Elizabeth A. Jennings, Megan M. Macdonald, Irina Romenskaia, Hao Yang, Grant A. Mitchell, Robert O. Ryan
The leucine catabolism pathway intermediate, trans-3-methylglutaconyl (3MGC) CoA, is considered to be the precursor of 3MGC acid, a urinary organic acid associated with specific inborn errors of metabolism (IEM). trans-3MGC CoA is an unstable molecule that can undergo a sequence of non-enzymatic chemical reactions that lead to either 3MGC acid or protein 3MGCylation. Herein, the susceptibility of trans-3MGC CoA to protein 3MGCylation was investigated. trans-3MGC CoA was generated through the activity of recombinant 3-methylcrotonyl CoA carboxylase (3MCCCase). Following enzyme incubations, reaction mixtures were spin-filtered to remove 3MCCCase. The recovered filtrates, containing trans-3MGC CoA, were then incubated in the presence of bovine serum albumin (BSA). Following this, sample aliquots were subjected to α-3MGC IgG immunoblot analysis to probe for 3MGCylated BSA. Experiments revealed a positive correlation between trans-3MGC CoA incubation temperature and 3MGCylated BSA immunoblot signal intensity. A similar correlation was observed between incubation time and 3MGCylated BSA immunoblot signal intensity. When trans-3MGC CoA hydratase (AUH) was included in incubations containing trans-3MGC CoA and BSA, 3MGCylated BSA immunoblot signal intensity decreased. Evidence that protein 3MGCylation occurs in vivo was obtained in studies with liver-specific 3-hydroxy-3-methylglutaryl (HMG) CoA lyase knockout mice. Therefore, trans-3MGC CoA is a reactive, potentially toxic metabolite, and under normal physiological conditions, lowering trans-3MGC CoA levels via AUH-mediated hydration to HMG CoA protects against aberrant non-enzymatic chemical reactions that lead to protein 3MGCylation and 3MGC acid production.
反式-3MGC CoA 是一种不稳定的分子，可通过一系列非酶化学反应生成 3MGC 酸或 3MGC 蛋白质。反式-3MGC CoA 是通过重组 3-甲基巴豆酰 CoA 羧化酶（3MCCCase）的活性生成的。酶培养后，对反应混合物进行旋流过滤以除去 3MCCCase。然后将含有反式-3MGC CoA 的回收滤液在牛血清白蛋白（BSA）存在下进行孵育。之后，对等分的样品进行α-3MGC IgG 免疫印迹分析，以检测 3MGCylated BSA。实验表明，反式-3MGC CoA 培养温度与 3MGCylated BSA 免疫印迹信号强度之间存在正相关。孵育时间与 3MGCylated BSA 免疫印迹信号强度之间也存在类似的相关性。在含有反式-3MGC CoA 和 BSA 的培养液中加入反式-3MGC CoA 水合酶（AUH）时，3MGCylated BSA 免疫印迹信号强度降低。在对肝脏特异性 3-hydroxy-3-methylglutaryl (HMG) CoA lyase 基因敲除小鼠的研究中，获得了蛋白质 3MGCylation 在体内发生的证据。因此，反式-3MGC CoA 是一种反应性、潜在毒性的代谢产物，在正常生理条件下，通过 AUH 介导的水合 HMG CoA 来降低反式-3MGC CoA 的水平，可以防止导致蛋白质 3MGCylation 和 3MGC 酸生成的非酶化学反应异常。
{"title":"Factors Affecting Non-Enzymatic Protein Acylation by trans-3-Methylglutaconyl Coenzyme A","authors":"Elizabeth A. Jennings, Megan M. Macdonald, Irina Romenskaia, Hao Yang, Grant A. Mitchell, Robert O. Ryan","doi":"10.3390/metabo14080421","DOIUrl":"https://doi.org/10.3390/metabo14080421","url":null,"abstract":"The leucine catabolism pathway intermediate, trans-3-methylglutaconyl (3MGC) CoA, is considered to be the precursor of 3MGC acid, a urinary organic acid associated with specific inborn errors of metabolism (IEM). trans-3MGC CoA is an unstable molecule that can undergo a sequence of non-enzymatic chemical reactions that lead to either 3MGC acid or protein 3MGCylation. Herein, the susceptibility of trans-3MGC CoA to protein 3MGCylation was investigated. trans-3MGC CoA was generated through the activity of recombinant 3-methylcrotonyl CoA carboxylase (3MCCCase). Following enzyme incubations, reaction mixtures were spin-filtered to remove 3MCCCase. The recovered filtrates, containing trans-3MGC CoA, were then incubated in the presence of bovine serum albumin (BSA). Following this, sample aliquots were subjected to α-3MGC IgG immunoblot analysis to probe for 3MGCylated BSA. Experiments revealed a positive correlation between trans-3MGC CoA incubation temperature and 3MGCylated BSA immunoblot signal intensity. A similar correlation was observed between incubation time and 3MGCylated BSA immunoblot signal intensity. When trans-3MGC CoA hydratase (AUH) was included in incubations containing trans-3MGC CoA and BSA, 3MGCylated BSA immunoblot signal intensity decreased. Evidence that protein 3MGCylation occurs in vivo was obtained in studies with liver-specific 3-hydroxy-3-methylglutaryl (HMG) CoA lyase knockout mice. Therefore, trans-3MGC CoA is a reactive, potentially toxic metabolite, and under normal physiological conditions, lowering trans-3MGC CoA levels via AUH-mediated hydration to HMG CoA protects against aberrant non-enzymatic chemical reactions that lead to protein 3MGCylation and 3MGC acid production.","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141867818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hanna M. Hennesy, Morgan E. Gravely, Daniela A. Alambarrio, Savannah R. Brannen, Jonathan J. McDonald, Sarah A. Devane, Kari K. Turner, Alexander M. Stelzleni, Travis G. O’Quinn, John M. Gonzalez
