Amino Acid Metabolic Pathways Research Articles

Proteomic study on nintedanib in gastric cancer cells.

Gastric cancer is a very common gastrointestinal tumor with a high mortality rate. Nintedanib has been shown to significantly reduce tumor cell proliferation and increase apoptosis in gastric cancer cells in vitro. However, its systemic action mechanism on gastric cancer cells remains unclear. A high-throughput proteomic approach should help identify the potential mechanisms and targets of nintedanib on gastric cancer cells. The effects of nintedanib on the biological behavior of gastric cancer cells were evaluated. A cytotoxic proliferation assay was performed to estimate the half maximal inhibitory concentration (IC50). AGS cells were divided into control, and nintedanib-treated groups (5 µM, 48 h), and differential protein expression was investigated using tandem mass tags (TMT) proteomics. The molecular mechanisms of these differentially expressed proteins and their network interactions were then analyzed using bioinformatics, and potential nintedanib targets were identified. This study identified 845 differentially expressed proteins in the nintedanib-treated group (compared to the control group), comprising 526 up-regulated and 319 down-regulated proteins. Bioinformatics analysis revealed that the differentially expressed proteins were primarily enriched in biological pathways for branched-chain amino acid metabolism, steroid biosynthesis, propionate metabolism, fatty acid metabolism, lysosome, peroxisome, and ferroptosis. Key driver analysis revealed that proteins, such as enoyl-CoA hydratase and 3-hydroxyacyl CoA dehydrogenase (EHHADH), isocitrate dehydrogenase 1 (IDH1), acyl-CoA oxidase 1 (ACOX1), acyl-CoA oxidase 2 (ACOX2), acyl-CoA oxidase 3 (ACOX3), and acetyl-CoA acyltransferase 1 (ACAA1) could be linked with nintedanib action. Nintedanib inhibits the proliferation, invasion, and metastasis of gastric cancer cells. The crossover pathways and protein networks predicted by proteomics should provide more detailed molecular information enabling the use of nintedanib against gastric cancer.

Amino acid metabolism and MAP kinase signaling pathway play opposite roles in the regulation of ethanol production during fermentation of sugarcane molasses in budding yeast

Sugarcane molasses is one of the main raw materials for bioethanol production, and Saccharomyces cerevisiae is the major biofuel-producing organism. In this study, a batch fermentation model has been used to examine ethanol titers of deletion mutants for all yeast nonessential genes in this yeast genome. A total of 42 genes are identified to be involved in ethanol production during fermentation of sugarcane molasses. Deletion mutants of seventeen genes show increased ethanol titers, while deletion mutants for twenty-five genes exhibit reduced ethanol titers. Two MAP kinases Hog1 and Kss1 controlling the high osmolarity and glycerol (HOG) signaling and the filamentous growth, respectively, are negatively involved in the regulation of ethanol production. In addition, twelve genes involved in amino acid metabolism are crucial for ethanol production during fermentation. Our findings provide novel targets and strategies for genetically engineering industrial yeast strains to improve ethanol titer during fermentation of sugarcane molasses.

Metabolomics analysis reveals novel serum metabolite alterations in cancer cachexia.

