Metabolites

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18 pages, 2968 KiB

Open AccessArticle

Novel Expression of GLUT3, GLUT6 and GLUT10 in Equine Gluteal Muscle Following Glycogen-Depleting Exercise: Impact of Dietary Starch and Fat

by Stephanie J. Valberg, Deborah Velez-Irizarry, Zoe J. Williams, Joe D. Pagan, Vanesa Mesquita, Brian Waldridge and Hailey Maresca-Fichter

Metabolites 2023, 13(6), 718; https://doi.org/10.3390/metabo13060718 - 1 Jun 2023

Cited by 2 | Viewed by 1790

Abstract

Horses have a slow rate of muscle glycogen repletion relative to other species for unknown reasons. Our aim was to determine the expression of glucose transporters (GLUT) and genes impacting GLUT4 expression and translocation in the gluteal muscle. Five fit Thoroughbred [...] Read more.

Horses have a slow rate of muscle glycogen repletion relative to other species for unknown reasons. Our aim was to determine the expression of glucose transporters (GLUT) and genes impacting GLUT4 expression and translocation in the gluteal muscle. Five fit Thoroughbred horses performed glycogen-depleting exercises on high-starch (HS, 2869 g starch/day) and low-starch, high-fat diets (LS-HF, 358 g starch/d) with gluteal muscle biopsies obtained before and after depletion and during repletion. Muscle glycogen declined by ≈30% on both diets with little increase during repletion on LS-HF. Transcriptomic analysis identified differential expression (DE) of only 2/12 genes impacting GLUT4 translocation (two subunits of AMP protein kinase) and only at depletion on LS-HF. Only 1/13 genes encoding proteins that promote GLUT4 transcription had increased DE (PPARGC1A at depletion LS-HF). GLUT4 comprised ≈30% of total GLUT mRNA expression at rest. Remarkably, by 72 h of repletion expression of GLUT3, GLUT6 and GLUT10 increased to ≈25% of total GLUT mRNA. Expression of GLUT6 and GLUT10 lagged from 24 h of repletion on HS to 72 h on LS-HF. Lacking an increase in GLUT4 gene expression in response to glycogen-depleting exercise, equine muscle increases GLUT3, GLUT6 and GLUT10 expression potentially to enhance glucose transport, resembling responses observed in resistance trained GLUT4-null mice. Full article

(This article belongs to the Special Issue Animal and Cellular Models in Metabolomics Research Volume 2)

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17 pages, 30225 KiB

Open AccessArticle

Effects of Saline-Alkaline Stress on Metabolome, Biochemical Parameters, and Histopathology in the Kidney of Crucian Carp (Carassius auratus)

by Lu Ding, Yingjie Liu, Xiaofeng Wei, Chuanye Geng, Wenzhi Liu, Lin Han, Fangying Yuan, Peng Wang and Yanchun Sun

Metabolites 2023, 13(2), 159; https://doi.org/10.3390/metabo13020159 - 20 Jan 2023

Cited by 7 | Viewed by 2635

Abstract

The salinization of the water environment caused by human activities and global warming has increased which has brought great survival challenges to aquatic animals. Crucian carp (Carassius auratus) is an essential freshwater economic fish with superior adaptability to saline-alkali water. However, [...] Read more.

The salinization of the water environment caused by human activities and global warming has increased which has brought great survival challenges to aquatic animals. Crucian carp (Carassius auratus) is an essential freshwater economic fish with superior adaptability to saline-alkali water. However, the physiological regulation mechanism of crucian carp adapting to saline-alkali stress remains still unclear. In this study, crucian carp were exposed to freshwater or 20, 40, and 60 mmol/L NaHCO₃ water environments for 30 days, the effects of saline-alkali stress on the kidney were evaluated by histopathology, biochemical assays and metabolomics analysis from renal function, antioxidant capacity and metabolites level. Our results showed different degrees of kidney damage at different exposure concentrations, which were characterized by glomerular atrophy and swelling, renal tubular degranulation, obstruction and degeneration, renal interstitial edema, renal cell proliferation and necrosis. Saline-alkali stress could change the levels of several physiological parameters with renal function and antioxidant capacity, including creatinine (CREA), urea nitrogen (BUN), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA). In addition, metabolomics analysis showed that differential metabolites (DMs) were involved in various metabolic pathways, including phenylalanine, tyrosine, and tryptophan biosynthesis, aminoacyl-tRNA biosynthesis, purine metabolism, glycerophospholipid metabolism, sphingolipid metabolism, glycolysis/gluconeogenesis and the TCA cycle. In general, our study revealed that saline-alkaline stress could cause significant changes in renal function and metabolic profiles, and induce severe damage in the crucian carp kidney through destroying the anti-oxidant system and energy homeostasis, inhibiting protein and amino acid catabolism, as well as disordering purine metabolism and lipid metabolism. This study could contribute to a deeper understanding the adverse effects of saline-alkali stress on crucian carp kidney and the regulatory mechanism in the crucian carp of saline-alkali adaptation at the metabolic level. Full article