The objective of this study was to determine the daily dietary nicotinamide riboside (NR) dose required to maximize the delay of subjective muscle fatigue onset. Barrows (N = 100) were assigned to one of five treatments: a conventional swine finishing diet containing 0 (CON), 15 (15NR), 30 (30NR), 45 (45NR) mg·kg body weight−1·d−1 NR, or CON supplemented with 45 mg·kg body weight−1·d−1 NR by drench or cookie dough (DRE). All treatments were administered for the final 11 days of feeding. On supplementation d 10, barrows individually experienced a performance test at 1.09 m/s until they were subjectively exhausted. Wireless electromyography (EMG) sensors were affixed to the biceps femoris (BF), tensor fascia latae (TFL), and semitendinosus (ST) to measure real-time muscle activity. There were no treatment effects for barrow speed (p = 0.57), a tendency for a treatment effect (p = 0.07) for distance, and a treatment effect (p = 0.04) on time to exhaustion. Barrows of the 15NR and DRE treatments had greater (p = 0.05) distances to exhaustion than CON barrows but did not differ from other NR barrows (p > 0.11). Barrows in the 45NR treatment did not differ (p = 0.11) in distance from 30NR barrows but tended to have a greater (p = 0.07) distance compared to CON barrows. All other treatment comparisons did not differ (p > 0.27). Barrows in the DRE treatment moved for longer (p < 0.01) than CON barrows, but all other treatments did not differ from each other (p > 0.15). There was no treatment × period interaction for all muscles’ root mean square (RMS) values (p > 0.16), but there were Period effects for all muscles (p < 0.01) and a Treatment effect (p = 0.04) in the TFL. For all muscles, period 4 had greater RMS values than all other periods (p < 0.01), who did not differ from each other (p > 0.29). In the TFL, CON barrows had greater RMS values during the performance test compared to all NR treatments (p < 0.02), who did not differ from each other (p > 0.18). Overall, NR demonstrates potential in being a useful tool in fatigue prevention, but efficient administration of the compound needs further investigation.
{"title":"Ability of Nicotinamide Riboside to Prevent Muscle Fatigue of Barrows Subjected to a Performance Test","authors":"Hanna M. Hennesy, Morgan E. Gravely, Daniela A. Alambarrio, Savannah R. Brannen, Jonathan J. McDonald, Sarah A. Devane, Kari K. Turner, Alexander M. Stelzleni, Travis G. O’Quinn, John M. Gonzalez","doi":"10.3390/metabo14080424","DOIUrl":"https://doi.org/10.3390/metabo14080424","url":null,"abstract":"The objective of this study was to determine the daily dietary nicotinamide riboside (NR) dose required to maximize the delay of subjective muscle fatigue onset. Barrows (N = 100) were assigned to one of five treatments: a conventional swine finishing diet containing 0 (CON), 15 (15NR), 30 (30NR), 45 (45NR) mg·kg body weight−1·d−1 NR, or CON supplemented with 45 mg·kg body weight−1·d−1 NR by drench or cookie dough (DRE). All treatments were administered for the final 11 days of feeding. On supplementation d 10, barrows individually experienced a performance test at 1.09 m/s until they were subjectively exhausted. Wireless electromyography (EMG) sensors were affixed to the biceps femoris (BF), tensor fascia latae (TFL), and semitendinosus (ST) to measure real-time muscle activity. There were no treatment effects for barrow speed (p = 0.57), a tendency for a treatment effect (p = 0.07) for distance, and a treatment effect (p = 0.04) on time to exhaustion. Barrows of the 15NR and DRE treatments had greater (p = 0.05) distances to exhaustion than CON barrows but did not differ from other NR barrows (p > 0.11). Barrows in the 45NR treatment did not differ (p = 0.11) in distance from 30NR barrows but tended to have a greater (p = 0.07) distance compared to CON barrows. All other treatment comparisons did not differ (p > 0.27). Barrows in the DRE treatment moved for longer (p < 0.01) than CON barrows, but all other treatments did not differ from each other (p > 0.15). There was no treatment × period interaction for all muscles’ root mean square (RMS) values (p > 0.16), but there were Period effects for all muscles (p < 0.01) and a Treatment effect (p = 0.04) in the TFL. For all muscles, period 4 had greater RMS values than all other periods (p < 0.01), who did not differ from each other (p > 0.29). In the TFL, CON barrows had greater RMS values during the performance test compared to all NR treatments (p < 0.02), who did not differ from each other (p > 0.18). Overall, NR demonstrates potential in being a useful tool in fatigue prevention, but efficient administration of the compound needs