Metabolites

16 pages, 2990 KiB

Open AccessArticle

In Vitro Metabolism of Helenalin Acetate and 11α,13-Dihydrohelenalin Acetate: Natural Sesquiterpene Lactones from Arnica

by Franziska M. Jürgens, Matthias Behrens, Hans-Ulrich Humpf, Sara M. Robledo and Thomas J. Schmidt

Metabolites 2022, 12(1), 88; https://doi.org/10.3390/metabo12010088 - 17 Jan 2022

Cited by 7 | Viewed by 4488

Abstract

Arnica tincture is a herbal medicinal preparation with anti-inflammatory activity which is used traditionally for the topical treatment of blunt injuries as well as rheumatic muscle and joint complaints. Its main bioactive constituents are sesquiterpene lactones (STLs) of the helenalin and 11α,13-dihydrohelenalin types. [...] Read more.

Arnica tincture is a herbal medicinal preparation with anti-inflammatory activity which is used traditionally for the topical treatment of blunt injuries as well as rheumatic muscle and joint complaints. Its main bioactive constituents are sesquiterpene lactones (STLs) of the helenalin and 11α,13-dihydrohelenalin types. Besides the mentioned activity, the tincture and its isolated STLs have antileishmanial activity. In a recent in vivo study, a treatment with Arnica tincture cured cutaneous Leishmaniasis (CL) in a golden hamster model. CL is a neglected tropical disease affecting more than two million people every year, for which new treatments are urgently needed. In order to use Arnica tincture on open CL lesions of human patients, it is important to know how the constituents are metabolized. Therefore, in vitro metabolism experiments with liver microsomes of different species (rat, pig and human) were performed with the Arnica STLs helenalin acetate and 11α,13-dihydrohelenalin acetate. Phase I and phase II metabolism experiments were performed, as well as a combination of both. Glutathione conjugation plays a major role in the metabolism of these STLs, as could be expected based on previous reports on their reactivity. Besides glutathione conjugates, several other metabolites were formed, e.g., water conjugates and hydroxides. Our results show for the first time a detailed picture of the metabolism of Arnica STLs. The fast and extensive formation of glutathione conjugates makes it unlikely that low absorbed levels of these compounds, as expected after dermal absorption from Arnica tincture, could be of toxicological concern. Full article

(This article belongs to the Special Issue Analysis and Metabolism of Bioactive Compounds)

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18 pages, 1125 KiB

Open AccessReview

A Checklist for Reproducible Computational Analysis in Clinical Metabolomics Research

by Xinsong Du, Juan J. Aristizabal-Henao, Timothy J. Garrett, Mathias Brochhausen, William R. Hogan and Dominick J. Lemas

Metabolites 2022, 12(1), 87; https://doi.org/10.3390/metabo12010087 - 17 Jan 2022

Cited by 12 | Viewed by 5900

Abstract

Clinical metabolomics emerged as a novel approach for biomarker discovery with the translational potential to guide next-generation therapeutics and precision health interventions. However, reproducibility in clinical research employing metabolomics data is challenging. Checklists are a helpful tool for promoting reproducible research. Existing checklists [...] Read more.

Clinical metabolomics emerged as a novel approach for biomarker discovery with the translational potential to guide next-generation therapeutics and precision health interventions. However, reproducibility in clinical research employing metabolomics data is challenging. Checklists are a helpful tool for promoting reproducible research. Existing checklists that promote reproducible metabolomics research primarily focused on metadata and may not be sufficient to ensure reproducible metabolomics data processing. This paper provides a checklist including actions that need to be taken by researchers to make computational steps reproducible for clinical metabolomics studies. We developed an eight-item checklist that includes criteria related to reusable data sharing and reproducible computational workflow development. We also provided recommended tools and resources to complete each item, as well as a GitHub project template to guide the process. The checklist is concise and easy to follow. Studies that follow this checklist and use recommended resources may facilitate other researchers to reproduce metabolomics results easily and efficiently. Full article

(This article belongs to the Special Issue Advances in Computational Metabolomics)

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14 pages, 453 KiB

Open AccessArticle

Metabolism of Imidazole Dipeptides, Taurine, Branched-Chain Amino Acids, and Polyamines of the Breast Muscle Are Affected by Post-Hatch Development in Chickens

by Shozo Tomonaga, Takahiro Kawase, Takamitsu Tsukahara, Yoshiyuki Ohta and Jun-ichi Shiraishi

Metabolites 2022, 12(1), 86; https://doi.org/10.3390/metabo12010086 - 17 Jan 2022

Cited by 6 | Viewed by 2603

Abstract

To explore metabolic characteristics during the post-hatch developmental period, metabolomic analyses of breast muscle and plasma were performed in chickens. The most significant growth-related changes in metabolite levels were observed between seven and 28 days of age. Some of these metabolites are essential [...] Read more.

To explore metabolic characteristics during the post-hatch developmental period, metabolomic analyses of breast muscle and plasma were performed in chickens. The most significant growth-related changes in metabolite levels were observed between seven and 28 days of age. Some of these metabolites are essential nutrients or reported as growth-promoting metabolites. In the muscle, two imidazole dipeptides—carnosine and its methylated metabolite, anserine—increased with the development. These dipeptide levels may be, in part, regulated transcriptionally because in the muscle mRNA levels of carnosine synthase and carnosine methylation enzyme increased. In contrast, taurine levels in the muscle decreased. This would be substrate availability-dependent because some upstream metabolites decreased in the muscle or plasma. In branched-chain amino acid metabolism, valine, leucine, and isoleucine decreased in the muscle, while some of their downstream metabolites decreased in the plasma. The polyamines, putrescine and spermidine, decreased in the muscle. Furthermore, mRNA levels associated with insulin/insulin-like growth factor 1 signaling, which play important roles in muscle growth, increased in the muscle. These results indicate that some metabolic pathways would be important to clarify metabolic characteristics and/or growth of breast muscle during the post-hatch developmental period in chickens. Full article

(This article belongs to the Special Issue Metabolomic Applications in Animal Science Volume 2)

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25 pages, 4406 KiB

Open AccessArticle

Metabolomic Profiling of Malaysian and New Zealand Honey Using Concatenated NMR and HRMS Datasets

by Yusnaini M. Yusoff, Grainne Abbott, Louise Young and RuAngelie Edrada-Ebel

Metabolites 2022, 12(1), 85; https://doi.org/10.3390/metabo12010085 - 17 Jan 2022

Cited by 7 | Viewed by 2745

Abstract

This study aims to compare the metabolomic profiles of Malaysian and New Zealand honey while determining their anti-oncogenic activity for potential prophylactic functions. Metabolomics tools including multivariate analysis were applied on concatenated LC-HRMS and NMR datasets to afford an intensive chemical profile of [...] Read more.

