Amino Acid Levels Research Articles

Selective host autophagy is induced during the intracellular parasite Toxoplasma gondii infection controlling amino acid levels.

Intracellular parasites employ several mechanisms to manipulate the cellular environment, enabling them to persist in the host. Toxoplasma gondii, a single-celled parasite, possesses the ability to infect virtually any nucleated cell of warm-blooded vertebrates, including nearly 2 billion people worldwide. Unfortunately, existing treatments and immune responses are not entirely effective in eliminating the chronic persisting forms of the parasite. This study reveals that T. gondii induces the host's autophagic pathway to boost amino acid levels in infected cells. The depletion of amino acids, in turn, influences the persistence of the parasite's chronic forms. Significantly, our investigation establishes the crucial role of host endoplasmic reticulum (ER)-phagy in the parasite's persistence within the host during latent infection.

Peptide production through enhanced solid-state fermentation of soybean meal with Bacillus subtilis SBM_1: Fermentation process and product characteristics

This study aimed to assess the impact of additional inoculation of Bacillus subtilis SBM_1 on solid-state fermentation (SSF) of soybean meal (SBM). The peptide yield of fermented SBM increased to 220.93 mg/g under the optimal SSF conditions, marking a 47.74 % rise compared to natural SSF. Throughout enhanced SSF, the physicochemical properties of metabolites were analyzed. The results showed that the pH and total bacterial counts increased in the initial 8 h, along with elevated levels of peptide, soluble protein, and free amino acid (FAA). Protease activities is maintained at a relatively high level (103.37–241.93 U/g), leading to the substantial degradation of trypsin inhibitor (TI) and macromolecular protein. Following enhanced SSF, the TI activity of the fermented SBM decreased by 76.11 %, and small peptides with molecular weight (MW) < 3000 Da dominated the fermented products (71.64 %). Additionally, the enhanced SSF process demonstrated an improvement in nutrient content in the fermented products. Structural analysis of the fermented SBM showed that macromolecular soybean globulin and allergenic proteins were degraded, with the unfolded and loosened protein spatial structures and the loosely packed and dispersed surface microstructure. Biosafety analysis revealed no detectable microbial contaminants, including mold, salmonella, and coliforms, in compliance with national standards.

Metabolic Profiling Changes Induced by Fermented Blackberries in High-Fat-Diet-Fed Mice Utilizing Gas Chromatography-Mass Spectrometry Analysis.

The aim of this study was to investigate the metabolic changes associated with the anti-obesity effects of fermented blackberry extracts in the liver tissues of high-fat-diet-fed mice using mass spectrometry-based metabolomics analysis. C57BL/6J mice were divided into eight groups: normal-diet-fed mice, high-fat-diet-fed mice, high-fat diet treated with blackberry extract, high-fat-diet mice treated with blackberry fermented by L. plantarum, and high-fat diet with blackberry fermented by L. brevis. After 12 weeks, the high-fat-diet group exhibited a greater increase in liver weight compared to the control group, and among the groups, the group administered with blackberry fermented with L. plantarum showed the most pronounced reduction in liver weight. As the primary organ responsible for amino acid metabolism, the liver is crucial for maintaining amino acid homeostasis. In our study, we observed that the levels of several essential amino acids, including isoleucine and valine, were decreased by the high-fat diet, and were recovered by administration of blackberry extract fermented with L. plantarum. Our results demonstrated the potential of blackberry extract fermented with L. plantarum as a functional material for metabolic disorders by restoring some of the amino acid metabolism disturbances induced by a high-fat diet.

The Characteristic of HBV Quasispecies Is Related to Occult HBV Infection of Infants Born to Highly Viremic Mothers.

Although a combination of immunoprophylaxis and antiviral therapy can effectively prevent mother-to-child transmission (MTCT) of hepatitis B virus (HBV), a considerable number of infants born to highly viremic mothers still develop occult HBV infection (OBI). To uncover the virological factor and risk predictor for OBI in infants, we found that the diversity and complexity of maternal HBV quasispecies in the case group were lower than those in the control group. Mutations with significant differences between the two groups were most enriched in the NTCPbd and PreC regions. Genetic distance at the amino-acid level of the PreC region, especially the combination of three amino-acid mutations in the PreC region, could strongly predict the risk of OBI in infants. HBV quasispecies in OBI infants were highly complex, and the non-synonymous substitutions were mainly found in the RT and HBsAg regions. The sK47E (rtQ55R) and sP49L mutations in OBI infants might contribute to OBI through inhibiting the production of HBV DNA and HBsAg, respectively. This study found the potential virological factors and risk predictors for OBI in infants born to highly viremic mothers, which might be helpful for controlling OBI in infants.