Cachexia is a body wasting syndrome that significantly affects well-being and prognosis of cancer patients, without effective treatment. Serum metabolites take part in pathophysiological processes of cancer cachexia, but apart from altered levels of select serum metabolites, little is known on the global changes of the overall serum metabolome, which represents a functional readout of the whole-body metabolic state. Here, we aimed to comprehensively characterize serum metabolite alterations and analyze associated pathways in cachectic cancer patients to gain new insights that could help instruct strategies for novel interventions of greater clinical benefit. Serum was sampled from 120 metastatic cancer patients (stage UICC IV). Patients were grouped as cachectic or non-cachectic according to the criteria for cancer cachexia agreed upon international consensus (main criterium: weight loss adjusted to body mass index). Samples were pooled by cachexia phenotype and assayed using non-targeted gas chromatography-mass spectrometry (GC-MS). Normalized metabolite levels were compared using t-test (p < 0.05, adjusted for false discovery rate) and partial least squares discriminant analysis (PLS-DA). Machine-learning models were applied to identify metabolite signatures for separating cachexia states. Significant metabolites underwent MetaboAnalyst 5.0 pathway analysis. Comparative analyses included 78 cachectic and 42 non-cachectic patients. Cachectic patients exhibited 19 annotable, significantly elevated (including glucose and fructose) or decreased (mostly amino acids) metabolites associating with aminoacyl-tRNA, glutathione and amino acid metabolism pathways. PLS-DA showed distinct clusters (accuracy: 85.6%), and machine-learning models identified metabolic signatures for separating cachectic states (accuracy: 83.2%; area under ROC: 88.0%). We newly identified altered blood levels of erythronic acid and glucuronic acid in human cancer cachexia, potentially linked to pentose-phosphate and detoxification pathways. We found both known and yet unknown serum metabolite and metabolic pathway alterations in cachectic cancer patients that collectively support a whole-body metabolic state with impaired detoxification capability, altered glucose and fructose metabolism, and substrate supply for increased and/or distinct metabolic needs of cachexia-associated tumors. These findings together imply vulnerabilities, dependencies and targets for novel interventions that have potential to make a significant impact on future research in an important field of cancer patient care.

Effect of different forms of tobacco on the oral microbiome in healthy adults: a systematic review.

The study aimed to evaluate the impact of tobacco use on the composition and functions of the oral microbiome in healthy adult humans. We conducted a systematic search on PubMed, Web of Science, and Cinhal databases for literature published until 15 December 2023, to identify studies that have evaluated the oral microbiome with culture-independent next-generation techniques comparing the oral microbiome of tobacco users and non-users. The search followed the PECO format. The outcomes included changes in microbial diversity and abundance of microbial taxa. The quality assessment was performed using the Newcastle-Ottawa Scale (NOS) (PROSPERO ID CRD42022340151). Out of 2,435 articles screened, 36 articles satisfied the eligibility criteria and were selected for full-text review. Despite differences in design, quality, and population characteristics, most studies reported an increase in bacterial diversity and richness in tobacco users. The most notable bacterial taxa enriched in users were Fusobacteria and Actinobacteria at the phylum level and Streptococcus, Prevotella, and Veillonella at the genus level. At the functional level, more similarities could be noted; amino acid metabolism and xenobiotic biodegradation pathways were increased in tobacco users compared to non-users. Most of the studies were of good quality on the NOS scale. Tobacco smoking influences oral microbial community harmony, and it shows a definitive shift towards a proinflammatory milieu. Heterogeneities were detected due to sampling and other methodological differences, emphasizing the need for greater quality research using standardized methods and reporting. CRD42022340151.

Transcriptome Analysis Reveals the Vital Role of ABA Plays in Drought Tolerance of the ABA-Insensitive Alfalfa (Medicago sativa L.)

Drought stress severely affects alfalfa (Medicago sativa L.) growth and production. It is particularly important to analyze the key networks of drought in alfalfa through physiological and molecular levels. However, how to quickly screen drought-tolerant alfalfa germplasm and how to elucidate the molecular pathways of alfalfa responding to drought are less studied. In this study, based on our previous research, we further verified the association between the heritability of ABA sensitivity during seed germination and drought tolerance of plants and identified the key pathways of drought tolerance differences between ABA-sensitivity (S1-0) and -insensitivity (S1-50) plants via RNA-seq and analysis. The results showed that the sensitivity to ABA in alfalfa seeds can be inherited and that plants that are insensitive to ABA during germination show stronger drought tolerance. An analysis of the differentially expressed genes (DEGs) revealed that ABA biosynthesis and signaling, amino acid metabolism, LEA, and wax synthesis-related pathways may be the key pathways that can be used for drought tolerance improvement in alfalfa. DEGs such as NCED, PYR/PYL, and PP2C may contribute to drought tolerance in the S1-50 plant. The study further confirms that screening with ABA at the seed germination stage can select alfalfa lines with good drought tolerance, which provides a new theoretical basis for alfalfa drought tolerance breeding. The expression of the key genes of alfalfa in response to drought stress was also tested.