This study aims to compare the metabolomic profiles of Malaysian and New Zealand honey while determining their anti-oncogenic activity for potential prophylactic functions. Metabolomics tools including multivariate analysis were applied on concatenated LC-HRMS and NMR datasets to afford an intensive chemical profile of honey samples and have a snapshot of the bioactive metabolites in the respective collections. Malaysian samples were found to have higher sugar and polyphenolic content, while New Zealand samples afforded higher concentration of low molecular weight (MW) lipids. However, New Zealand honey collected from the northern islands had higher concentration of acetylated saccharides, while those from the southern islands yielded higher low MW phenolic metabolites that were comparable to Malaysian honey. Mild anti-oncogenic compounds against breast cancer cell line ZR75 were putatively identified in Malaysian honey that included earlier described antioxidants such as gingerdiol, 2-hexylphenol-O-β-D-xylopyranoside, plastoquinone, tropine isovalerate, plumerinine, and 3,5-(12-phenyl-8-dodecenyl)resorcinol, along with several phenolic esters and lignans. Full article

(This article belongs to the Section Metabolomic Profiling Technology)

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12 pages, 1358 KiB

Open AccessArticle

Essential Amino Acid-Enriched Diet Alleviates Dexamethasone-Induced Loss of Muscle Mass and Function through Stimulation of Myofibrillar Protein Synthesis and Improves Glucose Metabolism in Mice

by Yeongmin Kim, Sanghee Park, Jinseok Lee, Jiwoong Jang, Jiyeon Jung, Jin-Ho Koh, Cheol Soo Choi, Robert R. Wolfe and Il-Young Kim

Metabolites 2022, 12(1), 84; https://doi.org/10.3390/metabo12010084 - 16 Jan 2022

Cited by 10 | Viewed by 3783

Abstract

Dexamethasone (DEX) induces dysregulation of protein turnover, leading to muscle atrophy and impairment of glucose metabolism. Positive protein balance, i.e., rate of protein synthesis exceeding rate of protein degradation, can be induced by dietary essential amino acids (EAAs). In this study, we investigated [...] Read more.

Dexamethasone (DEX) induces dysregulation of protein turnover, leading to muscle atrophy and impairment of glucose metabolism. Positive protein balance, i.e., rate of protein synthesis exceeding rate of protein degradation, can be induced by dietary essential amino acids (EAAs). In this study, we investigated the roles of an EAA-enriched diet in the regulation of muscle proteostasis and its impact on glucose metabolism in the DEX-induced muscle atrophy model. Mice were fed normal chow or EAA-enriched chow and were given daily injections of DEX over 10 days. We determined muscle mass and functions using treadmill running and ladder climbing exercises, protein kinetics using the D₂O labeling method, molecular signaling using immunoblot analysis, and glucose metabolism using a U-¹³C₆ glucose tracer during oral glucose tolerance test (OGTT). The EAA-enriched diet increased muscle mass, strength, and myofibrillar protein synthesis rate, concurrent with improved glucose metabolism (i.e., reduced plasma insulin concentrations and increased insulin sensitivity) during the OGTT. The U-¹³C₆ glucose tracing revealed that the EAA-enriched diet increased glucose uptake and subsequent glycolytic flux. In sum, our results demonstrate a vital role for the EAA-enriched diet in alleviating the DEX-induced muscle atrophy through stimulation of myofibrillar proteins synthesis, which was associated with improved glucose metabolism. Full article

(This article belongs to the Special Issue Amino Acid Metabolism and Physiological Resilience)

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11 pages, 954 KiB

Open AccessArticle

Central Taurine Attenuates Hyperthermia and Isolation Stress Behaviors Augmented by Corticotropin-Releasing Factor with Modifying Brain Amino Acid Metabolism in Neonatal Chicks

by Mohamed Z. Elhussiny, Phuong V. Tran, Yuriko Tsuru, Shogo Haraguchi, Elizabeth R. Gilbert, Mark A. Cline, Takashi Bungo, Mitsuhiro Furuse and Vishwajit S. Chowdhury

Metabolites 2022, 12(1), 83; https://doi.org/10.3390/metabo12010083 - 16 Jan 2022

Cited by 7 | Viewed by 3107

Abstract

The objective of this study was to determine the effects of centrally administered taurine on rectal temperature, behavioral responses and brain amino acid metabolism under isolation stress and the presence of co-injected corticotropin-releasing factor (CRF). Neonatal chicks were centrally injected with saline, 2.1 [...] Read more.

The objective of this study was to determine the effects of centrally administered taurine on rectal temperature, behavioral responses and brain amino acid metabolism under isolation stress and the presence of co-injected corticotropin-releasing factor (CRF). Neonatal chicks were centrally injected with saline, 2.1 pmol of CRF, 2.5 μmol of taurine or both taurine and CRF. The results showed that CRF-induced hyperthermia was attenuated by co-injection with taurine. Taurine, alone or with CRF, significantly decreased the number of distress vocalizations and the time spent in active wakefulness, as well as increased the time spent in the sleeping posture, compared with the saline- and CRF-injected chicks. An amino acid chromatographic analysis revealed that diencephalic leucine, isoleucine, tyrosine, glutamate, asparagine, alanine, β-alanine, cystathionine and 3-methylhistidine were decreased in response to taurine alone or in combination with CRF. Central taurine, alone and when co-administered with CRF, decreased isoleucine, phenylalanine, tyrosine and cysteine, but increased glycine concentrations in the brainstem, compared with saline and CRF groups. The results collectively indicate that central taurine attenuated CRF-induced hyperthermia and stress behaviors in neonatal chicks, and the mechanism likely involves the repartitioning of amino acids to different metabolic pathways. In particular, brain leucine, isoleucine, cysteine, glutamate and glycine may be mobilized to cope with acute stressors. Full article

(This article belongs to the Special Issue Regulation and Effect of Taurine on Metabolism)

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12 pages, 2102 KiB

Open AccessArticle

Hao1 Is Not a Pathogenic Factor for Ectopic Ossifications but Functions to Regulate the TCA Cycle In Vivo

by Atsushi Kimura, Akiyoshi Hirayama, Tatsuaki Matsumoto, Yuiko Sato, Tami Kobayashi, Satsuki Ikeda, Midori Maruyama, Mari Kaneko, Mayo Shigeta, Eri Ito, Tomoya Soma, Kana Miyamoto, Tomoyoshi Soga, Masaru Tomita, Akihito Oya, Morio Matsumoto, Masaya Nakamura, Arihiko Kanaji and Takeshi Miyamoto

Metabolites 2022, 12(1), 82; https://doi.org/10.3390/metabo12010082 - 15 Jan 2022

Cited by 3 | Viewed by 2879

Abstract

Ossification of the posterior longitudinal ligament (OPLL), a disease characterized by the ectopic ossification of a spinal ligament, promotes neurological disorders associated with spinal canal stenosis. While blocking ectopic ossification is mandatory to prevent OPLL development and progression, the mechanisms underlying the condition [...] Read more.

Ossification of the posterior longitudinal ligament (OPLL), a disease characterized by the ectopic ossification of a spinal ligament, promotes neurological disorders associated with spinal canal stenosis. While blocking ectopic ossification is mandatory to prevent OPLL development and progression, the mechanisms underlying the condition remain unknown. Here we show that expression of hydroxyacid oxidase 1 (Hao1), a gene identified in a previous genome-wide association study (GWAS) as an OPLL-associated candidate gene, specifically and significantly decreased in fibroblasts during osteoblast differentiation. We then newly established Hao1-deficient mice by generating Hao1-flox mice and crossing them with CAG-Cre mice to yield global Hao1-knockout (CAG-Cre/Hao1flox/flox; Hao1 KO) animals. Hao1 KO mice were born normally and exhibited no obvious phenotypes, including growth retardation. Moreover, Hao1 KO mice did not exhibit ectopic ossification or calcification. However, urinary levels of some metabolites of the tricarboxylic acid (TCA) cycle were significantly lower in Hao1 KO compared to control mice based on comprehensive metabolomic analysis. Our data indicate that Hao1 loss does not promote ectopic ossification, but rather that Hao1 functions to regulate the TCA cycle in vivo. Full article

(This article belongs to the Special Issue Metabolomics in Bone and Joint)

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6 pages, 363 KiB

Open AccessCommunication

Comparison of a Standardized High-Fat Meal versus a High-Fat Meal Scaled to Body Mass for Measuring Postprandial Triglycerides: A Randomized Crossover Study

by Bryant H. Keirns, Christina M. Sciarrillo, Samantha M. Hart and Sam R. Emerson

Metabolites 2022, 12(1), 81; https://doi.org/10.3390/metabo12010081 - 15 Jan 2022

Cited by 3 | Viewed by 1680

Abstract

Post-meal triglycerides are an independent cardiovascular disease (CVD) risk factor, but the ideal high-fat meal formulation has yet to be standardized and is one challenge prohibiting widespread clinical adoption of postprandial triglyceride assessment. Two general approaches often used are giving individuals a high-fat [...] Read more.

