Search Results (11)

Diabetes mellitus profoundly disturbs hepatic metabolism by impairing lipid and amino acid homeostasis, yet spatially resolved molecular evidence of these alterations remains limited. This study employed Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS) to visualise and quantify metabolic remodelling in rat liver under diabetic conditions and following metformin treatment. Liver cryosections from lean controls (LEAN), diabetic rats (P1), and metformin-treated diabetic rats (P2) were analysed in the negative ion mode, and all spectra were normalised to total ion counts. One-way ANOVA with false discovery rate (FDR) correction identified 43 lipid-related and 20 amino acid-related ions with significant group differences. Diabetic livers exhibited a marked depletion of phospholipid- and fatty acid-related ions (e.g., m/z 241.04, 281.25, 536.38) accompanied by increased ceramide fragments (m/z 805–806), indicating lipotoxic remodelling and mitochondrial stress. Simultaneously, aromatic and neutral amino acids such as phenylalanine, tyrosine, and glutamine were reduced, while small acidic fragments were elevated, consistent with enhanced proteolysis and gluconeogenic flux. Metformin administration partially restored both lipid and amino acid profiles toward the control phenotype. Hierarchical clustering and spatial ion maps revealed distinct group separation and partial normalisation of hepatic molecular patterns. These results demonstrate that ToF-SIMS provides label-free, spatially resolved insights into diabetes-induced metabolic disturbances and metformin-driven hepatoprotection. Full article

Given the reduced resilience of the Amazon rainforest due to deforestation, identifying high-quality genetic markers for the propagation of native species is crucial for forest regeneration. This study investigated metabolic dynamics during Brazil nut (Bertholletia excelsa) germination to identify biochemical markers for selecting superior genotypes. We analyzed primary reserves (carbohydrates, lipids, proteins) and minerals in two genotypes, 606 and Santa Fé, in seven germination stages. Our results revealed distinct metabolic patterns. Genotype 606 showed 101.73% greater efficiency in the transient accumulation of starch, 34.86% higher degradation of lipids, and 34.86% higher transitory synthesis of soluble proteins. Conversely, Santa Fé was 16.8% more efficient in amino acid synthesis and 795.33% in boron compartmentalization, though less so in sucrose (2.17%) and in lipid synthesis (24.84%). Overall, early germination stages involved starch, sucrose degradation and mineral consumption. During post-germinative stages, protein and lipid degradation likely fueled gluconeogenic pathways and supported carbohydrate synthesis and seedling growth. This work increases the knowledge on Brazil nut germination physiology and identifies metabolic markers that differentiate genotypes. These findings are fundamental for our understanding of primary metabolism turnover in B. excelsa and provide a basis to support forest restoration and genetic improvement programs. In addition, we hope to contribute to the selection of superior high-performance genotypes, which are essential for recovering degraded areas and enhancing productive plantations in the Amazon region. Full article

This study investigates the impact of propylene glycol (PRG) on ketotic cows, focusing on alleviating oxidative stress and enhancing immunity through modulating amino acid and lipid metabolism. Ketosis, a prevalent metabolic disease in dairy cows, negatively affects productivity and health. PRG, known for its gluconeogenic properties, was administered to cows with ketosis daily for three days and compared to an untreated group. Serum samples were taken to measure the biochemical parameters, and metabolomic and lipidomic analyses were performed with ultra-high-performance liquid chromatography–mass spectrometry. The results showed significant reductions in serum non-esterified fatty acids, beta-hydroxybutyrate, and C-reactive protein levels, alongside increased glucose, anti-inflammatory factor interleukin-10, superoxide dismutase, and glutathione peroxidase activities. Metabolomic and lipidomic analyses revealed significant alterations, including increased levels of glucogenic amino acids like glutamate and proline, and decreased levels of ceramide species. A pathway analysis indicated that PRG affects multiple metabolic pathways, including alanine, aspartate, glutamate metabolism, and sphingolipid metabolism. These findings suggest that PRG not only mitigates oxidative stress, but also enhances immune function by restoring metabolic homeostasis. This study provides valuable insights into the biochemical mechanisms underlying PRG’s therapeutic effects, offering potential strategies for the effective management and treatment of ketosis in dairy cows. Full article

The post-nutritional intervention modulation of miRNA expression has been previously investigated; however, post-acute dietary-ingestion-related miRNA expression dynamics in individuals with obesity and insulin resistance (IR) are unknown. We aimed to determine the acute effects of protein ingestion from different dietary sources on the postprandial metabolic response, amino acid levels, and circulating miRNA expression in adults with obesity and IR. This clinical trial included adults with obesity and IR who consumed (1) animal-source protein (AP; calcium caseinate) or (2) vegetable-source protein (VP; soy protein isolate). Glycaemic, insulinaemic, and glucagon responses, amino acid levels, and exosomal microRNAs isolated from plasma were analysed. Post-AP ingestion, the area under the curve (AUC) of insulin (p = 0.04) and the plasma concentrations of branched-chain (p = 0.007) and gluconeogenic (p = 0.01) amino acids increased. The effects of different types of proteins on the concentration of miRNAs were evaluated by measuring their plasma circulating levels. Compared with the baseline, the AP group presented increased circulating levels of miR-27a-3p, miR-29b-3p, and miR-122-5p (p < 0.05). Subsequent analysis over time at 0, 30, and 60 min revealed the same pattern and differences between treatments. We demonstrated that a single dose of dietary protein has acute effects on hormonal and metabolic regulation and increases exosomal miRNA expression in individuals with obesity and IR. Full article