further investigation.","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141867772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In the current study, two commercial industrial hemp (IH) fiber varieties (V1: CFX-2 and V2: Henola) were assessed for their ability to regulate salt-induced oxidative stress metabolism. For 30 days, plants were cultivated in greenhouse environments with five different salinity treatments (0, 50, 80, 100, 150, and 200 mM NaCl). Hydrogen peroxide (H2O2), malondialdehyde (MDA), and lipoxygenase (LOX) and antioxidant enzymes (superoxide dismutase (SOD), catalase, guaiacol peroxidase (GPOD), ascorbate peroxidase (APX), glutathione reductase (GR), and glutathione-S-transferase (GST)) were assessed in fully expanded leaves. At 200 and 100 mM NaCl concentrations, respectively, 30 days after saline treatment, plants in V1 and V2 did not survive. At 80 mM NaCl, the leaves of V2 showed higher concentrations of H2O2, MDA, and LOX than those of V1. Higher SOD, CAT, GPOD, APX, GR, and GST activity in the leaves of V1 up to 100 mM NaCl resulted in lower levels of H2O2 and MDA. At 80 mM NaCl, V2 demonstrated the total failure of the antioxidant defense mechanism. These results reveal that V1 demonstrated stronger salt tolerance than V2, in part due to better antioxidant metabolism.
本研究评估了两个商业工业大麻（IH）纤维品种（V1：CFX-2 和 V2：Henola）调节盐诱导的氧化应激代谢的能力。在温室环境中培养植物 30 天，采用五种不同的盐度处理（0、50、80、100、150 和 200 mM NaCl）。评估了完全展开叶片中的过氧化氢（H2O2）、丙二醛（MDA）、脂氧合酶（LOX）和抗氧化酶（超氧化物歧化酶（SOD）、过氧化氢酶、愈创木酚过氧化物酶（GPOD）、抗坏血酸过氧化物酶（APX）、谷胱甘肽还原酶（GR）和谷胱甘肽-S-转移酶（GST））。盐水处理 30 天后，在 NaCl 浓度分别为 200 mM 和 100 mM 时，V1 和 V2 的植株无法存活。在 80 mM NaCl 浓度下，V2 的叶片比 V1 的叶片显示出更高的 H2O2、MDA 和 LOX 浓度。在 100 mM NaCl 以下，V1 叶子中的 SOD、CAT、GPOD、APX、GR 和 GST 活性较高，导致 H2O2 和 MDA 水平较低。在 80 mM NaCl 下，V2 的抗氧化防御机制完全失效。这些结果表明，V1 比 V2 表现出更强的耐盐性，部分原因是更好的抗氧化新陈代谢。
{"title":"Differential Oxidative Stress Management in Industrial Hemp (IH: Cannabis sativa L.) for Fiber under Saline Regimes","authors":"Naveen Dixit","doi":"10.3390/metabo14080420","DOIUrl":"https://doi.org/10.3390/metabo14080420","url":null,"abstract":"In the current study, two commercial industrial hemp (IH) fiber varieties (V1: CFX-2 and V2: Henola) were assessed for their ability to regulate salt-induced oxidative stress metabolism. For 30 days, plants were cultivated in greenhouse environments with five different salinity treatments (0, 50, 80, 100, 150, and 200 mM NaCl). Hydrogen peroxide (H2O2), malondialdehyde (MDA), and lipoxygenase (LOX) and antioxidant enzymes (superoxide dismutase (SOD), catalase, guaiacol peroxidase (GPOD), ascorbate peroxidase (APX), glutathione reductase (GR), and glutathione-S-transferase (GST)) were assessed in fully expanded leaves. At 200 and 100 mM NaCl concentrations, respectively, 30 days after saline treatment, plants in V1 and V2 did not survive. At 80 mM NaCl, the leaves of V2 showed higher concentrations of H2O2, MDA, and LOX than those of V1. Higher SOD, CAT, GPOD, APX, GR, and GST activity in the leaves of V1 up to 100 mM NaCl resulted in lower levels of H2O2 and MDA. At 80 mM NaCl, V2 demonstrated the total failure of the antioxidant defense mechanism. These results reveal that V1 demonstrated stronger salt tolerance than V2, in part due to better antioxidant metabolism.","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141867767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stephanann M. Costello, Anastasia Schultz, Donald Smith, Danielle Horan, Martha Chaverra, Brian Tripet, Lynn George, Brian Bothner, Frances Lefcort, Valérie Copié
Neurodegenerative retinal diseases such as glaucoma, diabetic retinopathy, Leber’s hereditary optic neuropathy (LHON), and dominant optic atrophy (DOA) are marked by progressive death of retinal ganglion cells (RGC). This decline is promoted by structural and functional mitochondrial deficits, including electron transport chain (ETC) impairments, increased oxidative stress, and reduced energy (ATP) production. These cellular mechanisms associated with progressive optic nerve atrophy have been similarly observed in familial dysautonomia (FD) patients, who experience gradual loss of visual acuity due to the degeneration of RGCs, which is thought to be caused by a breakdown of mitochondrial structures, and a disruption in ETC function. Retinal metabolism plays a crucial role in meeting the elevated energetic demands of this tissue, and recent characterizations of FD patients’ serum and stool metabolomes have indicated alterations in central metabolic processes and potential systemic deficits of taurine, a small molecule essential for retina and overall eye health. The present study sought to elucidate metabolic alterations that contribute to the progressive degeneration of RGCs observed