Metabolic Changes Research Articles

NLRP6 overexpression improves nonalcoholic fatty liver disease by promoting lipid oxidation and decomposition in hepatocytes through the AMPK/CPT1A/PGC1A pathway.

To investigate the regulatory role of nucleotide-bound oligomerized domain-like receptor containing pyrin-domain protein 6 (NLRP6) in liver lipid metabolism and non-alcoholic fatty liver disease (NAFLD). Mouse models with high-fat diet (HFD) feeding for 16 weeks (n=6) or with methionine choline-deficient diet (MCD) feeding for 8 weeks (n=6) were examined for the development of NAFLD using HE and oil red O staining, and hepatic expressions of NLRP6 were detected with RT-qPCR, Western blotting, and immunohistochemical staining. Cultured human hepatocytes (LO2 cells) with adenovirus-mediated NLRP6 overexpression or knock-down were treated with palmitic acid (PA) in the presence or absence of compound C (an AMPK inhibitor), and the changes in cellular lipid metabolism were examined by measuring triglyceride, ATP and β-hydroxybutyrate levels and using oil red staining, RT-qPCR, and Western blotting. HFD and MCD feeding both resulted in the development of NAFLD in mice, which showed significantly decreased NLRP6 expression in the liver. In PA-treated LO2 cells, NLRP6 overexpression significantly decreased cellular TG content and lipid deposition, while NLRP6 knockdown caused the opposite effects. NLRP6 overexpression in PA-treated LO2 cells also increased mRNA and protein expressions of PGC1A and CPT1A, levels of ATP and β-hydroxybutyrate, and the phosphorylation level of AMPK pathway; the oxidative decomposition of lipids induced by Ad-NLRP6 was inhibited by the use of AMPK inhibitors. NLRP6 overexpression promotes lipid oxidation and decomposition through AMPK/CPT1A/PGC1A to alleviate lipid deposition in hepatocytes.

Dynamic development of gut microbiota and metabolism during and after weaning of kittens

BackgroundAs the pet population grows, there is increasing attention on the health and well-being of companion animals. Weaning, a common challenge for young mammals, often leads to issues such as diarrhea, growth retardation, and in severe cases, even mortality. However, the specific changes in gut microbiota and metabolites in kittens following weaning remain unclear. In this study, we conducted a comprehensive investigation of the dynamic changes in the gut microbiota, serum metabolism, antioxidant capacity, and immune function of kittens at various time points: days 0, 4, and 30 post-weaning.ResultsSignificant changes in the immune response and gut microbiota were observed in kittens following weaning. Specifically, IgM levels increased significantly (P < 0.01, n = 20), while IgA and IgG levels showed a sustained elevation. Weaning also disrupted the intestinal microbiota, leading to notable changes in serum metabolism. On day 4 post-weaning, there was a decrease in beneficial bacteria such as Bacteroides vulgatus, Fusobacterium nucleatum, Anaerostipes caccae, and Butyricico-ccaceae. However, by day 30, beneficial bacteria including Candidatus Arthro-mitus, Holdemanella, and Bifidobacterium had increased (P < 0.05, n = 20). Serum metabolites showed clear separation across time points, with day 0 and day 4 exhibiting similar patterns. A total of 45 significantly altered metabolites (P < 0.05, n = 20) were identified, primarily related to vitamins, steroids, peptides, organic acids, lipids, and carbohydrates. Pathway analysis revealed significant enrichment in eight metabolic pathways, with key changes in arginine metabolism and biosynthesis. Additionally, bacteria such as Bacteroides fragilis, Bacteroides stercoris, Leuconostoc citreum, and Bifidobacterium adolescentis were positively correlated with serum metabolic changes, emphasizing the link between gut microbiota and systemic metabolism (P < 0.05, n = 20).ConclusionOur study demonstrated that the composition and function of intestinal microorganisms as well as serum metabolic profiles of weaned kittens presented dynamic changes. These findings not only deepen our understanding of the effects of weaning on kitten health, but also provide valuable insights into post-weaning nutritional regulation strategies for kittens.