Characterization and differentiation of three rambutan seed oils using metabolomics coupled with chemometric methodology

Rambutan seed oil presents a promising source of edible vegetable oil. Nevertheless, there is a dearth of studies regarding the metabolite profile of rambutan seed oil. This study comprehensively characterized and compared the metabolite profiles of seed oils from three rambutan cultivars by integrating metabolomics and chemometrics. A total of 544 metabolites were identified. Lipids and terpenoids represent the predominant metabolites. Significant differences in the metabolite composition of rambutan seed oil were observed among the varieties. BR-7 contained high levels of flavonoids, BR-4 had high levels of organic acids and derivatives, and BR-5 had the lowest levels of amino acids and derivatives. Forty-two differential metabolites were identified through chemometric modeling. Isoricinoleic acid displayed positive correlations with the majority of differential metabolites. Furthermore, KEGG enrichment analyses revealed that alpha-Linolenic acid metabolism predominated among the metabolic pathways. Overall, the metabolite profiles distinguish the seed oils of these three rambutan varieties, potentially opening new avenues for researching the functionality of rambutan seed oil.

Physiological and biochemical characterisation of split and healthy Daisy mandarin (Citrus reticulata Burm.) fruits

ABSTRACT Fruit splitting is a prevalent physiological disorder that has a significant impact on Daisy mandarin fruit production, posing challenges to farmers in terms of productivity and economic viability. Despite its impact, no prior research on fruit splitting in Daisy mandarin has been conducted. This study aimed to assess the effect of fruit splitting on quality, morphological characteristics, biochemical composition and nutrient content in Daisy mandarin. In 2022, a comprehensive analysis was conducted on both split and healthy Daisy mandarin fruits, budded on Rough lemon rootstock, to investigate their morphological characteristics, biochemical characteristics, mineral content and cell wall components. Additionally, the study examined the activity of cell wall-degrading enzymes, such as peroxidase (POD), cellulase (Cx) and polygalacturonase (PG). The Results indicated that split fruits exhibited larger fruit size and weight and increased water content in both the fruits and peel compared to healthy fruits. However, split fruits had thinner peel thickness and lower peel content. The peels of split fruits also contained higher level of total soluble sugars, amino acids, and proline content. Furthermore, the peels of split fruits displayed much higher activity of cell wall-degrading enzymes than those of healthy fruits. The nutrient analysis of the split fruits revealed a decrease in boron, calcium and potassium content in the peel compared to healthy fruits. The study provides crucial insights into the mechanisms underlying fruit splitting, identifying biochemical and physiological differences between split and healthy fruits. These findings offer valuable information for developing strategies to mitigate fruit splitting, enhancing fruit quality and reducing economic losses for citrus growers. Future research should explore the genetic and environmental factors contributing to fruit splitting and investigate potential interventions to improve nutrient management and fruit integrity in Daisy mandarin cultivation.

Urinary metabolomics signature of animal and plant protein intake and its association with 24-h blood pressure: the African-PREDICT study.

The contrasting relationships of plant and animal protein intake with blood pressure (BP) may be partially attributed to the differential non-protein (e.g., saturated fat and fibre) and amino acid (AA) compositions. This study determined whether animal and plant protein intake were related to differential metabolomic profiles associated with BP. This study included 1008 adults from the African-PREDICT study (aged 20-30 years). Protein intake was determined using 24-h dietary recalls. Twenty-four-hour ambulatory BP was measured. Amino acids and acylcarnitines were analysed in spot urine samples using liquid chromatography-tandem mass spectrometry-based metabolomics. Participants with a low plant, high animal protein intake had higher SBP (by 3 mmHg, p = 0.011) than those with high plant, low animal protein intake (low-risk group). We found that the relationships of plant and animal protein intake with 24-h SBP were partially mediated by BMI and saturated fat intake, which were independently associated with SBP. Protein intake was therefore not related to SBP in multiple regression analysis after adjusting for confounders. In the low-risk group, methionine (Std. β = -0.217; p = 0.034), glutamic acid (Std. β = -0.220; p = 0.031), glycine (Std. β = -0.234; p = 0.025), and proline (Std. β = -0.266; p = 0.010) were inversely related to SBP, and beta-alanine (Std. β = -0.277; p = 0.020) to DBP. Ultimately a diet high in animal and low in plant protein intake may contribute to higher BP by means of increased BMI and saturated fat intake. Conversely, higher levels of urinary AAs observed in adults consuming a plant rich diet may contribute to lower BP.