How does temperature rise affect a freshwater catfish Rhamdia quelen? A proteomic approach

Outside of scientific circles, climate change is a hotly debated topic due to all its consequences. Changes in the temperature can affect aquatic organisms and it is important to understand and to detect earlier signals. This study aimed to analyze how a Neotropical fish species responds to temperature increases, using proteomic analysis as a tool. For this, fish of the species Rhamdia quelen, male and female, were exposed to two temperatures: 25 °C and 30 °C. After 96 h, the animals were anesthetized, euthanized and the liver was collected for proteomic analysis. Using freely available online software and databases (e.g. MetaboAnalyst, Gene Ontology and UniProt), we define the altered proteins in both sexes: 42 in females and 62 in males. Data are available via ProteomeXchange with identifier PXD046475. Differences between the two temperatures were observed mainly in the amino acid metabolic pathways. The cellular process and the immune response was altered, indicating that effects at lower levels of biological organization could serve as a predictor of higher-level effects when temperature rise affects wildlife populations. Thus, we conclude that the increase in temperature is capable of altering important cellular and physiological processes in R. quelen fish, with this response being different for males and females.

Functional analyses of TRAF6 gene in Argopecten scallops

The tumor necrosis factor (TNF) receptor-associated factor (TRAF) family has been reported to be involved in many immune pathways. In a previous study, we identified 5 TRAF genes, including TRAF2, 3, 4, 6, and 7, in the bay scallop (Argopecten irradians, Air) and the Peruvian scallop (Argopecten purpuratus, Apu). Since TRAF6 is a key molecular link in the TNF superfamily, we conducted a series of studies targeting the TRAF6 gene in the Air and Apu scallops as well as their hybrid progeny, Aip (Air ♀ × Apu ♂) and Api (Apu ♀ × Air ♂). Subcellular localization assay showed that the Air-, Aip-, and Api-TRAF6 were widely distributed in the cytoplasm of the human embryonic kidney cell line (HEK293T). Additionally, dual-luciferase reporter assay revealed that among TRAF3, TRAF4, and TRAF6, only the overexpression of TRAF6 significantly activated NF-κB activity in the HEK293T cells in a dose-dependent manner. These results suggest a crucial role of TRAF6 in the immune response in Argopecten scallops. To investigate the specific immune mechanism of TRAF6 in Argopecten scallops, we conducted TRAF6 knockdown using RNA interference. Transcriptomic analyses of the TRAF6 RNAi and control groups identified 1194, 2403, and 1099 differentially expressed genes (DEGs) in the Air, Aip, and Api scallops, respectively. KEGG enrichment analyses revealed that these DEGs were primarily enriched in transport and catabolism, amino acid metabolism, peroxisome, lysosome, and phagosome pathways. Expression profiles of 28 key DEGs were confirmed by qRT-PCR assays. The results of this study may provide insights into the immune mechanisms of TRAF in Argopecten scallops and ultimately benefit scallop breeding.

Integrative Analyses of Transcriptomics and Metabolomics in Immune Response of Leguminivora glycinivorella Mats to Beauveria bassiana Infection.

This study utilized Beauveria bassiana to infect Leguminivora glycinivorella, analyzed the effects on the transcriptome and metabolome, and further investigated the antibacterial function of L. glycinivorella. We performed transcriptome and metabolome sequencing on the L. glycinivorella infected with B. bassiana and its control groups, and performed a joint analysis of transcriptome and metabolome results. Upon screening, 4560 differentially expressed genes were obtained in the transcriptome and 71 differentially expressed metabolites were obtained in the metabolome. On this basis, further integration of the use of transcriptomics and metabonomics combined an analysis of common enrichments of pathways of which there were three. They were glutathione S-transferase (GSTs) genes, heat shock protein (HSP) genes, and cytochrome P450 (CYP450) genes. These three pathways regulate the transport proteins, such as ppars, and thus affect the digestion and absorption of sugars and fats, thus regulating the development of pests. The above conclusion indicates that B. bassiana can affect the sugar metabolism, lipid metabolism, and amino acid metabolism pathways of L. glycinivorella, and can consume the necessary energy, protein, and lipids of L. glycinivorella. The research on the immune response mechanism of pests against pathogens can provide an important scientific basis and target for the development of immunosuppressants. This study laid an information foundation for the application of entomogenous fungi to control soybean borer at the molecular level.

