1,299 results on '"intermediary metabolism"'
Search Results
2. Valine administration in the hypothalamus alters the brain and plasma metabolome in rainbow trout.
- Author
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Comesaña, Sara, Antomagesh, Femilarani, Soengas, José L., Blanco, Ayelén M., and Vijayan, Mathilakath M.
- Subjects
- *
PROTEIN kinase B , *AMINO acid metabolism , *LIQUID chromatography-mass spectrometry , *RAINBOW trout , *MEDULLA oblongata , *HYPOTHALAMUS - Abstract
Central administration of valine has been shown to cause hyperphagia in fish. Although mechanistic target of rapamycin (mTOR) is involved in this response, the contributions to feed intake of central and peripheral metabolite changes due to excess valine are unknown. Here, we investigated whether intracerebroventricular injection of valine modulates central and peripheral metabolite profiles and may provide insights into feeding response in fish. Juvenile rainbow trout (Oncorhynchus mykiss) were administered an intracerebroventricular injection of valine (10 µg·µL−1 at 1 μL·100·g−1 body wt), and the metabolite profile in plasma, hypothalamus, and rest of the brain (composing of telencephalon, optic tectum, cerebellum, and medulla oblongata) was carried out by liquid chromatography-mass spectrometry (LC/MS)-based metabolomics. Valine administration led to a spatially distinct metabolite profile at 1 h postinjection in the brain: enrichment of amino acid metabolism and energy production pathways in the rest of the brain but not in hypothalamus. This suggests a role for extrahypothalamic input in the regulation of feed intake. Also, there was enrichment of several amino acids, including tyrosine, proline, valine, phenylalanine, and methionine, in plasma in response to valine. Changes in liver transcript abundance and protein expression reflect an increased metabolic capacity, including energy production from glucose and fatty acids, and a lower protein kinase B (Akt) phosphorylation in the valine group. Altogether, valine intracerebroventricular administration affects central and peripheral metabolism in rainbow trout, and we propose a role for the altered metabolite profile in modulating the feeding response to this branched-chain amino acid. NEW & NOTEWORTHY: Valine causes hyperphagia in fish when it is centrally administered; however, the exact mechanisms are far from clear. We tested how intracerebroventricular injection of valine in rainbow trout affected the brain and plasma metabolome. The metabolite changes in response to valine were more evident in the rest of the brain compared with the hypothalamus. Furthermore, we demonstrated for the first time that central valine administration affects peripheral metabolism in rainbow trout. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
3. Nutritional Epigenetics
- Author
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Carlberg, Carsten and Carlberg, Carsten
- Published
- 2024
- Full Text
- View/download PDF
4. Chronic cortisol stimulation enhances hypothalamus-specific enrichment of metabolites in the rainbow trout brain.
- Author
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Blanco, Ayelén M., Antomagesh, Femilarani, Comesaña, Sara, Soengas, José L., and Vijayan, Mathilakath M.
- Subjects
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HYPOTHALAMUS , *RAINBOW trout , *HYDROCORTISONE , *LEUCINE , *METABOLITES , *AMP-activated protein kinases , *TRICARBOXYLIC acids - Abstract
The hypothalamus is a key integrating center that is involved in the initiation of the corticosteroid stress response, and in regulating nutrient homeostasis. Although cortisol, the principal glucocorticoid in humans and teleosts, plays a central role in feeding regulation, the mechanisms are far from clear. We tested the hypothesis that the metabolic changes to cortisol exposure signal an energy excess in the hypothalamus, leading to feeding suppression during stress in fish. Rainbow trout (Oncorhynchus mykiss) were administered a slow-release cortisol implant for 3 days, and the metabolite profiles in the plasma, hypothalamus, and the rest of the brain were assessed. Also, U-13C-glucose was injected into the hypothalamus by intracerebroventricular (ICV) route, and the metabolic fate of this energy substrate was followed in the brain regions by metabolomics. Chronic cortisol treatment reduced feed intake, and this corresponded with a downregulation of the orexigenic gene agrp, and an upregulation of the anorexigenic gene cart in the hypothalamus. The U-13C-glucose-mediated metabolite profiling indicated an enhancement of glycolytic flux and tricarboxylic acid intermediates in the rest of the brain compared with the hypothalamus. There was no effect of cortisol treatment on the phosphorylation status of AMPK or mechanistic target of rapamycin in the brain, whereas several endogenous metabolites, including leucine, citrate, and lactate were enriched in the hypothalamus, suggesting a tissue-specific metabolic shift in response to cortisol stimulation. Altogether, our results suggest that the hypothalamus-specific enrichment of leucine and the metabolic fate of this amino acid, including the generation of lipid intermediates, contribute to cortisol-mediated feeding suppression in fish. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
5. Ctp1 and Yhm2: Two Mitochondrial Citrate Transporters to Support Metabolic Flexibility of Saccharomyces cerevisiae.
- Author
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Assalve, Graziana, Lunetti, Paola, Zara, Vincenzo, and Ferramosca, Alessandra
- Subjects
- *
SACCHAROMYCES cerevisiae , *CARRIER proteins , *EUKARYOTIC cells , *KREBS cycle , *MITOCHONDRIA , *CITRATES - Abstract
Differently from higher eukaryotic cells, in the yeast Saccharomyces cerevisiae there are two mitochondrial carrier proteins involved in the transport of citrate: Ctp1 and Yhm2. Very little is known about the physiological role of these proteins. Wild-type and mutant yeast strains deleted in CTP1 and YHM2 were grown in media supplemented with a fermentable (glucose) or a nonfermentable (ethanol) carbon source. To assess changes in Ctp1 and Yhm2 mRNA expression levels, real-time PCR was performed after total RNA extraction. In the wild-type strain, the metabolic switch from the exponential to the stationary phase is associated with an increase in the expression level of the two citrate transporters. In addition, the results obtained in the mutant strains suggest that the presence of a single citrate transporter can partially compensate for the absence of the other. Ctp1 and Yhm2 differently contribute to fermentative and respiratory metabolism. Moreover, the two mitochondrial carriers represent a link between the Krebs cycle and the glyoxylate cycle, which play a key role in the metabolic adaptation strategies of S. cerevisiae. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
6. Exploring the effects of dietary inulin in rainbow trout fed a high-starch, 100% plant-based diet
- Author
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Raphaël Defaix, Jep Lokesh, Laura Frohn, Mickael Le Bechec, Thierry Pigot, Vincent Véron, Anne Surget, Sandra Biasutti, Frédéric Terrier, Sandrine Skiba-Cassy, Jérôme Roy, Stéphane Panserat, and Karine Ricaud
- Subjects
Aquaculture ,Fish nutrition ,Gut microbiota ,Immune markers ,Intermediary metabolism ,Inulin ,Animal culture ,SF1-1100 ,Veterinary medicine ,SF600-1100 - Abstract
Abstract Background High dietary carbohydrates can spare protein in rainbow trout (Oncorhynchus mykiss) but may affect growth and health. Inulin, a prebiotic, could have nutritional and metabolic effects, along with anti-inflammatory properties in teleosts, improving growth and welfare. We tested this hypothesis in rainbow trout by feeding them a 100% plant-based diet, which is a viable alternative to fishmeal and fish oil in aquaculture feeds. In a two-factor design, we examined the impact of inulin (2%) as well as the variation in the carbohydrates (CHO)/plant protein ratio on rainbow trout. We assessed the influence of these factors on zootechnical parameters, plasma metabolites, gut microbiota, production of short-chain fatty acids and lactic acid, as well as the expression of free-fatty acid receptor genes in the mid-intestine, intermediary liver metabolism, and immune markers in a 12-week feeding trial. Results The use of 2% inulin did not significantly change the fish intestinal microbiota, but interestingly, the high CHO/protein ratio group showed a change in intestinal microbiota and in particular the beta diversity, with 21 bacterial genera affected, including Ralstonia, Bacillus, and 11 lactic-acid producing bacteria. There were higher levels of butyric, and valeric acid in groups fed with high CHO/protein diet but not with inulin. The high CHO/protein group showed a decrease in the expression of pro-inflammatory cytokines (il1b, il8, and tnfa) in liver and a lower expression of the genes coding for tight-junction proteins in mid-intestine (tjp1a and tjp3). However, the 2% inulin did not modify the expression of plasma immune markers. Finally, inulin induced a negative effect on rainbow trout growth performance irrespective of the dietary carbohydrates. Conclusions With a 100% plant-based diet, inclusion of high levels of carbohydrates could be a promising way for fish nutrition in aquaculture through a protein sparing effect whereas the supplementation of 2% inulin does not appear to improve the use of CHO when combined with a 100% plant-based diet.