Exercise induces dynamic changes in intra-articular metabolism and inflammation associated with remodeling of the infrapatellar fat pad in mice

We hypothesized that daily exercise promotes joint health by upregulating anti-inflammatory mediators via adaptive molecular and metabolic changes in the infrapatellar fat pad (IFP). We tested this hypothesis by conducting time-resolved analyses between 1 and 14 days of voluntary wheel running exercise in C57BL/6J mice. IFP structure and cellularity were evaluated by histomorphology, picrosirius red collagen staining, and flow cytometry analysis of stromal vascular fraction cells. Joint inflammation and metabolism were evaluated by multiplex gene expression analysis of synovium-IFP tissue and synovial fluid metabolomics, respectively. Exercise transiently increased cytokine and chemokine gene expression in synovium-IFP tissue, resolving within the first 5 days of exercise. The acute inflammatory response was associated with decreased adipocyte size and elevated CD45+Gr1+ myeloid cells, increased collagen content, and oxidized phospholipids. Exercise acutely altered synovial fluid metabolites, characterized by increased amino acids, peptides, bile acids, sphingolipids, dicarboxylic acids, and straight medium chain fatty acids and decreased hydroxy fatty acids and diacylglycerols. Between 5 and 14 days of exercise, inflammation, collagen, and adipocyte size returned to pre-exercise levels, and CD206+ immuno-regulatory macrophages increased. Thus, although the onset of new daily exercise transiently induced synovium-IFP inflammation and altered tissue structure, sustained daily exercise promoted IFP homeostasis.

Change in Metabolic Markers and the Risk of Skin Cancer: Results from the Lifelines Cohort Study in the Netherlands.

Skin-cancers are the most common cancers in Caucasians, and their incidence is rising. Although metabolic and anthropometric markers play a role in cancer development, the relationship of metabolic and anthropometric changes with skin-cancer remains unclear. This study aimed to examine possible associations between these changes and the risk of skin-cancer. Participants without prior skin-cancer history from the Northern-Netherlands representative of the general population were included. Histopathology data were obtained from the Dutch Nationwide Pathology-Database. Adjusted-Cox-regression analyzed associations between metabolic changes and time to pathology-confirmed skin-cancer incidence over a 7-year follow-up, assessing overall skin-cancer risk and subtypes, including melanoma and non-melanoma skin-cancer. Out of 97,106 participants, 4,195 (4.3%) developed skin-cancer. Body-mass-index (BMI) decrease and increase were both associated with lower skin-cancer risk: adjusted-hazard-ratios(aHR) of 0.88(0.80-0.98) and 0.78(0.72-0.86), respectively. Triglyceride and waist-to-hip ratio (WHR)decreases were also associated with lower risk: aHR: 0.89(0.80-0.98) and 0.89(0.83-0.98), respectively. Increase in HbA1c was associated with higher risk in individuals under 45 years at baseline: aHR: 1.21(1.01-1.45). Subtype-analysis showed an increase in BMI was associated with lower melanoma risk: aHR: 0.72(0.58-0.91). Changes in BMI and decrease in triglycerides and WHR are related to lower skin-cancer risk, whereas increase in HbA1c may elevate risk in individuals younger than 45 at baseline. These findings highlight the importance of non-sunlight-related risk factors for skin-cancer prevention and the need for further research into underlying mechanisms. This study contributes to the broader understanding of how metabolic health impacts skin-cancer development, offering potential avenues for targeted prevention strategies.

Assays to Enhance Metabolic Phenotyping in the Kidney.

The kidney is highly metabolically active, and injury induces changes in metabolism that can impact repair and fibrosis progression. Changes in expression of metabolism-related genes and proteins provide valuable data, but functional metabolic assays are critical to confirm changes in metabolic activity. Stable isotope metabolomics are the gold standard, but these involve considerable cost and specialized expertise. Both the Seahorse bioflux assays and substrate oxidation assays in tissues ex vivo are two relatively cost-effective assays for interrogating metabolism. Many institutions have access to Seahorse bioflux analyzers, which can easily and quickly generate data, but guidelines to enhance reproducibility are lacking. We investigate how variables (e.g. primary versus immortalized cells, time in culture) impact the data generated by Seahorse bioflux analyzers. In addition, we show the utility of 3H-palmitate, a new approach for assessing fatty acid oxidation in the kidney, in uninjured and injured kidney cortices. The 3H-palmitate substrate oxidation assays also demonstrate significant sex-dependent and strain-dependent differences in rates of fatty acid oxidation. These data should facilitate metabolic interrogation in the kidney field with enhanced reproducibility.

