Metabolites

22 pages, 1500 KiB

Open AccessArticle

Identification of Anastatica hierochuntica L. Methanolic-Leaf-Extract-Derived Metabolites Exhibiting Xanthine Oxidase Inhibitory Activities: In Vitro and In Silico Approaches

by Saranya Rameshbabu, Zeyad Alehaideb, Sahar S. Alghamdi, Rasha S. Suliman, Feras Almourfi, Syed Ali Mohamed Yacoob, Anuradha Venkataraman, Safia Messaoudi and Sabine Matou-Nasri

Metabolites 2024, 14(7), 368; https://doi.org/10.3390/metabo14070368 (registering DOI) - 28 Jun 2024

Abstract

There is a growing interest in the discovery of novel xanthine oxidase inhibitors for gout prevention and treatment with fewer side effects. This study aimed to identify the xanthine oxidase (XO) inhibitory potential and drug-likeness of the metabolites present in the methanolic leaf [...] Read more.

There is a growing interest in the discovery of novel xanthine oxidase inhibitors for gout prevention and treatment with fewer side effects. This study aimed to identify the xanthine oxidase (XO) inhibitory potential and drug-likeness of the metabolites present in the methanolic leaf extract of Anastatica (A.) hierochuntica L. using in vitro and in silico models. The extract-derived metabolites were identified by liquid-chromatography–quadrupole-time-of-flight-mass-spectrometry (LC-QTOF-MS). Molecular docking predicted the XO inhibitory activity of the identified metabolites and validated the best scored in vitro XO inhibitory activities for experimental verification, as well as predictions of their anticancer, pharmacokinetic, and toxic properties; oral bioavailability; and endocrine disruption using SwissADMET, PASS, ProTox-II, and Endocrine Disruptome web servers. A total of 12 metabolites, with a majority of flavonoids, were identified. Rutin, quercetin, and luteolin flavonoids demonstrated the highest ranked docking scores of −12.39, −11.15, and −10.43, respectively, while the half-maximal inhibitory concentration (IC₅₀) values of these metabolites against XO activity were 11.35 µM, 11.1 µM, and 21.58 µM, respectively. In addition, SwissADMET generated data related to the physicochemical properties and drug-likeness of the metabolites. Similarly, the PASS, ProTox-II, and Endocrine Disruptome prediction models stated the safe and potential use of these natural compounds. However, in vivo studies are necessary to support the development of the prominent and promising therapeutic use of A. hierochuntica methanolic-leaf-extract-derived metabolites as XO inhibitors for the prevention and treatment of hyperuricemic and gout patients. Furthermore, the predicted findings of the present study open a new paradigm for these extract-derived metabolites by revealing novel oncogenic targets for the potential treatment of human malignancies. Full article

13 pages, 769 KiB

Open AccessStudy Protocol

Optimising Extracellular Vesicle Metabolomic Methodology for Prostate Cancer Biomarker Discovery

by Mahmoud Assem Hamed, Valerie Wasinger, Qi Wang, Joanna Biazik, Peter Graham, David Malouf, Joseph Bucci and Yong Li

Metabolites 2024, 14(7), 367; https://doi.org/10.3390/metabo14070367 (registering DOI) - 28 Jun 2024

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Abstract

Conventional diagnostic tools for prostate cancer (PCa), such as prostate-specific antigen (PSA), transrectal ultrasound (TRUS), digital rectal examination (DRE), and tissue biopsy face, limitations in individual risk stratification due to invasiveness or reliability issues. Liquid biopsy is a less invasive and more accurate [...] Read more.

Conventional diagnostic tools for prostate cancer (PCa), such as prostate-specific antigen (PSA), transrectal ultrasound (TRUS), digital rectal examination (DRE), and tissue biopsy face, limitations in individual risk stratification due to invasiveness or reliability issues. Liquid biopsy is a less invasive and more accurate alternative. Metabolomic analysis of extracellular vesicles (EVs) holds a promise for detecting non-genetic alterations and biomarkers in PCa diagnosis and risk assessment. The current research gap in PCa lies in the lack of accurate biomarkers for early diagnosis and real-time monitoring of cancer progression or metastasis. Establishing a suitable approach for observing dynamic EV metabolic alterations that often occur earlier than being detectable by other omics technologies makes metabolomics valuable for early diagnosis and monitoring of PCa. Using four distinct metabolite extraction approaches, the metabolite cargo of PC3-derived large extracellular vesicles (lEVs) was evaluated using a combination of methanol, cell shearing using microbeads, and size exclusion filtration, as well as two fractionation chemistries (pHILIC and C18 chromatography) that are also examined. The unfiltered methanol–microbeads approach (MB-UF), followed by pHILIC LC-MS/MS for EV metabolite extraction and analysis, is effective. Identified metabolites such as L-glutamic acid, pyruvic acid, lactic acid, and methylmalonic acid have important links to PCa and are discussed. Our study, for the first time, has comprehensively evaluated the extraction and separation methods with a view to downstream sample integrity across omics platforms, and it presents an optimised protocol for EV metabolomics in PCa biomarker discovery. Full article

(This article belongs to the Section Advances in Metabolomics)

21 pages, 2117 KiB

Open AccessReview

NAFLD/MASLD and the Gut–Liver Axis: From Pathogenesis to Treatment Options

by Natalia G. Vallianou, Dimitris Kounatidis, Sotiria Psallida, Nikolaos Vythoulkas-Biotis, Andreas Adamou, Tatiana Zachariadou, Sofia Kargioti, Irene Karampela and Maria Dalamaga

Metabolites 2024, 14(7), 366; https://doi.org/10.3390/metabo14070366 (registering DOI) - 28 Jun 2024

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Abstract

Nonalcoholic fatty liver disease (NAFLD) poses an emerging threat topublic health. Nonalcoholic steatohepatitis (NASH) is reported to be the most rapidly rising cause of hepatocellular carcinoma in the western world. Recently, a new term has been proposed: metabolic dysfunction-associated steatotic liver disease (MASLD). [...] Read more.

