Search Results (152)

High temperature typically decreases feed intake, milk production, and efficiency and increases metabolic disorders and health problems, greatly impacting farm economics. Supplements based on Saccharomyces cerevisiae have been suggested to benefit cows under heat stress, but effects on dairy cow performance are contradictory. This study aimed to evaluate the influence of heat stress on the effects of live yeast supplementation on the performance of dairy cows. Environmental temperature parameters were compared to two thermal humidity indices (THI1 and THI2) using wet bulb or dew point temperatures, as explanatory variables of dairy cow performance during the hot season. The experiment followed a randomized complete block design with 12 Holstein cows blocked by lactation number, days in milk, and milk production (two cows per block) and within each block, each cow was randomly assigned to a maize silage-based TMR with a concentrate mixture containing no yeast culture (Control) or 1 g/kg concentrate dry matter of a live yeast culture based on S. cerevisiae (Yeast) for 35 days. The experiment lasted for 35 d. Dry matter intake (DMI) was significantly higher for Yeast than it was for Control for all classes of temperature and THIs studied with an average increase of 2 kg DM per day, except for mean THI1 (from 54 to 60), for which the DMI was similar between treatments. Yeast promoted significantly higher milk yield than Control for all classes of daily maximum and mean temperature, averaging an increase of 4 kg of milk per day. Results suggest a more marked effect of temperature and indicate that yeast supplementation improved lactation performance of dairy cows exposed to hot weather. Full article

The transition period in dairy cows, spanning late pregnancy and early lactation, is associated with substantial metabolic and immunological challenges, leading to increased oxidative stress and inflammation. Selenium (Se), particularly in organic forms, supports antioxidant defenses, immune function, and metabolic regulation. This study investigated the effects of supplementing periparturient Holstein–Friesian cows with orally administered selenitetriglycerides (0.5 mg Se/kg body weight/day starting 12 days before the expected calving date and continuing until parturition) on antioxidant enzyme activity and on the hepatic expression of key inflammatory and metabolic genes. Serum selenium concentrations and erythrocyte glutathione peroxidase (GSH-Px) activity were assessed before and after parturition, and hepatic gene expression levels of tumor necrosis factor alpha (TNF-α), peroxisome proliferator-activated receptor alpha (PPAR-α) and delta (PPAR-δ) were assessed 24 h and 7 days postpartum. Supplemented cows showed significantly elevated serum Se levels and increased GSH-Px activity, reflecting improved antioxidant capacity. Moreover, hepatic expression of TNF-α and PPAR-δ was significantly reduced postpartum in the supplemented group, whereas PPAR-α expression remained stable. These findings indicate that selenitetriglycerides effectively enhance antioxidant defenses, moderate inflammation, and stabilize metabolic pathways during the periparturient phase, potentially reducing postpartum metabolic disorders and improving dairy-cow health. Full article

Oxidative and inflammatory stresses contribute to the development of many intestinal pathologies. This study characterized the polyphenolic profile and biological activity of a hydroalcoholic extract obtained from the fruit pulp of Feijoa sellowiana on HT29 intestinal epithelial cells subjected to oxidative (H₂O₂) and inflammatory (cytokines) stress. HPLC-DAD-MS analysis revealed an interesting phenolic composition, rich in hydrolyzable tannins (HHDP-glucose, pedunculagin and other ellagic acid derivatives) and condensed tannins (procyanidin dimers), with a total polyphenol content of 8.07 mg/g GAE. The extract was non-cytotoxic up to 160 µg/mL and exerted a protective effect against the cytokine-induced reduction in cell viability. In vitro assays confirmed its strong antioxidant and scavenging capacity. The scratch assay suggested enhanced cell migration. The extract modulated the activity of key metabolic enzymes restoring glucose-6-phosphate dehydrogenase and enolase activity, while supporting glycolytic flux through pyruvate kinase and lactate dehydrogenase. PCA and Pearson correlation analyses confirmed a treatment-dependent modulation of the metabolic and redox profile, suggesting a regulatory role beyond a mere scavenging effect. These findings highlight the nutraceutical potential of feijoa polyphenols, not only as direct antioxidants but also as modulators of cellular metabolism and redox homeostasis, supporting their application in gastrointestinal disorders with oxidative or inflammatory components. Full article