Irisin promotes tilapia muscle cell growth and amino acid uptake via IGF-1 signaling.

Irisin is a recently discovered myokine that facilitates the browning of white adipose tissue, increases glucose uptake in skeletal muscle, and influences metabolic processes in the liver. However, its potential effects on amino acid absorption remained largely unexplored. This study aimed to elucidate the role of irisin in modulating amino acid uptake and delineate the underlying molecular mechanisms involved. To this end, juvenile tilapia were administered intraperitoneal irisin injections at 100 ng/g body weight over 8 weeks. Evaluation of various physiological parameters revealed that irisin supplementation significantly improved the specific growth rate and feed conversion efficiency while reducing feed consumption. Muscle tissue analysis revealed that irisin significantly modified the proximate composition by increasing protein content and reducing lipid levels. It also significantly raised the levels of both essential and non-essential amino acids in the muscle. Histological analysis demonstrated that irisin-stimulated muscle growth through hyperplasia rather than hypertrophy, corroborated by upregulated IGF-1 mRNA and downregulated myostatin mRNA expression. Mechanistic studies in cultured tilapia muscle cells elucidated that irisin activated integrin receptors on muscle cells, which subsequently engaged IGF-1/IGF-1R signaling. Downstream of IGF-1R activation, irisin simultaneously stimulates the ERK1/2 and PI3K/mTORC2/Akt pathways. The convergence of these pathways upregulates L-type amino acid transporter 1 expression, thereby augmenting amino acid uptake into muscle cells. In summary, irisin supplementation in tilapia leads to improved muscle growth, predominantly via hyperplasia and augmented amino acid assimilation, governed by intricate cellular signaling pathways. These findings provide valuable aquaculture applications and novel insights into muscle development.

Probiotic Lactobacillus rhamnosus GG improves insulin sensitivity and offspring survival via modulation of gut microbiota and serum metabolite in a sow model

BackgroundSows commonly experience insulin resistance in late gestation and lactation, causing lower feed intake and milk production, which can lead to higher mortality rates in newborn piglets. The probiotic Lactobacillus rhamnosus GG (LGG) is known to improve insulin resistance. However, whether supplementing LGG can improve insulin sensitivity in sows and enhance lactation performance, particularly the early survival of offspring remains unclear. Hence, we explored the effects and mechanisms of supplementing LGG during late gestation and lactation on sow insulin sensitivity, lactation performance, and offspring survival. In total, 20 sows were randomly allocated to an LGG (n = 10) and control group (n = 10).ResultsIn sows, LGG supplementation significantly improved insulin sensitivity during late gestation and lactation, increased feed intake, milk production and colostrum lactose levels in early lactation, and enhanced newborn piglet survival. Moreover, LGG treatment significantly reshaped the gut microbiota in sows, notably increasing microbiota diversity and enriching the relative abundance of insulin sensitivity-associated probiotics such as Lactobacillus, Bifidobacterium, and Bacteroides. Serum metabolite and amino acid profiling in late-gestation sows also revealed decreased branched-chain amino acid and kynurenine serum levels following LGG supplementation. Further analyses highlighted a correlation between mitigated insulin resistance in late pregnancy and lactation by LGG and gut microbiota reshaping and changes in serum amino acid metabolism. Furthermore, maternal LGG enhanced immunity in newborn piglets, reduced inflammation, and facilitated the establishment of a gut microbiota.ConclusionsWe provide the first evidence that LGG mitigates insulin resistance in sows and enhances offspring survival by modulating the gut microbiota and amino acid metabolism.