Nonalcoholic fatty liver disease (NAFLD) poses an emerging threat topublic health. Nonalcoholic steatohepatitis (NASH) is reported to be the most rapidly rising cause of hepatocellular carcinoma in the western world. Recently, a new term has been proposed: metabolic dysfunction-associated steatotic liver disease (MASLD). The introduction of this new terminology has sparked a debate about the interchangeability of these terms. The pathogenesis of NAFLD/MASLD is thought to be multifactorial, involving both genetic and environmental factors. Among these factors, alterations in gut microbiota and gut dysbiosis have recently garnered significant attention. In this context, this review will further discuss the gut–liver axis, which refers to the bidirectional interaction between the human gut microbiota and the liver. Additionally, the therapeutic potential of probiotics, particularly next-generation probiotics and genetically engineered bacteria, will be explored. Moreover, the role of prebiotics, synbiotics, postbiotics, and phages as well as fecal microbiota transplantation will be analyzed. Particularly for lean patients with NAFLD/MASLD, who have limited treatment options, approaches that modify the diversity and composition of the gut microbiota may hold promise. However, due to ongoing safety concerns with approaches that modulate gut microbiota, further large-scale studies are necessary to better assess their efficacy and safety in treating NAFLD/MASLD. Full article

(This article belongs to the Special Issue New Insights into Gut Microbiota and Obesity)

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23 pages, 1784 KiB

Open AccessReview

Current State, Challenges, and Opportunities in Genome-Scale Resource Allocation Models: A Mathematical Perspective

by Wheaton L. Schroeder, Patrick F. Suthers, Thomas C. Willis, Eric J. Mooney and Costas D. Maranas

Metabolites 2024, 14(7), 365; https://doi.org/10.3390/metabo14070365 - 28 Jun 2024

Viewed by 139

Abstract

Stoichiometric genome-scale metabolic models (generally abbreviated GSM, GSMM, or GEM) have had many applications in exploring phenotypes and guiding metabolic engineering interventions. Nevertheless, these models and predictions thereof can become limited as they do not directly account for protein cost, enzyme kinetics, and [...] Read more.

Stoichiometric genome-scale metabolic models (generally abbreviated GSM, GSMM, or GEM) have had many applications in exploring phenotypes and guiding metabolic engineering interventions. Nevertheless, these models and predictions thereof can become limited as they do not directly account for protein cost, enzyme kinetics, and cell surface or volume proteome limitations. Lack of such mechanistic detail could lead to overly optimistic predictions and engineered strains. Initial efforts to correct these deficiencies were by the application of precursor tools for GSMs, such as flux balance analysis with molecular crowding. In the past decade, several frameworks have been introduced to incorporate proteome-related limitations using a genome-scale stoichiometric model as the reconstruction basis, which herein are called resource allocation models (RAMs). This review provides a broad overview of representative or commonly used existing RAM frameworks. This review discusses increasingly complex models, beginning with stoichiometric models to precursor to RAM frameworks to existing RAM frameworks. RAM frameworks are broadly divided into two categories: coarse-grained and fine-grained, with different strengths and challenges. Discussion includes pinpointing their utility, data needs, highlighting framework strengths and limitations, and appropriateness to various research endeavors, largely through contrasting their mathematical frameworks. Finally, promising future applications of RAMs are discussed. Full article

(This article belongs to the Special Issue Recent Developments and Emerging Trends in Metabolic Modelling and Metabolomics)

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23 pages, 2920 KiB

Open AccessArticle

Physicochemical Characterization of Moroccan Honey Varieties from the Fez-Meknes Region and Their Antioxidant and Antibacterial Properties

by Atika Ailli, Khalid Zibouh, Brahim Eddamsyry, Aziz Drioiche, Dounia Fetjah, Fatima Zahra Ayyad, Ramzi A. Mothana, Mohammed F. Hawwal, Mohamed Radi, Redouane Tarik, Abdelhakim Elomri, Aicha Mouradi and Touriya Zair

Metabolites 2024, 14(7), 364; https://doi.org/10.3390/metabo14070364 - 27 Jun 2024

Viewed by 199

Abstract

Honey, with its varied and extensive characteristics, is a complex and diverse biological substance that has been used since ancient times. The aim of this study is to thoroughly characterize the physicochemical, phytochemical, and biological properties of four floral honey varieties from the [...] Read more.

Honey, with its varied and extensive characteristics, is a complex and diverse biological substance that has been used since ancient times. The aim of this study is to thoroughly characterize the physicochemical, phytochemical, and biological properties of four floral honey varieties from the Fez-Meknes region in Morocco, with the goal of promoting the valorization of Moroccan honey in skincare and cosmetic products. The analyses of their physicochemical characteristics encompass various parameters such as pH, acidity, density, water content, Brix index, conductivity, ash content, hydroxymethylfurfural (HMF) content, and color. The levels of polyphenols range from 22.1 ± 0.4 to 69.3 ± 0.17 mg GAE/100 g of honey, measured using the Folin–Ciocalteu method for polyphenol quantification. Additionally, the estimation of flavonoid quantities in 100 g of honey, conducted using the aluminum trichloride method, reveals values ranging from 3.6 ± 0.2 to 7.2 ± 0.6 mg QE. Furthermore, it is noteworthy that honey exhibits high levels of glucose and relatively low concentrations of proteins. The quantitative evaluation of antioxidant effects, carried out through the 2,2-diphenyl-1-picrylhydrazyl free-radical-scavenging method and the ferric-reducing antioxidant power (FRAP) method, highlights the strong antioxidant capacity of multifloral honey, characterized by low inhibitory concentration values (IC₅₀ = 30.43 mg/mL and EC₅₀ = 16.06 mg/mL). Moreover, all honey varieties demonstrate antibacterial and antifungal properties, with multifloral honey standing out for its particularly pronounced antimicrobial activity. The correlation analyses between phytochemical composition and antioxidant and antibacterial activities reveal an inverse relationship between polyphenols and IC₅₀ (DPPH) and EC₅₀ (FRAP) concentrations of honey. The correlation coefficients are established at R² = −0.97 and R² = −0.99, respectively. Additionally, a significant negative correlation is observed between polyphenols, flavonoids, and antifungal power (R² = −0.95 and R² = −0.96). In parallel, a marked positive correlation is highlighted between antifungal efficacy, DPPH antioxidant activity (R² = 0.95), and FRAP (R² = 0.92). These results underscore the crucial importance of phytochemical components in the beneficial properties of honey, meeting international quality standards. Consequently, honey could serve as a natural alternative to synthetic additives. Full article

(This article belongs to the Special Issue Bioactive Compounds in Animal Nutrition Resources and Animal By-Products)

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17 pages, 482 KiB

Open AccessReview

The Effect of L-Carnitine on Critical Illnesses Such as Traumatic Brain Injury (TBI), Acute Kidney Injury (AKI), and Hyperammonemia (HA)

by Bharti Sharma, Lee Schmidt, Cecilia Nguyen, Samantha Kiernan, Jacob Dexter-Meldrum, Zachary Kuschner, Scott Ellis, Navin D. Bhatia, George Agriantonis, Jennifer Whittington and Kate Twelker

Metabolites 2024, 14(7), 363; https://doi.org/10.3390/metabo14070363 - 27 Jun 2024

Viewed by 181

Abstract

L-carnitine (LC) through diet is highly beneficial for critical patients. Studies have found that acetyl-L-carnitine (ALC) can reduce cerebral edema and neurological complications in TBI patients. It significantly improves their neurobehavioral and neurocognitive functions. ALC has also been shown to have a neuroprotective [...] Read more.