- Published
- 2024
- Full Text
- View/download PDF
7. Exploring the effects of dietary inulin in rainbow trout fed a high-starch, 100% plant-based diet.
- Author
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Defaix, Raphaël, Lokesh, Jep, Frohn, Laura, Le Bechec, Mickael, Pigot, Thierry, Véron, Vincent, Surget, Anne, Biasutti, Sandra, Terrier, Frédéric, Skiba-Cassy, Sandrine, Roy, Jérôme, Panserat, Stéphane, and Ricaud, Karine
- Subjects
- *
INULIN , *PLANT-based diet , *RAINBOW trout , *SHORT-chain fatty acids , *FISH farming , *BIOMARKERS - Abstract
Background: High dietary carbohydrates can spare protein in rainbow trout (Oncorhynchus mykiss) but may affect growth and health. Inulin, a prebiotic, could have nutritional and metabolic effects, along with anti-inflammatory properties in teleosts, improving growth and welfare. We tested this hypothesis in rainbow trout by feeding them a 100% plant-based diet, which is a viable alternative to fishmeal and fish oil in aquaculture feeds. In a two-factor design, we examined the impact of inulin (2%) as well as the variation in the carbohydrates (CHO)/plant protein ratio on rainbow trout. We assessed the influence of these factors on zootechnical parameters, plasma metabolites, gut microbiota, production of short-chain fatty acids and lactic acid, as well as the expression of free-fatty acid receptor genes in the mid-intestine, intermediary liver metabolism, and immune markers in a 12-week feeding trial. Results: The use of 2% inulin did not significantly change the fish intestinal microbiota, but interestingly, the high CHO/protein ratio group showed a change in intestinal microbiota and in particular the beta diversity, with 21 bacterial genera affected, including Ralstonia, Bacillus, and 11 lactic-acid producing bacteria. There were higher levels of butyric, and valeric acid in groups fed with high CHO/protein diet but not with inulin. The high CHO/protein group showed a decrease in the expression of pro-inflammatory cytokines (il1b, il8, and tnfa) in liver and a lower expression of the genes coding for tight-junction proteins in mid-intestine (tjp1a and tjp3). However, the 2% inulin did not modify the expression of plasma immune markers. Finally, inulin induced a negative effect on rainbow trout growth performance irrespective of the dietary carbohydrates. Conclusions: With a 100% plant-based diet, inclusion of high levels of carbohydrates could be a promising way for fish nutrition in aquaculture through a protein sparing effect whereas the supplementation of 2% inulin does not appear to improve the use of CHO when combined with a 100% plant-based diet. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
8. Intermediary metabolism.
- Author
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Dingezweni, S.
- Subjects
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METABOLISM , *CHEMICAL processes - Abstract
In humans, chemical unity in diversity prevails as metabolic pathways are coordinated, regulated, and integrated to protect the body against metabolic catastrophes. The end product of one metabolic pathway is connected to another metabolic pathway of the same or another metabolite. A basic understanding of the normal metabolic pathways and their abnormality is the foundation in the management of patients subjected to the stress of anaesthesia and surgery. Objective clinical evaluation, investigations, and perioperative risk stratification of patients are based on understanding the fundamentals of intermediate metabolism. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
9. Ethanol Metabolism
- Author
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Mueller, Sebastian, Mueller, Sebastian, editor, and Heilig, Markus, editor
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- 2023
- Full Text
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10. Nutritional Epigenetics, Signaling and Aging
- Author
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Carlberg, Carsten, Velleuer, Eunike, Molnár, Ferdinand, Carlberg, Carsten, Velleuer, Eunike, and Molnár, Ferdinand
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- 2023
- Full Text
- View/download PDF
11. Diagnosis of Wilson Disease and Its Phenotypes by Using Artificial Intelligence.
- Author
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Medici, Valentina, Czlonkowska, Anna, Litwin, Tomasz, and Giulivi, Cecilia
- Subjects
Krebs’ cycle ,Wilson disease ,amino acids ,artificial neural network ,copper ,diagnosis prediction ,intermediary metabolism ,liver ,mitochondria ,urea cycle ,Krebs' cycle ,Biochemistry and Cell Biology - Abstract
WD is caused by ATP7B variants disrupting copper efflux resulting in excessive copper accumulation mainly in liver and brain. The diagnosis of WD is challenged by its variable clinical course, onset, morbidity, and ATP7B variant type. Currently it is diagnosed by a combination of clinical symptoms/signs, aberrant copper metabolism parameters (e.g., low ceruloplasmin serum levels and high urinary and hepatic copper concentrations), and genetic evidence of ATP7B mutations when available. As early diagnosis and treatment are key to favorable outcomes, it is critical to identify subjects before the onset of overtly detrimental clinical manifestations. To this end, we sought to improve WD diagnosis using artificial neural network algorithms (part of artificial intelligence) by integrating available clinical and molecular parameters. Surprisingly, WD diagnosis was based on plasma levels of glutamate, asparagine, taurine, and Fischer's ratio. As these amino acids are linked to the urea-Krebs' cycles, our study not only underscores the central role of hepatic mitochondria in WD pathology but also that most WD patients have underlying hepatic dysfunction. Our study provides novel evidence that artificial intelligence utilized for integrated analysis for WD may result in earlier diagnosis and mechanistically relevant treatments for patients with WD.
- Published
- 2021
12. Changes in life table parameters and intermediary metabolism of Cryptolaemus montrouzieri Mulsant after infection by Beauveria bassiana
- Author
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Sara Aghaeepour, Arash Zibaee, Samar Ramzi, and Hassan Hoda
- Subjects
biology ,entomopathogenic fungi ,intermediary metabolism ,mealybug ladybird ,microbe-predator interaction ,Plant culture ,SB1-1110 - Abstract
The effects of two native isolates of Beauveria bassiana, AM-118 and BB3, were evaluated on the predatory coccinellid, Cryptolaemus montrouzieri by measuring several developmental parameters and intermediary metabolism. Treatment with both isolates significantly increased the length of each developmental stage compared to the control except for the eggs and adults. The preovipositional period in the adults treated with BB3 significantly increased compared to those treated with AM-118 and the control. Other parameters, including longevity, length of oviposition period and fecundity, showed no significant differences between treatments. Although there were no significant differences in the parameters of net reproduction rate ( R0) and gross reproduction rate ( GRR) between the control and fungal treated C. montrouzieri, the intrinsic rate of population increase ( r) and finite rate of population (λ) for the control treatments were significantly higher. The activities of both aminotransferases in the larvae and the adults treated with both isolates significantly increased 96 hours post-treatment compared to the control. Although similar results were recorded for acid phosphatase activity, alkaline phosphatase activity showed no significant differences in larvae and adults between the treatments. The amount of protein significantly decreased in the larvae and the adults treated with both isolates after 96 hours, while the amount of triglyceride significantly reduced in the treated larvae compared to control. No significant differences were observed in adults. Our results indicated that both native isolates of B. bassiana may affect life fitness of C. montrouzieri but isolate AM-118 was more compatible than BB3.
- Published
- 2023
- Full Text
- View/download PDF
13. Metabolic reprogramming and epigenetic changes of vital organs in SARS-CoV-2-induced systemic toxicity.
- Author
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Li, Shen, Ma, Feiyang, Yokota, Tomohiro, Garcia, Gustavo, Palermo, Amelia, Wang, Yijie, Farrell, Colin, Wang, Yu-Chen, Wu, Rimao, Zhou, Zhiqiang, Pan, Calvin, Morselli, Marco, Teitell, Michael A, Ryazantsev, Sergey, Fishbein, Gregory A, Hoeve, Johanna Ten, Arboleda, Valerie A, Bloom, Joshua, Dillon, Barbara, Pellegrini, Matteo, Lusis, Aldons J, Graeber, Thomas G, Arumugaswami, Vaithilingaraja, and Deb, Arjun
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Animals ,Animals ,Genetically Modified ,Humans ,Mice ,Wasting Syndrome ,Disease Models ,Animal ,Failure to Thrive ,Immunity ,DNA Methylation ,Epigenesis ,Genetic ,Citric Acid Cycle ,Oxidative Phosphorylation ,Renin-Angiotensin System ,Male ,COVID-19 ,Angiotensin-Converting Enzyme 2 ,SARS-CoV-2 ,Epigenetics ,Intermediary metabolism ,Metabolism ,Cardiovascular ,Infectious Diseases ,Prevention ,Biodefense ,Lung ,Genetics ,Vaccine Related ,2.1 Biological and endogenous factors - Abstract
Extrapulmonary manifestations of COVID-19 are associated with a much higher mortality rate than pulmonary manifestations. However, little is known about the pathogenesis of systemic complications of COVID-19. Here, we create a murine model of SARS-CoV-2-induced severe systemic toxicity and multiorgan involvement by expressing the human ACE2 transgene in multiple tissues via viral delivery, followed by systemic administration of SARS-CoV-2. The animals develop a profound phenotype within 7 days with severe weight loss, morbidity, and failure to thrive. We demonstrate that there is metabolic suppression of oxidative phosphorylation and the tricarboxylic acid (TCA) cycle in multiple organs with neutrophilia, lymphopenia, and splenic atrophy, mirroring human COVID-19 phenotypes. Animals had a significantly lower heart rate, and electron microscopy demonstrated myofibrillar disarray and myocardial edema, a common pathogenic cardiac phenotype in human COVID-19. We performed metabolomic profiling of peripheral blood and identified a panel of TCA cycle metabolites that served as biomarkers of depressed oxidative phosphorylation. Finally, we observed that SARS-CoV-2 induces epigenetic changes of DNA methylation, which affects expression of immune response genes and could, in part, contribute to COVID-19 pathogenesis. Our model suggests that SARS-CoV-2-induced metabolic reprogramming and epigenetic changes in internal organs could contribute to systemic toxicity and lethality in COVID-19.