in FD. Additionally, a critical subpopulation of retinal interneurons, the dopaminergic amacrine cells, mediate the integration and modulation of visual information in a time-dependent manner to RGCs. As these cells have been associated with RGC loss in the neurodegenerative disease Parkinson’s, which shares hallmarks with FD, a targeted analysis of the dopaminergic amacrine cells and their product, dopamine, was also undertaken. One dimensional (1D) proton (1H) nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry, and retinal histology methods were employed to characterize retinae from the retina-specific Elp1 conditional knockout (CKO) FD mouse model (Pax6-Cre; Elp1LoxP/LoxP). Metabolite alterations correlated temporally with progressive RGC degeneration and were associated with reduced mitochondrial function, alterations in ATP production through the Cahill and mini-Krebs cycles, and phospholipid metabolism. Dopaminergic amacrine cell populations were reduced at timepoints P30–P90, and dopamine levels were 25–35% lower in CKO retinae compared to control retinae at P60. Overall, this study has expanded upon our current understanding of retina pathology in FD. This knowledge may apply to other retinal diseases that share hallmark features with FD and may help guide new avenues for novel non-invasive therapeutics to mitigate the progressive optic neuropathy in FD.
{"title":"Metabolic Deficits in the Retina of a Familial Dysautonomia Mouse Model","authors":"Stephanann M. Costello, Anastasia Schultz, Donald Smith, Danielle Horan, Martha Chaverra, Brian Tripet, Lynn George, Brian Bothner, Frances Lefcort, Valérie Copié","doi":"10.3390/metabo14080423","DOIUrl":"https://doi.org/10.3390/metabo14080423","url":null,"abstract":"Neurodegenerative retinal diseases such as glaucoma, diabetic retinopathy, Leber’s hereditary optic neuropathy (LHON), and dominant optic atrophy (DOA) are marked by progressive death of retinal ganglion cells (RGC). This decline is promoted by structural and functional mitochondrial deficits, including electron transport chain (ETC) impairments, increased oxidative stress, and reduced energy (ATP) production. These cellular mechanisms associated with progressive optic nerve atrophy have been similarly observed in familial dysautonomia (FD) patients, who experience gradual loss of visual acuity due to the degeneration of RGCs, which is thought to be caused by a breakdown of mitochondrial structures, and a disruption in ETC function. Retinal metabolism plays a crucial role in meeting the elevated energetic demands of this tissue, and recent characterizations of FD patients’ serum and stool metabolomes have indicated alterations in central metabolic processes and potential systemic deficits of taurine, a small molecule essential for retina and overall eye health. The present study sought to elucidate metabolic alterations that contribute to the progressive degeneration of RGCs observed in FD. Additionally, a critical subpopulation of retinal interneurons, the dopaminergic amacrine cells, mediate the integration and modulation of visual information in a time-dependent manner to RGCs. As these cells have been associated with RGC loss in the neurodegenerative disease Parkinson’s, which shares hallmarks with FD, a targeted analysis of the dopaminergic amacrine cells and their product, dopamine, was also undertaken. One dimensional (1D) proton (1H) nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry, and retinal histology methods were employed to characterize retinae from the retina-specific Elp1 conditional knockout (CKO) FD mouse model (Pax6-Cre; Elp1LoxP/LoxP). Metabolite alterations correlated temporally with progressive RGC degeneration and were associated with reduced mitochondrial function, alterations in ATP production through the Cahill and mini-Krebs cycles, and phospholipid metabolism. Dopaminergic amacrine cell populations were reduced at timepoints P30–P90, and dopamine levels were 25–35% lower in CKO retinae compared to control retinae at P60. Overall, this study has expanded upon our current understanding of retina pathology in FD. This knowledge may apply to other retinal diseases that share hallmark features with FD and may help guide new avenues for novel non-invasive therapeutics to mitigate the progressive optic neuropathy in FD.","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141867769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Giuliano Roberto da Silva, Gerusa Dias Siqueira Vilela Terra, David Michel de Oliveira, Eduardo Vignoto Fernandes, Emerson José Zechin, Arthur Rizzi Soares, Dalton Muller Pessoa-Filho, Cassiano Merussi Neiva
