Search Results (11,580)

3-Hydroxybutyric acid (3-HB) is a bioactive ketone body involved in the regulation of intestinal inflammation and metabolic homeostasis. Although engineered bacterial probiotics have been developed for localized 3-HB delivery, their susceptibility to antibacterial antibiotics may limit their use during concurrent antibiotic treatment. The probiotic yeast Saccharomyces boulardii offers an alternative host for intestinal 3-HB delivery because of its compatibility with antibacterial antibiotics and the availability of well-established genetic engineering tools. Here, we engineered S. boulardii for 3-HB production using Cas9-mediated genome editing. A heterologous 3-HB biosynthetic pathway was introduced into S. boulardii MYA-797, and endogenous acetyl-CoA and ethanol metabolism was subsequently rewired by overexpressing ACS1, deleting ADH1, and overexpressing ADH7. The optimized strain, SbDY02, produced 1.7 g/L 3-HB under microaerobic conditions. Oral administration of SbDY02 to C57BL/6J mice increased fecal 3-HB and short-chain fatty acid (SCFA) concentrations by 1.89-fold and 1.68-fold, respectively, compared with mice receiving the parental strain. Repeated administration also increased fecal acetate and circulating total SCFAs, butyrate, and propionate. In human colonic epithelial cells, purified 3-HB attenuated lipopolysaccharide-induced p38 MAPK phosphorylation, supporting its direct activity toward inflammation-associated epithelial signaling. To our knowledge, this study provides the first demonstration of a 3-HB-producing probiotic yeast and links central metabolic engineering of S. boulardii with increased 3-HB availability, altered SCFA profiles, and a host-relevant epithelial response. Full article

Junken meat sheep display distinct coat-color phenotypes, including a white body with a black head and an entirely black coat at birth, but the transcriptional basis of variation across skin regions and phenotypic backgrounds remains unclear. We performed bulk RNA sequencing (RNA-seq) on nine skin samples from six 1-month-old lambs: black-haired head skin (BT), white-haired dorsal trunk skin (WT), and black-haired dorsal trunk skin from lambs born entirely black (B), with three biological replicates per group. The paired BT–WT comparison characterized within-individual regional differences, whereas B–WT represented a composite phenotypic-background comparison. Cross-comparison integration identified 2056 region-associated genes, 8027 phenotypic-background-associated genes, and 5615 shared genes. Region-associated genes were enriched in mitochondrial and lipid-metabolic processes, phenotypic-background-associated genes in cell communication and adhesion, and shared genes in epidermal keratinization, cytoskeletal organization, and extracellular matrix–integrin-related processes. Network analysis identified a pigmentation-effector subnetwork containing TYR, TYRP1, PMEL, OCA2, SLC45A2 and MYO5A. Signature scoring suggested that some contractile signals may reflect tissue-composition differences. Reverse transcription quantitative PCR broadly supported the RNA-seq expression trends. These findings provide a multilayered transcriptional framework for subsequent functional validation of coat-color variation in Junken meat sheep. Full article

The rice field eel (Monopterus albus) is an economically important aquaculture species widely distributed in Southeast Asia. However, the lack of nationally approved varieties and the increasing demand for high-quality eel products have highlighted the necessity of developing improved germplasm resources for aquaculture production. In this study, morphometric morphology and muscle texture traits were evaluated in 367 wild eel individuals, and a genome-wide association study (GWAS) based on whole-genome resequencing was conducted to identify genetic variants and candidate genes associated with economically important traits, including body length (BL), tail length (TL), tail height (TH), head length (HL), head width (HW), head height (HH), hardness, chewiness, springiness, and resilience. The GWAS identified three significant and seventeen suggestive SNPs associated with body shape traits, with most loci located on chromosome 4. Candidate gene analysis of the associated genomic regions revealed several candidate genes potentially associated with growth regulation, nutrient metabolism, and skeletal development, including b4galnt4a, tmem86a, cpt1b, mrpl23, lama1, gcm2, wnt3a, thrab, and bmpr1a. Additionally, four suggestive SNPs associated with muscle texture traits were detected, and candidate genes related to muscle development and extracellular matrix regulation, including fstl1b, col5a3a, and pnn, were identified. These findings provide new insights into the genetic basis underlying morphometric variation and muscle texture diversity in M. albus. The identified SNP markers and candidate genes provide potential molecular resources for understanding the genetic basis of body morphology and muscle texture variation in rice field eel. Full article