Alterations in newborn metabolite patterns with preterm birth and diabetes in pregnancy.

This study examines the influence of prematurity and diabetes (DM) in pregnancy on metabolite patterns at birth, and associations with adiposity development in a prospective cohort. Term and preterm (30-36 weeks gestational age [GA]) infants were enrolled and body composition assessments completed through discharge. Targeted metabolomics was used to assess metabolites in cord or infant blood in the first 2 days. Among 91 infants, 62 were preterm and 27 were exposed to DM. In factor analysis, variation in acylcarnitines' and non-essential amino acids differed by GA and DM exposure and were associated with adiposity at term age. DM-group had 1.95-fold increase in t4-OH-pro (p = 0.003) and 2.14-fold increase in taurine (p = 0.004) compared with non-DM group. Preterm infants had 1.77-fold increase in glycerophospholipid PC aa C32:2 versus term group (p < 0.001). Pathway analysis revealed differences across DM and GA groups in pathways associated with citrulline metabolism, amino acid transport/ synthesis, and fatty acid quantity/transport. In this cohort of infants, there are unique metabolite signatures associated with DM exposure, prematurity, and adiposity development after birth. These markers may reflect early metabolism changes in the developing infant which relate to known risks of adverse growth and cardiometabolic outcomes in this group. In this study of term and preterm infants, diabetes in pregnancy was associated with unique metabolic signatures at birth, including increased expression of metabolites related to protein synthesis and lipid metabolism. Metabolites related to lipid and protein metabolism were associated with adiposity development at term age, including estimated body fat percent, skin fold thickness measures, and arm circumference measures. Unique signatures of metabolites associated with prematurity and exposure to diabetes in pregnancy may reflect early metabolism changes in the developing infant which relate to known risks of adverse growth and cardiometabolic outcomes in this group.

Epigenetic Regulation of Innate and Adaptive Immune Cells in Salt-Sensitive Hypertension.

Access to excess dietary sodium has heightened the risk of cardiovascular diseases, particularly affecting individuals with salt sensitivity of blood pressure. Our research indicates that innate antigen-presenting immune cells contribute to rapid blood pressure increases in response to excess sodium intake. Emerging evidence suggests that epigenetic reprogramming, with subsequent transcriptional and metabolic changes, of innate immune cells allows these cells to have a sustained response to repetitive stimuli. Epigenetic mechanisms also steer T-cell differentiation in response to innate immune signaling. Immune cells respond to environmental and nutritional cues, such as salt, promoting epigenetic regulation changes. This article aims to identify and discuss the role of epigenetic mechanisms in the immune system contributing to salt-sensitive hypertension.

Cypermethrin induced physiological and metabolic changes in susceptible and resistant populations of Spodoptera litura (Fabricius).

Spodoptera litura (Lepidoptera: Noctuidae) is one of the most destructive insect pests. Insecticides remain the principal management tool to control this pest. However, indiscriminate use of insecticides has resulted in the development of resistance to a variety of insecticides in S. litura. Cypermethrin, a synthetic pyrethroid, is commonly used in pest management. In addition to the mortality produced by cypermethrin, S. litura may suffer a range of sublethal consequences when exposed to low or sublethal levels. This study investigates the effect of cypermethrin exposure on nutritional physiology, digestive, detoxifying, and antioxidant enzymes of lab-selected susceptible (Unsel-Lab) and resistant (CYP-Sel) populations of S. litura. Our findings demonstrated that cypermethrin exposure has a considerable impact on the nutritional physiology of S. litura, as revealed by altered nutrient assimilation and utilization, alongside varying responses in digestive enzymes. In the CYP-Sel population, activity levels of key digestive enzymes- α-amylase, α-glucosidase, ß-glucosidase, α-galactosidase, ß-galactosidase, lipases, and proteases- decreased by 69.30, 81.40, 49.18, 86.36, 73.94, 70.50, and 72.34%, respectively, compared to the control of Unsel-Lab population. Furthermore, detoxification enzymes including mixed-function oxidase (by 1.87 times), glutathione-S-transferase (by 1.71 times), and esterases (by 2.86 times) showed considerably increased activity in CYP-Sel population as compared to Unsel-Lab population, indicating an adaptive response to detoxification processes. Antioxidant enzyme activity, including SOD (increased by 19.66%) and CAT (decreased by 26.19%), changed significantly, indicating oxidative stress caused by cypermethrin. The study gives useful information for developing pest management strategies that reduce the unexpected impacts of chemical exposure.