- Published
- 2021
14. Ctp1 and Yhm2: Two Mitochondrial Citrate Transporters to Support Metabolic Flexibility of Saccharomyces cerevisiae
- Author
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Graziana Assalve, Paola Lunetti, Vincenzo Zara, and Alessandra Ferramosca
- Subjects
citrate ,intermediary metabolism ,metabolite carrier ,mitochondria ,metabolism ,subcellular compartments ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Differently from higher eukaryotic cells, in the yeast Saccharomyces cerevisiae there are two mitochondrial carrier proteins involved in the transport of citrate: Ctp1 and Yhm2. Very little is known about the physiological role of these proteins. Wild-type and mutant yeast strains deleted in CTP1 and YHM2 were grown in media supplemented with a fermentable (glucose) or a nonfermentable (ethanol) carbon source. To assess changes in Ctp1 and Yhm2 mRNA expression levels, real-time PCR was performed after total RNA extraction. In the wild-type strain, the metabolic switch from the exponential to the stationary phase is associated with an increase in the expression level of the two citrate transporters. In addition, the results obtained in the mutant strains suggest that the presence of a single citrate transporter can partially compensate for the absence of the other. Ctp1 and Yhm2 differently contribute to fermentative and respiratory metabolism. Moreover, the two mitochondrial carriers represent a link between the Krebs cycle and the glyoxylate cycle, which play a key role in the metabolic adaptation strategies of S. cerevisiae.
- Published
- 2024
- Full Text
- View/download PDF
15. Metabolic Control Analysis for Drug Target Selection Against Human Diseases
- Author
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Belmont-Díaz, Javier, Vázquez, Citlali, Encalada, Rusely, Moreno-Sánchez, Rafael, Michels, Paul A. M., Saavedra, Emma, Talevi, Alan, Series Editor, Scotti, Marcus T., editor, and Bellera, Carolina L., editor
- Published
- 2022
- Full Text
- View/download PDF
16. Redox Dynamic Homeostasis and Aging
- Author
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Lushchak, Volodymyr I., Rattan, Suresh I.S., Series Editor, Barbagallo, Mario, Editorial Board Member, Çakatay, Ufuk, Editorial Board Member, Fraifeld, Vadim E., Editorial Board Member, Fülöp, Tamàs, Editorial Board Member, Gruber, Jan, Editorial Board Member, Jin, Kunlin, Editorial Board Member, Kaul, Sunil, Editorial Board Member, Kaur, Gurcharan, Editorial Board Member, Le Bourg, Eric, Editorial Board Member, Lopez Lluch, Guillermo, Editorial Board Member, Moskalev, Alexey, Editorial Board Member, Nehlin, Jan, Editorial Board Member, Pawelec, Graham, Editorial Board Member, Rizvi, Syed Ibrahim, Editorial Board Member, Sholl, Jonathan, Editorial Board Member, Stambler, Ilia, Editorial Board Member, Szczerbińska, Katarzyna, Editorial Board Member, Trougakos, Ioannis P., Editorial Board Member, Wadhwa, Renu, Editorial Board Member, and Wnuk, Maciej, Editorial Board Member
- Published
- 2022
- Full Text
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17. Differential hepatic mitochondrial function and gluconeogenic gene expression in 2 Holstein strains in a pasture-based system
- Author
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Mercedes García-Roche, Daniel Talmón, Guillermo Cañibe, Ana Laura Astessiano, Alejandro Mendoza, Celia Quijano, Adriana Cassina, and Mariana Carriquiry
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intermediary metabolism ,gluconeogenesis ,dairy cows ,grazing ,Holstein-Friesian ,Dairy processing. Dairy products ,SF250.5-275 ,Dairying ,SF221-250 - Abstract
ABSTRACT: The objective of this study was to assess hepatic ATP synthesis in Holstein cows of North American and New Zealand origins and the gluconeogenic pathway, one of the pathways with the highest ATP demands in the ruminant liver. Autumn-calving Holstein cows of New Zealand and North American origins were managed in a pasture-based system with supplementation of concentrate that represented approximately 33% of the predicted dry matter intake during 2017, 2018, and 2019, and hepatic biopsies were taken during mid-lactation at 174 ± 23 days in milk. Cows of both strains produced similar levels of solids-corrected milk, and no differences in body condition score were found. Plasma glucose concentrations were higher for cows of New Zealand versus North American origin. Hepatic mitochondrial function evaluated measuring oxygen consumption rates showed that mitochondrial parameters related to ATP synthesis and maximum respiratory rate were increased for cows of New Zealand compared with North American origin. However, hepatic gene expression of pyruvate carboxylase, phosphoenolpyruvate carboxykinase, and pyruvate dehydrogenase kinase was increased in North American compared with New Zealand cows. These results altogether suggest an increased activity of the tricarboxylic cycle in New Zealand cows, leading to increased ATP synthesis, whereas North American cows pull tricarboxylic cycle intermediates toward gluconeogenesis. The fact that this occurs during mid-lactation could account for the increased persistency of North American cows, especially in a pasture-based system. In addition, we observed an augmented mitochondrial density in New Zealand cows, which could be related to feed efficiency mechanisms. In sum, our results contribute to the elucidation of hepatic molecular mechanisms in dairy cows in production systems with higher inclusion of pastures.
- Published
- 2022
- Full Text
- View/download PDF
18. Effects of Fasting on Intermediary Metabolism Enzymes in the Liver and Muscle of Rainbow Trout.
- Author
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Fernández-Muela, Montserrat, Bermejo-Poza, Rubén, Cabezas, Almudena, Pérez, Concepción, González de Chavarri, Elisabet, Díaz, María Teresa, Torrent, Fernando, Villarroel, Morris, and De la Fuente, Jesús
- Subjects
- *
LIVER enzymes , *RAINBOW trout , *ENZYME metabolism , *PHOSPHORYLASES , *GLYCOGEN phosphorylase , *PYRUVATE kinase , *LIVER - Abstract
Fish can go through periods of feed deprivation, either due to natural causes influenced by temperature or management techniques in animal production, affecting their energy metabolism differently, depending on the duration of fasting in days and water temperature. This study showed the effect of different days of fasting before slaughter in rainbow trout by analyzing the intermediary metabolic enzymes in the muscle and liver. For this purpose, a non-fasting group was compared with trout that fasted for 5, 10, and 20 days (55, 107, and 200 degree days (°C d), respectively). A first phase of increased activity of enzymes involved in glycolysis was observed, increasing hexokinase enzyme activity in muscle and pyruvate kinase enzyme activity in muscle and liver. As the fasting days progressed, enzymes involved in the gluconeogenic and glycogenolytic pathways in the liver such as lactate dehydrogenase and glycogen phosphorylase increased their activity regarding the no fasted group. After 20 days of fasting (200 °C d), lipogenic and protein related enzyme activity depletion was observed, leading to significant changes in energy metabolism. Therefore, prolonged fasting with high degree days duration may compromise the energy supply for the vital development of rainbow trout. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
19. Total fishmeal replacement by defatted Tenebrio molitor larvae meal induces alterations in intermediary metabolism of European sea bass (Dicentrarchus labrax).
- Author
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Basto, Ana, Valente, Luisa M. P., Sousa, Vera, Conde-Sieira, Marta, and Soengas, José L.
- Abstract
The replacement of fishmeal (FM) by insect meal (IM) in aquafeed formulation has been thoroughly studied lately, but little is known about their impact on nutrient metabolism of fish. This study evaluated the impact not only of partial but also total FM replacement by IM on intermediary metabolism of European sea bass (Dicentrarchus labrax). A fishmeal-based diet was used as a control (CTRL) and two other diets were formulated to include 20% and 40% of defatted Tenebrio molitor larvae meal (dTM), replacing 50% (TM50) and 100% (TM100) of fishmeal (FM), respectively. After a 16-week feeding trial, a multidisciplinary approach including assessment of histological, biochemical, molecular, and enzymatic parameters was adopted to investigate hepatic and plasmatic responses to the different dietary formulations. The results obtained demonstrated that dTM can be successfully used to replace 50% of FM in diets for European sea bass, without adversely affecting liver health or intermediary metabolism of nutrients. As for TM100, although no signs of steatosis were observed in the liver, the activity of glycolytic and lipogenic genes and enzymes increased when compared to CTRL diet (P < 0.05), resulting in higher levels of plasmatic non-esterified fatty acids and triacylglycerides (P < 0.05), which in the long-term may compromise fish health, thus precluding such a high degree of substitution for use in practical diets for European sea bass. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
20. Changes in life table parameters and intermediary metabolism of Cryptolaemus montrouzieri Mulsant after infection by Beauveria bassiana.