(This article belongs to the Special Issue Animal and Cellular Models in Metabolomics Research Volume 2)

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15 pages, 3006 KiB

Open AccessArticle

In Vitro Animal Model for Estimating the Time since Death with Attention to Early Postmortem Stage

by Michal Szeremeta, Paulina Samczuk, Karolina Pietrowska, Tomasz Kowalczyk, Katarzyna Przeslaw, Julia Sieminska, Adam Kretowski, Anna Niemcunowicz-Janica and Michal Ciborowski

Metabolites 2023, 13(1), 26; https://doi.org/10.3390/metabo13010026 - 23 Dec 2022

Cited by 4 | Viewed by 2102

Abstract

Estimating the postmortem interval (PMI) has remained the subject of investigations in forensic medicine for many years. Every kind of death results in changes in metabolites in body tissues and fluids due to lack of oxygen, altered circulation, enzymatic reactions, cellular degradation, and [...] Read more.

Estimating the postmortem interval (PMI) has remained the subject of investigations in forensic medicine for many years. Every kind of death results in changes in metabolites in body tissues and fluids due to lack of oxygen, altered circulation, enzymatic reactions, cellular degradation, and cessation of anabolic production of metabolites. Metabolic changes may provide markers determining the time since death, which is challenging in current analytical and observation-based methods. The study includes metabolomics analysis of blood with the use of an animal model to determine the biochemical changes following death. LC-MS is used to fingerprint postmortem porcine blood. Metabolites, significantly changing in blood after death, are selected and identified using univariate statistics. Fifty-one significant metabolites are found to help estimate the time since death in the early postmortem stage. Hypoxanthine, lactic acid, histidine, and lysophosphatidic acids are found as the most promising markers in estimating an early postmortem stage. Selected lysophosphatidylcholines are also found as significantly increased in blood with postmortal time, but their practical utility as PMI indicators can be limited due to a relatively low increasing rate. The findings demonstrate the great potential of LC-MS-based metabolomics in determining the PMI due to sudden death and provide an experimental basis for applying this attitude in investigating various mechanisms of death. As we assume, our study is also one of the first in which the porcine animal model is used to establish PMI metabolomics biomarkers. Full article

(This article belongs to the Special Issue Animal and Cellular Models in Metabolomics Research Volume 2)

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16 pages, 4241 KiB

Open AccessArticle

Sinomenine Ameliorates Colitis-Associated Cancer by Modulating Lipid Metabolism via Enhancing CPT1A Expression

by Jing Zhang, Dan Huang, Yue Dai and Yu-Feng Xia

Metabolites 2022, 12(10), 946; https://doi.org/10.3390/metabo12100946 - 5 Oct 2022

Cited by 7 | Viewed by 2102

Abstract

Colitis-associated cancer (CAC), arising from long-lasting intestinal inflammation, is a common type of colorectal cancer. Sinomenine (SIN), the major active compound of Sinomenium acutum, displays excellent antitumor activity. In modern pharmacological research, SIN has been proved to arrest proliferation of human colon [...] Read more.