Metabolic syndrome (MS) increases the risk of cardiovascular disease and affects children and adolescents. Butyrylcholinesterase (BChE) is an enzyme associated with obesity. The aim of this study was to investigate the effects of different physical training protocols on MS indicators and their relationship with BChE activity. This randomized clinical trial included 80 adolescents randomly assigned to 4 groups (CG: Control Group; ATG: Aerobic Training Group; STG: Strength Training Group; and CTG: Concurrent Training Group). The EFC, lipid profile, glycemia, waist circumference, and blood pressure were analyzed. With the exception of the CG, all the groups underwent training protocols for 12 consecutive weeks, 4 times a week, as follows: (ATG: 75% of heart rate on an electric treadmill; STG: 85% of 1 maximum repetition; CTG: 20 min of aerobic training at the same intensity as the ATG, and 20 min of resistance training in the same way as the STG). The training reduced MS-related biomarkers, such as the lipid profile, glycemia, waist circumference, and blood pressure. STG reduced BChE activity. The training methods led to improvements in the majority of the MS indicators. In addition, aerobic training significantly reduced BChE activity after a 12-week training protocol. The results suggest that different types of exercise can benefit MS.
{"title":"Effects of Different Physical Training Protocols on Metabolic Syndrome Indicators and the Activity of Butyrylcholinesterase in Adolescents: A Randomized Clinical Trial","authors":"Giuliano Roberto da Silva, Gerusa Dias Siqueira Vilela Terra, David Michel de Oliveira, Eduardo Vignoto Fernandes, Emerson José Zechin, Arthur Rizzi Soares, Dalton Muller Pessoa-Filho, Cassiano Merussi Neiva","doi":"10.3390/metabo14080422","DOIUrl":"https://doi.org/10.3390/metabo14080422","url":null,"abstract":"Metabolic syndrome (MS) increases the risk of cardiovascular disease and affects children and adolescents. Butyrylcholinesterase (BChE) is an enzyme associated with obesity. The aim of this study was to investigate the effects of different physical training protocols on MS indicators and their relationship with BChE activity. This randomized clinical trial included 80 adolescents randomly assigned to 4 groups (CG: Control Group; ATG: Aerobic Training Group; STG: Strength Training Group; and CTG: Concurrent Training Group). The EFC, lipid profile, glycemia, waist circumference, and blood pressure were analyzed. With the exception of the CG, all the groups underwent training protocols for 12 consecutive weeks, 4 times a week, as follows: (ATG: 75% of heart rate on an electric treadmill; STG: 85% of 1 maximum repetition; CTG: 20 min of aerobic training at the same intensity as the ATG, and 20 min of resistance training in the same way as the STG). The training reduced MS-related biomarkers, such as the lipid profile, glycemia, waist circumference, and blood pressure. STG reduced BChE activity. The training methods led to improvements in the majority of the MS indicators. In addition, aerobic training significantly reduced BChE activity after a 12-week training protocol. The results suggest that different types of exercise can benefit MS.","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141867768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ulises Edgardo De-Leon-Covarrubias, Jose Juan Perez-Trujillo, Sheila Adela Villa-Cedillo, Alejandra Guadalupe Martinez-Perez, Carlos Roberto Montes-de-Oca-Saucedo, Maria de Jesus Loera-Arias, Aracely Garcia-Garcia, Odila Saucedo-Cardenas, Roberto Montes-de-Oca-Luna
Caloric restriction (CR) and its related alternatives have been shown to be the only interventions capable of extending lifespan and decreasing the risk of cancer, along with a reduction in burden in pre-clinical trials. Nevertheless, the results from clinical trials have not been as conclusive as the pre-clinical results. Recognizing the challenges associated with long-term fasting, the application of caloric restriction mimetics (CRMs), pharmacological agents that mimic the molecular effects of CR, to harness the potential benefits while overcoming the practical limitations of fasting has resulted in an interesting alternative. This review synthesizes the findings of diverse clinical trials evaluating the safety and efficacy of CR and CRMs. In dietary interventions, a fast-mimicking diet was the most tolerated to reduce tumoral growth markers and chemotherapy side effects. CRMs were well tolerated, and metformin and aspirin showed the most promising effect in reducing cancer risk in a selected group of patients. The application of CR and/or CRMs shows promising effects in anti-cancer therapy; however, there is a need for more evidence to safely include these interventions in standard-of-care therapies.