Acute myeloid leukemia (AML) is an aggressive disease characterized by poor outcomes and therapy resistance. Devimistat is a novel agent that inhibits pyruvate dehydrogenase complex (PDH). A phase III clinical trial in AML patients combining devimistat and chemotherapy was terminated for futility, suggesting AML cells were able to circumvent the metabolic inhibition of devimistat. The means by which AML cells resist PDH inhibition is unknown. AML cell lines treated with devimistat or deleted for the essential PDH subunit, PDHA, showed a decrease in glycolysis and decreased glucose uptake due to a reduction of the glucose transporter GLUT1 and hexokinase II. Both devimistat-treated and PDHA knockout cells displayed increased sensitivity to 2-deoxyglucose, demonstrating reliance on residual glycolysis. The rate limiting gluconeogenic enzyme phosphoenolpyruvate carboxykinase 2 (PCK2) was significantly upregulated in devimistat-treated cells, and its inhibition increased sensitivity to devimistat. The gluconeogenic amino acids glutamine and asparagine protected AML cells from devimistat. Non-glycolytic sources of acetyl-CoA were also important with fatty acid oxidation, ATP citrate lyase (ACLY) and acyl-CoA synthetase short chain family member 2 (ACSS2) contributing to resistance. Finally, devimistat reduced fatty acid synthase (FASN) activity. Taken together, this suggests that AML cells compensate for PDH and glycolysis inhibition by gluconeogenesis for maintenance of essential glycolytic intermediates and fatty acid oxidation, ACLY and ACSS2 for non-glycolytic production of acetyl-CoA. Strategies to target these escape pathways should be explored in AML. Full article

Many physiological processes including ketogenesis are similar in dogs and humans, but there is little information available on the effect of carbohydrate restriction in dogs. Here, the ketogenicity and serum metabolic profiles of dogs were assessed after they had consumed high carbohydrate (HiCHO); high protein, low carbohydrate (PROT_LoCHO); or high fat, low carbohydrate (FAT_LoCHO) foods. Thirty-six dogs were fed HiCHO for 4 weeks, then randomized to PROT_LoCHO or FAT_LoCHO for 5 weeks. Dogs then crossed over to the other food for an additional 5 weeks. Generally, reduction of dietary carbohydrate by replacement with either protein or fat increased the energy required to maintain body weight, and fat had a greater effect. Postabsorptive energy availability derived mainly from glucose and triglycerides with HiCHO, from gluconeogenic amino acids and fatty acids with PROT_LoCHO, and from fatty acids and β-hydroxybutyrate with FAT_LoCHO. This study demonstrated that the reduction of carbohydrate in canine foods is potentially beneficial to dogs based on improvements in metabolism and supports the use of low-carbohydrate foods as safe and effective for healthy adult dogs. Full article

Understanding changes in biometric indices and metabolism in fish exposed to feed deprivation may be useful in aquaculture. The present study elucidates the effect of feed deprivation on physio-biochemical responses, such as changes in biometric indices, nutrient mobilization patterns, and enzyme activities in rohu (Labeo rohita). Experimental fish (av. wt. 3.41 ± 0.07 g) were deprived of feed and sampled at intervals of 0, 15, 30, 45, and 60 days to measure weight, length, body composition, and the activities of enzymes involved in digestion, metabolism, and antioxidation. A decrease in body weight, condition factor (CF), hepatosomatic index (HSI), and gastrosomatic index (GSI) was observed during the initial stage of feed deprivation (15 to 30 days) but remained unchanged thereafter. The total carbohydrate and lipid content also decreased rapidly up until 30 days, then stabilized. However, the reduction in tissue protein content (% wet weight) continued gradually with the duration of feed deprivation from 12.85 ± 0.36 at 0 days to 10.04 ± 0.67 at 15 days, 8.79 ± 0.59 at 30 days, 6.95 ± 0.69 at 45 days, and 6.16 ± 0.8 at 60 days, which was lower, compared to the other two body constituents. Amylase, protease. and lipase activities significantly reduced up until 30 days, but then stabilized. Although G6PDH enzyme activity decreased, gluconeogenic (LDH, AST, and ALT) and antioxidative (SOD and catalase) enzyme activities increased during initial feed deprivation (up to 30 days). A tissue-specific difference in amino acid metabolism with a major role of ALT in liver and AST in muscle was observed. This study revealed that rohu fingerlings adapted well to feed deprivation up until 30 days, beyond which there was an overall deterioration in the metabolic functions. Full article