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes (T2DM) have been associated with dyslipidemia. This study aimed to investigate the association between lipid values and markers of hepatic steatosis and fibrosis in patients with T2DM. Methods: This is a post hoc analysis of the AleCardio randomized controlled trial in patients with T2DM and recent acute coronary syndrome. Risk of liver steatosis was estimated with the Hepatic Steatosis Index (HSI), risk of liver fibrosis with the NAFLD Fibrosis Score (NFS). Results: Of 7226 participants, 526 were untreated with lipid-lowering medication and formed the analysis cohort. Mean age was 61 ± 10 years, and body mass index (BMI) was 28.5 ± 5.8 kg/m². A total of 75% of individuals had an HSI score > 36, associated with high risk of liver steatosis, elevated NFS scores > 0.67, associated with high risk of liver fibrosis, were present in 15%. Patients with elevated HSI scores had higher BMI, HOMA IR, triglycerides, remnant cholesterol, and lower high-density lipoprotein compared to those with lower scores. Patients with elevated NFS scores had greater BMI and HOMA IR, and had lower triglycerides, remnant cholesterol, and apolipoprotein B in linear regression analyses. Conclusion: Patients with T2DM, cardiovascular disease, and blood-based indices suggesting liver steatosis or fibrosis differed significantly with respect to the lipid profile. An elevated HSI score, suggesting steatosis, was associated with dyslipidemia, an elevated NFS score, suggesting fibrosis, was not. A possible explanation for the latter findings is reduced very-low-density lipoprotein (VLDL-C) synthesis or secretion accompanying advanced hepatocellular dysfunction. Full article

Metabolic dysfunction-associated steatohepatitis (MASH), a progressive form of metabolic dysfunction-associated steatotic liver disease, affects approximately 3–5% of the global population and lacks effective therapies. This study examined the impact of near-thermoneutral housing on MASH progression in mice fed a fast-food diet (FFD) enriched in fat, sucrose, and cholesterol. Male C57BL/6J mice were housed under standard (22 °C) or near-thermoneutral (27 °C) conditions and fed chow or FFD for 20 weeks. Body weight, composition, liver pathology, hepatic gene expression, plasma lipids, and adipose thermogenic and inflammatory markers were assessed. FFD increased body weight, fat mass, and lean mass at both temperatures. Near-thermoneutral housing markedly exacerbated MASH in FFD-fed mice, with increased steatosis, fibrosis, inflammation, and elevated liver enzymes. Hepatic lipogenic and fibrosis-related gene expression was upregulated, alongside higher plasma total cholesterol and very-low-density lipoprotein levels. Near-thermoneutral housing also impaired brown adipose tissue thermogenesis, reducing uncoupling protein 1 and other thermogenic genes, and modestly altered inguinal white adipose tissue inflammation and thermogenic signaling. These findings demonstrate that near-thermoneutral housing accelerates MASH progression, accompanied by increased hepatic lipid accumulation, fibrosis, and inflammation and reduced adipose thermogenic signatures. These findings identify environmental temperature as a critical modifier of MASH pathophysiology and suggest that enhancing adipose thermogenesis may offer therapeutic potential. Full article

Diabetes mellitus (DM) is a chronic metabolic disease which, if left untreated or poorly controlled, can lead to serious complications. This global public health challenge is frequently associated with a deficit of Mg, which is one of the most important elements in the human body and is indispensable for many metabolic processes and the maintenance of human health. Due to its antioxidant and anti-inflammatory properties, its mitochondrial-supportive function, and its crucial role in the secretion and action of insulin as well as metal ion homeostasis, Mg may have great potential in the treatment of diabetes and diabetic complications. Therefore, we collected studies on a possible association between Mg and diabetes in humans. In other words, we intended to summarize data on the efficacy of oral Mg supplementation on glycemic and insulinemic parameters and Mg levels in biological specimens from humans with DM, gestational diabetes (GDM), insulin resistance (IR), and prediabetes (Pre-D). Our work indicates that, in some cases, supplementation with Mg may improve glycemic and/or insulinemic indices in hypo- or normomagnesemic individuals suffering from diabetes or IR. However, the results of certain studies did not show any beneficial effects of Mg intervention. Therefore, based on the findings presented in the current review, it can be concluded that further long-term studies on a larger population are required to demonstrate the efficacy of oral Mg supplementation in hypo- or normomagnesemic subjects with diabetes or at risk of developing the disease. It also seems justified to introduce routine determination of blood Mg levels (especially the ionized Mg form) in patients with diabetes and in those at risk of IR and glucose metabolism disorders. Moreover, it remains to be clearly determined which patients could benefit most from supplementation with this mineral, as its deficiency may impair insulin sensitivity and glucose uptake. To sum up, the results reviewed in the present report do not definitively indicate that supplementation with Mg may be regarded as a public health strategy for improving the outcomes of diabetes despite the fact that, in some cases, Mg has been reported to have a positive effect on the metabolic profile in subjects with diabetes and may be used as an adjuvant therapy of this modern-age disease. Full article