{"title":"Unlocking the Potential: Caloric Restriction, Caloric Restriction Mimetics, and Their Impact on Cancer Prevention and Treatment","authors":"Ulises Edgardo De-Leon-Covarrubias, Jose Juan Perez-Trujillo, Sheila Adela Villa-Cedillo, Alejandra Guadalupe Martinez-Perez, Carlos Roberto Montes-de-Oca-Saucedo, Maria de Jesus Loera-Arias, Aracely Garcia-Garcia, Odila Saucedo-Cardenas, Roberto Montes-de-Oca-Luna","doi":"10.3390/metabo14080418","DOIUrl":"https://doi.org/10.3390/metabo14080418","url":null,"abstract":"Caloric restriction (CR) and its related alternatives have been shown to be the only interventions capable of extending lifespan and decreasing the risk of cancer, along with a reduction in burden in pre-clinical trials. Nevertheless, the results from clinical trials have not been as conclusive as the pre-clinical results. Recognizing the challenges associated with long-term fasting, the application of caloric restriction mimetics (CRMs), pharmacological agents that mimic the molecular effects of CR, to harness the potential benefits while overcoming the practical limitations of fasting has resulted in an interesting alternative. This review synthesizes the findings of diverse clinical trials evaluating the safety and efficacy of CR and CRMs. In dietary interventions, a fast-mimicking diet was the most tolerated to reduce tumoral growth markers and chemotherapy side effects. CRMs were well tolerated, and metformin and aspirin showed the most promising effect in reducing cancer risk in a selected group of patients. The application of CR and/or CRMs shows promising effects in anti-cancer therapy; however, there is a need for more evidence to safely include these interventions in standard-of-care therapies.","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141867770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nancy Shyrley García-Rojas, Carlos Daniel Sierra-Álvarez, Hilda E. Ramos-Aboites, Abigail Moreno-Pedraza, Robert Winkler
The presence and localization of plant metabolites are indicative of physiological processes, e.g., under biotic and abiotic stress conditions. Further, the chemical composition of plant parts is related to their quality as food or for medicinal applications. Mass spectrometry imaging (MSI) has become a popular analytical technique for exploring and visualizing the spatial distribution of plant molecules within a tissue. This review provides a summary of mass spectrometry methods used for mapping and identifying metabolites in plant tissues. We present the benefits and the disadvantages of both vacuum and ambient ionization methods, considering direct and indirect approaches. Finally, we discuss the current limitations in annotating and identifying molecules and perspectives for future investigations.
{"title":"Identification of Plant Compounds with Mass Spectrometry Imaging (MSI)","authors":"Nancy Shyrley García-Rojas, Carlos Daniel Sierra-Álvarez, Hilda E. Ramos-Aboites, Abigail Moreno-Pedraza, Robert Winkler","doi":"10.3390/metabo14080419","DOIUrl":"https://doi.org/10.3390/metabo14080419","url":null,"abstract":"The presence and localization of plant metabolites are indicative of physiological processes, e.g., under biotic and abiotic stress conditions. Further, the chemical composition of plant parts is related to their quality as food or for medicinal applications. Mass spectrometry imaging (MSI) has become a popular analytical technique for exploring and visualizing the spatial distribution of plant molecules within a tissue. This review provides a summary of mass spectrometry methods used for mapping and identifying metabolites in plant tissues. We present the benefits and the disadvantages of both vacuum and ambient ionization methods, considering direct and indirect approaches. Finally, we discuss the current limitations in annotating and identifying molecules and perspectives for future investigations.","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141867783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wenya Li, Hua Chen, Jianhu Cheng, Min Zhang, Yan Xu, Lihua Wang, Xueqiao Zhao, Jinyao Zhang, Bangdi Liu, Jing Sun
This study aimed to explore the effects of Bacillus amyloliquefaciens GSBa-1 treatment on anthracnose disease resistance and the metabolism of reactive oxygen species (ROS) and phenylpropanoids in mangoes during storage. Mangoes were soaked in a solution containing 1 × 108 CFU/mL of B. amyloliquefaciens GSBa-1. The anthracnose disease incidence, disease index, respiration intensity, ethylene release, reactive oxygen species content, and the activities of related metabolic enzymes, phenylpropanoid-related metabolic enzymes, and phenolic acids in the skin and pulp of mangoes were investigated under normal temperature storage conditions. The results showed that the antagonistic bacterial treatment (ABT) did not significantly inhibit the growth of Colletotrichum gloeosporioides in vitro. However, it significantly reduced the incidence of mango anthracnose disease when applied to the mango peel. ABT enhanced the latent resistance of mango to anthracnose disease by activating its reactive oxygen and phenylpropanoid metabolism. It maintained higher levels of ROS production and elimination in the peel. Moreover, it rapidly activated manganese superoxide dismutase, induced the accumulation of H2O2, and enhanced the activity of manganese superoxide dismutase, catalase, ascorbate peroxidase, and peroxidase in the mango peel. Furthermore, ABT activated phenylalanine ammonia-lyase, cinnamic acid-4-hydroxylase, 4-coumaroyl-CoA ligase, and cinnamyl alcohol dehydrogenase in the mango peel and pulp, promoting the accumulation of antifungal phenolic acids such as gallic acid, catechins, and ellagic acid. Bacillus amyloliquefaciens GSBa-1 may be a potent inhibitor of mango anthracnose, primarily enhancing the resistance of mangoes to anthracnose by synergistically activating ROS in the peel and phenylpropanoid metabolism in the pulp, thereby reducing the incidence of anthracnose effectively.