Post-meal triglycerides are an independent cardiovascular disease (CVD) risk factor, but the ideal high-fat meal formulation has yet to be standardized and is one challenge prohibiting widespread clinical adoption of postprandial triglyceride assessment. Two general approaches often used are giving individuals a high-fat meal scaled to body weight or a standardized high-fat meal containing a set fat bolus. A recent expert panel statement has endorsed the latter, specifying 75 g of fat as an appropriate fat dosage. Despite this recommendation, no study to date has tested whether there is a difference in postprandial triglycerides or if risk classification is affected based on these different approaches. We recruited 16 generally healthy individuals with roughly equal distribution among body mass index (BMI)class (n = 5–6/per BMI category) and sex (n = 2–3 M/F) within each BMI class. Each participant underwent two abbreviated fat tolerance tests separated by ~1 week: one with a scaled to body weight high-fat meal (9 kcal/kg; 70% fat) and a standardized meal containing 75 g of fat (70% fat). Fasting, 4 h, and absolute change in triglycerides across the entire sample and within each BMI category were similar regardless of high-fat meal. Only one participant with obesity had discordant postprandial responses between the fat tolerance tests (i.e., different CVD risk classification). These findings suggest that, within a certain range of fat intake, generally healthy individuals will have a similar postprandial triglyceride response. Considering the greater convenience of utilizing standardized high-fat meals, our data suggest that a standardized high-fat meal may be acceptable for large-scale studies and clinical implementation. Full article

(This article belongs to the Special Issue Metabolites for Screening and Evaluation of Cardiometabolic Risk)

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24 pages, 20302 KiB

Open AccessArticle

Different Metabolomic and Proteomic Profiles of Cerebrospinal Fluid in Ventricular and Lumbar Compartments in Relation to Leptomeningeal Metastases

by Ji-Woong Kwon, Ji Hye Im, Kyue-Yim Lee, Byong Chul Yoo, Jun Hwa Lee, Kyung-Hee Kim, Jong Heon Kim, Sang Hoon Shin, Heon Yoo and Ho-Shin Gwak

Metabolites 2022, 12(1), 80; https://doi.org/10.3390/metabo12010080 - 14 Jan 2022

Cited by 6 | Viewed by 2754

Abstract

The different molecular profiles of cerebrospinal fluid (CSF) between ventricular and lumbar compartments remain elusive, especially in the context of leptomeningeal metastasis (LM), which affects CSF flow. We evaluated CSF metabolomic and proteomic profiles based on the compartments and the diagnosis of spinal [...] Read more.

The different molecular profiles of cerebrospinal fluid (CSF) between ventricular and lumbar compartments remain elusive, especially in the context of leptomeningeal metastasis (LM), which affects CSF flow. We evaluated CSF metabolomic and proteomic profiles based on the compartments and the diagnosis of spinal LM, proved by MRI from 20 paired ventricular and lumbar CSF samples of LM patients, including 12 spinal LM (+) samples. In metabolome analysis, 9512 low-mass ions (LMIs) were identified—7 LMIs were abundant in all lumbar versus paired ventricular CSF samples, and 3 LMIs were significantly abundant in all ventricular CSF. In comparisons between spinal LM (+) CSF and LM (−) CSF, 105 LMIs were discriminative for spinal LM (+) CSF. In proteome analysis, a total of 1536 proteins were measured. A total of 18 proteins, including complement C3, were more highly expressed in all lumbar CSF, compared with paired ventricular CSF, while 82 proteins, including coagulation factor V, were higher in the ventricular CSF. Of 37 discriminative proteins, including uteroglobin and complement component C8 gamma chain, 4 were higher in all spinal LM (+) CSF versus spinal LM (−) CSF. We further evaluated metabolic pathways associated with these discriminative proteins using the Gene Ontology database. We found that 16/17 spinal LM (+) pathways, including complement activation, were associated with lumbar discriminative proteins, whereas only 2 pathways were associated with ventricular-discriminative proteins. In conclusion, we determined that metabolite and protein profiles differed between paired lumbar and ventricular CSF samples. The protein profiles of spinal LM (+) CSF showed more similarity with the lumbar CSF than the ventricular CSF. Thus, we suggest that CSF LMIs and proteins could reflect LM disease activity and that LM-associated differences in CSF are more likely to be present in the lumbar compartment. Full article

(This article belongs to the Special Issue Cerebrospinal Fluid Biomarkers for Understanding Disease Pathogenesis)

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15 pages, 1745 KiB

Open AccessArticle

Metabolite Profiling and Classification of Highbush Blueberry Leaves under Different Shade Treatments

by Yaqiong Wu, Hao Yang, Zhengjin Huang, Chunhong Zhang, Lianfei Lyu, Weilin Li and Wenlong Wu

Metabolites 2022, 12(1), 79; https://doi.org/10.3390/metabo12010079 - 14 Jan 2022

Cited by 21 | Viewed by 3827

Abstract

Blueberry belongs to the genus Vaccinium L. in the Ericaceae and is an economically important shrub that produces small berries that are rich in nutrients. There were differences in the appearance of blueberry leaves under different shade treatments. To explore the differences in [...] Read more.

Blueberry belongs to the genus Vaccinium L. in the Ericaceae and is an economically important shrub that produces small berries that are rich in nutrients. There were differences in the appearance of blueberry leaves under different shade treatments. To explore the differences in metabolites in blueberry leaves under different shading treatments, nontargeted liquid chromatography–mass spectrometry (LC–MS) metabonomic analysis was performed. Different shade intensities resulted in significant differences in the contents of metabolites. A total of 6879 known metabolites were detected, including 750 significantly differentially expressed metabolites, including mainly lipids and lipid-like molecules and phenylpropanoid and polyketide superclass members. Based on a Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, the flavone and flavonol biosynthesis pathways were the most significantly enriched. The results of this study provide a reference and scientific basis for the establishment of a high-quality and high-yield shaded blueberry cultivation system. Full article

(This article belongs to the Section Plant Metabolism)

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15 pages, 12601 KiB

Open AccessStudy Protocol

Improving Infant Hydrocephalus Outcomes in Uganda: A Longitudinal Prospective Study Protocol for Predicting Developmental Outcomes and Identifying Patients at Risk for Early Treatment Failure after ETV/CPC

by Taylor A. Vadset, Ajay Rajaram, Chuan-Heng Hsiao, Miriah Kemigisha Katungi, Joshua Magombe, Marvin Seruwu, Brian Kaaya Nsubuga, Rutvi Vyas, Julia Tatz, Katharine Playter, Esther Nalule, Davis Natukwatsa, Moses Wabukoma, Luis E. Neri Perez, Ronald Mulondo, Jennifer T. Queally, Aaron Fenster, Abhaya V. Kulkarni, Steven J. Schiff, Patricia Ellen Grant, Edith Mbabazi Kabachelor, Benjamin C. Warf, Jason D. B. Sutin and Pei-Yi Lin Show full author list Hide full author list

Metabolites 2022, 12(1), 78; https://doi.org/10.3390/metabo12010078 - 14 Jan 2022

Cited by 3 | Viewed by 3933

Abstract

Infant hydrocephalus poses a severe global health burden; 80% of cases occur in the developing world where patients have limited access to neurosurgical care. Surgical treatment combining endoscopic third ventriculostomy and choroid plexus cauterization (ETV/CPC), first practiced at CURE Children’s Hospital of Uganda [...] Read more.