- Author
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Aghaeepour, Sara, Zibaee, Arash, Ramzi, Samar, and Hoda, Hassan
- Subjects
BEAUVERIA bassiana ,LIFE tables ,REPRODUCTION ,ACID phosphatase ,ALKALINE phosphatase ,METABOLISM ,EGGS ,BIOPESTICIDES - Abstract
The effects of two native isolates of Beauveria bassiana, AM-118 and BB3, were evaluated on the predatory coccinellid, Cryptolaemus montrouzieri by measuring several developmental parameters and intermediary metabolism. Treatment with both isolates significantly increased the length of each developmental stage compared to the control except for the eggs and adults. The preovipositional period in the adults treated with BB3 significantly increased compared to those treated with AM-118 and the control. Other parameters, including longevity, length of oviposition period and fecundity, showed no significant differences between treatments. Although there were no significant differences in the parameters of net reproduction rate (R0) and gross reproduction rate (GRR) between the control and fungal treated C. montrouzieri, the intrinsic rate of population increase (r) and finite rate of population (?) for the control treatments were significantly higher. The activities of both aminotransferases in the larvae and the adults treated with both isolates significantly increased 96 hours post-treatment compared to the control. Although similar results were recorded for acid phosphatase activity, alkaline phosphatase activity showed no significant differences in larvae and adults between the treatments. The amount of protein significantly decreased in the larvae and the adults treated with both isolates after 96 hours, while the amount of triglyceride significantly reduced in the treated larvae compared to control. No significant differences were observed in adults. Our results indicated that both native isolates of B. bassiana may affect life fitness of C. montrouzieri but isolate AM-118 was more compatible than BB3. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
21. The regulation of cardiac intermediary metabolism by NADPH oxidases.
- Author
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Nabeebaccus, Adam A, Reumiller, Christina M, Shen, Jie, Zoccarato, Anna, Santos, Celio X C, and Shah, Ajay M
- Subjects
- *
HEART metabolism , *OXIDASES , *NICOTINAMIDE adenine dinucleotide phosphate , *REACTIVE oxygen species , *GENERATING functions , *CARDIAC contraction , *OXYGEN consumption - Abstract
NADPH oxidases (NOXs), enzymes whose primary function is to generate reactive oxygen species, are important regulators of the heart's physiological function and response to pathological insults. The role of NOX-driven redox signalling in pathophysiological myocardial remodelling, including processes such as interstitial fibrosis, contractile dysfunction, cellular hypertrophy, and cell survival, is well recognized. While the NOX2 isoform promotes many detrimental effects, the NOX4 isoform has attracted considerable attention as a driver of adaptive stress responses both during pathology and under physiological states such as exercise. Recent studies have begun to define some of the NOX4-modulated mechanisms that may underlie these adaptive responses. In particular, novel functions of NOX4 in driving cellular metabolic changes have emerged. Alterations in cellular metabolism are a recognized hallmark of the heart's response to physiological and pathological stresses. In this review, we highlight the emerging roles of NOX enzymes as important modulators of cellular intermediary metabolism in the heart, linking stress responses not only to myocardial energetics but also other functions. The novel interplay of NOX-modulated redox signalling pathways and intermediary metabolism in the heart is unravelling a new aspect of the fascinating biology of these enzymes which will inform a better understanding of how they drive adaptive responses. We also discuss the implications of these new findings for therapeutic approaches that target metabolism in cardiac disease. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
22. Insights into the toxicity, behavioral responses, biochemical activity, and molecular docking of three Cymbopogon essential oils and their major constituents on Reticulitermes flaviceps.
- Author
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Jin, Chunzhe, Wu, Ziwei, Chen, Yiyang, Gong, Xue, Yang, Shimeng, Zhang, Zhilin, Zhang, Dayu, and Xie, Yongjian
- Subjects
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CYMBOPOGON , *ESSENTIAL oils , *MOLECULAR docking , *POISONS , *INSECTICIDE application , *GLUTATHIONE transferase , *GLUTATHIONE - Abstract
The global impact of termites that damage wood products causes quite significant losses. Synthetic insecticides have been extensively employed to combat termites. However, as the long-term application of insecticides developed adverse effects on humans and the environment, the use of essential oils (EOs) has emerged as an alternative approach for controlling termites. Hence, the present report assessed the fumigation activity of three Cymbopogon EOs toward Reticulitermes flaviceps workers. The results showed that C. citratus (with the major constituent citral (mixture of neral and geranial) at 78.58 %), C. khasans (geraniol, 38.54 %), and C. nardus (citronellal, 26.99 %) had respective LC 50 values of 0.39, 0.45 and 0.48 μL/L. These values for citral, geraniol, and citronellal were 0.35, 0.34, and 0.40 μL/L. The duration of fumigation using Cymbopogon EOs and their primary compounds exhibited a positive correlation with the knockdown and mortality rates of R. flaviceps while displaying a negative correlation with grasping ability. In addition, each component caused a concentration-dependent reaction measured using electroantennography (EAG) and triggered a significant response at 100 μg/μL. The activities of detoxifying enzymes like β-esterase and glutathione S-transferase were remarkably increased in treated R. flaviceps. The findings also demonstrated that both Cymbopogon EOs and their primary components effectively suppressed acetylcholinesterase (AChE) in vitro and in vivo. In silico structural analyses of citral, geraniol, and citronellal revealed that citronellal exhibited the highest potential for binding to the active site of AChE. Similarly, the activity of acid phosphatases, alkaline phosphatases, aspartate aminotransferase, and lactate dehydrogenase was elevated in treated R. flaviceps , whereas that of alanine aminotransferase was diminished. This study may provide a robust foundation for developing and using Cymbopogon EOs to control R. flaviceps in an environmentally friendly manner. [Display omitted] • Cymbopogon EOs and their major constituents have toxic effects on R. flaviceps. • Major detoxifying agents are affected by Cymbopogon EOs and their major constituents. • Cymbopogon and their constituents inhibited activity of AChE in in vivo and in vitro. [ABSTRACT FROM AUTHOR]
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- 2024
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23. The nexus between redox state and intermediary metabolism.
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Zoccarato, Anna, Nabeebaccus, Adam A., Oexner, Rafael R., Santos, Celio X. C., and Shah, Ajay M.
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- *
METABOLIC regulation , *ENZYME regulation , *OXIDATION-reduction reaction , *REACTIVE oxygen species , *METABOLISM , *GLYCOLYSIS , *CELL metabolism - Abstract
Reactive oxygen species (ROS) are not just a by‐product of cellular metabolic processes but act as signalling molecules that regulate both physiological and pathophysiological processes. A close connection exists in cells between redox homeostasis and cellular metabolism. In this review, we describe how intracellular redox state and glycolytic intermediary metabolism are closely coupled. On the one hand, ROS signalling can control glycolytic intermediary metabolism by direct regulation of the activity of key metabolic enzymes and indirect regulation via redox‐sensitive transcription factors. On the other hand, metabolic adaptation and reprogramming in response to physiological or pathological stimuli regulate intracellular redox balance, through mechanisms such as the generation of reducing equivalents. We also discuss the impact of these intermediary metabolism–redox circuits in physiological and disease settings across different tissues. A better understanding of the mechanisms regulating these intermediary metabolism–redox circuits will be crucial to the development of novel therapeutic strategies. [ABSTRACT FROM AUTHOR]
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- 2022
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24. Balancing protein and energy in Nile tilapia feeds: A meta‐analysis.
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Konnert, Gauthier D. P., Gerrits, Walter J. J., Gussekloo, Sander W. S., and Schrama, Johan W.
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NILE tilapia ,MUSCLE proteins ,NONLINEAR regression ,DIETARY proteins ,BODY composition ,FISH growth - Abstract
Farmed fish are increasingly grown in intensive and semi‐intensive systems where most nutrients are provided by formulated feeds. These are formulated to minimise costs and optimise growth, notably the rate of muscle protein synthesis (i.e., fillet). Protein synthesis depends on the availability of amino acids (i.e., protein) and energy. Thus, fish feeds are often formulated to provide a balanced ratio of protein to energy (P:E). Above and below the optimal dietary P:E, absorbed protein and energy are expected to be under‐utilised for body protein synthesis, respectively. Estimates of the optimal dietary P:E vary largely for Nile tilapia (Oreochromis niloticus (L., 1758)). Published values range from 13 to 26 g of dietary protein per MJ of energy. Here, we challenge the idea that growth, protein utilisation efficiency and body composition can all be simultaneously optimised, when Nile tilapia are fed an optimal dietary P:E. Through linear and non‐linear regression meta‐analyses, we quantitatively describe the effects of protein and energy intake on nutrient partitioning, feed efficiency and growth. We find linear relationships between the dietary P:E and protein retention efficiency. The lack of an inflection contradicts the existence of an optimal P:E. Our regressions of protein and energy intake versus protein gain, indicate that protein gain is often simultaneously limited by both protein and energy intake, and may be limited by other factors than protein and energy intake, such as a maximal protein deposition capacity (PDmax). We conclude that there is no physiological basis for an optimal P:E in Nile tilapia feeds. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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25. Multiple roles played by the mitochondrial citrate carrier in cellular metabolism and physiology.
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Zara, Vincenzo, Assalve, Graziana, and Ferramosca, Alessandra
- Abstract
The citrate carrier (CIC) is an integral protein of the inner mitochondrial membrane which catalyzes the efflux of mitochondrial citrate (or other tricarboxylates) in exchange with a cytosolic anion represented by a tricarboxylate or a dicarboxylate or phosphoenolpyruvate. In this way, the CIC provides the cytosol with citrate which is involved in many metabolic reactions. Several studies have been carried out over the years on the structure, function and regulation of this metabolite carrier protein both in mammals and in many other organisms. A lot of data on the characteristics of this protein have therefore accumulated over time thereby leading to a complex framework of metabolic and physiological implications connected to the CIC function. In this review, we critically analyze these data starting from the multiple roles played by the mitochondrial CIC in many cellular processes and then examining the regulation of its activity in different nutritional and hormonal states. Finally, the metabolic significance of the citrate flux, mediated by the CIC, across distinct subcellular compartments is also discussed. [ABSTRACT FROM AUTHOR]
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- 2022
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26. Dietary lysine level affects digestive enzyme, amino acid transport and hepatic intermediary metabolism in turbot (Scophthalmus maximus).