{"title":"Improving Resistance of Mango to Colletotrichum gloeosporioides by Activating Reactive Oxygen Species and Phenylpropane Metabolism of Bacillus amyloliquefaciens GSBa-1","authors":"Wenya Li, Hua Chen, Jianhu Cheng, Min Zhang, Yan Xu, Lihua Wang, Xueqiao Zhao, Jinyao Zhang, Bangdi Liu, Jing Sun","doi":"10.3390/metabo14080417","DOIUrl":"https://doi.org/10.3390/metabo14080417","url":null,"abstract":"This study aimed to explore the effects of Bacillus amyloliquefaciens GSBa-1 treatment on anthracnose disease resistance and the metabolism of reactive oxygen species (ROS) and phenylpropanoids in mangoes during storage. Mangoes were soaked in a solution containing 1 × 108 CFU/mL of B. amyloliquefaciens GSBa-1. The anthracnose disease incidence, disease index, respiration intensity, ethylene release, reactive oxygen species content, and the activities of related metabolic enzymes, phenylpropanoid-related metabolic enzymes, and phenolic acids in the skin and pulp of mangoes were investigated under normal temperature storage conditions. The results showed that the antagonistic bacterial treatment (ABT) did not significantly inhibit the growth of Colletotrichum gloeosporioides in vitro. However, it significantly reduced the incidence of mango anthracnose disease when applied to the mango peel. ABT enhanced the latent resistance of mango to anthracnose disease by activating its reactive oxygen and phenylpropanoid metabolism. It maintained higher levels of ROS production and elimination in the peel. Moreover, it rapidly activated manganese superoxide dismutase, induced the accumulation of H2O2, and enhanced the activity of manganese superoxide dismutase, catalase, ascorbate peroxidase, and peroxidase in the mango peel. Furthermore, ABT activated phenylalanine ammonia-lyase, cinnamic acid-4-hydroxylase, 4-coumaroyl-CoA ligase, and cinnamyl alcohol dehydrogenase in the mango peel and pulp, promoting the accumulation of antifungal phenolic acids such as gallic acid, catechins, and ellagic acid. Bacillus amyloliquefaciens GSBa-1 may be a potent inhibitor of mango anthracnose, primarily enhancing the resistance of mangoes to anthracnose by synergistically activating ROS in the peel and phenylpropanoid metabolism in the pulp, thereby reducing the incidence of anthracnose effectively.","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141867671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
João Guilherme de Moraes Pontes, Milka Jadranin, Márcia Regina Assalin, Melissa Quintero Escobar, Danijela Stanisic, Tássia Brena Barroso Carneiro Costa, André van Helvoort Lengert, Érica Boldrini, Sandra Regina Morini da Silva, Daniel Onofre Vidal, Leticia Huan Bacellar Liu, Mariana Maschietto, Ljubica Tasic
Cancer is a complex disease that can also affect the younger population; however, it is responsible for a relatively high mortality rate of children and youth, especially in low- and middle-income countries (LMICs). Besides that, lipidomic studies in this age range are scarce. Therefore, we analyzed blood serum samples from young patients (12 to 35 years) with bone sarcoma (osteosarcoma) and compared their lipidomics to the ones from the control group of samples, named healthy control (HC group), using NMR and LC-MS techniques. Furthermore, differences in the lipidomic profiles between OS patients with and without metastasis indicate higher glycerophosphocholine (GPC) and glycerophospholipid (GPL) levels in osteosarcoma and increased cholesterol, choline, polyunsaturated fatty acids (PUFAs), and glycerols during the metastasis. These differences, detected in the peripheral blood, could be used as biomarkers for liquid biopsy.