Infant hydrocephalus poses a severe global health burden; 80% of cases occur in the developing world where patients have limited access to neurosurgical care. Surgical treatment combining endoscopic third ventriculostomy and choroid plexus cauterization (ETV/CPC), first practiced at CURE Children’s Hospital of Uganda (CCHU), is as effective as standard ventriculoperitoneal shunt (VPS) placement while requiring fewer resources and less post-operative care. Although treatment focuses on controlling ventricle size, this has little association with treatment failure or long-term outcome. This study aims to monitor the progression of hydrocephalus and treatment response, and investigate the association between cerebral physiology, brain growth, and neurodevelopmental outcomes following surgery. We will enroll 300 infants admitted to CCHU for treatment. All patients will receive pre/post-operative measurements of cerebral tissue oxygenation (SO₂), cerebral blood flow (CBF), and cerebral metabolic rate of oxygen consumption (CMRO₂) using frequency-domain near-infrared combined with diffuse correlation spectroscopies (FDNIRS-DCS). Infants will also receive brain imaging, to monitor tissue/ventricle volume, and neurodevelopmental assessments until two years of age. This study will provide a foundation for implementing cerebral physiological monitoring to establish evidence-based guidelines for hydrocephalus treatment. This paper outlines the protocol, clinical workflow, data management, and analysis plan of this international, multi-center trial. Full article

(This article belongs to the Special Issue Optical Assessment of Metabolism)

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16 pages, 2670 KiB

Open AccessArticle

Untargeted Metabolomics Combined with Solid Phase Fractionation for Systematic Characterization of Bioactive Compounds in Hemp with Methane Mitigation Potential

by Rikke Hald Jensen, Marie Rønn, Mirka Thorsteinsson, Dana W. Olijhoek, Mette Olaf Nielsen and Natalja P. Nørskov

Metabolites 2022, 12(1), 77; https://doi.org/10.3390/metabo12010077 - 13 Jan 2022

Cited by 5 | Viewed by 2733

Abstract

This study systematically evaluates the presence of methane mitigating metabolites in two hemp (Cannabis sativa L.) varieties, Futura 75 and Finola. Hemp metabolites were extracted with methanol and fractionated using Solid Phase Extraction (SPE). Extracts, fractions, and the remaining pulp were [...] Read more.

This study systematically evaluates the presence of methane mitigating metabolites in two hemp (Cannabis sativa L.) varieties, Futura 75 and Finola. Hemp metabolites were extracted with methanol and fractionated using Solid Phase Extraction (SPE). Extracts, fractions, and the remaining pulp were screened for their methane mitigating potential using an in vitro model of rumen fermentation. The bioactive metabolites were identified with Liquid Chromatography-Mass Spectrometry (LC-MS). When incubated with a standard feed (maize silage), the extract of Futura 75 significantly reduced methane production compared to that of control (without added extract) and without negative effects on feed degradability and volatile fatty acid patterns. The compounds responsible for the methane mitigating effect were assigned to flavonoid glycosides. However, none of the fractions of Futura 75 or the pulp exhibited similar effect on methane emission. Butyric acid concentration in the fermentation inoculum was significantly increased, which could indicate why methane production was higher, when incubated with the fractions and the pulp. The extract of Finola did not show a similar significant effect, however, there was a numerical tendency towards lower methane production. The difference in methane mitigating properties between Cannabis sativa L. Futura 75 and Finola, could be related to the content of bioactive flavonoids. Full article

(This article belongs to the Special Issue Application of Metabolomics in Characterization of Novel Bioactive Natural Products)

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17 pages, 2157 KiB

Open AccessReview

Multi-Omics-Based Discovery of Plant Signaling Molecules

by Fei Luo, Zongjun Yu, Qian Zhou and Ancheng Huang

Metabolites 2022, 12(1), 76; https://doi.org/10.3390/metabo12010076 - 13 Jan 2022

Cited by 17 | Viewed by 4236

Abstract

Plants produce numerous structurally and functionally diverse signaling metabolites, yet only relatively small fractions of which have been discovered. Multi-omics has greatly expedited the discovery as evidenced by increasing recent works reporting new plant signaling molecules and relevant functions via integrated multi-omics techniques. [...] Read more.

Plants produce numerous structurally and functionally diverse signaling metabolites, yet only relatively small fractions of which have been discovered. Multi-omics has greatly expedited the discovery as evidenced by increasing recent works reporting new plant signaling molecules and relevant functions via integrated multi-omics techniques. The effective application of multi-omics tools is the key to uncovering unknown plant signaling molecules. This review covers the features of multi-omics in the context of plant signaling metabolite discovery, highlighting how multi-omics addresses relevant aspects of the challenges as follows: (a) unknown functions of known metabolites; (b) unknown metabolites with known functions; (c) unknown metabolites and unknown functions. Based on the problem-oriented overview of the theoretical and application aspects of multi-omics, current limitations and future development of multi-omics in discovering plant signaling metabolites are also discussed. Full article

(This article belongs to the Special Issue Integration of Metabolomics with Other Omics Technologies to Investigate Metabolism and Signaling in Plants)

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21 pages, 45403 KiB

Open AccessArticle

Effect of Storage Temperatures on Physico-Chemicals, Phytochemicals and Antioxidant Properties of Watermelon Juice (Citrullus lanatus)

by Nur Shafinaz Mohamad Salin, Wan Mazlina Md Saad, Hairil Rashmizal Abdul Razak and Fatimah Salim

Metabolites 2022, 12(1), 75; https://doi.org/10.3390/metabo12010075 - 13 Jan 2022

Cited by 17 | Viewed by 4077

Abstract

Watermelon (Citrullus lanatus) consists of high moisture content and is favoured for its juice products. The popular fruit has a tempting taste, sweet aroma and attractive flesh colour. It is enriched with phytochemicals and antioxidant properties that are beneficial to human [...] Read more.

Watermelon (Citrullus lanatus) consists of high moisture content and is favoured for its juice products. The popular fruit has a tempting taste, sweet aroma and attractive flesh colour. It is enriched with phytochemicals and antioxidant properties that are beneficial to human health. Due to convenience, the majority of individuals are likely to consume watermelon juice. However, little is known about the fruit juice storage and temperatures that may affect its beneficial properties. This study investigated the effect of storage temperature at room temperature, refrigerator cold, refrigerator freeze and freeze-dried, and analyzed the juice physico-chemicals (weight loss, pH, ash, moisture, total soluble solid, browning and turbidity), phytochemicals (total phenolic, total flavonoid, lycopene and β-carotene) and antioxidant scavenging activities during 9 days of storage. The results showed that watermelon juice was affected by storage temperatures and conditions with significant changes in physico-chemical appearance and decrease in total phytochemical content, thus consequently affecting their antioxidant activities during 9 days of storage. Although fresh watermelon juice can be consumed for its high nutritional values, freeze-drying is the preferable technique to retain its benefits and to delay juice degradation. Full article

(This article belongs to the Collection Natural Antioxidants to Food Preservation)

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23 pages, 2753 KiB

Open AccessReview

Kinetic Modeling of Saccharomyces cerevisiae Central Carbon Metabolism: Achievements, Limitations, and Opportunities

by David Lao-Martil, Koen J. A. Verhagen, Joep P. J. Schmitz, Bas Teusink, S. Aljoscha Wahl and Natal A. W. van Riel

Metabolites 2022, 12(1), 74; https://doi.org/10.3390/metabo12010074 - 13 Jan 2022

Cited by 7 | Viewed by 4412

Abstract

Central carbon metabolism comprises the metabolic pathways in the cell that process nutrients into energy, building blocks and byproducts. To unravel the regulation of this network upon glucose perturbation, several metabolic models have been developed for the microorganism Saccharomyces cerevisiae. These dynamic [...] Read more.