Background/Objectives: Metabolic syndrome (MetS) and low socioeconomic status (SES) are each established drivers of coronary artery disease (CAD), a leading cause of acute cardiovascular presentations to emergency and acute care services. Whether SES modifies the long-term association between MetS and CAD in a universal health coverage setting is unclear. We examined the independent and joint associations of MetS and income-based SES with 20-year incident CAD. Methods: In this nationwide retrospective cohort study using the Korean National Health Insurance Service database, 489,521 adults aged 40–79 years who underwent a national health examination in 2005 and were free of CAD at baseline were followed through 31 December 2024 (up to 20 years). At baseline, the mean age was 54.1 ± 9.2 years, and 252,818 participants (51.6%) were men. MetS was defined by modified harmonized criteria, with body mass index (BMI) ≥ 25 kg/m² substituted for waist circumference. SES was measured by health insurance premium deciles and classified as high (deciles 8–10), middle (4–7), low income (1–3), and Medical Aid (decile 0). The outcome was incident CAD (myocardial infarction or angina pectoris). Multivariable Cox proportional hazards models were adjusted for age, sex, smoking, alcohol consumption, regular exercise, BMI, chronic kidney disease, alternate exposure, and estimated adjusted hazard ratios (aHRs); joint exposure and additive interaction (relative excess risk due to interaction, RERI) were assessed. Results: MetS prevalence was 30.6%. During follow-up, 48,428 participants (9.9%) developed CAD. MetS was independently associated with CAD (aHR 1.84; 95% CI 1.78–1.91), as was a graded socioeconomic gradient (Medical Aid vs. high SES aHR 1.62; 1.54–1.70). Incidence rates ranged from 3.13 (high-SES without MetS) to 11.40 (Medical Aid with MetS) per 1000 person-years. In the joint analysis, Medical Aid beneficiaries with MetS had the highest risk (aHR 2.92; 2.78–3.08 vs. high-SES without MetS; p for interaction < 0.001), with positive additive interaction (RERI 0.68). Conclusions: Over two decades, low SES amplified the CAD burden associated with MetS. Adults living in the most severe material deprivation who also had MetS constituted the highest risk group, of direct relevance to risk stratification and disparities in emergency and acute cardiovascular care. Full article

Metabolic rate is closely linked to body mass and is widely used to relate physiological processes to ecological and evolutionary patterns. In small aquatic organisms, measurements of oxygen consumption rate ($M{o}_2$) are often limited by instrument sensitivity. Although pooled respirometry is commonly used as a practical alternative, its reliability remains insufficiently evaluated in small freshwater invertebrates. This study examined measurement consistency among respirometry approaches and explored the relationship between body mass and metabolic rate in the freshwater shrimp Neocaridina denticulata. Oxygen consumption rate was measured in single individuals and pooled groups of three and five individuals. No significant differences were detected among treatments (one-way ANOVA, p > 0.05), and estimates were generally comparable across methods. Metabolic rate increased with body mass (R² = 0.746), and log–log regression yielded a scaling exponent of 0.99 (95% CI: 0.75–1.22), indicating an approximately isometric relationship. Overall, pooled respirometry produced results comparable to individual measurements. Within the experimental range examined, pooled respirometry provided reliable metabolic estimates without detectable systematic bias. These findings provide preliminary experimental support for pooled respirometry as a practical approach for metabolic measurements of small N. denticulata within the experimental conditions examined, particularly when individual measurements are constrained by instrument sensitivity. Full article

Pumpkin (Cucurbita pepo L.) seed oil (PSO) is rich in polyunsaturated fatty acids and bioactive compounds, but evidence regarding its biological effects in small ruminants remains limited. This study evaluated the effects of oral PSO supplementation in 45 clinically healthy weaned male Pırlak lambs with a mean initial age of 119.64 ± 35.25 days and a mean initial body weight of 37.55 ± 9.77 kg, allocated to three groups: control (n = 9), 0.5 mL/kg PSO (n = 18), and 1 mL/kg PSO (n = 18). PSO was administered orally once daily for 45 days. Body weight was measured, and blood samples were collected on days 0, 15, 30, and 45. Serum growth hormone, immunoglobulin G (IgG), oxidative status, and selected biochemical parameters were evaluated. PSO supplementation did not significantly affect body weight gain or serum growth hormone concentrations. Total oxidant status was lower in both PSO groups than in the control group on day 30, whereas the oxidative stress index was lower in the 1 mL/kg group than in the control group on day 45. Serum IgG concentrations were higher in the PSO groups throughout the study, although between-group differences were already present at baseline. Serum high-density lipoprotein cholesterol (HDL) concentrations increased over time, particularly in the 1 mL/kg group, whereas low-density lipoprotein cholesterol (LDL) concentrations remained unchanged. Serum glucose concentrations decreased over time and were lower on day 45 than at baseline. No consistent dose-dependent adverse changes were observed in liver or kidney function indicators. Oral PSO supplementation did not improve growth performance but was associated with selective changes in oxidative balance and lipid metabolism without evident hepatic or renal adverse effects. Longer-term studies are required to confirm these effects and clarify their biological significance. Full article