L-carnitine (LC) through diet is highly beneficial for critical patients. Studies have found that acetyl-L-carnitine (ALC) can reduce cerebral edema and neurological complications in TBI patients. It significantly improves their neurobehavioral and neurocognitive functions. ALC has also been shown to have a neuroprotective effect in cases of global and focal cerebral ischemia. Moreover, it is an effective agent in reducing nephrotoxicity by suppressing downstream mitochondrial fragmentation. LC can reduce the severity of renal ischemia-reperfusion injury, renal cast formation, tubular necrosis, iron accumulation in the tubular epithelium, CK activity, urea levels, Cr levels, and MDA levels and restore the function of enzymes such as SOD, catalase, and GPx. LC can also be administered to patients with hyperammonemia (HA), as it can suppress ammonia levels. It is important to note, however, that LC levels are dysregulated in various conditions such as aging, cirrhosis, cardiomyopathy, malnutrition, sepsis, endocrine disorders, diabetes, trauma, starvation, obesity, and medication interactions. There is limited research on the effects of LC supplementation in critical illnesses such as TBI, AKI, and HA. This scarcity of studies highlights the need for further research in this area. Full article

(This article belongs to the Special Issue Impact of Food and Bioactive Compounds on Metabolic Diseases)

18 pages, 2035 KiB

Open AccessArticle

miR-21/SMAD2 Is Involved in the Decrease in Progesterone Synthesis Caused by Lipopolysaccharide Exposure in Follicular Granulosa Cells of Laying Goose

by Xinyi Guo, Shijia Ying, Huiping Xiao, Hao An, Rihong Guo, Zichun Dai and Wenda Wu

Metabolites 2024, 14(7), 362; https://doi.org/10.3390/metabo14070362 - 27 Jun 2024

Viewed by 138

Abstract

Lipopolysaccharide (LPS) is one of the important pathogenic substances of E. coli and Salmonella, which causes injury to the reproductive system. Ovarian dysfunction due to Gram-negative bacterial infections is a major cause of reduced reproductive performance in geese. However, the specific molecular [...] Read more.

Lipopolysaccharide (LPS) is one of the important pathogenic substances of E. coli and Salmonella, which causes injury to the reproductive system. Ovarian dysfunction due to Gram-negative bacterial infections is a major cause of reduced reproductive performance in geese. However, the specific molecular mechanisms of LPS-induced impairment of sex steroid hormone synthesis have not been determined. The regulatory mechanism of miRNA has been proposed in many physiological and pathogenic mechanisms. Therefore, the role of miRNA in breeding geese exposed to LPS during the peak laying period was investigated. In this study, twenty Yangzhou geese at peak laying period were injected with LPS for 0 h, 24 h, and 36 h. The follicular granulosa layer was taken for RNA-seq and analyzed for differentially expressed miRNAs. It was observed that LPS changed the appearance of hierarchical follicles. miRNA sequencing analysis was applied, and miR-21 and SMAD2 (SMAD family member 2) were selected from 51 differentially expressed miRNAs through bioinformatics prediction. The results showed that miR-21 down-regulated SMAD2 expression and progesterone (P4) production in LPS-treated goose granulosa cells (GCs). It also determined that overexpression of miR-21 or silence of SMAD2 suppressed the sex steroid biosynthesis pathway by decreasing STAR and CYP11A1 expression. Down-regulation of miR-21 exacerbates the LPS-induced decline in P4 synthesis and vice versa. The findings indicated that miR-21 was involved in LPS regulation of P4 synthesis in goose granulosa cells by down-regulating SMAD2. This study provides theoretical support for the prevention of LPS-induced ovarian dysfunction in geese. Full article

(This article belongs to the Special Issue Animal Nutritional Metabolism and Toxicosis Disease)

18 pages, 337 KiB

Open AccessReview

Association of DNA Methylation with Infant Birth Weight in Women with Gestational Diabetes

by Renata Saucedo, Aldo Ferreira-Hermosillo, Magalhi Robledo-Clemente, Mary Flor Díaz-Velázquez and Jorge Valencia-Ortega

Metabolites 2024, 14(7), 361; https://doi.org/10.3390/metabo14070361 - 27 Jun 2024

Viewed by 188

Abstract

Offspring exposed to gestational diabetes mellitus (GDM) exhibit greater adiposity at birth. This early-life phenotype may increase offspring risk of developing obesity, metabolic syndrome, type 2 diabetes, and cardiovascular disease later in life. Infants born to women with GDM have a dysregulation of [...] Read more.

Offspring exposed to gestational diabetes mellitus (GDM) exhibit greater adiposity at birth. This early-life phenotype may increase offspring risk of developing obesity, metabolic syndrome, type 2 diabetes, and cardiovascular disease later in life. Infants born to women with GDM have a dysregulation of several hormones, cytokines, and growth factors related to fetal fat mass growth. One of the molecular mechanisms of GDM influencing these factors is epigenetic alterations, such as DNA methylation (DNAm). This review will examine the role of DNAm as a potential biomarker for monitoring fetal growth during pregnancy in women with GDM. This information is relevant since it may provide useful new biomarkers for the diagnosis, prognosis, and treatment of fetal growth and its later-life health consequences. Full article

(This article belongs to the Special Issue Adipose Tissue, Reproduction and Metabolic Health in Women)

12 pages, 989 KiB

Open AccessArticle

A Novel UHPLC-MS/MS Based Method for Isomeric Separation and Quantitative Determination of Cyanogenic Glycosides in American Elderberry

by Deepak M. Kasote, Zhentian Lei, Clayton D. Kranawetter, Ashley Conway-Anderson, Barbara W. Sumner and Lloyd W. Sumner

Metabolites 2024, 14(7), 360; https://doi.org/10.3390/metabo14070360 - 26 Jun 2024

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Abstract

LC-MS/MS analyses have been reported as challenging for the reliable separation and quantification of cyanogenic glycosides (CNGs), especially (R)-prunasin and sambunigrin isomers found in American elderberry (Sambucus nigra L. subsp. canadensis (L.) Bolli). Hence, a novel multiple reaction monitoring (MRM)-based [...] Read more.

