, synaptic protein expression (synaptophysin, PSD95, phospho-PSD95, drebrin), cortical gene expression (NR2B, BDNF), behavioral outcomes, and liver and kidney histology. Magnesium from the multi-form supplement increased serum Mg without affecting glucose homeostasis and modulated proteins involved in synaptic plasticity, accompanied by mild anxiolytic-like effects without changes in locomotion. No adverse histological alterations were observed, while preserved renal CLDN-19 expression indicated maintained tubular integrity. These findings suggest that supplementation with the multi-form Mg BT™ supplement influences multiple evaluated biological domains, including systemic, behavioral and molecular parameters, with effects comparable to those observed with individual magnesium compounds under the experimental conditions applied. Full article

Metabolic reprogramming at the maternal–fetal interface remodels enzymes, metabolites, and pathways to orchestrate decidualization, placentation, and immune tolerance, thereby sustaining cellular homeostasis and maternal-fetal adaptation. Disruption of this precisely coordinated metabolic reprogramming impairs these processes, contributing to recurrent pregnancy loss (RPL). This review focuses on the two most abundant cell types at the maternal–fetal interface: maternal-derived decidual stromal cells (DSCs) and embryo-derived trophoblasts, and systematically delineates their metabolic reprogramming in healthy pregnancy versus RPL. Recent advances reveal that altered glucose, lipid, amino acid, redox, and one-carbon metabolism in DSCs and trophoblasts drives defective decidualization, placentation, and immune tolerance, offering novel mechanistic insights into RPL etiology. These findings highlight potential metabolic biomarkers and therapeutic strategies, bridging mechanistic discoveries with translational opportunities for RPL. Full article