- Author
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Huang, Xinrui, Song, Xinxin, Wang, Xuan, Zhou, Huihui, Liu, Chengdong, Mai, Kangsen, and He, Gen
- Abstract
Lysine is one of the most important essential amino acids in fish, especially in the feed formulated with high levels of plant ingredients. Lysine restriction always led to growth inhibition and poor feed utilization. However, little information was available on its effects on digestion, absorption, and metabolism response in fish. In the present study, three experimental diets were formulated with three lysine levels, 1.69% (LL group), 3.32% (ML group), and 4.90% (HL group). A 10-week feeding trial was carried out to explore the effects of dietary lysine levels on the digestive enzymes, amino acid transporters, and hepatic intermediary metabolism in turbot (Scophthalmus maximus). As the results showed, the activities of lipase and trypsin in ML group were higher than in other groups. Lysine restriction inhibited the expression levels of peptides and amino acid transporters such as PpeT1, y
+ LAT2, b0,+ AT, and rBAT but significantly induced the expression of CAT1. Meanwhile, lysine deficiency elevated the content of T-CHO and LDL-C in plasma, while a higher HDL-C/LDL-C ratio was observed in ML group. For hepatic intermediary metabolism, the increase of lysine level induced the mRNA expression of G6Pase1 and FBPase, but no differences were observed in the expression of the key regulators in glycolysis pathway, such as GK and PK. Furthermore, an appropriate increase in the level of lysine promoted the genes involved in lipolysis, including PPARα, ACOX1, CPT1A, and LPL. However, no differences were observed in the expression of PPARγ, FAS, SREBP1, and LXR, which were important genes related to lipid synthesis. These results provide clues on the metabolic responses on dietary lysine in teleost. [ABSTRACT FROM AUTHOR]- Published
- 2022
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27. Regulation of macrophage and preadipocyte proliferation and migration by C1P
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Gómez Muñoz, Antonio, Carracedo Pérez, Arkaitz, Bioquímica y biología molecular, Biokimika eta biologia molekularra, Domínguez Herrera, Asier, Gómez Muñoz, Antonio, Carracedo Pérez, Arkaitz, Bioquímica y biología molecular, Biokimika eta biologia molekularra, and Domínguez Herrera, Asier
- Abstract
154 p., Chronic inflammatory diseases are the most significant cause of death in the world. Indeed, according to the World Health Organization (WHO), 3 out of 5 people die due to chronic inflammatory diseases such as stroke, chronic respiratory diseases, heart disorders, cancer, obesity or diabetes. It has been demonstrated that sphingolipid metabolism is altered in this type of disorders. Therefore, understanding the molecular mechanisms by which bioactive sphingolipids participate in the establishment or progression of those diseases may be useful for developing novel therapeutic strategies to control them. In the first chapter of this thesis, we demonstrate that the bioactive sphingolipid ceramide 1-phosphate (C1P) induces survival, proliferation and migration of preadipocytes through mechanisms that implicate the PI3K/Akt, MEK/ERK1-2 and JAK/STAT3 signaling pathways. These biological actions suggest a possible role of this phosphosphingolipid in fat accumulation and dysfunction of adipose tissue, which might lead to metabolic diseases, most notably, obesity. In the second chapter we show that exogenous C1P inhibits alveolar macrophage migration, an action that seems to be caused by dephosphorylation of important proteins that are involved in the regulation of cell migration, such as, PKB/Akt, ERK1-2, PAK1 and Paxillin. In addition, the latter study provides evidence that granular nanosized silica (SiO2)-conditioned medium enhances alveolar macrophage migration through activation of PI3K/Akt signaling cascade and that C1P inhibits this action by blocking PKB/Akt phosphorylation. Taken together, the results of this thesis support the notion that C1P may have anti-inflammatory properties in lung cells.
- Published
- 2024
28. Effects of Fasting on Intermediary Metabolism Enzymes in the Liver and Muscle of Rainbow Trout
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Jin, J., Fernández-Muela Garrote, Montserrat, Bermejo Poza, Rubén, Cabezas Albéniz, Almudena, Pérez Marcos, Concepción, González De Chávarri Echániz, Elisabeth, Díaz Díaz Chirón, María Teresa, Torrent, Fernando, Villarroel, Morris, Fuente Vázquez, Jesús De La, Jin, J., Fernández-Muela Garrote, Montserrat, Bermejo Poza, Rubén, Cabezas Albéniz, Almudena, Pérez Marcos, Concepción, González De Chávarri Echániz, Elisabeth, Díaz Díaz Chirón, María Teresa, Torrent, Fernando, Villarroel, Morris, and Fuente Vázquez, Jesús De La
- Abstract
Fish can go through periods of feed deprivation, either due to natural causes influenced by temperature or management techniques in animal production, affecting their energy metabolism differently, depending on the duration of fasting in days and water temperature. This study showed the effect of different days of fasting before slaughter in rainbow trout by analyzing the intermediary metabolic enzymes in the muscle and liver. For this purpose, a non-fasting group was compared with trout that fasted for 5, 10, and 20 days (55, 107, and 200 degree days (°C d), respectively). A first phase of increased activity of enzymes involved in glycolysis was observed, increasing hexokinase enzyme activity in muscle and pyruvate kinase enzyme activity in muscle and liver. As the fasting days progressed, enzymes involved in the gluconeogenic and glycogenolytic pathways in the liver such as lactate dehydrogenase and glycogen phosphorylase increased their activity regarding the no fasted group. After 20 days of fasting (200 °C d), lipogenic and protein related enzyme activity depletion was observed, leading to significant changes in energy metabolism. Therefore, prolonged fasting with high degree days duration may compromise the energy supply for the vital development of rainbow trout., Ministerio de Economía y Competitividad (MINECO) (España), Depto. de Producción Animal, Fac. de Veterinaria, TRUE, pub
- Published
- 2024
29. Pipeline of New Drug Treatment for Non-alcoholic Fatty Liver Disease/Metabolic Dysfunction-associated Steatotic Liver Disease.
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Hu Y, Sun C, Chen Y, Liu YD, and Fan JG
- Abstract
Given the global prevalence and rising incidence of metabolic dysfunction-associated steatotic liver disease (MASLD), the absence of licensed medications is striking. A deeper understanding of the heterogeneous nature of MASLD has recently contributed to the discovery of novel groups of agents and the potential repurposing of currently available medications. MASLD therapies center on four major pathways. Considering the close relationship between MASLD and type 2 diabetes, the first approach involves antidiabetic medications, including incretins, thiazolidinedione insulin sensitizers, and sodium-glucose cotransporter 2 inhibitors. The second approach targets hepatic lipid accumulation and the resultant metabolic stress. Agents in this group include peroxisome proliferator-activated receptor agonists (e.g., pioglitazone, elafibranor, saroglitazar), bile acid-farnesoid X receptor axis regulators (obeticholic acid), de novo lipogenesis inhibitors (aramchol, NDI-010976), and fibroblast growth factor 21/19 analogs. The third approach focuses on targeting oxidative stress, inflammation, and fibrosis. Agents in this group include antioxidants (vitamin E), tumor necrosis factor α pathway regulators (emricasan, pentoxifylline, ZSP1601), and immune modulators (cenicriviroc, belapectin). The final group targets the gut (IMM-124e, solithromycin). Combination therapies targeting different pathogenetic pathways may provide an alternative to MASLD treatment with higher efficacy and fewer side effects. This review aimed to provide an update on these medications., Competing Interests: JGF has been an Associate Editor of Journal of Clinical and Translational Hepatology since 2013. The other authors have no conflict of interests related to this publication., (© 2024 Authors.)
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- 2024
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30. Mitochondrial bioenergetics and cardiolipin remodeling abnormalities in mitochondrial trifunctional protein deficiency.
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Vieira Neto E, Wang M, Szuminsky AJ, Ferraro L, Koppes E, Wang Y, Van't Land C, Mohsen AW, Zanatta G, El-Gharbawy AH, Anthonymuthu TS, Tyurina YY, Tyurin VA, Kagan V, Bayır H, and Vockley J
- Subjects
- Animals, Humans, Mice, Mitochondrial Trifunctional Protein, beta Subunit metabolism, Mitochondrial Trifunctional Protein, beta Subunit genetics, Mitochondria metabolism, Mutation, Mitochondrial Trifunctional Protein deficiency, Mitochondrial Trifunctional Protein metabolism, Mitochondrial Trifunctional Protein genetics, Rhabdomyolysis metabolism, Rhabdomyolysis genetics, Rhabdomyolysis pathology, Mitochondrial Myopathies metabolism, Mitochondrial Myopathies genetics, Mitochondrial Myopathies pathology, Oxygen Consumption, Male, Disease Models, Animal, Lysophospholipids, Cardiomyopathies, Nervous System Diseases, Cardiolipins metabolism, Mitochondrial Trifunctional Protein, alpha Subunit metabolism, Mitochondrial Trifunctional Protein, alpha Subunit genetics, Energy Metabolism genetics, Fibroblasts metabolism, Lipid Metabolism, Inborn Errors metabolism, Lipid Metabolism, Inborn Errors genetics, Lipid Metabolism, Inborn Errors pathology
- Abstract
Mitochondrial trifunctional protein (TFP) deficiency is an inherited metabolic disorder leading to a block in long-chain fatty acid β-oxidation. Mutations in HADHA and HADHB, which encode the TFP α and β subunits, respectively, usually result in combined TFP deficiency. A single common mutation, HADHA c.1528G>C (p.E510Q), leads to isolated 3-hydroxyacyl-CoA dehydrogenase deficiency. TFP also catalyzes a step in the remodeling of cardiolipin (CL), a phospholipid critical to mitochondrial membrane stability and function. We explored the effect of mutations in TFP subunits on CL and other phospholipid content and composition and the consequences of these changes on mitochondrial bioenergetics in patient-derived fibroblasts. Abnormalities in these parameters varied extensively among different fibroblasts, and some cells were able to maintain basal oxygen consumption rates similar to controls. Although CL reduction was universally identified, a simultaneous increase in monolysocardiolipins was discrepant among cells. A similar profile was seen in liver mitochondria isolates from a TFP-deficient mouse model. Response to new potential drugs targeting CL metabolism might be dependent on patient genotype.