Background: Dietary advice for Paralympic athletes (PAs) with a spinal cord injury (PAs-SCI) requires particular attention and has been widely studied. However, currently, no particular attention has been addressed to nutritional guidelines for athletes with an amputation (PAs-AMP). This study aimed at filling up this gap, at least partially, and compared veteran PAs-SCI with PAs-AMP. Methods: A sample of 25 male PAs (12 with SCI and 13 with AMP), recruited during two training camps, was submitted to the following questionnaires: allergy questionnaire for athletes (AQUA), Nordic Musculoskeletal Questionnaire (NMQ), Starvation Symptom Inventory (SSI), neurogenic bowel dysfunction (NBD), orthorexia (ORTO-15/ORTO-7), alcohol use disorders identification test (AUDIT), and Mediterranean diet adherence (MDS). The PAs were also submitted to the following measurements: dietary Oxygen Radical Absorbance Capacity (ORAC) and intakes, body composition, handgrip strength (HGS), basal energy expenditure (BEE), peak oxygen uptake (VO_2peak), peak power, peak heart rate (HR), post-exercise ketosis, and antioxidant response after a cardiopulmonary exercise test (CPET) to voluntary fatigue. Results: Compared to PAs-AMP, PAs-SCI had higher NBD and lower VO_2peak (p < 0.05), peak power, peak HR, peak lactate, phase angle (PhA) of the dominant leg (p < 0.05), and ORTO15 (p < 0.05). The latter was related to NBD (r = −0.453), MDS (r = −0.638), and ORAC (r = −0.529), whereas ORTO7 correlated with PhA of the dominant leg (r = 0.485). Significant differences between PAs-AMP and PAs-SCI were not found in the antioxidant response, glucose, and ketone levels after CPET, nor in dietary intake, AUDIT, AQUA, NMQ, SSI, BEE, HGS, and FM%. Conclusions: The present study showed that PAs-SCI and PAs-AMP display similar characteristics in relation to lifestyle, energy intake, basal energy expenditure, and metabolic response to CPET. Based on both the similarities with PAs-SCI and the consequences of the limb deficiency impairment, PAs-AMP and PAs-SCI require personalized nutritional advice. Full article

The gut microbiota of macaques, highly homologous to humans in biological characteristics and metabolic functions, serves as an ideal model for studying the mechanisms of human intestinal diseases and therapeutic approaches. A comprehensive characterization of the macaque gut microbiota provides unique insights into human health and disease. This study employs metagenomic sequencing to assess the gut microbiota of wild M. mulatta brevicaudus across various ages, sexes, and physiological states. The results revealed that the dominant bacterial species in various age groups included Segatella copri and Bifidobacterium adolescentis. The predominant bacterial species in various sexes included Alistipes senegalensis and Parabacteroides (specifically Parabacteroides merdae, Parabacteroides johnsonii, and Parabacteroides sp. CT06). The dominant species during lactation and non-lactation periods were identified as Alistipes indistinctus and Capnocytophaga haemolytica. Functional analysis revealed significant enrichment in pathways such as global and overview maps, carbohydrate metabolism and amino acid metabolism. This study enhances our understanding of how age, sex, and physiological states shape the gut microbiota in M. mulatta brevicaudus, offering a foundation for future research on (1) host–microbiome interactions in primate evolution, and (2) translational applications in human health, such as microbiome-based therapies for metabolic or immune-related disorders. Full article