Colitis-associated cancer (CAC), arising from long-lasting intestinal inflammation, is a common type of colorectal cancer. Sinomenine (SIN), the major active compound of Sinomenium acutum, displays excellent antitumor activity. In modern pharmacological research, SIN has been proved to arrest proliferation of human colon cancer cells in vitro, but its functional role and specific mechanism in CAC were still elusive. This study explored the molecular mechanism of SIN on CAC. The results showed that orally administered SIN could decrease the occurrence and development of CAC. Metabolomics results revealed SIN could reprogram metabolism in CAC mice by reversing 34 endogenous metabolites. Importantly, the most prominent metabolic alteration was lipid metabolism. Mechanistically, SIN improved lipid metabolism by enhancing the expression of CPT1A in CAC mice. Moreover, the inhibitory effect of SIN on the proliferation of human colon cancer cells was blunted via CPT1A inhibitor. The results of this study added further evidence of the molecular mechanisms that allow SIN to exert anti-CAC effect by facilitating lipid metabolism and reaffirmed its potential and distinctive role as a chemopreventive agent in CAC. Full article

(This article belongs to the Special Issue Animal and Cellular Models in Metabolomics Research Volume 2)

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12 pages, 1886 KiB

Open AccessArticle

The Quantitative Profiling of Oxylipins from Arachidonic Acid by LC-MS/MS in Feces at Birth 3 Days and 21 Days of Piglets

by Ningning Huang, Xiangchen Liu, Xiaoqi Pei, Jian Peng and Hongkui Wei

Metabolites 2022, 12(8), 702; https://doi.org/10.3390/metabo12080702 - 28 Jul 2022

Cited by 2 | Viewed by 2099

Abstract

Oxylipins (also called eicosanoids) are enzymatically or nonenzymatically generated by oxidation of arachidonic acid (ARA) and are major mediators of ARA effects in the body. Previous studies demonstrated the importance of ARA in infant growth, brain development, immune response, and health. With the [...] Read more.

Oxylipins (also called eicosanoids) are enzymatically or nonenzymatically generated by oxidation of arachidonic acid (ARA) and are major mediators of ARA effects in the body. Previous studies demonstrated the importance of ARA in infant growth, brain development, immune response, and health. With the developments in lipidomic methodologies, it is important for exploring more ARA-deprived oxylipins to better understand the physiological functions of ARA. The concentrations of oxylipins in feces were determined from days 3 to 21 postnatally of suckling piglets in vivo. Feces were collected at two critical time points of the suckling piglets (3d and 21d after birth) and about 48 oxylipins were analyzed by using a target metabolomics approach based on Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS). Here, 21 oxylipins were derived from ARA, and 11 differential oxylipins (Log2|fold change| ≥ 1.0) at birth 3d and 21d were identified. Particularly, 12-HETE was more abundant in feces at birth 3 days rather than 21 days. Considering that 12-HETE was a racemic mixture of stereoisomers containing the S and R enantiomers, we further detected the concentrations of 12(S)-HETE and 12(R)-HETE between the two time points by chiral LC-MS/MS analysis. There was no significant difference in the concentrations of 12(S)-HETE and 12(R)-HETE. It was showed that ARA - derived oxylipins might be related to the physiological changes of piglets during growing. Our results provided new information for describing the physiological changes of the piglets over the suckling period. Full article

(This article belongs to the Special Issue Animal and Cellular Models in Metabolomics Research Volume 2)

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11 pages, 1515 KiB

Open AccessArticle

Comparative Metabolomics of Small Molecules Specifically Expressed in the Dorsal or Ventral Marginal Zones in Vertebrate Gastrula

by Yukako Suzuki, Ryosuke Hayasaka, Masako Hasebe, Satsuki Ikeda, Tomoyoshi Soga, Masaru Tomita, Akiyoshi Hirayama and Hiroki Kuroda

Metabolites 2022, 12(6), 566; https://doi.org/10.3390/metabo12060566 - 20 Jun 2022

Cited by 7 | Viewed by 2801

Abstract

Many previous studies have reported the various proteins specifically secreted as inducers in the dorsal or ventral regions in vertebrate gastrula. However, little is known about the effect on cell fate of small molecules below 1000 Da. We therefore tried to identify small [...] Read more.