Unveiling cellular changes in leukaemia cell lines after cannabidiol treatment through lipidomics

The present study was aimed at revealing the metabolic changes that occurred in the cellular lipid pattern of acute and chronic myeloid leukaemia cells following treatment with cannabidiol (CBD). CBD is a non-psychoactive compound present in Cannabis sativa L., which has shown an antiproliferative action in these type of cancer cells. CBD treatment reduced cell viability and initiated apoptotic and necrotic processes in both cancer cell lines in a time and dose-dependent manner, showing acute myeloid leukaemia (HL-60) cells greater sensitivity than chronic myeloid leukaemia ones (K-562), without differences in the activation of caspases 3/7. Then, control and treated cells of HL-60 and K-562 cell lines were studied through an untargeted lipidomic approach. The treatment was carried out with CBD at a concentration of 10 μM for HL-60 cells and 23 µM CBD for K-562 cells for 48 h. After the extraction of the lipid content from cell lysates, the samples were analysed by UHPLC-QTOF-MS/MS both in the positive and the negative ionization modes. The comprehensive characterization of cellular lipids unveiled several classes significantly affected by CBD treatment. Most of the differences correspond to phospholipids, including cardiolipins (CL), phosphatidylcholines (PC) and phosphosphingolipids (SM), and also triacylglycerols (TG), being many TG species increased after CBD treatment in the acute and chronic models, whereas phospholipids were found to be decreased. The results highlight some important lipid alterations related to CBD treatment, plausibly connected with different metabolic mechanisms involved in the process of cell death by apoptosis in cancer cell lines.

A new mechanism of arterial calcification in diabetes: interaction between H3K18 lactylation and CHI3L1.

Metabolic changes are an important characteristic of vascular complications in diabetes. The accumulation of lactate in the microenvironment can promote VSMC calcification in diabetes, although the specific mechanism remains to be fully elucidated. In this study, we explored the characteristics of lactylation in diabetic arterial calcification and the underlying molecular mechanism. We found that in high-glucose calcified VSMC, the overall lactylationlevel was significantly increased. Mass spectrometry analysis revealed significant upregulation of H3 histone lactylation. After site-specific point-mutation at K18 to simulate the delactylation modification, VSMC calcification was significantly reduced. Through a combination of H3K18la ChIP-seq, RNA-seq, H3K18la ChIP-qPCR and point-mutation experiments, we confirmed that H3K18la can upregulate CHI3L1. CHI3L1 knockout significantly alleviated VSMC osteogenic phenotype transformation and mouse arterial calcification. RNA-seq analysis of the downstream molecular signaling showed that CHI3L1 activates the IL-13-IL-13Ra2-JAK1-STAT3 pathway. Targeted inhibition of IL-13Ra2 reduced VSMC calcification. We conclude that in a diabetic calcification environment, the H3 histone K18 site undergoes lactylation modification in VSMCs, upregulating CHI3L1, which in turn regulates the IL-13-IL-13Ra2-JAK1-STAT3 signaling pathway, ultimately exacerbating arterial calcification. Our study elucidates the epigenetic mechanism by which lactate promotes arterial calcification in diabetes.

Mouse models for metabolic health research: molecular mechanism of exercise effects on health improvement through adipose tissue remodelling.

Exercise provides health benefits to multiple metabolic tissues through complex biological pathways and interactions between organs. However, investigating these complex mechanisms in humans is still limited, making mouse models extremely useful for exploring exercise-induced changes in whole-body metabolism and health. In this review, we focus on gaining a broader understanding of the metabolic phenotypes and molecular mechanisms induced by exercise in mouse models. We first discuss the differences in adaptations induced by aerobic and resistance exercise, and compare voluntary wheel running and forced treadmill exercise, the two main methods of aerobic exercise research in mice, to show the similarities and differences between the same aerobic exercise but different methods, and their impact on experimental outcomes. The effects of exercise on metabolic phenotypes, including alleviation of obesity and metabolic disorders, and the mechanisms involved in adipose tissue remodelling and browning are explored, as well as the role of the gut microbiota in mediating the physiological responses and metabolic effects of exercise. Understanding these molecular mechanisms and methodological aspects of exercise experiments in mouse models can serve as a valuable template for the design of future basic research in exercise physiology and will provide a strong scientific evidence base for optimizing the design of exercise intervention programmes for metabolic health.