- Published
- 2024
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31. dldhcri3 zebrafish exhibit altered mitochondrial ultrastructure, morphology, and dysfunction partially rescued by probucol or thiamine.
- Author
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Lavorato M, Iadarola D, Remes C, Kaur P, Broxton C, Mathew ND, Xiao R, Seiler C, Nakamaru-Ogiso E, Anderson VE, and Falk MJ
- Subjects
- Animals, Dihydrolipoamide Dehydrogenase metabolism, Dihydrolipoamide Dehydrogenase genetics, Zebrafish Proteins metabolism, Zebrafish Proteins genetics, Mitochondrial Diseases drug therapy, Mitochondrial Diseases pathology, Mitochondrial Diseases metabolism, Amino Acids, Branched-Chain metabolism, Zebrafish, Mitochondria drug effects, Mitochondria metabolism, Mitochondria ultrastructure, Mitochondria pathology, Disease Models, Animal, Probucol pharmacology
- Abstract
Dihydrolipoamide dehydrogenase (DLD) deficiency is a recessive mitochondrial disease caused by variants in DLD, the E3 subunit of mitochondrial α-keto (or 2-oxo) acid dehydrogenase complexes. DLD disease symptoms are multisystemic, variably manifesting as Leigh syndrome, neurodevelopmental disability, seizures, cardiomyopathy, liver disease, fatigue, and lactic acidemia. While most DLD disease symptoms are attributed to dysfunction of the pyruvate dehydrogenase complex, the effects of other α-keto acid dehydrogenase deficiencies remain unclear. Current therapies for DLD deficiency are ineffective, with no vertebrate animal model available for preclinical study. We created a viable Danio rerio (zebrafish) KO model of DLD deficiency, dldhcri3. Detailed phenotypic characterization revealed shortened larval survival, uninflated swim bladder, hepatomegaly and fatty liver, and reduced swim activity. These animals displayed increased pyruvate and lactate levels, with severe disruption of branched-chain amino acid catabolism manifest as increased valine, leucine, isoleucine, α-ketoisovalerate, and α-ketoglutarate levels. Evaluation of mitochondrial ultrastructure revealed gross enlargement, severe cristae disruption, and reduction in matrix electron density in liver, intestines, and muscle. Therapeutic modeling of candidate therapies demonstrated that probucol or thiamine improved larval swim activity. Overall, this vertebrate model demonstrated characteristic phenotypic and metabolic alterations of DLD disease, offering a robust platform to screen and characterize candidate therapies.
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- 2024
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32. Metabolic Reprogramming and Signaling to Chromatin Modifications in Tumorigenesis
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Díaz-Hirashi, Zyanya, Gao, Tian, Verdeguer, Francisco, Crusio, Wim E., Series Editor, Dong, Haidong, Series Editor, Radeke, Heinfried H., Series Editor, Rezaei, Nima, Series Editor, Steinlein, Ortrud, Series Editor, Xiao, Junjie, Series Editor, and Serpa, Jacinta, editor
- Published
- 2020
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33. Nutritional Epigenetics
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Carlberg, Carsten, Ulven, Stine Marie, Molnár, Ferdinand, Carlberg, Carsten, Ulven, Stine Marie, and Molnár, Ferdinand
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- 2020
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34. Differential hepatic mitochondrial function and gluconeogenic gene expression in 2 Holstein strains in a pasture-based system.
- Author
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García-Roche, Mercedes, Talmón, Daniel, Cañibe, Guillermo, Astessiano, Ana Laura, Mendoza, Alejandro, Quijano, Celia, Cassina, Adriana, and Carriquiry, Mariana
- Subjects
- *
HOLSTEIN-Friesian cattle , *OXYGEN consumption , *PYRUVATE dehydrogenase kinase , *ANIMAL herds , *GENE expression , *BLOOD sugar , *PYRUVATE carboxylase , *MITOCHONDRIA - Abstract
The objective of this study was to assess hepatic ATP synthesis in Holstein cows of North American and New Zealand origins and the gluconeogenic pathway, one of the pathways with the highest ATP demands in the ruminant liver. Autumn-calving Holstein cows of New Zealand and North American origins were managed in a pasture-based system with supplementation of concentrate that represented approximately 33% of the predicted dry matter intake during 2017, 2018, and 2019, and hepatic biopsies were taken during mid-lactation at 174 ± 23 days in milk. Cows of both strains produced similar levels of solids-corrected milk, and no differences in body condition score were found. Plasma glucose concentrations were higher for cows of New Zealand versus North American origin. Hepatic mitochondrial function evaluated measuring oxygen consumption rates showed that mitochondrial parameters related to ATP synthesis and maximum respiratory rate were increased for cows of New Zealand compared with North American origin. However, hepatic gene expression of pyruvate carboxylase, phosphoenolpyruvate carboxykinase, and pyruvate dehydrogenase kinase was increased in North American compared with New Zealand cows. These results altogether suggest an increased activity of the tricarboxylic cycle in New Zealand cows, leading to increased ATP synthesis, whereas North American cows pull tricarboxylic cycle intermediates toward gluconeogenesis. The fact that this occurs during mid-lactation could account for the increased persistency of North American cows, especially in a pasture-based system. In addition, we observed an augmented mitochondrial density in New Zealand cows, which could be related to feed efficiency mechanisms. In sum, our results contribute to the elucidation of hepatic molecular mechanisms in dairy cows in production systems with higher inclusion of pastures. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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35. واکنش بیوشیمیایی ش بپره مدیتران ها ی آر د به سمیت ترانس آنتول Ephestia kuehniella Zeller (Lep.: Pyralidae)
- Author
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مرتضی شهریاری, نجمه صاحب زاده, and آرش زیبای ی
- Abstract
Background and Objectives Essential oils are a variety of compounds, and their monoterpenoids, as the main constituents may impair insects' physiological and behavioral functions and could thus be applied in pest management. In addition to causing damage to stored products, the Mediterranean flour moth, Ephestia kuehniella Zeller, 1879 (Lep.: Pyralidae), is actually an easy model to grow in the laboratory and is one of the suitable insects to determine toxicity and in vivo interactions of xenobiotics with physiological systems of insects. In the present study, in order to better understand the mechanism of action of trans-anethole as one of the most important secondary metabolites of the Apiaceae family, the oral toxicity of this compound was evaluated on the activities of digestive and detoxifying enzymes, and metabolites involving in intermediate metabolism of the fourth instar of E. kuehniella. Materials and Methods Fourth instar larvae of E. kuehniella were randomly selected and separately exposed to 1 g of the artificial diet containing 1, 2, 4, 8, and 16 μL/g of trans-anethole while the control larvae fed on the diet containing acetone. The bioassay test was performed in 3 replicates with 10 larvae per replication. Mortality was determined after 24 h and LC50 value was calculated by POLO-plus software. Ephestia kuehniella larvae were exposed to the LC50 value of transanethole to determine its effects on the enzymatic and non-enzymatic components. After 24 of exposure, the larvae hemolymph, midgut, and fat bodies were extracted. Hemolymph samples were immediately centrifuged at 15000 × g at 4°C for 20 min, while samples of midgut and fat bodies were initially homogenized by a glass pestle and then centrifuged under the same conditions. The hemolymph samples were used to assay the detoxifying enzymes and enzymes of intermediary metabolism, while the midgut samples were used to assess the digestive enzymes. Fat body samples and head capsules were also used for energy reserves. Results The LC50 value of trans-anethole against the larvae was 7.03 μL g-1. Significant decrease in the digestive enzyme activities (α-amylase, α and β-glucosidase, lipase) and specific proteases (trypsin, chymotrypsin, elastase, amino and carboxy peptidase) were observed. In contrast, the activity of the detoxifying enzymes (esterases, and glutathione S-transferase) increased in the treated insects. The activities of amino transferases (alanine, aspartate, and gamma-glutamyl) significantly increased in the treated larvae by trans-anethole. Significant decreases in lactate dehydrogenase and phosphatase (acid and alkaline) were observed after treatment. Moreover, the amount of storage macromolecules (total protein, glycogen, and triglyceride) in the treated insects was significantly decreased compared to the control. Discussion Our research revealed that trans-anethole is a toxic compound to E. kuehniella by reducing the survival and digestive efficiency of the larvae. Moreover, trans-anethole significantly enhanced the detoxifying enzymes activities. When the larvae were exposed to LC50 of transanethole, the digestive activity was reduced due to the cytotoxic effects of trans-anethole on epithelial cells of the larval alimentary canal. Our results demonstrated that trans-anethole might have a promising potential to develop as a safe compound to suppress E. kuehniella population. For the practical use of trans-anethole to control E. kuehniella, it is required to determine the accurate mode of action, and using appropriate formulations to increase its efficacy in long-term applications. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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36. Effects of Moderate–Intensity Physical Training on Skeletal Muscle Substrate Transporters and Metabolic Parameters of Ovariectomized Rats.