LC-MS/MS analyses have been reported as challenging for the reliable separation and quantification of cyanogenic glycosides (CNGs), especially (R)-prunasin and sambunigrin isomers found in American elderberry (Sambucus nigra L. subsp. canadensis (L.) Bolli). Hence, a novel multiple reaction monitoring (MRM)-based ultra-high-performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS) method was developed and validated in the present study for simultaneous separation and quantification of five CNGs, including amygdalin, dhurrin, linamarin, (R)-prunasin, and (S)-prunasin (commonly referred to as sambunigrin). Initially, the role of ammonium formate was investigated as an aqueous mobile-phase additive in developing MRM-based UHPLC-MS/MS. Later, chromatographic conditions for the resolved separation of (R)-prunasin and sambunigrin were identified. Validation studies confirmed that the developed method has good linearity and acceptable precision and accuracy. A noticeable matrix effect (mainly signal enhancement) was observed in leaf samples only. This method was used to detect and quantify CNGs, including (R)-prunasin and sambunigrin, in leaf and fruit samples of American elderberry. Among the studied CNGs, only (R)-prunasin was detected in the leaf samples. Interestingly, (S)-prunasin (sambunigrin) was not detected in the samples analyzed, even though it has been previously reported in elderberry species. Full article

(This article belongs to the Topic Advances in Separation Methods for Metabolomics and Lipidomics)

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14 pages, 3930 KiB

Open AccessArticle

Investigation of Rhizopus oligosporus Metabolites in Fermented Wheat Bran and Its Bio Function in Alleviating Colitis in Mice Model

by Afifah Zahra Agista, Yu-Shan Chien, Takuya Koseki, Hazuki Nagaoka, Takuto Ohnuma, Yusuke Ohsaki, Chiu-Li Yeh, Suh-Ching Yang, Ardiansyah, Slamet Budijanto, Michio Komai and Hitoshi Shirakawa

Metabolites 2024, 14(7), 359; https://doi.org/10.3390/metabo14070359 - 26 Jun 2024

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Abstract

Wheat bran (WB) is a low-value by-product of the wheat milling industry. Solid-state fermentation with Rhizopus oligosporus is performed to improve WB’s nutritional quality (RH). Twenty-five mice (11-week-old C57BL/6N male mice) were divided into three groups. The first group was fed a control [...] Read more.

Wheat bran (WB) is a low-value by-product of the wheat milling industry. Solid-state fermentation with Rhizopus oligosporus is performed to improve WB’s nutritional quality (RH). Twenty-five mice (11-week-old C57BL/6N male mice) were divided into three groups. The first group was fed a control diet (n = 8), the second group a 10% WB-supplemented diet (n = 8), and the last group had a 10% RH-supplemented diet (n = 9). The diet treatment was administered for 4 days before dextran sodium sulfate (DSS, 3% in drinking water) was administered for 9 days. RH supplementation prevented bodyweight loss and reduced the disease activity index in mice. An increase in the level of SCFAs in mouse intestines was detected post-RH supplementation, suggesting that SCFAs might have contributed to its anti-colitis effect. Metabolome analysis was conducted to explore other bioactive compounds in RH. R. oligosporus fermentation significantly increased the amounts of ergothioneine, arginine, branched-chain amino acids, and adenosine in wheat bran. All of these compounds are known to have antioxidant and anti-inflammatory capacities. These bioactive compounds might also have contributed to the RH’s ability to ameliorate DSS-induced colitis. Full article

(This article belongs to the Special Issue Emerging Applications of Metabolomics in Fermented Food)

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26 pages, 2507 KiB

Open AccessArticle

Comparison of Ten Surrogate Insulin Resistance and Obesity Markers to Identify Metabolic Syndrome in Mexican Adults

by Iván Filiberto Contreras-Hernández, Cruz Vargas-De-León, Luis Rey García-Cortes, Adriana Flores-Miranda, Rodrigo Romero-Nava and María Esther Ocharán-Hernández

Metabolites 2024, 14(7), 358; https://doi.org/10.3390/metabo14070358 - 26 Jun 2024

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Abstract

Metabolic syndrome (MetS) is a group of clinical traits directly linked to type 2 diabetes mellitus and cardiovascular diseases, whose prevalence has been rising nationally and internationally. We aimed to evaluate ten known and novel surrogate markers of insulin resistance and [...] Read more.

Metabolic syndrome (MetS) is a group of clinical traits directly linked to type 2 diabetes mellitus and cardiovascular diseases, whose prevalence has been rising nationally and internationally. We aimed to evaluate ten known and novel surrogate markers of insulin resistance and obesity to identify MetS in Mexican adults. The present cross-sectional study analyzed 10575 participants from ENSANUT-2018. The diagnosis of MetS was based on the Adult Treatment Panel III (ATP III) criteria and International Diabetes Federation (IDF) criteria, stratified by sex and age group. According to ATP III, the best biomarker was the metabolic score for insulin resistance (METS-IR) in men aged 20–39 and 40–59 years and lipid accumulation product (LAP) in those aged ≥60 years. The best biomarker was LAP in women aged 20–39 and triglyceride–glucose index (TyG) in those aged 40–59 and ≥60 years. Using the IDF criteria, the best biomarker was LAP in men of all ages. TyG gave the best results in women of all ages. The best biomarker for diagnosis of MetS in Mexican adults depends on the criteria, including sex and age group. LAP and TyG are easy to obtain, inexpensive, and especially useful at the primary care level. Full article

19 pages, 4982 KiB

Open AccessArticle

Skeletal Muscle Metabolism Is Dynamic during Porcine Postnatal Growth

by Linnea A. Rimmer, Erika R. Geisbrecht, Michael D. Chao, Travis G. O’Quinn, Jason C. Woodworth and Morgan D. Zumbaugh

Metabolites 2024, 14(7), 357; https://doi.org/10.3390/metabo14070357 - 26 Jun 2024

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Abstract

Skeletal muscle metabolism has implications for swine feed efficiency (FE); however, it remains unclear if the metabolic profile of skeletal muscle changes during postnatal growth. To assess the metabolic changes, samples were collected from the longissimus dorsi (LD, glycolytic muscle), latissimus dorsi (LAT, [...] Read more.