A murine model of acute and prolonged abdominal sepsis, supported by intensive care, reveals time-dependent metabolic alterations in the heart

BackgroundSepsis-induced cardiomyopathy (SICM) often occurs in the acute phase of sepsis and is associated with increased mortality due to cardiac dysfunction. The pathogenesis remains poorly understood, and no specific treatments are available. Although SICM is considered reversible, emerging evidence suggests potential long-term sequelae. We hypothesized that metabolic and inflammatory cardiac changes, previously observed in acute sepsis as potential drivers of SICM, partially persist in prolonged sepsis.MethodsIn 24-week-old C57BL/6J mice, sepsis was induced by cecal ligation and puncture, followed by intravenous fluid resuscitation, subcutaneous analgesics and antibiotics, and, in the prolonged phase, by parenteral nutrition. Mice were killed after 5 days of sepsis (prolonged sepsis, n = 15). For comparison, we included acutely septic mice killed at 30 h (acute sepsis, n = 15) and healthy controls animals (HC, n = 15). Cardiac tissue was collected for assessment of inflammatory and metabolic markers through gene expression, metabolomic analysis and histological assessment.ResultsIn prolonged sepsis, cardiac expression of IL-1β and IL-6 and macrophage infiltration remained upregulated (p ≤ 0.05). In contrast, tissue levels of Krebs cycle intermediates and adenosine phosphates were normal, whereas NADPH levels were low in prolonged sepsis (p ≤ 0.05). Gene expression of fatty acid transporters and of the glucose transporter Slc2a1 was upregulated in prolonged sepsis (p ≤ 0.01). Lipid staining and glycogen content were elevated in prolonged sepsis together with increased gene expression of enzymes responsible for lipogenesis and glycogen synthesis (p ≤ 0.05). Intermediate glycolytic metabolites (hexose-phosphates, GADP, DHAP) were elevated (p ≤ 0.05), but gene expression of several enzymes for glycolysis and mitochondrial oxidation of pyruvate, fatty-acyl-CoA and ketone bodies to acetyl-CoA were suppressed in prolonged sepsis (p ≤ 0.05). Key metabolic transcription factors PPARα and PGC-1α were downregulated in acute, but upregulated in prolonged, sepsis (p ≤ 0.05 for both). Ketone body concentrations were normal but ketolytic enzymes remained suppressed (p ≤ 0.05). Amino acid metabolism showed mild, mixed changes.ConclusionsOur results suggest myocardial lipid and glycogen accumulation and suppressed mitochondrial oxidation, with a functionally intact Krebs cycle, in the prolonged phase of sepsis, together with ongoing myocardial inflammation. Whether these alterations have functional consequences and predispose to long-term sequelae of SICM needs further research.

The Entry of Pollinating Fig Wasps Plays a Pivotal Role in the Developmental Phase and Metabolic Expression Changes in Ficus hookeriana Figs

The fig (the syconium of the Ficus tree) and its pollinating fig wasp represent exceptional examples for researching plant–insect interactions due to their remarkable specificity in species interaction and mutually beneficial symbiotic relationship. However, the mechanisms underlying the developmental process of monoecious figs in response to the entry of pollinating fig wasps (pollinators) and the metabolic changes occurring during this process remain elusive. Our study employed a combination of controlled experiments in the field and LC-MS methods to investigate the impact of pollinating fig wasp entry on the developmental phase of figs, as well as the metabolic alterations occurring during this process. A total of 381 metabolites and 155 differential metabolites were identified, with the predominant classes of metabolites being organic acids, lipids, and benzene aromatic compounds. The results suggest that in the absence of wasp entry, the receptive phase of fig would exhibit an extended duration. However, upon the entry of fig wasps, the receptive phase of figs would terminate within a span of 1 to 2 days, concomitant with substantial fluctuations in the composition and proportions of metabolites within the fig. Our research focuses on the analysis of linoleic acid metabolism, phenylpropanoid biosynthesis, and flavonoid biosynthesis pathways. Our findings suggest that the entry of wasps triggers alterations in the metabolic regulatory mechanisms of figs. Prior to wasp entry, metabolites primarily regulate fig growth and development. However, after wasp entry, metabolites predominantly govern lipid accumulation and the establishment of defense mechanisms, indicating a transition in fig development. This metabolic perspective explains why figs promptly enter an interflower phase that is not attractive to pollinating fig wasps after their entry, and how figs achieve reproductive balance through the regulation of different metabolic pathways. This study provides scientific evidence for elucidating the stability mechanism of the fig wasp mutualistic system.