Evaluating the Metabolic Basis of α-Gal A mRNA Therapy for Fabry Disease.

mRNA injection-based protein supplementation has emerged as a feasible treatment for Fabry disease. However, whether the introduction of LNP-encapsulated mRNA results in the alteration of metabolomics in an in vivo system remains largely unknown. In the present study, α-galactosidase A (α-Gal A) mRNA was generated and injected into the Fabry disease mouse model. The α-Gal A protein was successfully expressed. The level of globotriaosylsphingosine (Lyso-Gb3), a biomarker for Fabry disease, as well as pro-inflammatory cytokines such as nuclear factor kappa-B (NF-κB), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α), were greatly decreased compared to the untreated control, indicating the therapeutic outcome of the mRNA drug. Metabolomics analysis found that the level of 20 metabolites was significantly altered in the plasma of mRNA-injected mice. These compounds are primarily enriched in the arachidonic acid metabolism, alanine, aspartate and glutamate metabolism, and glycolysis/gluconeogenesis pathways. Arachidonic acid and 5-hydroxyeicosatetraenoic acid (5-HETE), both of which are important components in the eicosanoid pathway and related to inflammation response, were significantly increased in the injected mice, possibly due to the presence of lipid nanoparticles. Moreover, mRNA can effectively alter the level of metabolites in the amino acid and energy metabolic pathways that are commonly found to be suppressed in Fabry disease. Taken together, the present study demonstrated that in addition to supplementing the deficient α-Gal A protein, the mRNA-based therapeutic agent can also affect levels of metabolites that may help in the recovery of metabolic homeostasis in the full body system.

Dynamic changes of volatile compounds and small molecule compounds during curing and drying processes of Megalobrama amblycephala

SummaryIn this study, the changes in volatile compounds, lipids, and small molecule compounds during the curing and drying processes were examined. The results showed that lipid oxidation was enhanced during curing and drying processes. A total of fifty‐two types of volatile compounds in the dry‐cured fish were detected, and the contents of alcohols (such as 3‐methyl‐1‐butanol, 1‐octen‐3‐ol), ketones (such as 2‐heptanone, 2‐octanone), and aldehydes (such as 3‐methylbutyraldehyde, hexanal, nonanal, decanal) were increased during curing and drying processes. A total of 812 metabolites were identified. The metabolites in linoleate, arachidonate, nucleotide, amino acid, and other metabolic pathways showed significant differences between drying stage and curing stage. The oxidative degradation of arachidonate acid, linoleate acid, and amino acid may contribute to the changes in volatile compounds during the curing and drying stages. Seven compounds including shikimic acid, carnitine C5: DC, carnitine C7: DC, 2‐hydroxybutanoic acid, 3‐hydroxybutanoic acid, malonic acid, and methylmalonic acid could be key small molecule compounds in curing and drying processing. These findings are valuable for understanding the mechanisms underlying flavour changes occurring during fish curing and drying processes.