Dietary sodium sulphate supplementation during mid-to-late gestation improves placental angiogenesis, bile acid metabolism, and serum amino acid concentrations of sows

Sulphate plays a vital role in the growth and development of the foetus. Sodium sulphate (Na2SO4) is utilised as a dietary protein nutrient factor and helps replenish sulphur elements in livestock and poultry. Therefore, this study aimed to investigate the effects of Na2SO4 supplementation in mid to late pregnancy on bile acid metabolism, amino acid metabolism, placental vascular development and antioxidant capacity of sows. At day 1 of gestation (G1), a total of twenty-six primiparous sows were carefully chosen and randomised into two groups: (1) control group, (2) Na2SO4 group (1.40 g/kg). Blood samples and placentas from sows were collected to measure biochemistry parameters, antioxidant indexes, placental vascular density, and indicators related to bile acid metabolism and amino acid concentrations, respectively. We found that dietary supplementation with Na2SO4 had a tendency for a reduction of incidence of stillborn at farrowing. Further observation showed that sows supplemented with Na2SO4 had decreased total bile acid level in cord blood, and increased placental gene expression of sulphotransferase and organic anion transport peptide. Na2SO4 supplementation increased catalase and total superoxide dismutase activity in cord blood, decreased placental malondialdehyde content, and enhanced placental protein expression of Sirtuin 1. Moreover, Na2SO4 consumption resulted in increased vascular density of placental stroma and elevated amino acid levels in sows and cord blood. Furthermore, maternal Na2SO4 consumption reduced serum urea concentrations of sows and umbilical cord blood at G114. In addition, dietary supplementation with Na2SO4 activated the protein expression of the placental mechanistic target of rapamycin complex 1. Collectively, these findings indicated that maternal supplementation with Na2SO4 during mid-to-late gestation elevated foetal survival via improving placental angiogenesis, bile acid metabolism and amino acid utilisation.

Branched-Chain Amino Acids Deficiency Promotes Diabetic Neuropathic Pain Through Upregulating LAT1 and Inhibiting Kv1.2 Channel.

Diabetic neuropathic pain (DNP), one of the most common complications of diabetes, is characterized by bilateral symmetrical distal limb pain and substantial morbidity. To compare the differences is aimed at serum metabolite levels between 81 DNP and 73 T2DM patients without neuropathy and found that the levels of branched-chain amino acids (BCAA) are significantly lower in DNP patients than in T2DM patients. In high-fat diet/low-dose streptozotocin (HFD/STZ)-induced T2DM and leptin receptor-deficient diabetic (db/db) mouse models, it is verified that BCAA deficiency aggravated, whereas BCAA supplementation alleviated DNP symptoms. Mechanistically, using a combination of RNA sequencing of mouse dorsal root ganglion (DRG) tissues and label-free quantitative proteomic analysis of cultured cells, it is found that BCAA deficiency activated the expression of L-type amino acid transporter 1 (LAT1) through ATF4, which is reversed by BCAA supplementation. Abnormally upregulated LAT1 reduced Kv1.2 localization to the cell membrane, and inhibited Kv1.2 channels, thereby increasing neuronal excitability and causing neuropathy. Furthermore, intraperitoneal injection of the LAT1 inhibitor, BCH, alleviated DNP symptoms in mice, confirming that BCAA-deficiency-induced LAT1 activation contributes to the onset of DNP. These findings provide fresh insights into the metabolic differences between DNP and T2DM, and the development of approaches for the management of DNP.

Quantification of amino acids secreted by yeast cells by hydrophilic interaction liquid chromatography-tandem mass spectrometry.

Monitoring the levels of amino acids (AAs) in biological cell cultures provides key information to understand the regulation of cell growth and metabolism. Saccharomyces cerevisiae can naturally excrete AAs, making accurate detection and determination of amino acid levels within the cultivation medium pivotal for gaining insights into this still poorly known process. Given that most AAs lack ultraviolet (UV) chromophores or fluorophores necessary for UV and fluorescence detection, derivatization is commonly utilized to enhance amino acid detectability via UV absorption. Unfortunately, this can lead to drawbacks such as derivative instability, labor intensiveness, and poor reproducibility. Hence, this study aimed to develop an accurate and stable hydrophilic interaction liquid chromatography-tandem mass spectrometry analytical method for the separation of all 20 AAs within a short 17-min run time. The method provides satisfactory linearity and sensitivity for all analytes. The method has been validated for intra- and inter-day precision, accuracy, recovery, matrix effect, and stability. It has been successfully applied to quantify 20 AAs in samples of yeast cultivation medium. This endeavor seeks to enhance our comprehension of amino acid profiles in the context of cell growth and metabolism within yeast cultivation media.