Ageing and obesity represent major public health challenges and are associated with metabolic dysfunction, chronic inflammation, and loss of skeletal muscle mass. Resistance training (RT) is an effective strategy to increase muscle mass; however, its effects on metabolic and immune parameters in older women with obesity remain unclear. The study aimed to compare the effects of 12-week progressive overload RT programme on metabolic and immune responses in women aged 60–79 years with obesity and normal-weight women. Thirty older women were allocated into two groups according to body composition: women with obesity (OB: 68 ± 4.21 years; body mass index [BMI] = 33.01 ± 2.62 kg/m²; body fat percentage = 42.23% ± 2.98%; n = 16) and normal-weight women (NW: 66 ± 4.31 years; BMI = 22.60 ± 1.36 kg/m²; body fat percentage = 33.11% ± 3.61%; n = 14). At baseline, the OB group showed higher serum concentrations of leptin, insulin, triglycerides, and HOMA-IR and lower HDL cholesterol concentrations compared with the NW group, while no differences were observed in circulating cytokines or NETosis. After 12 weeks of RT, fasting glucose decreased only in the OB group (p = 0.030). Both groups exhibited reductions in total cholesterol and adiponectin, along with an increase in NETosis. Leptin, insulin, and pro-inflammatory cytokines were associated with lower muscle quality, whereas higher baseline adiponectin concentrations were associated with greater muscle mass gains in the NW group (p < 0.05). In conclusion, baseline metabolic differences were observed between normal-weight older women and those with obesity; however, both groups showed changes after 12 weeks of RT in metabolic and immune parameters. Furthermore, higher baseline adiponectin concentrations were associated with greater muscle mass gains in the NW group. Full article

Background: Achieving remission of type 2 diabetes mellitus (T2DM) after bariatric surgery represents a critical opportunity to reduce long-term diabetes-related complications, including cardiovascular disease, nephropathy, neuropathy, and retinopathy. However, remission rates vary widely across patients, and identifying modifiable clinical and behavioral determinants remains essential for optimizing integrated metabolic care. Objectives: In the current study, we aimed to (1) classify type 2 diabetes mellitus (T2DM) remission status after bariatric surgery through clinical, anthropometric, and behavioral variables at follow-up; (2) identify the main model-based determinants of remission status and explainable machine learning using the preoperative model for baseline risk stratification with surgical candidates. Methods: We performed a retrospective cross-sectional study on 233 patients with T2DM who had bariatric surgery at a tertiary referral center. We made use of two analytical frameworks: a full-feature approach to identify the current remission status in a cross-sectional manner and a preoperative approach to make a temporal classification of the baseline for the first time. We trained and internally assessed 14 machine learning and deep learning classifiers. We evaluated model interpretability using SHAP. Results: In the full-feature cross-sectional classification, the Bottleneck Network performed best (ROC AUC = 0.889). SHAP data identified percentage weight regain, pre- and post-surgical body mass index, HbA1c, and oral hypoglycemic agent use as the dominant model-associated factors. In the restricted preoperative setting, the Extra Trees model achieved an AUC of 0.707, which is a lower level but still represents good baseline risk stratification performance. Conclusions: The findings indicate that remission status after bariatric surgery is both clinical as well as behavioral, but the post-operative or contemporaneously assessed variables should be looked at as classification (as opposed to prediction) models. The preoperative model may be able to be used in risk stratification, but clinical validation and prospective evaluation should be made prior to 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: Metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with ectopic fat accumulation and alterations in adipose tissue function. However, the relationships of structural and thermogenic adipose imaging markers with hepatic steatosis remain incompletely understood. This study aimed to jointly evaluate the cross-sectional associations of epicardial adipose tissue (EAT) thickness and infrared thermography (IRT)-derived brown adipose tissue (BAT)-related thermogenic activity with controlled attenuation parameter (CAP)-defined hepatic steatosis severity in adults with suspected MASLD. Methods: In this cross-sectional study, 207 adults undergoing clinical evaluation for suspected MASLD underwent transient elastography to obtain the controlled attenuation parameter (CAP) for hepatic steatosis assessment. EAT thickness was measured by transthoracic echocardiography, and BAT-related thermogenic activity was assessed by infrared thermography using the supraclavicular-to-chest temperature difference (ΔTemp). Associations of these adipose imaging phenotypes with CAP were evaluated using correlation analyses, sequential multivariable linear regression models, and BAT-stratified analyses. Results: EAT thickness increased progressively across CAP-defined steatosis grades (p < 0.001) and was positively correlated with CAP (r = 0.637, p < 0.001), whereas ΔTemp decreased with increasing steatosis severity and was inversely correlated with CAP (ρ = −0.277, p < 0.001). In sequential multivariable regression models, EAT thickness remained independently associated with CAP across adjustments for age, sex, body mass index, metabolic variables, and ΔTemp (standardized β = 0.559–0.623; all p < 0.001). Both EAT thickness and ΔTemp were independently associated with CAP in the fully adjusted model, with a stronger association for EAT thickness (standardized β = 0.559 vs. −0.167; p < 0.001 and p = 0.004, respectively). Stratified analyses demonstrated consistent associations between EAT thickness and CAP across both BAT-low and BAT-high activity groups. Conclusions: Greater EAT thickness and lower IRT-derived ΔTemp were independently associated with greater CAP-defined hepatic steatosis severity, with EAT thickness showing the stronger standardized association. These complementary structural and thermogenic imaging correlates warrant prospective evaluation to clarify their directionality and clinical relevance. Full article