Integrated characterizations of intestinal bacteria and transcriptomics revealed the acute stress response to carbonate alkalinity in white shrimp Penaeusvannamei

The impact of carbonate alkalinity in saline-alkaline water on aquatic organisms, particularly Penaeus vannamei, a significant species in aquaculture, remains a critical area of study. To elucidate the acute response mechanisms of P. vannamei to elevated carbonate alkalinity environments, we utilized 16S rRNA gene and transcriptome sequencing technologies to analyze intestinal bacteria and gene expressions within various tissues. Our investigation revealed notable changes in specific intestinal bacterial OTUs, whose abundances varied preceding the overall bacterial community, indicating the sensitivity to carbonate alkalinity exposure. These shifts are accompanied by a simplification in bacterial networks and alterations in pathogenic OTUs, notably Aeromonas OTU. Concurrently, gene expression variations were observed across the hepatopancreas, gills, muscles, and intestines, with decreasing numbers of DEGs in the mentioned order. Annotation of these DEGs revealed enrichments in pathways related to transport, catabolism, immune responses, circulatory functions, and lipid metabolism. Notably, correlations between specific intestinal bacterial OTUs and gene expression shifts were identified across these tissues. Several OTUs, attributed to Rhizobiales, Saccharimonadales, Acidovora, and Aeromona, exhibited a correlation with DEGs in all four tissues, primarily associated with amino acid metabolism, signal transduction, and transport and catabolism pathways. Our study provides comprehensive insights into the dynamic responses of P. vannamei to elevated carbonate alkalinity stress. These findings contribute crucial knowledge for effective P. vannamei cultivation in saline-alkaline water, advancing our understanding in this field.

Nontargeted metabolomics reveals sequential changes in amino acid and ferroptosis-related metabolism in Parkinson's disease.

Parkinson's disease (PD) is inseparable from metabolic disorders but lacks assessment of specific metabolite alteration. To explore the sequential metabolic changes in PD progression, we evenly divided 78 C57BL/6 mice (10weeks) into six groups (one control group and five experimental groups) and collected the hippocampus tissue of mice after treating with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, and probenecid (twice a week) at five periods (1, 2, 3, 4, and 5weeks) for metabolome analysis. Our study identified 567 differentially abundant metabolites (DAMs) (total 4348 metabolites). Compared with controls, 145, 146, 171, 208, and 213 DAMs were obtained from the five experimental groups, respectively. Notably, 40 shared DAMs were present in five experimental groups, of which 22 shared DAMs formed a new metabolic network based on amino acid metabolism. Compared with group W3, 84 DAMs were identified in group W5, including 12 unique DAMs. DAMs in different stages of PD were significantly enriched in amino acid metabolism pathway, lipid metabolism pathway, and ferroptosis pathway. l-Glutamine, spermidine, and l-tryptophan were the key hubs in the whole metabolic process of PD. N-Formyl-l-methionine gradually increased in abundance with PD progression, whereas 5-methylcytosine gradually decreased. The study emphasized the sequential changes in DAMs in PD progression, stimulating subsequent studies.

Metabolomic interference induced by short-chain chlorinated paraffins in human normal hepatic cells

Short-chain chlorinated paraffins (SCCPs) are an emerging class of persistent organic pollutants (POPs) that are widely detected in environmental matrices and human samples. Because of their environmental persistence, long-range transport potential, bioaccumulation potential, and biotoxicity, SCCPs pose a significant threat to human health. In this study, metabolomics technology was applied to reveal the metabolomic interference in human normal hepatic (L02) cells after exposure to low (1 μg/L), moderate (10 μg/L), and high (100 μg/L) doses of SCCPs. Principal component analysis (PCA) and metabolic effect level index (MELI) values showed that all three SCCP doses caused notable metabolic perturbations in L02 cells. A total of 72 metabolites that were annotated by MS/MS and matched with the experimental spectra in the Human Metabolome Database (HMDB) or validated by commercially available standards were selected as differential metabolites (DMs) across all groups. The low-dose exposure group shared 33 and 36 DMs with the moderate- and high-dose exposure groups, respectively. The moderate-dose exposure group shared 46 DMs with the high-dose exposure group. In addition, 33 DMs were shared among the three exposure groups. Among the 72 DMs, 9, 9, and 45 metabolites participated in the amino acid, nucleotide, and lipid metabolism pathways, respectively. The results of pathway enrichment analysis showed that the most relevant metabolic pathways affected by SCCPs were the lipid metabolism, fatty acid β-oxidation, and nucleotide metabolism pathways, and that compared with low-dose exposure, moderate- and high-dose SCCP exposures caused more notable perturbations of these metabolic pathways in L02 cells. Exposure to SCCPs perturbed glycerophospholipid and sphingolipid metabolism. Significant alterations in the levels of phosphatidylcholines, phosphatidylethanolamines, and sphingomyelins indicated SCCP-induced biomembrane damage. SCCPs inhibited fatty acid β-oxidation by decreasing the levels of short- and medium-chain acylcarnitines in L02 cells, indicating that the energy supplied by fatty acid oxidation was reduced in these cells. Furthermore, compared with low- and moderate-dose SCCPs, high-dose SCCPs produced a significantly stronger inhibition of fatty acid β-oxidation. In addition, SCCPs perturbed nucleotide metabolism. The higher hypoxanthine levels observed in L02 cells after SCCP exposures indicate that SCCPs may induce several adverse effects, including hypoxia, reactive oxygen species production, and mutagenesis in L02 cells.