Many previous studies have reported the various proteins specifically secreted as inducers in the dorsal or ventral regions in vertebrate gastrula. However, little is known about the effect on cell fate of small molecules below 1000 Da. We therefore tried to identify small molecules specifically expressed in the dorsal marginal zone (DMZ) or ventral marginal zone (VMZ) in vertebrate gastrula. Small intracellular and secreted molecules were detected using explants and supernatant samples. Hydrophilic metabolites were analyzed by capillary ion chromatography–mass spectrometry and liquid chromatography–mass spectrometry, and lipids were analyzed by supercritical fluid chromatography–tandem mass spectrometry. In total, 190 hydrophilic metabolites and 396 lipids were identified. The DMZ was found to have high amounts of glycolysis- and glutathione metabolism-related metabolites in explants, and the VMZ was richer in purine metabolism-related metabolites. We also discovered some hydrophilic metabolites and lipids differentially contained in the DMZ or VMZ. Our research would contribute to a deeper understanding of the cellular physiology that regulates early embryogenesis. Full article

(This article belongs to the Special Issue Animal and Cellular Models in Metabolomics Research Volume 2)

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7 pages, 208 KiB

Open AccessCommunication

Sanitary Conditions on the Farm Alters Fecal Metabolite Profile in Growing Pigs

by Soumya K. Kar, Marinus F. W. te Pas, Leo Kruijt, Jacques J. M. Vervoort, Alfons J. M. Jansman and Dirkjan Schokker

Metabolites 2022, 12(6), 538; https://doi.org/10.3390/metabo12060538 - 11 Jun 2022

Cited by 1 | Viewed by 2062

Abstract

The aim of this study was to use fecal metabolite profiling to evaluate the effects of contrasting sanitary conditions and the associated subclinical health status of pigs. We analyzed fecal metabolite profiles by nuclear magnetic resonance (¹H NMR) from pigs aged [...] Read more.

The aim of this study was to use fecal metabolite profiling to evaluate the effects of contrasting sanitary conditions and the associated subclinical health status of pigs. We analyzed fecal metabolite profiles by nuclear magnetic resonance (¹H NMR) from pigs aged 14 and 22 weeks. Pigs kept under low and high sanitary conditions differed in fecal metabolites related to the degradation of dietary starch, metabolism of the gut microbiome, and degradation of components of animal (host) origin. The metabolites that differed significantly (FDR < 0.1) were from metabolic processes involved in either maintaining nutrient digestive capacity, including purine metabolism, energy metabolism, bile acid breakdown and recycling, or immune system metabolism. The results show that the fecal metabolite profiles reflect the sanitary conditions under which the pigs are kept. The fecal metabolite profiles closely resembled the profiles of metabolites found in the colon of pigs. Fecal valerate and kynurenic acid could potentially be used as “non-invasive” biomarkers of immune or inflammatory status that could form the basis for monitoring subclinical health status in pigs. Full article

(This article belongs to the Special Issue Animal and Cellular Models in Metabolomics Research Volume 2)

12 pages, 1977 KiB

Open AccessArticle

High Resolution Magic Angle Spinning Proton NMR Study of Alzheimer’s Disease with Mouse Models

by Mark V. Füzesi, Isabella H. Muti, Yannick Berker, Wei Li, Joseph Sun, Piet Habbel, Johannes Nowak, Zhongcong Xie, Leo L. Cheng and Yiying Zhang

Metabolites 2022, 12(3), 253; https://doi.org/10.3390/metabo12030253 - 17 Mar 2022

Cited by 2 | Viewed by 3063

Abstract

Alzheimer’s disease (AD) is a crippling condition that affects millions of elderly adults each year, yet there remains a serious need for improved methods of diagnosis. Metabolomic analysis has been proposed as a potential methodology to better investigate and understand the progression of [...] Read more.

Alzheimer’s disease (AD) is a crippling condition that affects millions of elderly adults each year, yet there remains a serious need for improved methods of diagnosis. Metabolomic analysis has been proposed as a potential methodology to better investigate and understand the progression of this disease; however, studies of human brain tissue metabolomics are challenging, due to sample limitations and ethical considerations. Comprehensive comparisons of imaging measurements in animal models to identify similarities and differences between aging- and AD-associated metabolic changes should thus be tested and validated for future human non-invasive studies. In this paper, we present the results of our highresolution magic angle spinning (HRMAS) nuclear magnetic resonance (NMR) studies of AD and wild-type (WT) mouse models, based on animal age, brain regions, including cortex vs. hippocampus, and disease status. Our findings suggest the ability of HRMAS NMR to differentiate between AD and WT mice using brain metabolomics, which potentially can be implemented in in vivo evaluations. Full article

(This article belongs to the Special Issue Animal and Cellular Models in Metabolomics Research Volume 2)

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