Skeletal muscle metabolism has implications for swine feed efficiency (FE); however, it remains unclear if the metabolic profile of skeletal muscle changes during postnatal growth. To assess the metabolic changes, samples were collected from the longissimus dorsi (LD, glycolytic muscle), latissimus dorsi (LAT, mixed muscle), and masseter (MS, oxidative muscle) at 20, 53, 87, 120, and 180 days of age from barrows. Muscles were assessed to determine the abundance of several metabolic enzymes. Lactate dehydrogenase (LDHα) decreased in all muscles from 20 to 87 d (p < 0.01), which may be attributed to the muscles being more glycolytic at weaning from a milk-based diet. Pyruvate carboxylase (PC) increased in all muscles at 53 d compared to the other time points (p < 0.01), while pyruvate dehydrogenase α 1 (PDHα1) increased at 87 and 180 d in MS compared to LD (p < 0.05), indicating that potential changes occur in pyruvate entry into the tricarboxylic acid (TCA) cycle during growth. Isolated mitochondria from each muscle were incubated with ¹³C-labeled metabolites to assess isotopomer enrichment patterns of TCA intermediates. Citrate M + 2 and M + 4 derived from [¹³C₃]-pyruvate increased at 87 d in LAT and MS mitochondria compared to LD mitochondria (p < 0.05). Regardless of the muscle, citrate M+3 increased at 87 d compared to 20, 53, and 120 d, while 180 d showed intermediate values (p < 0.01). These data support the notion that pyruvate metabolism is dynamic during growth. Our findings establish a metabolic fingerprint associated with postnatal muscle hypertrophy. Full article

(This article belongs to the Special Issue Unlocking the Mysteries of Muscle Metabolism in the Animal Sciences)

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17 pages, 3018 KiB

Open AccessArticle

Disturbances in Muscle Energy Metabolism in Patients with Amyotrophic Lateral Sclerosis

by Petra Parvanovova, Petra Hnilicova, Martin Kolisek, Zuzana Tatarkova, Erika Halasova, Egon Kurca, Simona Holubcikova, Monika Turcanova Koprusakova and Eva Baranovicova

Metabolites 2024, 14(7), 356; https://doi.org/10.3390/metabo14070356 - 23 Jun 2024

Viewed by 436

Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal neuromuscular disease type of motor neuron disorder characterized by degeneration of the upper and lower motor neurons resulting in dysfunction of the somatic muscles of the body. The ALS condition is manifested in progressive skeletal muscle [...] Read more.

Amyotrophic lateral sclerosis (ALS) is a fatal neuromuscular disease type of motor neuron disorder characterized by degeneration of the upper and lower motor neurons resulting in dysfunction of the somatic muscles of the body. The ALS condition is manifested in progressive skeletal muscle atrophy and spasticity. It leads to death, mostly due to respiratory failure. Within the pathophysiology of the disease, muscle energy metabolism seems to be an important part. In our study, we used blood plasma from 25 patients with ALS diagnosed by definitive El Escorial criteria according to ALSFR-R (Revised Amyotrophic Lateral Sclerosis Functional Rating Scale) criteria and 25 age and sex-matched subjects. Aside from standard clinical biochemical parameters, we used the NMR (nuclear magnetic resonance) metabolomics approach to determine relative plasma levels of metabolites. We observed a decrease in total protein level in blood; however, despite accelerated skeletal muscle catabolism characteristic for ALS patients, we did not detect changes in plasma levels of essential amino acids. When focused on alterations in energy metabolism within muscle, compromised creatine uptake was accompanied by decreased plasma creatinine. We did not observe changes in plasma levels of BCAAs (branched chain amino acids; leucine, isoleucine, valine); however, the observed decrease in plasma levels of all three BCKAs (branched chain alpha-keto acids derived from BCAAs) suggests enhanced utilization of BCKAs as energy substrate. Glutamine, found to be increased in blood plasma in ALS patients, besides serving for ammonia detoxification, could also be considered a potential TCA (tricarboxylic acid) cycle contributor in times of decreased pyruvate utilization. When analyzing the data by using a cross-validated Random Forest algorithm, it finished with an AUC of 0.92, oob error of 8%, and an MCC (Matthew’s correlation coefficient) of 0.84 when relative plasma levels of metabolites were used as input variables. Although the discriminatory power of the system used was promising, additional features are needed to create a robust discriminatory model. Full article

(This article belongs to the Special Issue Metabolomics in Neurodegenerative Diseases)

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23 pages, 1088 KiB

Open AccessReview

The Cellular Stability Hypothesis: Evidence of Ferroptosis and Accelerated Aging-Associated Diseases as Newly Identified Nutritional Pentadecanoic Acid (C15:0) Deficiency Syndrome

by Stephanie Venn-Watson

Metabolites 2024, 14(7), 355; https://doi.org/10.3390/metabo14070355 - 23 Jun 2024

Viewed by 1430

Abstract

Ferroptosis is a newly discovered form of cell death caused by the peroxidation of fragile fatty acids in cell membranes, which combines with iron to increase reactive oxygen species and disable mitochondria. Ferroptosis has been linked to aging-related conditions, including type 2 diabetes, [...] Read more.

Ferroptosis is a newly discovered form of cell death caused by the peroxidation of fragile fatty acids in cell membranes, which combines with iron to increase reactive oxygen species and disable mitochondria. Ferroptosis has been linked to aging-related conditions, including type 2 diabetes, cardiovascular disease, and nonalcoholic fatty liver disease (NAFLD). Pentadecanoic acid (C15:0), an odd-chain saturated fat, is an essential fatty acid with the primary roles of stabilizing cell membranes and repairing mitochondrial function. By doing so, C15:0 reverses the underpinnings of ferroptosis. Under the proposed “Cellular Stability Hypothesis”, evidence is provided to show that cell membranes optimally need >0.4% to 0.64% C15:0 to support long-term health and longevity. A pathophysiology of a newly identified nutritional C15:0 deficiency syndrome (“Cellular Fragility Syndrome”) is provided that demonstrates how C15:0 deficiencies (≤0.2% total circulating fatty acids) can increase susceptibilities to ferroptosis, dysmetabolic iron overload syndrome, type 2 diabetes, cardiovascular disease, and NAFLD. Further, evidence is provided that C15:0 supplementation can reverse the described C15:0 deficiency syndrome, including the key components of ferroptosis. Given the declining dietary intake of C15:0, especially among younger generations, there is a need for extensive studies to understand the potential breadth of Cellular Fragility Syndrome across populations. Full article

(This article belongs to the Special Issue Impact of Macronutrients on Metabolism)

10 pages, 4124 KiB

Open AccessArticle

Microwave Radiation Caused Dynamic Metabolic Fluctuations in the Mammalian Hippocampus

by Yu Xin, Shu-Ting Guan, Ke Ren, Hui Wang, Ji Dong, Hao-Yu Wang, Jing Zhang, Xin-Ping Xu, Bin-Wei Yao, Li Zhao, Chang-Xiu Shi and Rui-Yun Peng

Metabolites 2024, 14(7), 354; https://doi.org/10.3390/metabo14070354 - 23 Jun 2024

Viewed by 325

Abstract

To investigate the dynamic changes in hippocampal metabolism after microwave radiation using liquid chromatography in tandem with mass spectrometry/mass spectrometry (LC‒MS/MS) and to identify potential biomarkers. Wistar rats were randomly assigned to a sham group and a microwave radiation group. The rats in [...] Read more.