Effect of Lactiplantibacillus plantarum CCFM8661 on serum metabolites and gut microbiota in a lead-exposed population

In this study, we investigated the impact of Lactiplantibacillus plantarum (L. plantarum) CCFM8661 on the gut microbiota, and the serum and fecal metabolomes in lead (Pb)-exposed individuals. The volunteers recruited for this study were divided into two treatment groups, (i) the placebo (control) and (ii) the L. plantarum CCFM8661 treatment groups. The analysis revealed that probiotic intervention reversed some of the changes in Pb exposure-induced intestinal bacterial abundance, including the abundance of Parabacteroides, Bacteroides, Clostridiaceae, and Erysipelotrichaceae. An analysis of the fecal metabolome identified 26 differential metabolites involved in purine metabolism, unsaturated fatty acid metabolism, and other pathways. Serum metabolite analysis showed that L. plantarum CCFM8661 treatment altered the serum metabolite levels of various metabolic pathways, such as the glycerophospholipid, amino acid, and glutathione metabolism pathways. These results suggest that L. plantarum CCFM8661 may have beneficial effects on Pb-exposed populations by modulating the gut microbiota, host serum metabolism, and the metabolism of the gut microbiota.

Insights into the mechanism of L-malic acid on drip loss of chicken meat under commercial conditions

BackgroundA deterioration in the meat quality of broilers has attracted much more attention in recent years. L-malic acid (MA) is evidenced to decrease meat drip loss in broilers, but the underlying molecular mechanisms are still unclear. It’s also not sure whether the outputs obtained under experimental conditions can be obtained in a commercial condition. Here, we investigated the effects and mechanisms of dietary MA supplementation on chicken meat drip loss at large-scale rearing.ResultsResults showed that the growth performance and drip loss were improved by MA supplementation. Meat metabolome revealed that L-2-aminoadipic acid, β-aminoisobutyric acid, eicosapentaenoic acid, and nicotinamide, as well as amino acid metabolism pathways connected to the improvements of meat quality by MA addition. The transcriptome analysis further indicated that the effect of MA on drip loss was also related to the proper immune response, evidenced by the enhanced B cell receptor signaling pathway, NF-κB signaling pathway, TNF signaling pathway, and IL-17 signaling pathway.ConclusionsWe provided evidence that MA decreased chicken meat drip loss under commercial conditions. Metabolome and transcriptome revealed a comprehensive understanding of the underlying mechanisms. Together, MA could be used as a promising dietary supplement for enhancing the water-holding capacity of chicken meat.