Depression (major depressive disorder, MDD) is a globally prevalent, highly disabling, and complex mental disorder whose pathogenesis has not been fully elucidated. In recent years, the role of the gut microbiota in depression via the “microbiota–gut–brain axis” (MGB axis) has attracted increasing attention. A large body of evidence indicates that the gut microbiota and its metabolites can engage in bidirectional communication with the central nervous system through three core pathways—neural, immune, and metabolic—thereby profoundly influencing the onset and progression of depression. This article reviews the specific mechanisms by which the gut microbiota affects depression through the aforementioned pathways, including regulating the balance of neurotransmitters (e.g., GABA and 5-HT), mediating neuroinflammatory responses, and adjusting the levels of metabolites such as short-chain fatty acids. This study aims to provide a theoretical basis for an in-depth understanding of the pathophysiological mechanisms of depression and the development of novel microbiota-based intervention therapeutic strategies. Full article

Intensive yak fattening in cold alpine regions requires essential long-term high-concentration feeding, which disrupts rumen microbial homeostasis and causes inefficient digestion of nutrients. Lactobacillus may have probiotic potential for ruminants, yet its regulation of rumen function is poorly understood under high-energy diets. During a 120-day feeding experiment, 120 male Pamir yaks were allocated to four dietary treatments, with LEG and LLG serving as the primary comparison for evaluating 0.02% Lactobacillus supplementation to explore the regulatory effects of Lactobacillus supplementation on the rumen microbiota and host metabolism of yaks during a fattening process based on a concentrate feed diet via phenotypic data (body wight and nutrient digestibility) and multi-omics analyses (rumen microbial sequencing and rumen epithelial transcriptome) in a concentrate-based rearing yak model. The results showed that Lactobacillus intervention reduced OTU (Operational Taxonomic Unit) richness during the early fattening period and subsequently promoted microbial recovery through colonization resistance, which significantly enhanced microbial diversity (p < 0.05), and restructured the microbial community structure toward efficient energy utilization under high-concentrate feeding by reducing Prevotellaceae and Ruminococcaceae abundance, increasing the Bacillota/Bacteroidota ratio (p < 0.05). Concurrently, Lactobacillus enhanced the apparent digestibility of dry matter, crude protein, and fibrous components (p < 0.05). According to the transcriptomic analysis, there was an activation of signaling pathways related to IL-18 and TNF, and up-regulation of immune-and metabolism-related genes, in addition to strengthening the rumen mucosal barrier function. Multi-omics integration supported that dietary supplementation of Lactobacillus can optimize rumen fermentation, enhance nutrient digestion, and strengthen immune defense in Pamir yaks fed high-concentrate in cold seasons. These modifications demonstrate the positive effects of the Lactobacillus supplementation strategy on yak rumen health without interfering with the high-energy intensive rearing pattern. The present research presents a scientific basis for the use of targeted probiotic strategies to improve the rumen health and efficiency of alpine yak production systems. Full article