12/15-Lipoxygenase-Derived Electrophilic Lipid Modifications in Phagocytic Macrophages.

Macrophages remove apoptotic cells via phagocytosis, also known as efferocytosis, during inflammation to maintain tissue homeostasis. This process is accompanied by various metabolic changes in macrophages including the production of lipid metabolites by fatty acid oxygenases. Among these, highly reactive metabolites, called lipid-derived electrophiles (LDEs), modify cysteines and other nucleophilic amino acids in intracellular proteins. However, the landscape and functions of the modifications by these electrophilic metabolites have been poorly characterized. In this study, we used activity-based protein profiling to quantitatively profile the cysteine reactivity landscape and identify the potential targets of endogenous LDE modification during efferocytosis in mouse peritoneal macrophages. Using this methodology, we identified multiple cysteine sites that are highly likely to be modified by LDEs generated by 12/15-lipoxygenase (12/15-LOX), an efferocytosis-related fatty acid oxygenase that is highly expressed in peritoneal macrophages. Among these, actin-depolymerizing protein Cofilin-1 was found to be a target of 12/15-LOX-derived LDEs. In vitro Cofilin-1 activity was attenuated by 12/15-LOX-derived LDEs, and intracellular actin stabilization and efferocytosis were substantially enhanced by the LDE treatment of mouse peritoneal macrophages. These results highlighted the role of intracellular LDE modification during efferocytosis in macrophages.

Characterization of Cutaneous Radiation Syndrome in a Mouse Model Using [18F]F- Fluorodeoxyglucose Positron Emission Tomography.

Ionizing radiation on the skin has the potential to cause various sequelae affecting quality of life and even leading to death due to multi-system failure. The development of radiation dermatitis is attributed to oxidative damage to the skin's basal layer and alterations in immune response, leading to inflammation. Past studies have shown that [18F]F-2-fluoro-2-deoxyglucose positron emission tomography-computed tomography ([18F]F-FDG PET/CT) can be used effectively for the detection of inflammatory activity, especially in conditions like hidradenitis suppurativa, psoriasis, and early atherosclerosis. Since currently there are no specific tests for radiation dermatitis, our study aimed to validate whether radiation dermatitis induced in mice can be accurately visualized and measured using [18F]F-FDG PET/CT. We induced cutaneous radiation syndrome in BALB/c mice with different radiation absorbed doses and monitored symptom development through photography, PET imaging, and histopathology, marking the first attempt at non-invasively quantifying radiation dermatitis effects at the molecular level using PET imaging. Our results showed that there were progressive changes in the dorsal skin of irradiated mice, with notable differences between those exposed to varying doses of radiation. Erythema, epilation, and desquamation were more pronounced in mice exposed to lower doses (25 Gy and 35 Gy) than at 45 Gy; however, by the third week, severe skin deterioration, including ulceration and dermal atrophy, was evident in mice irradiated with 35 Gy and 45 Gy. PET/CT imaging revealed increased [18F]F-FDG uptake in the irradiated dorsal skin area of all mice compared to controls, with more pronounced avidity for the lesion in the 25 Gy and 35 Gy than the 45 Gy. Comparison of tissue-normalized SUVMax values showed that both the 25 Gy and 35 Gy mice exhibited fourfold [18F]F-FDG uptake in the dorsal skin compared to controls, while a twofold uptake was seen at 45 Gy, thus indicating substantial metabolic changes in the dorsal skin induced by radiation exposure. Histopathological analyses correlated with the above findings, demonstrating generalized hypertrophy and epidermal thickening in all irradiated mice compared to controls, with thicker epidermis observed with higher radiation doses and increased destruction of microvasculature. In conclusion, PET/CT emerges as a successful tool for imaging cutaneous radiation syndrome, with the observed dermal changes in irradiated mice closely aligning with metabolic alterations of the affected area.