Serum and CSF metabolomics analysis shows Mediterranean Ketogenic Diet mitigates risk factors of Alzheimer’s disease

Alzheimer’s disease (AD) is influenced by a variety of modifiable risk factors, including a person’s dietary habits. While the ketogenic diet (KD) holds promise in reducing metabolic risks and potentially affecting AD progression, only a few studies have explored KD’s metabolic impact, especially on blood and cerebrospinal fluid (CSF). Our study involved participants at risk for AD, either cognitively normal or with mild cognitive impairment. The participants consumed both a modified Mediterranean Ketogenic Diet (MMKD) and the American Heart Association diet (AHAD) for 6 weeks each, separated by a 6-week washout period. We employed nuclear magnetic resonance (NMR)-based metabolomics to profile serum and CSF and metagenomics profiling on fecal samples. While the AHAD induced no notable metabolic changes, MMKD led to significant alterations in both serum and CSF. These changes included improved modifiable risk factors, like increased HDL-C and reduced BMI, reversed serum metabolic disturbances linked to AD such as a microbiome-mediated increase in valine levels, and a reduction in systemic inflammation. Additionally, the MMKD was linked to increased amino acid levels in the CSF, a breakdown of branched-chain amino acids (BCAAs), and decreased valine levels. Importantly, we observed a strong correlation between metabolic changes in the CSF and serum, suggesting a systemic regulation of metabolism. Our findings highlight that MMKD can improve AD-related risk factors, reverse some metabolic disturbances associated with AD, and align metabolic changes across the blood-CSF barrier.

Effects of Latilactobacillus sakei LZ217 on Gastric Mucosal Colonization, Metabolic Interference, and Urease Expression in Helicobacter pylori Infection.

Emerging evidence suggests differential antagonism of lactic acid-producing bacteria (LAB) to Helicobacter pylori, posing challenges to human health and food safety due to unclear mechanisms. This study assessed 21 LAB strains from various sources on H. pylori growth, urease activity, and coaggregation. Composite scoring revealed that Latilactobacillus sakei LZ217, derived from fresh milk, demonstrates strong inhibitory effects on both H. pylori growth and urease activity. L. sakei LZ217 significantly reduced H. pylori adherence of gastric cells invitro, with inhibition ratios of 47.62%. Furthermore, invivo results showed that L. sakei LZ217 alleviated H. pylori-induced gastric mucosa damage and inflammation in mice. Metabolomic exploration revealed metabolic perturbations in H. pylori induced by L. sakei LZ217, including reduced amino acid levels (e.g., isoleucine, leucine, glutamate, aspartate, and phenylalanine) and impaired carbohydrate and nucleotide synthesis, contributing to the suppression of ureA (28.30%), ureE (84.88%), and ureF (59.59%) expressions in H. pylori. This study underscores the efficacy of LAB against H. pylori and highlights metabolic pathways as promising targets for future interventions against H. pylori growth and colonization.

Influence of Controlled Condition Ice Encasement of Creeping Bentgrass and Annual Bluegrass on Plant Recovery, Gas Evolution, and Metabolites

Two cool-season putting green turfgrass species, annual bluegrass and creeping bentgrass, are differential in ice encasement tolerance. Physiological mechanisms associated with creeping bentgrass ice encasement tolerance and annual bluegrass susceptibility are not understood. The objectives were to evaluate oxygen, ethylene, and CO2 content within the upper soil space of the plants while frozen and immediately after ice melt after 0, 5, 10, 20, and 28 days of ice encasement (2.54 cm of ice) in growth chamber conditions. Following ice melt, plant samples were separated into leaf, crown, and root tissues and used to evaluate carbohydrate and amino acid content. Annual bluegrass exhibited higher damage (slower recovery rates) on most sampling days compared with creeping bentgrass. The organs that were most damaged and exhibited a differential principal component analysis snapshot, were the leaf and crown tissues. Creeping bentgrass may preserve leaf and crown tissues for postwinter recovery whereas significant metabolic changes occur in annual bluegrass leaves and crowns. Creeping bentgrass retained total amino acids in leaves following ice encasement whereas total leaf amino acid levels declined in annual bluegrass. Specific carbohydrates and amino acids such as the ability to maintain high levels of fructose, asparagine, and proline may be important indicators of the tolerance to ice encasement stress. On the basis of more prominent carbohydrate and amino acid loss in leaves and crowns and higher levels of CO2 evolution, annual bluegrass may exhibit a higher metabolism and/or tissue damage during ice encasement compared with creeping bentgrass, which could reduce spring recuperative potential.