To investigate the dynamic changes in hippocampal metabolism after microwave radiation using liquid chromatography in tandem with mass spectrometry/mass spectrometry (LC‒MS/MS) and to identify potential biomarkers. Wistar rats were randomly assigned to a sham group and a microwave radiation group. The rats in the microwave radiation group were exposed to 2.856 GHz for 15 min for three times, with 5 min intervals. The rats in the sham group were not exposed. Transmission electron microscope revealed blurring of the synaptic cleft and postsynaptic dense thickening in hippocampal neurons after microwave radiation. Metabolomic analysis revealed 38, 24, and 39 differentially abundant metabolites at 3, 7, and 14 days after radiation, respectively, and the abundance of 9 metabolites, such as argininosuccinic acid, was continuously decreased. After microwave radiation, the abundance of metabolites such as argininosuccinic acid was successively decreased, indicating that these metabolites could be potential biomarkers for hippocampal tissue injury. Full article

(This article belongs to the Section Animal Metabolism)

32 pages, 4651 KiB

Open AccessArticle

Changes in Plasma Free Amino Acid Profile in Endurance Athletes over a 9-Month Training Cycle

by Krzysztof Kusy, Monika Ciekot-Sołtysiak, Jan Matysiak, Agnieszka Klupczyńska-Gabryszak, Szymon Plewa, Ewa Anna Zarębska, Zenon J. Kokot, Paweł Dereziński and Jacek Zieliński

Metabolites 2024, 14(7), 353; https://doi.org/10.3390/metabo14070353 - 23 Jun 2024

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Abstract

We aimed to evaluate long-term changes in proteinogenic and non-proteinogenic plasma free amino acids (PFAA). Eleven male endurance triathletes participated in a 9-month study. Blood was collected at rest, immediately after exhaustive exercise, and during 30-min recovery, in four consecutive training phases: transition, [...] Read more.

We aimed to evaluate long-term changes in proteinogenic and non-proteinogenic plasma free amino acids (PFAA). Eleven male endurance triathletes participated in a 9-month study. Blood was collected at rest, immediately after exhaustive exercise, and during 30-min recovery, in four consecutive training phases: transition, general, specific, and competition. Twenty proteinogenic and 22 non-proteinogenic PFAAs were assayed using the LC-ESI-MS/MS technique. The structured training modified the patterns of exercise-induced PFAA response, with the competition phase being the most distinct from the others. Branched-chain amino acids (p = 0.002; η² = 0.216), phenylalanine (p = 0.015; η² = 0.153), methionine (p = 0.002; η² = 0.206), and lysine (p = 0.006; η² = 0.196) declined more rapidly between rest and exhaustion in the competition phase. Glutamine (p = 0.008; η² = 0.255), glutamate (p = 0.006; η² = 0.265), tyrosine (p = 0.001; η² = 0.195), cystine (p = 0.042; η² = 0.183), and serine (p < 0.001; η² = 0.346) levels were reduced in the competition phase. Arginine (p = 0.046; η² = 0.138) and aspartate (p = 0.011; η² = 0.171) levels were highest during exercise in the transition phase. During the competition phase, α-aminoadipic acid (p = 0.023; η² = 0.145), β-aminoisobutyric acid (p = 0.007; η² = 0.167), β-alanine (p < 0.001; η² = 0.473), and sarcosine (p = 0.017; η² = 0.150) levels increased, whereas phosphoethanolamine (p = 0.037; η² = 0.189) and taurine (p = 0.008; η² = 0.251) concentrations decreased. Overtraining indicators were not elevated. The altered PFAA profile suggests adaptations within energy metabolic pathways such as the tricarboxylic acid cycle, oxidative phosphorylation, ammonia neutralization, the purine nucleotide cycle, and buffering of intracellular H⁺ ions. The changes seem to reflect normal adaptations. Full article

(This article belongs to the Special Issue Metabolomic Advances in Promoting Exercise-Induced Metabolic Changes)

35 pages, 1389 KiB

Open AccessReview

Interaction between α-Synuclein and Bioactive Lipids: Neurodegeneration, Disease Biomarkers and Emerging Therapies

by Chiara Sanluca, Paolo Spagnolo, Romina Mancinelli, Maria Ilenia De Bartolo, Marina Fava, Mauro Maccarrone, Simone Carotti, Eugenio Gaudio, Alessandro Leuti and Giorgio Vivacqua

Metabolites 2024, 14(7), 352; https://doi.org/10.3390/metabo14070352 - 22 Jun 2024

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Abstract

The present review provides a comprehensive examination of the intricate dynamics between α-synuclein, a protein crucially involved in the pathogenesis of several neurodegenerative diseases, including Parkinson’s disease and multiple system atrophy, and endogenously-produced bioactive lipids, which play a pivotal role in neuroinflammation and [...] Read more.