Central carbon metabolism comprises the metabolic pathways in the cell that process nutrients into energy, building blocks and byproducts. To unravel the regulation of this network upon glucose perturbation, several metabolic models have been developed for the microorganism Saccharomyces cerevisiae. These dynamic representations have focused on glycolysis and answered multiple research questions, but no commonly applicable model has been presented. This review systematically evaluates the literature to describe the current advances, limitations, and opportunities. Different kinetic models have unraveled key kinetic glycolytic mechanisms. Nevertheless, some uncertainties regarding model topology and parameter values still limit the application to specific cases. Progressive improvements in experimental measurement technologies as well as advances in computational tools create new opportunities to further extend the model scale. Notably, models need to be made more complex to consider the multiple layers of glycolytic regulation and external physiological variables regulating the bioprocess, opening new possibilities for extrapolation and validation. Finally, the onset of new data representative of individual cells will cause these models to evolve from depicting an average cell in an industrial fermenter, to characterizing the heterogeneity of the population, opening new and unseen possibilities for industrial fermentation improvement. Full article

(This article belongs to the Special Issue Metabolic Functionality of Microorganisms under Dynamic Environments)

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11 pages, 285 KiB

Open AccessArticle

Relationship of Inflammatory Markers and Metabolic Syndrome in Postmenopausal Women

by Renata Vargas Sinatora, Eduardo Federighi Baisi Chagas, Fernando Otavio Pires Mattera, Luciano Junqueira Mellem, Ana Rita de Oliveira dos Santos, Larissa Pires Pereira, Ana Luíza de Carvalho Aranão, Elen Landgraf Guiguer, Adriano Cressoni Araújo, Jesselina F. dos Santos Haber, Leila Campos Guissoni and Sandra Maria Barbalho

Metabolites 2022, 12(1), 73; https://doi.org/10.3390/metabo12010073 - 13 Jan 2022

Cited by 15 | Viewed by 2390

Abstract

The increased deposition of visceral fat in the postmenopause period increases the production of inflammatory cytokines and the release of tumor necrosis factor- α (TNF-α), interleukin-6 (IL-6), and decrease in IL-10. This study investigated the relationship between inflammatory biomarkers and metabolic syndrome (MS) [...] Read more.

The increased deposition of visceral fat in the postmenopause period increases the production of inflammatory cytokines and the release of tumor necrosis factor- α (TNF-α), interleukin-6 (IL-6), and decrease in IL-10. This study investigated the relationship between inflammatory biomarkers and metabolic syndrome (MS) in postmenopausal women considering different diagnostic criteria. We conducted a cross-sectional observational study based on STROBE. Data were collected regarding the diagnostic criteria for MS (International Diabetes Federation; NCEP (International Diabetes Federation (IDF), National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP-III), and Harmonized criteria), body composition, comorbidities, time without menstruation, values of IL-6, IL-10, and TNF-α. ANOVA, Kruskal–Wallis, Levene tests, ROC, and odds ratio were performed to analyze the data. The results showed no significant difference between the methods and no interaction between the method and the presence of MS. However, for the values of WC, body fat percentage, TNF-α, and IL-10/TNF-α ratio, a significant effect of MS was observed. In subjects with MS, lower values of body fat percentage and TNF-α and higher values of the IL-10/TNF-α ratio were also observed. The higher IL-10/TNF-α ratio in the MS group is related to the greater anti-inflationary action of IL-10. The IL-10/TNF-α ratio showed significant accuracy to discriminate patients with MS according to the NCEP-ATP III criteria. Full article

(This article belongs to the Special Issue Biomarkers for Metabolism and Cardiometabolic Diseases)

11 pages, 668 KiB

Open AccessOpinion

Aerobic Glycolysis: A DeOxymoron of (Neuro)Biology

by Avital Schurr and Salvatore Passarella

Metabolites 2022, 12(1), 72; https://doi.org/10.3390/metabo12010072 - 13 Jan 2022

Cited by 10 | Viewed by 3365

Abstract

The term ‘aerobic glycolysis’ has been in use ever since Warburg conducted his research on cancer cells’ proliferation and discovered that cells use glycolysis to produce adenosine triphosphate (ATP) rather than the more efficient oxidative phosphorylation (oxphos) pathway, despite an abundance of oxygen. [...] Read more.

The term ‘aerobic glycolysis’ has been in use ever since Warburg conducted his research on cancer cells’ proliferation and discovered that cells use glycolysis to produce adenosine triphosphate (ATP) rather than the more efficient oxidative phosphorylation (oxphos) pathway, despite an abundance of oxygen. When measurements of glucose and oxygen utilization by activated neural tissue indicated that glucose was consumed without an accompanied oxygen consumption, the investigators who performed those measurements also termed their discovery ‘aerobic glycolysis’. Red blood cells do not contain mitochondria and, therefore, produce their energy needs via glycolysis alone. Other processes within the central nervous system (CNS) and additional organs and tissues (heart, muscle, and so on), such as ion pumps, are also known to utilize glycolysis only for the production of ATP necessary to support their function. Unfortunately, the phenomenon of ‘aerobic glycolysis’ is an enigma wherever it is encountered, thus several hypotheses have been produced in attempts to explain it; that is, whether it occurs in cancer cells, in activated neural tissue, or during postprandial or exercise metabolism. Here, it is argued that, where the phenomenon in neural tissue is concerned, the prefix ‘aerobic’ in the term ‘aerobic glycolysis’ should be removed. Data collected over the past three decades indicate that L-lactate, the end product of the glycolytic pathway, plays an essential role in brain energy metabolism, justifying the elimination of the prefix ‘aerobic’. Similar justification is probably appropriate for other tissues as well. Full article

(This article belongs to the Special Issue Biochemical and Physiological Perspectives of Brain Energy Metabolism)

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15 pages, 2472 KiB

Open AccessArticle

Sex-Dependent Social and Repetitive Behavior and Neurochemical Profile in Mouse Model of Autism Spectrum Disorder

by Helena Ferreira, Ana Catarina Sousa, José Sereno, João Martins, Miguel Castelo-Branco and Joana Gonçalves

Metabolites 2022, 12(1), 71; https://doi.org/10.3390/metabo12010071 - 12 Jan 2022

Cited by 11 | Viewed by 3493

Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by deficits in social interaction, impaired communication, and repetitive behaviors. ASD presents a 3:1 ratio of diagnosed boys and girls, raising the question regarding sexual dimorphic mechanisms underlying ASD symptoms, and their molecular basis. [...] Read more.

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by deficits in social interaction, impaired communication, and repetitive behaviors. ASD presents a 3:1 ratio of diagnosed boys and girls, raising the question regarding sexual dimorphic mechanisms underlying ASD symptoms, and their molecular basis. Here, we performed in vivo proton magnetic resonance spectroscopy in juvenile male and female Tsc2^+/⁻ mice (an established genetic animal model of ASD). Moreover, behavior and ultrasonic vocalizations during social and repetitive tasks were analyzed. We found significant sexual dimorphisms in the levels of metabolites in the hippocampus and prefrontal cortex. Further, we observed that female mutant animals had a differential social behavior and presented an increase in repetitive behavior. Importantly, while mutant females displayed a more simplified communication during social tasks, mutant males exhibited a similar less complex vocal repertoire but during repetitive tasks. These results hint toward sex-dependent alterations in molecular and metabolic pathways, which can lead to the sexual dimorphic behaviors and communication observed in social and repetitive environments. Full article

(This article belongs to the Special Issue Sex Differences in Behavioral and Metabolic Effects of Gene Manipulation and Mutation)

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13 pages, 907 KiB

Open AccessReview

Gene Therapy Targeting PCSK9

by Julius L. Katzmann, Arjen J. Cupido and Ulrich Laufs

Metabolites 2022, 12(1), 70; https://doi.org/10.3390/metabo12010070 - 12 Jan 2022

Cited by 29 | Viewed by 4730

Abstract

The last decades of research in cardiovascular prevention have been characterized by successful bench-to-bedside developments for the treatment of low-density lipoprotein (LDL) hypercholesterolemia. Recent examples include the inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) with monoclonal antibodies, small interfering RNA and antisense [...] Read more.