Background/Objectives: An important new consideration when studying autism spectrum disorder (ASD) is the bioenergetic mechanisms underlying the relatively recent rapid evolutionary expansion of the human brain, which pose fundamental risks for mitochondrial dysfunction and calcium signaling abnormalities and their potential role in ASD, as recently highlighted by insights from the BTBR mouse model of ASD. The rapid brain expansion taking place as Homo sapiens evolved, particularly in the parietal lobe, led to increased energy demands, making the brain vulnerable to such metabolic disruptions as are seen in ASD. Methods: Mitochondrial dysfunction in ASD is characterized by impaired oxidative phosphorylation, elevated lactate and alanine levels, carnitine deficiency, abnormal reactive oxygen species (ROS), and altered calcium homeostasis. These dysfunctions are primarily functional, rather than being due to mitochondrial DNA mutations. Calcium signaling plays a crucial role in neuronal ATP production, with disruptions in inositol 1,4,5-trisphosphate receptor (ITPR)-mediated endoplasmic reticulum (ER) calcium release being observed in ASD patient-derived cells. Results: This impaired signaling affects the ER–mitochondrial calcium axis, leading to mitochondrial energy deficiency, particularly in high-energy regions of the developing brain. The BTBR mouse model, with its unique Itpr3 gene mutation, exhibits core autism-like behaviors and metabolic syndromes, providing valuable insights into ASD pathophysiology. Conclusions: Various interventions have been tested in BTBR mice, as in ASD, but none have directly targeted the Itpr3 mutation or its calcium signaling pathway. This review presents current genetic, biochemical, and neurological findings in ASD and its model systems, highlighting the need for further research into metabolic resilience and calcium signaling as potential diagnostic and therapeutic targets for ASD. Full article

Ketosis and fatty liver syndrome are metabolic disorders apparent in dairy cows during the transition period. The study focused on examining how varying levels of milk production in dairy cows might reflect or influence specific blood biochemical markers and liver health as assessed through ultrasonography. A total of 65 Holstein-Friesian cows from six farms were evaluated at three time points as follows: 7 days before expected calving and at 7 and 21 ± 3 days postpartum. Each evaluation included the body condition score (BCS), blood sampling for biochemical analysis, and liver ultrasonography. Based on average farm milk yield, cows were divided into three production groups as follows: GR1 (38.4 ± 6.45 L/day, n = 23), GR2 (42.9 ± 2.77 L/day, n = 24), and GR3 (45.69 ± 7.49 L/day, n = 18). Parameters assessed included liver lipid content and ultrasonographic measurements such as portal vein diameter and depth, liver depth, and liver angle. Significant time-dependent changes were observed in liver size, fat metabolism, and electrolyte balance, especially postpartum. However, no significant differences emerged among the production groups, indicating that these changes likely represent physiological adaptations to lactation. These findings support the use of blood analysis and ultrasonography as practical, minimally invasive tools for routine metabolic health monitoring in dairy cows during the transition period. Full article

This study systematically investigated the effects of dietary tea polyphenols (TPs, major bioactive polyphenols from Camellia sinensis with potent antioxidant and anti-inflammatory properties) on the growth performance and intestinal health of hybrid crucian carp HCC2 under chronic crowding stress. A low-density control group (44.4 fish/m³, basal diet without TPs) and four high-density crowding stress groups (222.2 fish/m³) were established, one fed the basal diet without TPs (CS) and three fed basal diets supplemented with 100 (CSLTP), 200 (CSMTP), or 400 (CSHTP) mg/kg TPs. We analyzed the impacts of TPs on growth performance, serum biochemical parameters, antioxidant capacity, expression of lipid metabolism-related genes, and intestinal microbiota composition. The results demonstrated that chronic crowding stress significantly suppressed the final body weight, weight gain rate, and specific growth rate of HCC2, while increasing serum lactate LDH, TG, and ALB and decreasing GLU, LDL-C, ALT, AST, and ALP levels. Dietary TPs supplementation enhanced antioxidant capacity (T-AOC, SOD, CAT, and GSH) and alleviated lipid metabolic disorders by activating the Nrf2/Keap1 and PPARα signaling pathways, thereby upregulating the expression of liver antioxidant genes (CAT and SOD) and fatty acid oxidation genes (CPT1 and acox1). Furthermore, intestinal microbiota analysis revealed that chronic crowding stress significantly increased the abundance of Proteobacteria and decreased the proportion of Firmicutes compared to the low-density control. Dietary TPs intervention, particularly at higher doses, partially restored the Firmicutes abundance and reduced the enrichment of potential pathogenic bacteria associated with stress. This study is the first to comprehensively elucidate the mechanism by which TPs alleviate crowding stress through enhanced antioxidant capacity, metabolic regulation, and microbiota remodeling, providing robust theoretical support for the application of plant-based additives in aquaculture. Full article