The present review provides a comprehensive examination of the intricate dynamics between α-synuclein, a protein crucially involved in the pathogenesis of several neurodegenerative diseases, including Parkinson’s disease and multiple system atrophy, and endogenously-produced bioactive lipids, which play a pivotal role in neuroinflammation and neurodegeneration. The interaction of α-synuclein with bioactive lipids is emerging as a critical factor in the development and progression of neurodegenerative and neuroinflammatory diseases, offering new insights into disease mechanisms and novel perspectives in the identification of potential biomarkers and therapeutic targets. We delve into the molecular pathways through which α-synuclein interacts with biological membranes and bioactive lipids, influencing the aggregation of α-synuclein and triggering neuroinflammatory responses, highlighting the potential of bioactive lipids as biomarkers for early disease detection and progression monitoring. Moreover, we explore innovative therapeutic strategies aimed at modulating the interaction between α-synuclein and bioactive lipids, including the development of small molecules and nutritional interventions. Finally, the review addresses the significance of the gut-to-brain axis in mediating the effects of bioactive lipids on α-synuclein pathology and discusses the role of altered gut lipid metabolism and microbiota composition in neuroinflammation and neurodegeneration. The present review aims to underscore the potential of targeting α-synuclein-lipid interactions as a multifaceted approach for the detection and treatment of neurodegenerative and neuroinflammatory diseases. Full article

(This article belongs to the Special Issue Bioactive Lipids in Neuroinflammatory Diseases)

21 pages, 6974 KiB

Open AccessArticle

Integrated Microbiome-Metabolomics Analysis Reveals the Potential Mechanism of Dandelion Root Polysaccharides to Ameliorate Ulcerative Colitis

by Shengkun Yan and Rong Dong

Metabolites 2024, 14(7), 351; https://doi.org/10.3390/metabo14070351 - 22 Jun 2024

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Abstract

In the conducted research, a murine model for ulcerative colitis (UC) was established utilizing dextran sodium sulfate (DSS) to investigate the therapeutic potential of dandelion root polysaccharide extracts on this disease. This study employed an analysis of gut microbiota composition and serum metabolomics [...] Read more.

In the conducted research, a murine model for ulcerative colitis (UC) was established utilizing dextran sodium sulfate (DSS) to investigate the therapeutic potential of dandelion root polysaccharide extracts on this disease. This study employed an analysis of gut microbiota composition and serum metabolomics to understand the biochemical effects of these polysaccharides. Sequencing of the 16S ribosomal DNA component indicated an increased presence of Bacteroides in the DSS-treated model group, contrasting with a significant enhancement in Faecalibaculum populations in mice treated with dandelion root polysaccharides (DPs). This shift suggests a pivotal role of DPs in elevating fecal N-butyric acid levels—a crucial factor in the maintenance of gut microbiota equilibrium. Through metabolomic profiling of serum, this research identified distinct metabolic changes across the control, DSS model, and DP treatment groups, highlighting four major differential metabolites: (2S)-2-amino-3-[[(2R)-2-butanoyloxy-3-propanoyloxypropoxy]-hydroxyphosphoryl]oxypropanoic acid; (1R,8S,9S)-3,4-dihydroxy-8-methoxy-11,11-dimethyl-5-propan-2-yl-16-oxatetracyclo [7.5.2.01,10.02,7]hexadeca-2,4,6-trien-15-one; Aspartylasparagine; and Nap-Phe-OH. These metabolites are implicated in mitigating oxidative stress, suggesting that DPs facilitate a protective mechanism for the intestinal lining through various biochemical pathways. Additionally, a notable correlation was established between the altered gut microbiota and the serum metabolomic profiles, underscoring the intricate interplay between these two biological systems in the context of UC. This study’s outcomes illustrate that UC induces significant alterations in both gut microbiota and metabolic signatures, whereas dandelion root polysaccharides exhibit a profound ameliorative effect on these disruptions. This investigation underscores the therapeutic promise of dandelion root polysaccharides in the management of UC by modulating gut microbiota and metabolic pathways. Full article

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17 pages, 4804 KiB

Open AccessArticle

The Application of Resveratrol Derivatives in Oral Cells Reduces the Oxidative Stress Induced by Glucocorticoids

by Emira D’Amico, Chiara Cinquini, Morena Petrini, Antonio Barone, Giovanna Iezzi, Simonetta D’Ercole, Barbara De Filippis and Tania Vanessa Pierfelice

Metabolites 2024, 14(7), 350; https://doi.org/10.3390/metabo14070350 - 22 Jun 2024

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Abstract

Oxidative stress and high levels of reactive oxygen species (ROS) are linked to various age-related diseases and chronic conditions, including damage to oral tissues. Dexamethasone (DEX), a widely used glucocorticoid in dentistry, can have side effects like increased ROS production and delayed wound [...] Read more.

Oxidative stress and high levels of reactive oxygen species (ROS) are linked to various age-related diseases and chronic conditions, including damage to oral tissues. Dexamethasone (DEX), a widely used glucocorticoid in dentistry, can have side effects like increased ROS production and delayed wound healing. Resveratrol (RSV) is known for its antioxidant properties, but its limited bioavailability hinders its clinical use. This study investigated the potential of two RSV derivatives (1d and 1h) to address these limitations. The antioxidant abilities of 1d and 1h (5 μM) against DEX-induced oxidative stress (200 μM) were evaluated in human gingival fibroblasts (hGFs) and osteoblasts (hOBs). The effects of these compounds on cell viability, morphology, ROS levels, SOD activity, gene expression, and collagen production were evaluated. RSV derivatives, under DEX-induced oxidative stress condition, improved cell growth at 72 h (191.70 ± 10.92% for 1d+DEX and 184.80 ± 13.87% for 1h+DEX), morphology, and SOD activity (77.33 ± 3.35 OD for 1d+DEX; 76.87 ± 3.59 OD for 1h+DEX at 1 h), while reducing ROS levels (2417.33 ± 345.49 RFU for 1d+DEX and 1843.00 ± 98.53 RFU at 4 h), especially in hOBs. The co-treatment of RSV or derivatives with DEX restored the expression of genes that were downregulated by DEX, such as HO-1 (1.76 ± 0.05 for 1d+DEX and 1.79 ± 0.01 for 1h+DEX), CAT (0.97 ± 0.06 for 1d+DEX and 0.99 ± 0.03 for 1h+DEX), NRF2 (1.62 ± 0.04 for 1d+DEX and 1.91 ± 0.05 for 1h+DEX), SOD1 (1.63 ± 0.15 for 1d+DEX and 1.69 ± 0.04 for 1h+DEX). In addition, 1d and 1h preserved collagen production (111.79 ± 1.56 for 1d+DEX and 122.27 ± 1.56 for 1h+DEX). In conclusion, this study suggests that the RSV derivatives 1d and 1h hold promise as potential antioxidant agents to counteract DEX-induced oxidative stress. These findings contribute to the development of novel therapeutic strategies for managing oxidative stress-related oral conditions. Full article

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20 pages, 2420 KiB

Open AccessArticle

Metabolomics Analysis of Rabbit Plasma after Ocular Exposure to Vapors of Sulfur Mustard

by Jihéne Bouhlel, Fanny Caffin, Fanny Gros-Désormeaux, Thierry Douki, Jean-François Benoist, Florence A. Castelli, Emeline Chu-Van, Christophe Piérard, Christophe Junot and François Fenaille

Metabolites 2024, 14(7), 349; https://doi.org/10.3390/metabo14070349 - 21 Jun 2024

Viewed by 273

Abstract

Sulfur mustard (SM) is a highly potent alkylating vesicant agent and remains a relevant threat to both civilians and military personnel. The eyes are the most sensitive organ after airborne SM exposure, causing ocular injuries with no antidote or specific therapeutics available. In [...] Read more.