Dietary Paper Mulberry Silage Supplementation Improves the Growth Performance, Carcass Characteristics, and Meat Quality of Yangzhou Goose

There have been few investigations into the health benefits and meat quality of supplementing Yangzhou geese with paper mulberry silage. One hundred and twenty 28-day-old Yangzhou geese were selected for the experiment and randomly divided into two groups: a control group (CON) and a paper mulberry silage group (PM), with six replicates in each group. The experiment lasted for a total of 6 weeks. The experiment found that compared with CON, PM had a promoting effect on the average daily weight gain of Yangzhou geese (p = 0.056). Sensory and nutritional analysis of breast muscles revealed a decrease in a* value (p &lt; 0.05) and an increase in protein content (p &lt; 0.05) following PM treatment. Through untargeted metabolomics analysis of breast muscle samples, it was found that 11 different metabolites, including guanidinoacetic acid and other substances, had a positive effect on amino acid metabolism and lipid antioxidant pathways of PM treatment. Overall, the strategy of feeding Yangzhou geese with paper mulberry silage is feasible, which can improve the sensory quality and nutritional value of goose meat. The experiment provides basic data for the application form of goose breeding, so exploring the impact of substances within paper mulberry on goose meat should be focused on in the future.

Dietary selenium levels affect mineral absorbability, rumen fermentation, microbial composition and metabolites of the grazing sheep

Selenium (Se) is an essential trace element for the growth of all livestock. However, little is known about the effects of dietary selenium levels on production metrics, nutrient digestion and absorption, ruminal microbiota, and metabolites in grazing sheep. Therefore, in this research, 28 individually-housed grazing sheep were randomly divided into a low-Se feeding group (LSe) and a control group for the low-Se feeding phase (LCG), supplemented with multi-nutrient salts containing 0 mg Se and 0.63 mg Se, respectively, for 53 days. After 53 days of feeding, a 7-day digestion test was conducted, then seven sheep in each group were randomly slaughtered. Then, the remaining sheep in LSe and LCG were transferred to a high-Se supplementation group (SSe) and a control group for the high-Se feeding phase (SCG), supplemented with multi-nutrient salts containing 1.90 mg and 0.63 mg Se, respectively. This phase consisted of a 34-day diet adaptation period, a 7-day digestive test, and eventual slaughter. LSe reduced and elevated ruminal Se and copper (Cu) content, respectively, and decreased Se apparent absorbability compared to LCG (P < 0.05). Conversely, SSe reduced and increased ruminal Cu and Se content, respectively, and increased Se apparent absorption in comparison to SCG (P < 0.05). It also increased the ruminal NH3-N concentration (P < 0.05). Amplicon sequencing analysis revealed a decrease in Lentimicrobium and Treponema abundance and an increase in Lawsonibacter and Sporobacter abundance (P < 0.05) in LSe group. Metabolomic analysis confirmed an elevated level of ruminal citrulline, ornithine and glutathione affecting amino acid and glutathione metabolic pathways (P < 0.05) in LSe group. In SSe group, Alistipes were significantly reduced (P < 0.05) with metabolomics showing elevated levels of L-carnitine and arginine, affecting ruminal antioxidant capacity and arginine biosynthesis pathways (P < 0.05). Notably, both treatments had no significant effect on production metrics and apparent digestibility of organic nutrients (P > 0.05). In conclusion, Se deficiency affects Se absorption and amino acid metabolism in grazing sheep, while supplementing Se in diet effectively ameliorates these deficiencies and improves ruminal antioxidant capacity.

Citrus p-Synephrine Improves Energy Homeostasis by Regulating Amino Acid Metabolism in HFD-Induced Mice.

p-Synephrine is a common alkaloid widely distributed in citrus fruits. However, the effects of p-synephrine on the metabolic profiles of individuals with energy abnormalities are still unclear. In the study, we investigated the effect of p-synephrine on energy homeostasis and metabolic profiles using a high fat diet (HFD)-induced mouse model. We found that p-synephrine inhibited the gain in body weight, liver weight and white adipose tissues weight induced by HFD. p-Synephrine supplementation also reduced levels of serum total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) but not to a statistically significant degree. Histological analysis showed that HFD induced excessive lipid accumulation and glycogen loss in the liver and adipocyte enlargement in perirenal fat tissue, while p-synephrine supplementation reversed the changes induced by HFD. Moreover, HFD feeding significantly increased mRNA expression levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) and reduced the mRNA expression level of interleukin-10 (IL-10) compared to the control group, while p-synephrine supplementation significantly reversed these HFD-induced changes. Liver and serum metabolomic analysis showed that p-synephrine supplementation significantly altered small molecule metabolites in liver and serum in HFD mice and that the changes were closely associated with improvement of energy homeostasis. Notably, amino acid metabolism pathways, both in liver and serum samples, were significantly enriched. Our study suggests that p-synephrine improves energy homeostasis probably by regulating amino acid metabolism in HFD mice, which provides a novel insight into the action mechanism of p-synephrine modulating energy homeostasis.