Long-acting Erwinia chrysanthemi, Pegcrisantaspase, induces alternate amino acid biosynthetic pathways in a preclinical model of pancreatic ductal adenocarcinoma

BackgroundPancreatic ductal adenocarcinoma (PDAC) is an aggressive disease without meaningful therapeutic options beyond the first salvage therapy. Targeting PDAC metabolism through amino acid restriction has emerged as a promising new strategy, with asparaginases, enzymes that deplete plasma glutamine and asparagine, reaching clinical trials. In this study, we investigated the anti-PDAC activity of the asparaginase formulation Pegcrisantaspase (PegC) alone and in combination with standard-of-care chemotherapeutics.MethodsUsing mouse and human PDAC cell lines, we assessed the impact of PegC on cell proliferation, cell death, and cell cycle progression. We further characterized the in vitro effect of PegC on protein synthesis as well as the generation of reactive oxygen species and levels of glutathione, a major cellular antioxidant. Additional cell line studies examined the effect of the combination of PegC with standard-of-care chemotherapeutics. In vivo, the tolerability and efficacy of PegC, as well as the impact on plasma amino acid levels, was assessed using the C57BL/6-derived KPC syngeneic mouse model.ResultsHere we report that PegC demonstrated potent anti-proliferative activity in a panel of human and murine PDAC cell lines. This decrease in proliferation was accompanied by inhibited protein synthesis and decreased levels of glutathione. In vivo, PegC was tolerable and effectively reduced plasma levels of glutamine and asparagine, leading to a statistically significant inhibition of tumor growth in a syngeneic mouse model of PDAC. There was no observable in vitro or in vivo benefit to combining PegC with standard-of-care chemotherapeutics, including oxaliplatin, irinotecan, 5-fluorouracil, paclitaxel, and gemcitabine. Notably, PegC treatment increased tumor expression of asparagine and serine biosynthetic enzymes.ConclusionsTaken together, our results demonstrate the potential therapeutic use of PegC in PDAC and highlight the importance of identifying candidates for combination regimens that could improve cytotoxicity and/or reduce the induction of resistance pathways.

Metabolic abnormalities in the bone marrow cells of young offspring born to mothers with obesity.

Intrauterine metabolic reprogramming occurs in mothers with obesity during gestation, putting the offspring at high risk of developing obesity and associated metabolic disorders even before birth. We have generated a mouse model of maternal high-fat diet-induced obesity that recapitulates the metabolic changes seen in humans born to women with obesity. Here, we profiled and compared the metabolic characteristics of bone marrow cells of newly weaned 3-week-old offspring of dams fed either a high-fat (Off-HFD) or a regular diet (Off-RD). We utilized a state-of-the-art flow cytometry, and targeted metabolomics approach coupled with a Seahorse metabolic analyzer. We revealed significant metabolic perturbation in the offspring of HFD-fed vs. RD-fed dams, including utilization of glucose primarily via oxidative phosphorylation. We also show a reduction in levels of amino acids, a phenomenon previously linked to bone marrow aging. Using flow cytometry, we found changes in the immune complexity of bone marrow cells and identified a unique B cell population expressing CD19 and CD11b in the bone marrow of three-week-old offspring of high-fat diet-fed mothers. Our data also revealed increased expression of Cyclooxygenase-2 (COX-2) on myeloid CD11b, and on CD11bhi B cells. Altogether, we demonstrate that the offspring of mothers with obesity show metabolic and immune changes in the bone marrow at a very young age and prior to any symptomatic metabolic disease.