Background/Objectives: Diets high in simple carbohydrates and saturated fats, commonly consumed in Westernized countries, have been linked to a greater predisposition to metabolic disorders, which are partly attributed to oxidative stress. This study aimed to investigate the impact of an obesogenic diet consumed during the pregnancy and lactation periods on hepatic metabolism and REDOX balance in rats. Methods: Sixteen pregnant Wistar rats were divided into two groups: control (CD), which received a vivarium diet, and obesogenic (OD), which received an obesogenic diet (high-fat diet plus condensed milk), from early pregnancy to late lactation. Thirty-six hours after weaning, the rats were euthanized, and blood, adipose tissue, and liver samples were collected for analysis. Results: These results demonstrate that exposure to an obesogenic diet during pregnancy and lactation in rats leads to adverse changes in hepatic metabolic, inflammatory, and REDOX balance. This experimental animal model serves as a valuable tool for investigating the mechanisms of metabolic dysfunction associated with diets that mimic human eating habits. However, it is essential to note that these findings pertain to an experimental model and therefore require validation in clinical studies to confirm their relevance and applicability in human health. Conclusions: The consumption of an obesogenic diet during pregnancy and lactation in rats induces adverse alterations in hepatic metabolic, inflammatory, and redox homeostasis. This animal model helps investigate the mechanisms of metabolic dysfunctions associated with human dietary habits. However, these findings still need to be confirmed in clinical studies to verify their relevance in humans. Full article

Salivary cortisol is widely used to assess stress and circadian rhythms, yet its control variables in neonates, particularly regarding postnatal age, remain poorly understood. To elucidate age-specific effects of clinical variables on cortisol levels, 91 neonates with a mean (standard deviation) gestational age of 34.2 (3.8) weeks and postnatal age of 38.3 (35.4) days were categorised into Early, Medium, and Late groups by quartiles (days 10 and 56). Interactions with postnatal age were evaluated by comparing Early-to-Medium or Early-to-Late differences in regression coefficients between independent variables and cortisol levels. In the whole cohort, maternal hypertensive disorders of pregnancy and morning sampling were associated with reduced cortisol levels (both p = 0.001). Mean regression coefficients (95% CI) between variables and cortisol levels were as follows: for postconceptional age, Early, −0.102 (−0.215, 0.010) and Late, 0.065 (−0.203, 0.332) (p = 0.035); for feeding duration, Early, 0.796 (−0.134, 1.727) and Late, −0.702 (−2.778, 1.376) (p = 0.010); for time elapsed since feeding, Early, −0.748 (−1.275, −0.221) and Late, −0.071 (−1.230, 1.088) (p = 0.036); and for blood lactate, Early, 0.086 (0.048 to 0.124), Medium, 0.022 (−0.063, 0.108), and Late, −0.018 (−0.106, 0.070) (p = 0.008 and <0.001 vs. Medium and Late, respectively). The influence of postconceptional age, oral feeding, and anaerobic metabolism on salivary cortisol levels was observed during the birth transition period but not beyond 10 days of life. Given the age-specific dependence of cortisol levels on clinical variables, including postconceptional age, feeding, and oxygen metabolism, caution is warranted when interpreting findings from studies on salivary cortisol in newborn infants. Full article