Sulfur mustard (SM) is a highly potent alkylating vesicant agent and remains a relevant threat to both civilians and military personnel. The eyes are the most sensitive organ after airborne SM exposure, causing ocular injuries with no antidote or specific therapeutics available. In order to identify relevant biomarkers and to obtain a deeper understanding of the underlying biochemical events, we performed an untargeted metabolomics analysis using liquid chromatography coupled to high-resolution mass spectrometry of plasma samples from New Zealand white rabbits ocularly exposed to vapors of SM. Metabolic profiles (332 unique metabolites) from SM-exposed (n = 16) and unexposed rabbits (n = 8) were compared at different time intervals from 1 to 28 days. The observed time-dependent changes in metabolic profiles highlighted the profound dysregulation of the sulfur amino acids, the phenylalanine, the tyrosine and tryptophan pathway, and the polyamine and purine biosynthesis, which could reflect antioxidant and anti-inflammatory activities. Taurine and 3,4-dihydroxy-phenylalanine (Dopa) seem to be specifically related to SM exposure and correspond well with the different phases of ocular damage, while the dysregulation of adenosine, polyamines, and acylcarnitines might be related to ocular neovascularization. Additionally, neither cysteine, N-acetylcysteine, or guanine SM adducts were detected in the plasma of exposed rabbits at any time point. Overall, our study provides an unprecedented view of the plasma metabolic changes post-SM ocular exposure, which may open up the development of potential new treatment strategies. Full article

(This article belongs to the Special Issue Challenges and Opportunities in Application of Mass Spectrometry for Metabolomics and Lipidomics)

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19 pages, 1774 KiB

Open AccessReview

Bile Acids in Pancreatic Carcinogenesis

by Bharti Sharma, Kate Twelker, Cecilia Nguyen, Scott Ellis, Navin D. Bhatia, Zachary Kuschner, Andrew Agriantonis, George Agriantonis, Monique Arnold, Jasmine Dave, Juan Mestre, Zahra Shafaee, Shalini Arora, Hima Ghanta and Jennifer Whittington

Metabolites 2024, 14(7), 348; https://doi.org/10.3390/metabo14070348 - 21 Jun 2024

Viewed by 286

Abstract

Pancreatic cancer (PC) is a dangerous digestive tract tumor that is becoming increasingly common and fatal. The most common form of PC is pancreatic ductal adenocarcinoma (PDAC). Bile acids (BAs) are closely linked to the growth and progression of PC. They can change [...] Read more.

Pancreatic cancer (PC) is a dangerous digestive tract tumor that is becoming increasingly common and fatal. The most common form of PC is pancreatic ductal adenocarcinoma (PDAC). Bile acids (BAs) are closely linked to the growth and progression of PC. They can change the intestinal flora, increasing intestinal permeability and allowing gut microbes to enter the bloodstream, leading to chronic inflammation. High dietary lipids can increase BA secretion into the duodenum and fecal BA levels. BAs can cause genetic mutations, mitochondrial dysfunction, abnormal activation of intracellular trypsin, cytoskeletal damage, activation of NF-κB, acute pancreatitis, cell injury, and cell necrosis. They can act on different types of pancreatic cells and receptors, altering Ca²⁺ and iron levels, and related signals. Elevated levels of Ca²⁺ and iron are associated with cell necrosis and ferroptosis. Bile reflux into the pancreatic ducts can speed up the kinetics of epithelial cells, promoting the development of pancreatic intraductal papillary carcinoma. BAs can cause the enormous secretion of Glucagon-like peptide-1 (GLP-1), leading to the proliferation of pancreatic β-cells. Using Glucagon-like peptide-1 receptor agonist (GLP-1RA) increases the risk of pancreatitis and PC. Therefore, our objective was to explore various studies and thoroughly examine the role of BAs in PC. Full article

(This article belongs to the Special Issue Metabolic Cancer Therapy: Targeting Tumor Metabolism for Innovative Adjuvant Treatment)

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20 pages, 1188 KiB

Open AccessReview

Effects of the Menstrual Cycle and Hormonal Contraceptive Use on Metabolic Outcomes, Strength Performance, and Recovery: A Narrative Review

by Hannah E. Cabre, Lacey M. Gould, Leanne M. Redman and Abbie E. Smith-Ryan

Metabolites 2024, 14(7), 347; https://doi.org/10.3390/metabo14070347 - 21 Jun 2024

Viewed by 297

Abstract

The effects of female sex hormones on optimal performance have been increasingly recognized as an important consideration in exercise and sport science research. This narrative review explores the findings of studies evaluating the effects of menstrual cycle phase in eumenorrheic women and the [...] Read more.

The effects of female sex hormones on optimal performance have been increasingly recognized as an important consideration in exercise and sport science research. This narrative review explores the findings of studies evaluating the effects of menstrual cycle phase in eumenorrheic women and the use of hormonal contraception (oral contraceptives and hormonal intrauterine devices) on metabolism, muscular strength, and recovery in active females. Ovarian hormones are known to influence metabolism because estrogen is a master regulator of bioenergetics. Importantly, the menstrual cycle may impact protein synthesis, impacting skeletal muscle quality and strength. Studies investigating muscular strength in eumenorrheic women report equivocal findings between the follicular phase and luteal phase with no differences compared to oral contraceptive users. Studies examining recovery measures (using biomarkers, blood lactate, and blood flow) do not report clear or consistent effects of the impact of the menstrual cycle or hormonal contraception use on recovery. Overall, the current literature may be limited by the evaluation of only one menstrual cycle and the use of group means for statistical significance. Hence, to optimize training and performance in females, regardless of hormonal contraception use, there is a need for future research to quantify the intra-individual impact of the menstrual cycle phases and hormonal contraceptive use in active females. Full article

(This article belongs to the Special Issue Sports: Nutrition and Metabolism in Relation to Athletes’ Health and Performance)

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Metabolites, Volume 14, Issue 7 (July 2024) – 22 articles

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