Exploration of the metabolomic mechanisms of postmenopausal hypertension induced by low estrogen state.

Estrogen significantly impacts women's health, and postmenopausal hypertension is a common issue characterized by blood pressure fluctuations. Current control strategies for this condition are limited in efficacy, necessitating further research into the underlying mechanisms. Although metabolomics has been applied to study various diseases, its use in understanding postmenopausal hypertension is scarce. Therefore, an ovariectomized rat model was used to simulate postmenopausal conditions. Estrogen levels, blood pressure, and aortic tissue metabolomics were analyzed. Animal models were divided into Sham, OVX, and OVX +E groups. Serum estrogen levels, blood pressure measurements, and aortic tissue metabolomics analyses were performed using radioimmunoassay, UHPLC-Q-TOF, and bioinformatics techniques. Based on the above research content, we successfully established a correlation between low estrogen levels and postmenopausal hypertension in rats. Notable differences in blood pressure parameters and aortic tissue metabolites were observed across the experimental groups. Specifically, metabolites that were differentially expressed, particularly L-alpha-aminobutyric acid (L-AABA), showed potential as a biomarker for postmenopausal hypertension, potentially exerting a protective function through macrophage activation and vascular remodeling. Enrichment analysis revealed alterations in sugar metabolism pathways, such as the Warburg effect and glycolysis, indicating their involvement in postmenopausal hypertension. Overall, this current research provides insights into the metabolic changes associated with postmenopausal hypertension, highlighting the role of L-AABA and sugar metabolism reprogramming in aortic tissue. The findings suggest a potential link between low estrogen levels, macrophage function, and vascular remodeling in the pathogenesis of postmenopausal hypertension. Further investigations are needed to validate these findings and explore their clinical implications for postmenopausal women.

Undernutrition affects metabolism and immune response in subcutaneous adipose tissue of pregnant ewes.

Pregnant ewes mobilize body fat to increase energy supply for fetal growth and development upon undernutrition, which disrupts the metabolic homeostasis of the body. However, the comprehensive metabolic changes in subcutaneous adipose tissue upon undernutrition are poorly understood. In this study, an undernutrition sheep model was established to investigate the effects of undernutrition on metabolic changes, immune response, and inflammation in subcutaneous fat through transcriptome, RT-qPCR, and metabolome analysis. Results showed that undernutrition changed the total transcriptional and metabolic profiles of adipose tissue. Compared to the controls, differentially expressed genes (DEGs) involved in fatty acid synthesis, triglyceride genesis, and lipid transport were downregulated in undernourished ewes, while DEGs related to fatty acid and triglyceride degradation were upregulated. Almost all lipid-related differential metabolites (DMs) were downregulated. DEGs and DMs involved in glucose metabolism and glycogen degradation were downregulated, while glycogen synthesis and carbohydrate transport were upregulated. DEGs linked to amino acid degradation were upregulated and some amino acids and derivatives were downregulated. KEGG pathway analysis showed complement and coagulation cascades were enriched significantly by DEGs, and DEGs related to coagulation, macrophage, and inflammation were upregulated while DEGs associated with the complement system were downregulated. Undernutrition during late gestation disrupted the metabolism of lipids, carbohydrates, and amino acids in adipose tissue, which weakened the complement system and immune response and may have ultimately led to inflammation.

ИССЛЕДОВАНИЕ ЭФФЕКТА ДИСТАНЦИОННОГО ИШЕМИЧЕСКОГО ПРЕКОНДИЦИОНИРОВАНИЯ НА МЕТАБОЛОМ У ПАЦИЕНТОВ, ПЕРЕНЕСШИХ СОСУДИСТУЮ ХИРУРГИЮ