Hyperketonemia (HYK) is a common disorder in high-producing dairy cows, resulting in significant economic losses. Defined by elevated beta-hydroxybutyrate (BHB; ≥1.2 mmol/L) without clinical signs, HYK is often considered a gateway disease, predisposing cows to other metabolic and infectious problems. Our objective was to investigate the association between previous lactation risk factors and both BHB concentration and HYK status during the first week postpartum in the subsequent lactation. A retrospective study was conducted using previously collected blood samples from 2336 Holstein multiparous dairy cows from 7 dairy herds, where BHB concentration was measured during the first week postpartum. Data from the previous lactation were extracted from electronic farm records. Log-transformed BHB concentrations and HYK status were each modeled using separate linear mixed models. Both models included the same set of risk factors—lactation, previous lactation total times bred, dry length period, previous lactation days in milk, previous lactation days open, previous lactation days carried calf, previous lactation peak milk production, previous lactation total milk production, previous lactation total milk fat, and previous lactation total milk protein—to investigate their association with these outcomes. Potential confounding variables were offered to the models, and stepwise backward elimination was used to determine which covariates to retain. Significant associations were detected between BHB concentration and dry period length (DDRY), lactation number (LACT), previous lactation total milk protein (TOTP), and previous lactation days open (PDOPN). Inclusive, significant associations were detected between HYK status and previous lactation total milk production (PTOTM), DDRY, LACT, TOTP, and PDOPN. Our results suggest that a dry period longer than 60 days, days open exceeding 130 days, being in their third or greater lactation, and each additional 1000 kg of milk produced in the previous lactation are associated with an increased risk of having high BHB and HYK in the first week postpartum in the subsequent lactation. Full article

A balanced excitatory/inhibitory (E/I) tone is crucial for proper brain function, and disruptions can lead to neurological disorders. This review explores the role of astrocytes in maintaining a balanced E/I tone in the brain, which is crucial for proper functioning. It highlights the potential for dysfunctional astrocyte metabolism to disrupt E/I balance, leading to neuronal dysfunction and potentially causing neurological disease pathogenesis. The review focuses on glucose, lactate shuttling, and glutamate metabolism. This review synthesizes findings from in vitro, in vivo, and human studies examining the interplay between astrocyte metabolism, neuronal activity, and E/I balance. Literature searches were conducted using keywords including “astrocyte metabolism”, “excitatory/inhibitory balance”, “glutamate”, “lactate shuttle”, “neurometabolic coupling”, and “neurological disorders” in databases such as PubMed and Web of Science. Disruptions in astrocyte glucose uptake or glycolysis can impair lactate production, reducing neuronal energy supply and affecting neuronal excitability. Impaired glutamate uptake and conversion to glutamine within astrocytes leads to elevated extracellular glutamate, promoting excitotoxicity. Altered glycogen metabolism and other metabolic impairments within astrocytes can also affect neuronal health and contribute to imbalances between excitation and inhibition. Dysfunctional astrocyte metabolism represents a significant contributor to E/I imbalance in the brain. Understanding the specific metabolic vulnerabilities of astrocytes and their impact on neuronal function provides potential therapeutic targets for neurological disorders characterized by E/I dysregulation. Targeting astrocyte metabolism may offer a novel approach to restoring E/I balance and improving neurological outcomes. Full article

Objectives: Osteoarthritis (OA) is a prevalent chronic degenerative joint disorder marked by cartilage degradation, subchondral bone remodeling, and synovial inflammation. Despite its widespread occurrence, effective pharmacological interventions to halt or reverse OA progression remain elusive. Thus, an in-depth understanding of its pathogenesis is imperative for developing novel therapeutic strategies. Methods: Sixty-four male Sprague-Dawley rats (8 weeks old, weighing 180–220 g) were randomly assigned to two groups: the anterior cruciate ligament transection (ACLT) group and the sham-operated group. Primary osteoblasts were isolated from the subchondral bone at 0, 4, 8, and 12 weeks after ACLT. Nuclear magnetic resonance (NMR)-based metabolomics was used to elucidate metabolic changes and the underlying mechanisms in osteoblasts. Results: A total of 26 metabolites were identified from the NMR spectra of osteoblasts. Distinct metabolic profiles were observed in the ACLT group at 0, 4, 8, and 12 weeks after surgery. In particular, several differential metabolites were identified, including glucose, lactate, NADP⁺, phosphocreatine, and alanine, as well as eight perturbed pathways, such as alanine, aspartate, and glutamate metabolism, phenylalanine metabolism, and taurine metabolism. Conclusions: Key energy-related metabolites, including glucose, lactate, creatine phosphate, and creatine, were identified as key markers of osteoblast dysfunction in OA, underscoring the profound metabolic perturbations induced by ACL injury. These disturbances in energy homeostasis are strongly implicated in the progression of OA. In addition, branched-chain amino acids emerged as potential biomarkers, further highlighting the metabolic dysregulation associated with the disease. Taken together, the metabolic changes observed in rat osteoblasts following ACL injury reveal a complex interplay between energy and amino acid metabolism, providing critical insights into the pathogenesis of post-traumatic OA and highlighting potential therapeutic targets. Full article