{"title":"Lipidomics by Nuclear Magnetic Resonance Spectroscopy and Liquid Chromatography–High-Resolution Mass Spectrometry in Osteosarcoma: A Pilot Study","authors":"João Guilherme de Moraes Pontes, Milka Jadranin, Márcia Regina Assalin, Melissa Quintero Escobar, Danijela Stanisic, Tássia Brena Barroso Carneiro Costa, André van Helvoort Lengert, Érica Boldrini, Sandra Regina Morini da Silva, Daniel Onofre Vidal, Leticia Huan Bacellar Liu, Mariana Maschietto, Ljubica Tasic","doi":"10.3390/metabo14080416","DOIUrl":"https://doi.org/10.3390/metabo14080416","url":null,"abstract":"Cancer is a complex disease that can also affect the younger population; however, it is responsible for a relatively high mortality rate of children and youth, especially in low- and middle-income countries (LMICs). Besides that, lipidomic studies in this age range are scarce. Therefore, we analyzed blood serum samples from young patients (12 to 35 years) with bone sarcoma (osteosarcoma) and compared their lipidomics to the ones from the control group of samples, named healthy control (HC group), using NMR and LC-MS techniques. Furthermore, differences in the lipidomic profiles between OS patients with and without metastasis indicate higher glycerophosphocholine (GPC) and glycerophospholipid (GPL) levels in osteosarcoma and increased cholesterol, choline, polyunsaturated fatty acids (PUFAs), and glycerols during the metastasis. These differences, detected in the peripheral blood, could be used as biomarkers for liquid biopsy.","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141867667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ayenachew Bezawork-Geleta, Diane Moujalled, David P. De Souza, Vinod K. Narayana, James Dimou, Rodney Luwor, Matthew J. Watt
Glioblastoma (IDH-wildtype) represents a formidable challenge in oncology, lacking effective chemotherapeutic or biological interventions. The metabolic reprogramming of cancer cells is a hallmark of tumor progression and drug resistance, yet the role of metabolic reprogramming in glioblastoma during drug treatment remains poorly understood. The dihydroorotate dehydrogenase (DHODH) inhibitor BAY2402234 is a blood–brain barrier penetrant drug showing efficiency in in vivo models of many brain cancers. In this study, we investigated the effect of BAY2402234 in regulating the metabolic phenotype of EGFRWT and EGFRvIII patient-derived glioblastoma cell lines. Our findings reveal the selective cytotoxicity of BAY2402234 toward EGFRWT glioblastoma subtypes with minimal effect on EGFRvIII patient cells. At sublethal doses, BAY2402234 induces triglyceride synthesis at the expense of membrane lipid synthesis and fatty acid oxidation in EGFRWT glioblastoma cells, while these effects are not observed in EGFRvIII glioblastoma cells. Furthermore, BAY2402234 reduced the abundance of signaling lipid species in EGFRWT glioblastoma. This study elucidates genetic mutation-specific metabolic plasticity and efficacy in glioblastoma cells in response to drug treatment, offering insights into therapeutic avenues for precision medicine approaches.
{"title":"Metabolic Plasticity of Glioblastoma Cells in Response to DHODH Inhibitor BAY2402234 Treatment","authors":"Ayenachew Bezawork-Geleta, Diane Moujalled, David P. De Souza, Vinod K. Narayana, James Dimou, Rodney Luwor, Matthew J. Watt","doi":"10.3390/metabo14080413","DOIUrl":"https://doi.org/10.3390/metabo14080413","url":null,"abstract":"Glioblastoma (IDH-wildtype) represents a formidable challenge in oncology, lacking effective chemotherapeutic or biological interventions. The metabolic reprogramming of cancer cells is a hallmark of tumor progression and drug resistance, yet the role of metabolic reprogramming in glioblastoma during drug treatment remains poorly understood. The dihydroorotate dehydrogenase (DHODH) inhibitor BAY2402234 is a blood–brain barrier penetrant drug showing efficiency in in vivo models of many brain cancers. In this study, we investigated the effect of BAY2402234 in regulating the metabolic phenotype of EGFRWT and EGFRvIII patient-derived glioblastoma cell lines. Our findings reveal the selective cytotoxicity of BAY2402234 toward EGFRWT glioblastoma subtypes with minimal effect on EGFRvIII patient cells. At sublethal doses, BAY2402234 induces triglyceride synthesis at the expense of membrane lipid synthesis and fatty acid oxidation in EGFRWT glioblastoma cells, while these effects are not observed in EGFRvIII glioblastoma cells. Furthermore, BAY2402234 reduced the abundance of signaling lipid species in EGFRWT glioblastoma. This study elucidates genetic mutation-specific metabolic plasticity and efficacy in glioblastoma cells in response to drug treatment, offering insights into therapeutic avenues for precision medicine approaches.","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141778368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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