- Author
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Pejon, Taciane Maria Melges, Scariot, Pedro Paulo Menezes, Selistre-de-Araujo, Heloísa Sobreiro, Gobatto, Claudio Alexandre, Cornachione, Anabelle Silva, and Beck, Wladimir Rafael
- Subjects
EXERCISE physiology ,SKELETAL muscle ,ANIMAL swimming ,RATS ,PHYSICAL activity ,PHYSICAL training & conditioning - Abstract
A deficit of estrogen is associated with energy substrate imbalance, raising the risk of metabolic diseases. Physical training (PT) is a potent metabolic regulator through oxidation and storage of substrates transported by GLUT4 and FAT CD36 in skeletal muscle. However, little is known about the effects of PT on these carriers in an estrogen-deficit scenario. Thus, the aim of this study was to determine the influence of 12 weeks of PT on metabolic variables and GLUT4 and FAT CD36 expression in the skeletal muscle of animals energetically impaired by ovariectomy (OVX). The trained animals swam 30 min/day, 5 days/week, at 80% of the critical load intensity. Spontaneous physical activity was measured biweekly. After training, FAT CD36 and GLUT4 expressions were quantified by immunofluorescence in the soleus, as well as muscular glycogen and triglyceride of the soleus, gluteus maximus and gastrocnemius. OVX significantly reduced FAT CD36, GLUT4 and spontaneous physical activity (p < 0.01), while PT significantly increased FAT CD36, GLUT4 and spontaneous physical activity (p < 0.01). PT increased soleus glycogen, and OVX decreased muscular triglyceride of gluteus maximus. Therefore, OVX can cause energy disarray through reduction in GLUT4 and FAT CD36 and their muscle substrates and PT prevented these metabolic consequences, masking ovarian estrogen's absence. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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37. The chondrichthyan glucagon-like peptide 3 regulates hepatic ketone metabolism in the Pacific spiny dogfish Squalus suckleyi.
- Author
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Weinrauch, Alyssa M, Bouyoucos, Ian A, Conlon, J Michael, and Anderson, W Gary
- Subjects
- *
KETONES , *PEPTIDES , *METABOLISM , *TISSUE metabolism , *OLEIC acid - Abstract
• Chondrichthyan specific glucagon-like peptide 3 (GLP-3) has metabolic effects. • No effects of GLP-3 were found on spiral valve. • GLP-3 exerts metabolic effects on ketone, but not glucose liver metabolism. Chondrichthyans have a novel proglucagon-derived peptide, glucagon-like peptide (GLP)-3, in addition to GLP-1 and GLP-2 that occur in other vertebrates. Given that the GLPs are important regulators of metabolic homeostasis across vertebrates, we sought to investigate whether GLP-3 displays functional actions on metabolism within a representative chondrichthyan, the Pacific spiny dogfish Squalus suckleyi. There were no observed effects of GLP-3 perfusion (10 nM for 15 min) on the rate of glucose or oleic acid acquisition at the level of the spiral valve nor were there any measured effects on intermediary metabolism within this tissue. Despite no effects on apparent glucose transport or glycolysis in the liver, a significant alteration to ketone metabolism occurred. Firstly, ketone flux through the perfused liver switched from a net endogenous production to consumption following hormone application. Accompanying this change, significant increases in mRNA transcript abundance of putative ketone transporters and in the activity of β-hydroxybutyrate dehydrogenase (a key enzyme regulating ketone flux in the liver) were observed. Overall, while these results show effects on hepatic metabolism, the physiological actions of GLP are distinct between this chondrichthyan and those of GLP-1 on teleost fishes. Whether this is the result of the particular metabolic dependency on ketone bodies in chondrichthyans or a differential function of a novel GLP remains to be fully elucidated. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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38. Effects of Fasting on Intermediary Metabolism Enzymes in the Liver and Muscle of Rainbow Trout
- Author
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Montserrat Fernández-Muela, Rubén Bermejo-Poza, Almudena Cabezas, Concepción Pérez, Elisabet González de Chavarri, María Teresa Díaz, Fernando Torrent, Morris Villarroel, and Jesús De la Fuente
- Subjects
fasting ,rainbow trout ,liver ,muscle ,intermediary metabolism ,enzyme activity ,Biology (General) ,QH301-705.5 ,Genetics ,QH426-470 - Abstract
Fish can go through periods of feed deprivation, either due to natural causes influenced by temperature or management techniques in animal production, affecting their energy metabolism differently, depending on the duration of fasting in days and water temperature. This study showed the effect of different days of fasting before slaughter in rainbow trout by analyzing the intermediary metabolic enzymes in the muscle and liver. For this purpose, a non-fasting group was compared with trout that fasted for 5, 10, and 20 days (55, 107, and 200 degree days (°C d), respectively). A first phase of increased activity of enzymes involved in glycolysis was observed, increasing hexokinase enzyme activity in muscle and pyruvate kinase enzyme activity in muscle and liver. As the fasting days progressed, enzymes involved in the gluconeogenic and glycogenolytic pathways in the liver such as lactate dehydrogenase and glycogen phosphorylase increased their activity regarding the no fasted group. After 20 days of fasting (200 °C d), lipogenic and protein related enzyme activity depletion was observed, leading to significant changes in energy metabolism. Therefore, prolonged fasting with high degree days duration may compromise the energy supply for the vital development of rainbow trout.
- Published
- 2023
- Full Text
- View/download PDF
39. Methionine as a regulator of bone remodeling with fasting.
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Amorim T, Kumar NG, David NL, Dion W, Pagadala T, Doshi NK, Zhu B, Parkhitko A, Steinhauser ML, and Fazeli PK
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- Animals, Humans, Mice, Male, Female, Osteoblasts metabolism, Procollagen metabolism, Procollagen blood, Middle Aged, Adult, Absorptiometry, Photon, Peptide Fragments metabolism, Peptide Fragments blood, Caloric Restriction, Methionine metabolism, Methionine administration & dosage, Bone Remodeling drug effects, Bone Remodeling physiology, Fasting, Bone Density drug effects
- Abstract
Caloric restriction improves metabolic health but is often complicated by bone loss. We studied bone parameters in humans during a 10-day fast and identified candidate metabolic regulators of bone turnover. Pro-collagen 1 intact N-terminal pro-peptide (P1NP), a bone formation marker, decreased within 3 days of fasting. Whereas dual-energy x-ray absorptiometry measures of bone mineral density were unchanged after 10 days of fasting, high-resolution peripheral quantitative CT demonstrated remodeling of bone microarchitecture. Pathway analysis of longitudinal metabolomics data identified one-carbon metabolism as fasting dependent. In cultured osteoblasts, we tested the functional significance of one-carbon metabolites modulated by fasting, finding that methionine - which surged after 3 days of fasting - affected markers of osteoblast cell state in a concentration-dependent manner, in some instances exhibiting a U-shaped response with both low and high concentrations driving putative antibone responses. Administration of methionine to mice for 5 days recapitulated some fasting effects on bone, including a reduction in serum P1NP. In conclusion, a 10-day fast in humans led to remodeling of bone microarchitecture, potentially mediated by a surge in circulating methionine. These data support an emerging model that points to a window of optimal methionine exposure for bone health.
- Published
- 2024
- Full Text
- View/download PDF
40. Over-Generalizing About GC (Hypoxia): Pitfalls of Limiting Breadth of Experimental Systems and Analyses in Framing Informatics Conclusions
- Author
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Mark R. Boothby, Ariel Raybuck, Sung Hoon Cho, Kristy R. Stengel, Volker H. Haase, Scott Hiebert, and Jingxin Li
- Subjects
hypoxia ,intermediary metabolism ,Germinal center (GC) B cells ,RNA-Seq ,polyclonal preimmune repertoire ,BCR transgenic mice ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Accumulating evidence suggests that many immune responses are influenced by local nutrient concentrations in addition to the programming of intermediary metabolism within immune cells. Humoral immunity and germinal centers (GC) are settings in which these factors are under active investigation. Hypoxia is an example of how a particular nutrient is distributed in lymphoid follicles during an antibody response, and how oxygen sensors may impact the qualities of antibody output after immunization. Using exclusively a bio-informatic analysis of mRNA levels in GC and other B cells, recent work challenged the concept that there is any hypoxia or that it has any influence. To explore this proposition, we performed new analyses of published genomics data, explored potential sources of disparity, and elucidated aspects of the apparently conflicting conclusions. Specifically, replicability and variance among data sets derived from different naïve as well as GC B cells were considered. The results highlight broader issues that merit consideration, especially at a time of heightened focus on scientific reports in the realm of immunity and antibody responses. Based on these analyses, a standard is proposed under which the relationship of new data sets should be compared to prior “fingerprints” of cell types and reported transparently to referees and readers. In light of independent evidence of diversity within and among GC elicited by protein immunization, avoidance of overly broad conclusions about germinal centers in general when experimental systems are subject to substantial constraints imposed by technical features also is warranted.
- Published
- 2021
- Full Text
- View/download PDF
41. Over-Generalizing About GC (Hypoxia): Pitfalls of Limiting Breadth of Experimental Systems and Analyses in Framing Informatics Conclusions.