Whey protein hydrolysate maintains the homeostasis of muscle metabolism in exercise mice and releases potential anti-fatigue peptides after gastrointestinal digestion

Whey protein hydrolysate (WPH) has been proven to possess anti-fatigue effects, but its regulatory mechanism on muscle metabolism in exercise mice is unclear. In the present study, the effects of WPH on muscle metabolites in mice before and after exercise were explored using metabolomics techniques. Results showed that 34 muscle metabolites were significantly altered by exercise in the WPH group, which was less than 71 in the WP group and 101 in the control group. Specifically, supplementation of WPH significantly increased the levels of amino acid and carbohydrate metabolites (i.e., 1-methylhistamine, guanidoacetic acid, melibiose, and xylulose 5-phosphate) pre-exercise, thereby delaying energy depletion and maintaining metabolic homeostasis during exercise. Furthermore, simulated gastrointestinal digestion (SGID), peptidomics and bioinformatics tools were employed to screen potential peptides in WPH. A total of 37 peptides with 2–5 residues in WPH were resistant to SGID (peak intensity > 105). Among them, YGLF showed favorable potentials in physicochemical property, bioavailability, bioactivity, SwissTargetPrediction, and molecular docking. In addition, the anti-fatigue activity of YGLF was evaluated in vivo. YGLF (100 mg/kg) significantly increased the contents of glucose, glycogens, and amino acids and decreased the levels of lactate and urea nitrogen in mice after exercise. These findings may serve as a reference for the screening of anti-fatigue peptides.

ErbB3 is required for hyperaminoacidemia-induced pancreatic α cell hyperplasia

Blood amino acid levels are maintained in a narrow physiological range. The pancreatic α cells have emerged as the primary aminoacidemia regulator through glucagon secretion to promote hepatic amino acid catabolism. Interruption of glucagon signaling disrupts the liver - α cells axis leading to hyperaminoacidemia, which triggers a compensatory rise in glucagon secretion and α cell hyperplasia. The mechanisms of hyperaminoacidemia-induced α cell hyperplasia remain incompletely understood. Using a mouse α cell line and in vivo studies in zebrafish and mice, we found that hyperaminoacidemia-induced α cell hyperplasia requires ErbB3 signaling. In addition to mTORC1, another ErbB3 downstream effector STAT3 also plays a role in α cell hyperplasia. Mechanistically, ErbB3 may partner with ErbB2 to stimulate cyclin D2 and suppress p27 via mTORC1 and STAT3. Our study identifies ErbB3 as a new regulator for hyperaminoacidemia-induced α cell proliferation and a critical component of the liver-α cells axis that regulates aminoacidemia.

Proteomics and metabolomics analysis of American shad (Alosa sapidissima) liver responses to heat stress

The dramatic changes in the global climate pose a major threat to the survival of many organisms, including fish. To date, the regulatory mechanisms behind the physiological responses of fish to temperature changes have been studied, and a comprehensive analysis of the regulatory mechanisms of temperature tolerance will help to propose effective strategies for fish to cope with global warming. In this study, we investigated the expression profiles of proteins and metabolites in liver tissues of American shad (Alosa sapidissima) corresponding to different water temperatures (24 °C, 27 °C and 30 °C) at various times (1-month intervals) under natural culture conditions. Proteomic analysis showed that the expression levels of the heat shock protein family (e.g. HSPE1, HSP70, HSPA5 and HSPA.1) increase significantly with temperature and that many differentially expressed proteins were highly enriched especially in pathways related to the endoplasmic reticulum, oxidative phosphorylation and glycolysis/gluconeogenesis processes. In addition, the results of conjoint metabolomics and proteomics analysis suggested that the contents of several important amino acids and chemical compounds, including L-serine, L-isoleucine, L-cystine, choline and betaine, changed significantly under high-temperature environmental stress, affecting the metabolic levels of starch, amino acid and glucose, which is thought to represent a possible energy conservation method for A. sapidissima to cope with rapid changes in external temperature. In summary, our findings demonstrate that living under high temperatures for a long period of time leads to different physiological defense responses in A. sapidissima, which provides some new ideas for analyzing the molecular regulatory patterns of adaptation to high temperature and also provides a theoretical basis for the subsequent improvement of fish culture in response to global warming.