The last decades of research in cardiovascular prevention have been characterized by successful bench-to-bedside developments for the treatment of low-density lipoprotein (LDL) hypercholesterolemia. Recent examples include the inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) with monoclonal antibodies, small interfering RNA and antisense RNA drugs. The cumulative effects of LDL cholesterol on atherosclerosis make early, potent, and long-term reductions in LDL cholesterol desirable—ideally without the need of regular intake or application of medication and importantly, without side effects. Current reports show durable LDL cholesterol reductions in primates following one single treatment with PCSK9 gene or base editors. Use of the CRISPR/Cas system enables precise genome editing down to single-nucleotide changes. Provided safety and documentation of a reduction in cardiovascular events, this novel technique has the potential to fundamentally change our current concepts of cardiovascular prevention. In this review, the application of the CRISPR/Cas system is explained and the current state of in vivo approaches of PCSK9 editing is presented. Full article

(This article belongs to the Special Issue The PCSK9 Story: Advances in Cholesterol Metabolism, Cardiovascular Complications and Beyond)

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12 pages, 1249 KiB

Open AccessArticle

Metabolite Signature of Physical Activity and the Risk of Type 2 Diabetes in 7271 Men

by Susanna Maria Kemppainen, Lilian Fernandes Silva, Maria Anneli Lankinen, Ursula Schwab and Markku Laakso

Metabolites 2022, 12(1), 69; https://doi.org/10.3390/metabo12010069 - 12 Jan 2022

Cited by 8 | Viewed by 6716

Abstract

Large population-based studies investigating the association of physical activity (PA) with the metabolite signature contribute significantly to the understanding of the effects of PA on metabolic pathways associated with the risk of type2 diabetes. Our study included 8749 Finnish men without diabetes at [...] Read more.

Large population-based studies investigating the association of physical activity (PA) with the metabolite signature contribute significantly to the understanding of the effects of PA on metabolic pathways associated with the risk of type2 diabetes. Our study included 8749 Finnish men without diabetes at baseline recruited from the Metabolic Syndrome in Men (METSIM) cohort. We used a questionnaire to measure leisure-time PA. Metabolites were measured in 7271 men as a part of Metabolon’s untargeted Discovery HD4 platform using ultrahigh-performance liquid chromatography–tandem mass spectrometry. We found 198 metabolites significantly associated with PA. Several of these metabolites were novel including especially steroids, amino acids, imidazoles, carboxylic acids, and hydroxy acids. Increased PA was significantly associated with high levels of choline plasmalogens, lysophosphatidylcholines, polyunsaturated fatty acids, carotenoids, long chain acylcarnitines, imidazoles, bilirubins, aryl sulfates, hydroxy acids, indolepropionate, and indolelactate. Several of these metabolites have been previously associated with a decreased risk of type 2 diabetes and with a healthy diet. Our population-based study shows that the metabolite signature of increased PA includes multiple metabolic pathways and is associated with better adherence to a healthy lifestyle. Full article

(This article belongs to the Section Endocrinology and Clinical Metabolic Research)

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19 pages, 4128 KiB

Open AccessArticle

Evaluating the Accuracy of the QCEIMS Approach for Computational Prediction of Electron Ionization Mass Spectra of Purines and Pyrimidines

by Jesi Lee, Tobias Kind, Dean Joseph Tantillo, Lee-Ping Wang and Oliver Fiehn

Metabolites 2022, 12(1), 68; https://doi.org/10.3390/metabo12010068 - 12 Jan 2022

Cited by 5 | Viewed by 3103

Abstract

Mass spectrometry is the most commonly used method for compound annotation in metabolomics. However, most mass spectra in untargeted assays cannot be annotated with specific compound structures because reference mass spectral libraries are far smaller than the complement of known molecules. Theoretically predicted [...] Read more.

Mass spectrometry is the most commonly used method for compound annotation in metabolomics. However, most mass spectra in untargeted assays cannot be annotated with specific compound structures because reference mass spectral libraries are far smaller than the complement of known molecules. Theoretically predicted mass spectra might be used as a substitute for experimental spectra especially for compounds that are not commercially available. For example, the Quantum Chemistry Electron Ionization Mass Spectra (QCEIMS) method can predict 70 eV electron ionization mass spectra from any given input molecular structure. In this work, we investigated the accuracy of QCEIMS predictions of electron ionization (EI) mass spectra for 80 purine and pyrimidine derivatives in comparison to experimental data in the NIST 17 database. Similarity scores between every pair of predicted and experimental spectra revealed that 45% of the compounds were found as the correct top hit when QCEIMS predicted spectra were matched against the NIST17 library of >267,000 EI spectra, and 74% of the compounds were found within the top 10 hits. We then investigated the impact of matching, missing, and additional fragment ions in predicted EI mass spectra versus ion abundances in MS similarity scores. We further include detailed studies of fragmentation pathways such as retro Diels–Alder reactions to predict neutral losses of (iso)cyanic acid, hydrogen cyanide, or cyanamide in the mass spectra of purines and pyrimidines. We describe how trends in prediction accuracy correlate with the chemistry of the input compounds to better understand how mechanisms of QCEIMS predictions could be improved in future developments. We conclude that QCEIMS is useful for generating large-scale predicted mass spectral libraries for identification of compounds that are absent from experimental libraries and that are not commercially available. Full article

(This article belongs to the Special Issue Advanced Strategies and Tools for Metabolomics Data Analysis, Metabolite Annotation and Identification)

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8 pages, 575 KiB

Open AccessPerspective

The Role of Fructose as a Cardiovascular Risk Factor: An Update

by Stefan-Sebastian Busnatu, Teodor Salmen, Maria-Alexandra Pana, Manfredi Rizzo, Tiziana Stallone, Nikolaos Papanas, Djordje Popovic, Denisa Tanasescu, Dragos Serban and Anca Pantea Stoian

Metabolites 2022, 12(1), 67; https://doi.org/10.3390/metabo12010067 - 12 Jan 2022

Cited by 27 | Viewed by 5321

Abstract

There is increasing presence of fructose in food and drinks, and some evidence suggests that its higher consumption increases cardiovascular risk, although the mechanisms still remain not fully elucidated. Cardiovascular diseases (CVD) are still responsible for one-third of deaths worldwide, and therefore, their [...] Read more.