The aim was to investigate the effect of remote ischemic preconditioning (RIPC) on the metabolic profile of patients undergoing elective vascular surgery 24 hours after the intervention. Materials and methods. A randomized, double-blind, placebo-controlled trial was conducted at the Republican Clinical Hospital in Makhachkala from January 1, 2023 to March 1, 2024. We studied patients who had to undergo surgery for an infrarenal abdominal aortic aneurysm, carotid endarterectomy, or revascularization of the lower extremities. Participants received RIPC or placebo, after which 103 metabolites and metabolic ratios were analyzed using the AbsoluteIDQ®p180 kit. Results. The study included 26 patients, 12 of them in the RIPC group and 14 in the control group. In the RIPC group, significant correlations were found between changes in metabolites (for example, the kynurenine/tryptophan ratio) and cardiomarkers (hs-TnT, NT-proBNP), which were absent in the control group. In the control group, blood pressure correlated with creatinine and beta-2-microglobulin levels. Conclusions. RIPC can affect specific metabolic changes after vascular surgery, which is confirmed by correlations with cardiomarkers not found in the control group.

Eight weeks of aerobic exercise, but not four, improves insulin sensitivity and cardiovascular performance in young women

Regular aerobic exercise has a significant impact on glucose metabolism and lipid profiles, contributing to overall health improvement. However, evidence for optimal exercise duration to achieve these effects is limited. This study aims to explore the effects of 4 and 8 weeks of moderate-intensity aerobic exercise on glucose metabolism, lipid profiles, and associated metabolic changes in young female students with insulin resistance and varying body mass, seeking to determine the optimal duration for physiological adaptations. Twenty-eight physically semi-active female students were randomly assigned to 4-week (G4, n = 13, age = 23.31 ± 5.19, BMI = 24.78 ± 5.87) and 8-week (G8, n = 15, age = 21.8 ± 2.56, BMI = 24.95 ± 4.81) training groups. The aerobic intervention maintained an intensity of 40–70% of maximum heart rate (HRmax). 6-min-walk test (6MWT), handgrip strength tests, insulin, HOMA-IR, lipid profiles, and metabolic profiles were assessed pre- and post-intervention. Following the intervention, G8, but not G4, exhibited a significant decrease in HOMA-IR (-14.59%, p = 0.047). The improvement in HOMA-IR was accompanied by notable improvements in 6-MWT (+ 38.18%, p < 0.001) and handgrip strength (+ 11.62, p = 0.027 and + 17.59%, p = 0.013), and increased levels of bilirubin degradation products, ribose, and glutarate. The elevated levels of bilirubin degradation products, known for their antioxidant properties, suggested a potential antioxidative response triggered by prolonged aerobic exercise. Additionally, an increase in ribose and glutarate indicated improved metabolic flexibility and enhanced utilization of alternative energy substrates. The 8-week aerobic exercise regimen demonstrated enhanced insulin sensitivity, upper body strength, and cardiovascular performance in young females compared to a 4-week regimen by triggering specific metabolic adaptations. These findings emphasize the complex relationship between exercise duration, metabolic adaptations, and overall well-being in young women, providing valuable insights for optimizing exercise prescriptions in promoting metabolic health.

Chemical Diversity of UK-Grown Tea Explored Using Metabolomics and Machine Learning

Background/Objectives: Dartmoor Estate Tea plantation in Devon, UK, is renowned for its unique microclimate and varied soil conditions, which contribute to the distinctive flavours and chemical profiles of tea. The chemical diversity of fresh leaf samples from various garden locations was explored within the plantation. Methods: Fresh leaf, which differed by location, cultivar, time of day, and variety, was analysed using Flow Infusion Electrospray Ionisation Mass Spectrometry (FIE-MS). Results: Random forest classification revealed no significant differences between Georgian N2 cultivar garden locations. However, a significant degree of variability was observed within four tri-clonal variants (Tocklai Variety) with TV9 exhibiting greater similarity to the Georgian N2 cultivar compared to TV8 and TV11, while TV11 was found to be most like TV1. The intraclass variability in leaf composition was similar between the varieties. We explored the metabolic changes over the day in one variant (Camellia assamica Masters), yielding a model with a significant R2 value of 0.617 (p &lt; 0.01, 3000 permutations). Starch and sucrose metabolism was found to be significant where the abundance of these chemical features increased throughout the day and then began to decrease at night. Conclusions: This research highlights the complex interplay of cultivars, geographical location, and temporal factors on the chemical composition of tea. It provides insightful data on the metabolic pathways influencing tea cultivation and production and underscores the importance of these variables in determining the final chemical profile and organoleptic characteristics of tea products.