While periodontitis is increasingly linked to systemic disorders through the oral–gut axis, the molecular mediators driving gut microbiota dysbiosis and barrier disruption remain elusive. Hepatocyte growth factor (HGF), a novel regulator of inflammatory bone loss in periodontitis, may serve as a critical communicator between oral infection and distal intestinal pathology. This study investigates how HGF overexpression modulates the gut microbial ecosystem and intestinal barrier integrity in a transgenic periodontitis model. In this study, we combined 16S rRNA sequencing of fecal microbiota with comprehensive gut barrier assessments, including systemic markers (D-lactate, LPS, and DAO ELISA), structural integrity (villous morphology), and molecular analysis (ZO-1, occludin, and NOD2 immunohistochemistry), using HGF-overexpressing transgenic (HGF-Tg) mice with periodontitis. The results demonstrated that HGF increased gut permeability in the context of periodontitis, as evidenced by elevated serum levels of D-lactate and LPS compared to wild type (WT) mice. In addition, gut villous morphology disorder was observed in HGF-Tg mice with periodontitis. HGF also diminished the protein level of occludin and upregulated NOD2 expression in mice with periodontitis. Moreover, HGF-Tg mice with periodontitis exhibited significant dysbiosis of gut microbiota, with reduced levels of probiotics (e.g., Faecalibaculum). Notably, HGF also increased the enrichment of the periodontitis-associated pathogens (e.g., Desulfovibrio and Streptococcus) in the gut. Microbial functions, particularly metabolic pathways, were significantly altered by HGF when periodontitis occurred. Some microorganisms like g_Desulfovibrio may play a role in gut barrier disorder in HGF-Tg mice with periodontitis. Overall, our findings position HGF as a novel orchestrator of oral–gut crosstalk, where its overexpression reshapes gut microbial ecology toward a “leaky gut” phenotype to compromise intestinal barrier integrity, further deepening our understanding of the oral–gut axis. Full article

Inherited metabolic disorders (IMDs) are genetic disorders that occur in as many as 1:2500 births worldwide. Nevertheless, they are quite rare individually and even more rare is the co-occurrence of two IMDs in one individual. To better understand the metabolic cross-talk between glycosylation changes and deficient energy metabolism, and its potential effect on outcomes, we evaluated patient fibroblasts with likely pathogenic variants in PGM1 and pathogenic variants in NDUFA13 derived from a patient who passed away at 16 years of age. The patient presented with characteristic of PGM1-CDG including bifid uvula, muscle involvement, abnormal glycosylation in blood, and elevated liver transaminases. In addition, hearing loss, seizures, elevated plasma and CSF lactate and a Leigh-like MRI brain pattern were present, which are commonly associated with Leigh syndrome. PGM1-CDG has been reported in about 70 individuals, while NDUFA13 deficiency has so far only been reported in 13 patients. As abundant energy is essential for glycosylation, and both PGM1 and NDUFA13 are linked to energy metabolism, we sought to better understand the underlying biochemical cause of the patient’s clinical presentation. To do so, we performed extensive investigations including tracer metabolomics, lipidomics and enzymatic studies on the patient’s fibroblasts. We found a profound depletion of UDP-hexoses, consistent with PGM1-CDG. Complex I enzyme activity and mitochondrial function were also impaired, corroborating complex I deficiency and Leigh syndrome. Further, lipidomics analysis showed similarities with both PGM1-CDG and OXPHOS-deficient patients. Based on our results, the patient was diagnosed with both PGM1-CDG and Leigh syndrome. In summary, we present the first case of combined CDG and Leigh syndrome, caused by (likely) pathogenic variants in PGM1 and NDUFA13, and underline the importance of considering the synergistic effects of multiple disease-causing variants in patients with complex clinical presentation, leading to the patient’s early demise. Full article