The metabolic pathway regulation in kidney injury and repair.

Kidney injury and repair are accompanied by significant disruptions in metabolic pathways, leading to renal cell dysfunction and further contributing to the progression of renal pathology. This review outlines the complex involvement of various energy production pathways in glucose, lipid, amino acid, and ketone body metabolism within the kidney. We provide a comprehensive summary of the aberrant regulation of these metabolic pathways in kidney injury and repair. After acute kidney injury (AKI), there is notable mitochondrial damage and oxygen/nutrient deprivation, leading to reduced activity in glycolysis and mitochondrial bioenergetics. Additionally, disruptions occur in the pentose phosphate pathway (PPP), amino acid metabolism, and the supply of ketone bodies. The subsequent kidney repair phase is characterized by a metabolic shift toward glycolysis, along with decreased fatty acid β-oxidation and continued disturbances in amino acid metabolism. Furthermore, the impact of metabolism dysfunction on renal cell injury, regeneration, and the development of renal fibrosis is analyzed. Finally, we discuss the potential therapeutic strategies by targeting renal metabolic regulation to ameliorate kidney injury and fibrosis and promote kidney repair.

Silencing of crustacean hyperglycemic hormone gene expression reveals the characteristic energy and metabolic changes in the gills and epidermis of crayfish Procambarus clarkii.

The crustacean hyperglycemic hormone (CHH) is a multifaceted neuropeptide instrumental in regulating carbohydrate and lipid metabolism, reproduction, osmoregulation, molting, and metamorphosis. Despite its significance, there is a dearth of research on its metabolic impact on the gills and epidermis-key organs in osmoregulation and molting processes. This study employed CHH dsRNA injections to silence CHH gene expression in Procambarus clarkii, followed by a metabolomic analysis of the gills and epidermis using nuclear magnetic resonance spectroscopy. Metabolic profiling through principal component analysis revealed the most pronounced changes at 24h post-injection (hpi) in the epidermis and at 48hpi in the gills. At 24hpi, the epidermis exhibited significant modulation in 25 enrichment sets and 20 KEGG pathways, while at 48hpi, 5 metabolite sets and 6 KEGG pathways were prominently regulated. Notably, pathways associated with amino acid metabolism, carbohydrate metabolism, and cofactor and vitamin metabolism were affected. A marked decrease in glucose and other carbohydrates suggested a compromised carbohydrate supply, whereas increased levels of citrate cycle intermediates implied a potential boost in energy provision. The silencing of CHH gene expression hampered the carbohydrate supply, which was possibly the main energy derived substrates. Conversely, the gills displayed significant alterations in 15 metabolite sets and 16 KEGG pathways at 48 hpi, with no significant changes at 24hpi. These changes encompassed amino acid, carbohydrate, and lipid metabolism pathways. The decline in TCA cycle intermediates pointed to a potential downregulation of the cycle, whereas a decrease in ketone bodies indicated a shift towards lipid metabolism for energy production. Additionally, increased levels of nicotinate, nicotinamide, and quinolinate were observed in both organs. Overall, CHH's impact on the epidermis was prominent at 24hpi and diminished thereafter, whereas its influence on metabolism in gills was delayed but intensified at 48hpi. This differential CHH effect between gills and epidermis in P. clarkii provides new insights into the organ-specific regulatory mechanisms of CHH on energy metabolism and osmoregulation, warranting further comparative studies to elucidate the distinct roles of CHH in these organs.