There is increasing presence of fructose in food and drinks, and some evidence suggests that its higher consumption increases cardiovascular risk, although the mechanisms still remain not fully elucidated. Cardiovascular diseases (CVD) are still responsible for one-third of deaths worldwide, and therefore, their prevention should be assessed and managed comprehensively and not by the evaluation of individual risk factor components. Lifestyle risk factors for CVD include low degree of physical activity, high body mass index, alcohol consumption, smoking, and nutritional factors. Indeed, nutritional risk factors for CVD include unhealthy dietary behaviors, such as high intake of refined foods, unhealthy fats, added sugars, and sodium and a low intake of fruits, vegetables, whole grains, fiber, fish, and nuts. Even though there is no definitive association between CVD incidence and high consumption of total sugar, such as sucrose and fructose, there is, however, evidence that total sugars, added sugars, and fructose are harmfully associated with CVD mortality. Since high fructose intake is associated with elevated plasma triglyceride levels, as well as insulin resistance, diabetes hyperuricemia, and non-alcoholic fatty liver disease, further longitudinal studies should be conducted to fully elucidate the potential association between certain sugars and CVD. Full article

(This article belongs to the Special Issue Advances in Cholesterol and Lipid Metabolism)

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12 pages, 2519 KiB

Open AccessArticle

Involvement of TauT/SLC6A6 in Taurine Transport at the Blood–Testis Barrier

by Yoshiyuki Kubo, Sakiko Ishizuka, Takeru Ito, Daisuke Yoneyama, Shin-ichi Akanuma and Ken-ichi Hosoya

Metabolites 2022, 12(1), 66; https://doi.org/10.3390/metabo12010066 - 12 Jan 2022

Cited by 10 | Viewed by 3428

Abstract

Taurine transport was investigated at the blood–testis barrier (BTB) formed by Sertoli cells. An integration plot analysis of mice showed the apparent influx permeability clearance of [³H]taurine (27.7 μL/(min·g testis)), which was much higher than that of a non-permeable paracellular marker, [...] Read more.

Taurine transport was investigated at the blood–testis barrier (BTB) formed by Sertoli cells. An integration plot analysis of mice showed the apparent influx permeability clearance of [³H]taurine (27.7 μL/(min·g testis)), which was much higher than that of a non-permeable paracellular marker, suggesting blood-to-testis transport of taurine, which may involve a facilitative taurine transport system at the BTB. A mouse Sertoli cell line, TM4 cells, showed temperature- and concentration-dependent [³H]taurine uptake with a K_m of 13.5 μM, suggesting that the influx transport of taurine at the BTB involves a carrier-mediated process. [³H]Taurine uptake by TM4 cells was significantly reduced by the substrates of taurine transporter (TauT/SLC6A6), such as β-alanine, hypotaurine, γ-aminobutyric acid (GABA), and guanidinoacetic acid (GAA), with no significant effect shown by L-alanine, probenecid, and L-leucine. In addition, the concentration-dependent inhibition of [³H]taurine uptake revealed an IC₅₀ of 378 μM for GABA. Protein expression of TauT in the testis, seminiferous tubules, and TM4 cells was confirmed by Western blot analysis and immunohistochemistry by means of anti-TauT antibodies, and knockdown of TauT showed significantly decreased [³H]taurine uptake by TM4 cells. These results suggest the involvement of TauT in the transport of taurine at the BTB. Full article

(This article belongs to the Special Issue Regulation and Effect of Taurine on Metabolism)

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14 pages, 5243 KiB

Open AccessReview

The Interaction between the Gut Microbiome and Bile Acids in Cardiometabolic Diseases

by Cengiz Callender, Ilias Attaye and Max Nieuwdorp

Metabolites 2022, 12(1), 65; https://doi.org/10.3390/metabo12010065 - 11 Jan 2022

Cited by 15 | Viewed by 3855

Abstract

Cardio-metabolic diseases (CMD) are a spectrum of diseases (e.g., type 2 diabetes, atherosclerosis, non-alcohol fatty liver disease (NAFLD), and metabolic syndrome) that are among the leading causes of morbidity and mortality worldwide. It has long been known that bile acids (BA), which are [...] Read more.

Cardio-metabolic diseases (CMD) are a spectrum of diseases (e.g., type 2 diabetes, atherosclerosis, non-alcohol fatty liver disease (NAFLD), and metabolic syndrome) that are among the leading causes of morbidity and mortality worldwide. It has long been known that bile acids (BA), which are endogenously produced signalling molecules from cholesterol, can affect CMD risk and progression and directly affect the gut microbiome (GM). Moreover, studies focusing on the GM and CMD risk have dramatically increased in the past decade. It has also become clear that the GM can function as a “new” endocrine organ. BA and GM have a complex and interdependent relationship with several CMD pathways. This review aims to provide a comprehensive overview of the interplay between BA metabolism, the GM, and CMD risk and progression. Full article

(This article belongs to the Special Issue Bile Acid Metabolism and Gut Microbiota)

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16 pages, 3624 KiB

Open AccessArticle

Unlike Glycerophosphocholine or Choline Chloride, Dietary Phosphatidylcholine Does Not Increase Plasma Trimethylamine-N-Oxide Levels in Sprague-Dawley Rats

by Bungo Shirouchi, Ayano Fukuda and Taiki Akasaka

Metabolites 2022, 12(1), 64; https://doi.org/10.3390/metabo12010064 - 11 Jan 2022

Cited by 17 | Viewed by 4197

Abstract

Choline, betaine, and L-carnitine are transformed into trimethylamine (TMA) by gut microbiota, absorbed into the liver, and oxidized into trimethylamine-N-oxide (TMAO) by flavin-containing monooxygenases. Elevated TMAO levels may negatively affect human health. As phosphatidylcholine (PC) is the main source of dietary [...] Read more.

Choline, betaine, and L-carnitine are transformed into trimethylamine (TMA) by gut microbiota, absorbed into the liver, and oxidized into trimethylamine-N-oxide (TMAO) by flavin-containing monooxygenases. Elevated TMAO levels may negatively affect human health. As phosphatidylcholine (PC) is the main source of dietary choline, its intake or PC-rich foods may be harmful to human health; however, quantitative comparative information among dietary choline compounds (PC, glycerophosphocholine [GPC], and choline chloride [CC]) regarding in vivo generation of TMAO is lacking. Here, we compared the effects of PC, GPC, and CC on plasma TMAO levels in rats. Furthermore, we investigated their effects on gut microbiota at the genus level. Dietary PC did not affect plasma TMAO levels, whereas dietary GPC and CC significantly increased them. At the genus level, plasma TMAO levels were significantly negatively correlated with relative abundances of Anaerotruncus, Actinomyces, Enterococcus, Dialister, Clostridium XIVa, and Granulicatella; they were significantly positively correlated with that of Coprobacter. Moreover, the relative abundances of Anaerotruncus and Coprobacter were found to predict plasma TMAO levels. Therefore, dietary PC, unlike GPC or CC, does not increase plasma TMAO levels in rats. Furthermore, several gut microbes are associated with changes in plasma TMAO levels in rats fed with choline compounds. Full article

(This article belongs to the Special Issue Prevention and Alleviation of Metabolic Syndrome with Food Factors)

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27 pages, 835 KiB

Open AccessReview

Yeast Protein as an Easily Accessible Food Source

by Monika Elżbieta Jach, Anna Serefko, Maria Ziaja and Marek Kieliszek

Metabolites 2022, 12(1), 63; https://doi.org/10.3390/metabo12010063 - 11 Jan 2022

Cited by 116 | Viewed by 14532

Abstract

In recent years, the awareness and willingness of consumers to consume healthy food has grown significantly. In order to meet these needs, scientists are looking for innovative methods of food production, which is a source of easily digestible protein with a balanced amino [...] Read more.