Histidine (His) is considered to be the first-limiting amino acid (AA) on grass silage-based diets in lactation cows, which correlate positively with lactose yield. The higher glucose requirements of lactating cows can be met through a combination of increased capacity for gluconeogenesis and increased supply of gluconeogenic precursors. However, the effect of His on the expression of gluconeogenic genes in the bovine hepatocytes is less known. Therefore, this study aimed to investigate the regulatory effect of His on the key gluconeogenic genes and glucose output in bovine hepatocytes. The addition of 0.15, 0.6, and 1.2 mM His in a medium significantly enhanced (p < 0.05) the viability of bovine hepatocytes. Remarkably, 1.2 mM His induced profound changes (p < 0.05) in the mRNA level of key genes involved in gluconeogenesis, including PCK1, PCK2, FBP1, and G6PC in vitro. Furthermore, the mRNA expression of PCK1 was significantly elevated (p < 0.05) by the addition of 1.2 mM His at 3, 6, 12, and 24 h of incubation. The hepatic glucose output increased (p < 0.05) linearly with increasing His concentration. These findings indicate that the addition of His may be efficiently converted into glucose via the upregulation of genes related to the gluconeogenic pathway. Full article

The metabolic alterations associated with the increase in milk production make the transition period critical to the health of dairy cows, usually leading to a higher incidence of disease in periparturient animals. In this manuscript, we describe the use of NMR-based untargeted metabolomics to follow how these changes impact the serum metabolome in a group of 28 transition dairy cows with no initial clinical diseases. Principal component analysis (PCA) of serum ¹H NMR data from four weeks before calving to 8 weeks after parturition allowed us to clearly identify four stages during the transition period. Pairwise comparisons using orthogonal partial least square discriminant analysis (OPLS-DA) and univariate data analysis led to the identification of 18 metabolites that varied significantly through these stages. Species such as acetate, betaine, and creatine are observed early after calving, while other markers of metabolic stress, including acetone, β-hydroxybutyrate (BHB), and choline, accumulate significantly at the height of milk production. Furthermore, marked variations in the levels of lactate, allantoin, alanine, and other amino acids reveal the activation of different gluconeogenic pathways following parturition. Concomitant with a return to homeostasis, a gradual normalization of the serum metabolome occurs 8 weeks after calving. Correlations of metabolite levels with dietary and metabolic adaptations based on animal parity could also be identified. Overall, these results show that NMR-based chemometric methods are ideally suited to monitor manifestations of metabolic diseases throughout the transition period and to assess the impact of nutritional management schemes on the metabolism of dairy cows. Full article

Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by chronic hyperglycemia associated with alterations in carbohydrate, lipid, and protein metabolism. The prognosis of T2DM patients is highly dependent on the development of complications, and therefore the identification of biomarkers of T2DM progression, with minimally invasive techniques, is a huge need. In the present study, we applied a ¹H-Nuclear Magnetic Resonance (¹H-NMR)-based metabolomic approach coupled with multivariate data analysis to identify serum metabolite profiles associated with T2DM development and progression. To perform this, we compared the serum metabolome of non-diabetic subjects, treatment-naïve non-complicated T2DM patients, and T2DM patients with complications in insulin monotherapy. Our analysis revealed a significant reduction of alanine, glutamine, glutamate, leucine, lysine, methionine, tyrosine, and phenylalanine in T2DM patients with respect to non-diabetic subjects. Moreover, isoleucine, leucine, lysine, tyrosine, and valine levels distinguished complicated patients from patients without complications. Overall, the metabolic pathway analysis suggested that branched-chain amino acid (BCAA) metabolism is significantly compromised in T2DM patients with complications, while perturbation in the metabolism of gluconeogenic amino acids other than BCAAs characterizes both early and advanced T2DM stages. In conclusion, we identified a metabolic serum signature associated with T2DM stages. These data could be integrated with clinical characteristics to build a composite T2DM/complications risk score to be validated in a prospective cohort. Full article

Continuous intake of green tea catechins (GTC) increases fatty acid utilization as an energy source and improves endurance capacity. Conversely, the single pre-exercise intake of maltodextrin (MD) as a carbohydrate source and the gluconeogenic amino acids alanine (Ala) and proline (Pro) effectively maintain blood glucose levels and increase endurance performance. In this study, we investigated the synergistic combinational effect of these interventions on endurance performance in mice. Male BALB/c mice were fed a 0.5% GTC diet or Control diet for 8 weeks. Maximum running time was measured every 2 weeks. MD (2 g/kg body weight (B.W.)), MD (1 g/kg B.W.) + AlaPro (9:1, 1 g/kg B.W.), and vehicle were orally administrated 60 mins before measurements in each diet group. The GTC + MD + AlaPro group showed significantly higher endurance performance than the Control-Vehicle group at all measurements. Indirect calorimetry analysis during running exercise at 4 weeks in the Control and GTC groups supplemented with pre-exercise MD + AlaPro administration revealed significantly higher fat oxidation in the GTC groups compared to the Control group. The combined increase in fatty acid utilization through continuous GTC intake and pre-exercise MD + AlaPro carbohydrate energy supplementation synergistically improves endurance capacity. Full article