In recent years, the awareness and willingness of consumers to consume healthy food has grown significantly. In order to meet these needs, scientists are looking for innovative methods of food production, which is a source of easily digestible protein with a balanced amino acid composition. Yeast protein biomass (single cell protein, SCP) is a bioavailable product which is obtained when primarily using as a culture medium inexpensive various waste substrates including agricultural and industrial wastes. With the growing population, yeast protein seems to be an attractive alternative to traditional protein sources such as plants and meat. Moreover, yeast protein biomass also contains trace minerals and vitamins including B-group. Thus, using yeast in the production of protein provides both valuable nutrients and enhances purification of wastes. In conclusion, nutritional yeast protein biomass may be the best option for human and animal nutrition with a low environmental footprint. The rapidly evolving SCP production technology and discoveries from the world of biotechnology can make a huge difference in the future for the key improvement of hunger problems and the possibility of improving world food security. On the market of growing demand for cheap and environmentally clean SCP protein with practically unlimited scale of production, it may soon become one of the ingredients of our food. The review article presents the possibilities of protein production by yeast groups with the use of various substrates as well as the safety of yeast protein used as food. Full article

(This article belongs to the Special Issue Metabolomics in Yeast and Fermentation Volume 2)

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13 pages, 1877 KiB

Open AccessArticle

Stability of Wheat Floret Metabolites during Untargeted Metabolomics Studies

by Kristin Whitney, Gerardo Gracia-Gonzalez and Senay Simsek

Metabolites 2022, 12(1), 62; https://doi.org/10.3390/metabo12010062 - 11 Jan 2022

Cited by 2 | Viewed by 2034

Abstract

A typical metabolomic analysis consists of a multi-step procedure. Variation can be introduced in any analysis segment if proper care in quality assurance is not taken, thus compromising the final results. Sample stability is one of those factors. Although sophisticated studies addressing sample [...] Read more.

A typical metabolomic analysis consists of a multi-step procedure. Variation can be introduced in any analysis segment if proper care in quality assurance is not taken, thus compromising the final results. Sample stability is one of those factors. Although sophisticated studies addressing sample decay over time have been performed in the medical field, they are emerging in plant metabolomics. Here, we focus on the stability of wheat floret extracts on queue inside an auto-injector held at 25 °C. The objective was to locate an analytical time window from extraction to injection with no significant difference occurring in the sample. Total ion current chromatograms, principal component analysis, and volcano plots were used to measure changes in the samples. Results indicate a maximum work window time of 7:45 h for Steele-ND wheat methanolic extractions in an auto-sampler at 25 °C. Comparisons showed a significant gradual increase in the number and intensity of compounds observed that may be caused by the degradation of other molecules in the sample extract. The approach can be applied as preliminary work in a metabolite profiling study, helping to set the appropriate workload to produce confident results. Full article

(This article belongs to the Special Issue Metabolomics Methodologies and Applications II)

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13 pages, 891 KiB

Open AccessArticle

Metabolome Genome-Wide Association Study Identifies 74 Novel Genomic Regions Influencing Plasma Metabolites Levels

by Pirro G. Hysi, Massimo Mangino, Paraskevi Christofidou, Mario Falchi, Edward D. Karoly, NIHR Bioresource Investigators, Robert P. Mohney, Ana M. Valdes, Tim D. Spector and Cristina Menni

Metabolites 2022, 12(1), 61; https://doi.org/10.3390/metabo12010061 - 11 Jan 2022

Cited by 20 | Viewed by 8091

Abstract

Metabolites are small products of metabolism that provide a snapshot of the wellbeing of an organism and the mechanisms that control key physiological processes involved in health and disease. Here we report the results of a genome-wide association study of 722 circulating metabolite [...] Read more.

Metabolites are small products of metabolism that provide a snapshot of the wellbeing of an organism and the mechanisms that control key physiological processes involved in health and disease. Here we report the results of a genome-wide association study of 722 circulating metabolite levels in 8809 subjects of European origin, providing both breadth and depth. These analyses identified 202 unique genomic regions whose variations are associated with the circulating levels of 478 different metabolites. Replication with a subset of 208 metabolites that were available in an independent dataset for a cohort of 1768 European subjects confirmed the robust associations, including 74 novel genomic regions not associated with any metabolites in previous works. This study enhances our knowledge of genetic mechanisms controlling human metabolism. Our findings have major potential for identifying novel targets and developing new therapeutic strategies. Full article

(This article belongs to the Special Issue The Intersection of Metabolomics and Genomics and Their Role in Human Health)

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20 pages, 1540 KiB

Open AccessReview

Major Nutritional Metabolic Alterations Influencing the Reproductive System of Postpartum Dairy Cows

by Abdul Sammad, Muhammad Zahoor Khan, Zaheer Abbas, Lirong Hu, Qudrat Ullah, Yajing Wang, Huabin Zhu and Yachun Wang

Metabolites 2022, 12(1), 60; https://doi.org/10.3390/metabo12010060 - 10 Jan 2022

Cited by 26 | Viewed by 7343

Abstract

Early successful conception of postpartum dairy cows is crucial in determining the optimum reproductive efficiency and profitability in modern dairy farming. Due to the inherent high production potential of modern dairy cows, the extra stress burden of peri-parturient events, and associated endocrine and [...] Read more.

Early successful conception of postpartum dairy cows is crucial in determining the optimum reproductive efficiency and profitability in modern dairy farming. Due to the inherent high production potential of modern dairy cows, the extra stress burden of peri-parturient events, and associated endocrine and metabolic changes causes negative energy balance (NEBAL) in postpartum cows. The occurrence of NEBAL is associated with excessive fat mobilization in the form of non-esterified fatty acids (NEFAs). The phenomenon of NEFA mobilization furthers with occurrence of ketosis and fatty liver in postpartum dairy cows. High NEFAs and ketones are negatively associated with health and reproductive processes. An additional burden of hypocalcemia, ruminal acidosis, and high protein metabolism in postpartum cows presents further consequences for health and reproductive performance of postpartum dairy cows. This review intends to comprehend these major nutritional metabolic alterations, their mechanisms of influence on the reproduction process, and relevant mitigation strategies. Full article

(This article belongs to the Special Issue Metabolism and Reproduction)

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13 pages, 3507 KiB

Open AccessArticle

Validation of Urinary Charged Metabolite Profiles in Colorectal Cancer Using Capillary Electrophoresis-Mass Spectrometry

by Toru Sakurai, Kenji Katsumata, Ryutaro Udo, Tomoya Tago, Kenta Kasahara, Junichi Mazaki, Hiroshi Kuwabara, Hideaki Kawakita, Masanobu Enomoto, Tetsuo Ishizaki, Yukako Nemoto, Yoshiaki Osaka, Yuichi Nagakawa, Masahiro Sugimoto and Akihiko Tsuchida

Metabolites 2022, 12(1), 59; https://doi.org/10.3390/metabo12010059 - 10 Jan 2022

Cited by 9 | Viewed by 2297

Abstract

This study aimed to validate and reanalyze urinary biomarkers for detecting colorectal cancers (CRCs). We previously conducted urinary metabolomic analyses using capillary electrophoresis-mass spectrometry and found a significant difference in various metabolites, especially polyamines, between patients with CRC and healthy controls (HC). We [...] Read more.

This study aimed to validate and reanalyze urinary biomarkers for detecting colorectal cancers (CRCs). We previously conducted urinary metabolomic analyses using capillary electrophoresis-mass spectrometry and found a significant difference in various metabolites, especially polyamines, between patients with CRC and healthy controls (HC). We analyzed additional samples and confirmed consistency between the newly and previously analyzed data. In total, we included 36 HC, 34 adenoma (AD), and 214 CRC samples, which were used for subsequent analyses. Among the 132 quantified metabolites, 16 exhibited consistent differences in both datasets, which included polyamines, etc. Pathway analyses of the integrated data revealed significant differences in many metabolites, such as glutamine, and metabolites of the TCA (tricarboxylic acid cycle) and urea cycles. The discrimination ability of the combination of multiple metabolites among the three groups was evaluated, which yielded higher sensitivity than tumor markers. The Mann–Whitney test was employed to evaluate the prognosis predictivity of the assessed metabolites and the difference between the patients with or without recurrence, which yielded 16 significantly different metabolites. Among these 16 metabolites, 11 presented significant prognosis predictivity. These data indicated the potential of metabolite-based discrimination of patients with CRC and AD from HC and prognosis predictivity of the monitored metabolites. Full article

(This article belongs to the Section Metabolomic Profiling Technology)

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