- Author
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Boothby, Mark R., Raybuck, Ariel, Cho, Sung Hoon, Stengel, Kristy R., Haase, Volker H., Hiebert, Scott, and Li, Jingxin
- Subjects
GERMINAL centers ,ANTIBODY formation ,HYPOXEMIA ,B cells ,OXYGEN detectors - Abstract
Accumulating evidence suggests that many immune responses are influenced by local nutrient concentrations in addition to the programming of intermediary metabolism within immune cells. Humoral immunity and germinal centers (GC) are settings in which these factors are under active investigation. Hypoxia is an example of how a particular nutrient is distributed in lymphoid follicles during an antibody response, and how oxygen sensors may impact the qualities of antibody output after immunization. Using exclusively a bio-informatic analysis of mRNA levels in GC and other B cells, recent work challenged the concept that there is any hypoxia or that it has any influence. To explore this proposition, we performed new analyses of published genomics data, explored potential sources of disparity, and elucidated aspects of the apparently conflicting conclusions. Specifically, replicability and variance among data sets derived from different naïve as well as GC B cells were considered. The results highlight broader issues that merit consideration, especially at a time of heightened focus on scientific reports in the realm of immunity and antibody responses. Based on these analyses, a standard is proposed under which the relationship of new data sets should be compared to prior "fingerprints" of cell types and reported transparently to referees and readers. In light of independent evidence of diversity within and among GC elicited by protein immunization, avoidance of overly broad conclusions about germinal centers in general when experimental systems are subject to substantial constraints imposed by technical features also is warranted. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
42. Restricted feeding benefits the growth performance and glucose homeostasis of blunt snout bream Megalobrama amblycephala fed high-carbohydrate diets
- Author
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Chao Xu, Wen-Bin Liu, Bing-Ke Wang, and Xiang-Fei Li
- Subjects
Carbohydrate utilization ,Intestinal function ,Intermediary metabolism ,Fish farming ,Aquaculture. Fisheries. Angling ,SH1-691 - Abstract
This study was conducted to investigate the effects of restricted feeding on the growth performance, glycolipid metabolism and glucose homeostasis of Megalobrama amblycephala fed a high-carbohydrate (HC) diet. A total of 240 fish (46.94 ± 0.04 g) were randomly assigned to four groups containing the satiation of a control diet (30 % carbohydrate) and three satiety levels (100 %, HC1; 80 %, HC2; and 60 %, HC3) of the HC diet (43 % carbohydrate) for 8 weeks. High carbohydrate levels remarkably decreased daily growth coefficient (DGC), growth rate per metabolic body weight (GRMBW), feed intake (FI) and the transcriptions of growth hormone (GH), growth hormone receptor (GHR), fructose-1,6-biphosphatase peroxisome (FBPase), proliferator-activated receptor α (PPARα) and carnitine palmitoyl transferase I (CPT I) compared to the control group, but intestinal enzymes activities, tissue glycogen and lipid contents, and the transcriptions of glucokinase (GK), pyruvate kinase (PK), sterol regulatory element-binding protein 1 (SREBP 1), fatty acid synthase (FAS) and acetyl-CoA carboxylase α (ACCα) showed an opposite trend. Furthermore, HC2 group obtained relatively high values of DGC, GRMBW, feed efficiency ratio (FER), intestinal enzymes activities and the transcriptions of GH, GHR, IGF-I, GK, PK, PPARα and CPT I. Meanwhile, the HC2 group enhanced the glucose tolerance of fish fed HC diet after glucose administration. Overall, the satiation level at 80 % benefited the growth rate, feed efficiency and glucose homeostasis of M. amblycephala fed a high-carbohydrate diet.
- Published
- 2020
- Full Text
- View/download PDF
43. Effects of Moderate–Intensity Physical Training on Skeletal Muscle Substrate Transporters and Metabolic Parameters of Ovariectomized Rats
- Author
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Taciane Maria Melges Pejon, Pedro Paulo Menezes Scariot, Heloísa Sobreiro Selistre-de-Araujo, Claudio Alexandre Gobatto, Anabelle Silva Cornachione, and Wladimir Rafael Beck
- Subjects
estrogen ,GLUT4 ,FAT CD36 ,energetic balance ,intermediary metabolism ,physical exercise ,Microbiology ,QR1-502 - Abstract
A deficit of estrogen is associated with energy substrate imbalance, raising the risk of metabolic diseases. Physical training (PT) is a potent metabolic regulator through oxidation and storage of substrates transported by GLUT4 and FAT CD36 in skeletal muscle. However, little is known about the effects of PT on these carriers in an estrogen-deficit scenario. Thus, the aim of this study was to determine the influence of 12 weeks of PT on metabolic variables and GLUT4 and FAT CD36 expression in the skeletal muscle of animals energetically impaired by ovariectomy (OVX). The trained animals swam 30 min/day, 5 days/week, at 80% of the critical load intensity. Spontaneous physical activity was measured biweekly. After training, FAT CD36 and GLUT4 expressions were quantified by immunofluorescence in the soleus, as well as muscular glycogen and triglyceride of the soleus, gluteus maximus and gastrocnemius. OVX significantly reduced FAT CD36, GLUT4 and spontaneous physical activity (p < 0.01), while PT significantly increased FAT CD36, GLUT4 and spontaneous physical activity (p < 0.01). PT increased soleus glycogen, and OVX decreased muscular triglyceride of gluteus maximus. Therefore, OVX can cause energy disarray through reduction in GLUT4 and FAT CD36 and their muscle substrates and PT prevented these metabolic consequences, masking ovarian estrogen’s absence.
- Published
- 2022
- Full Text
- View/download PDF
44. Circulating markers of NADH-reductive stress correlate with mitochondrial disease severity.
- Author
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Sharma, Rohit, Reinstadler, Bryn, Engelstad, Kristin, Skinner, Owen S., Stackowitz, Erin, Haller, Ronald G., Clish, Clary B., Pierce, Kerry, Walker, Melissa A., Fryer, Robert, Oglesbee, Devin, Xiangling Mao, Shungu, Dikoma C., Khatri, Ashok, Michio Hirano, De Vivo, Darryl C., Mootha, Vamsi K., Mao, Xiangling, and Hirano, Michio
- Subjects
- *
MELAS syndrome , *MITOCHONDRIAL DNA , *CYTOKINES , *RESEARCH , *GENETIC mutation , *CLINICAL trials , *RESEARCH methodology , *MEDICAL cooperation , *EVALUATION research , *MITOCHONDRIAL encephalomyopathies , *ALANINE , *SEVERITY of illness index , *COMPARATIVE studies , *KARNOFSKY Performance Status , *RESEARCH funding , *LACTIC acid , *BUTYRIC acid , *HYDROXY acids - Abstract
Mitochondrial disorders represent a large collection of rare syndromes that are difficult to manage both because we do not fully understand biochemical pathogenesis and because we currently lack facile markers of severity. The m.3243A>G variant is the most common heteroplasmic mitochondrial DNA mutation and underlies a spectrum of diseases, notably mitochondrial encephalomyopathy lactic acidosis and stroke-like episodes (MELAS). To identify robust circulating markers of m.3243A>G disease, we first performed discovery proteomics, targeted metabolomics, and untargeted metabolomics on plasma from a deeply phenotyped cohort (102 patients, 32 controls). In a validation phase, we measured concentrations of prioritized metabolites in an independent cohort using distinct methods. We validated 20 analytes (1 protein, 19 metabolites) that distinguish patients with MELAS from controls. The collection includes classic (lactate, alanine) and more recently identified (GDF-15, α-hydroxybutyrate) mitochondrial markers. By mining untargeted mass-spectra we uncovered 3 less well-studied metabolite families: N-lactoyl-amino acids, β-hydroxy acylcarnitines, and β-hydroxy fatty acids. Many of these 20 analytes correlate strongly with established measures of severity, including Karnofsky status, and mechanistically, nearly all markers are attributable to an elevated NADH/NAD+ ratio, or NADH-reductive stress. Our work defines a panel of organelle function tests related to NADH-reductive stress that should enable classification and monitoring of mitochondrial disease. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
45. Guanosine triphosphate links MYC-dependent metabolic and ribosome programs in small-cell lung cancer.
- Author
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Fang Huang, Huffman, Kenneth E., Zixi Wang, Xun Wang, Kailong Li, Feng Cai, Chendong Yang, Ling Cai, Shih, Terry S., Zacharias, Lauren G., Chung, Andrew, Qian Yang, Chalishazar, Milind D., Ireland, Abbie S., Stewart, C. Allison, Cargill, Kasey, Girard, Luc, Yi Liu, Min Ni, and Jian Xu
- Subjects
- *
GUANOSINE triphosphate , *LUNG cancer , *ORGANELLE formation , *PROTEIN metabolism , *PROTEIN synthesis , *RIBOSOMAL DNA , *RIBOSOMAL proteins , *NUCLEOTIDE metabolism , *PROTEINS , *RESEARCH , *GENETIC mutation , *ANIMAL experimentation , *RESEARCH methodology , *LUNG tumors , *MEDICAL cooperation , *EVALUATION research , *HYDROLASES , *NUCLEOTIDES , *COMPARATIVE studies , *TRANSFERASES , *RESEARCH funding , *CELL lines , *CYTOPLASM , *CARRIER proteins , *MICE - Abstract
MYC stimulates both metabolism and protein synthesis, but how cells coordinate these complementary programs is unknown. Previous work reported that, in a subset of small-cell lung cancer (SCLC) cell lines, MYC activates guanosine triphosphate (GTP) synthesis and results in sensitivity to inhibitors of the GTP synthesis enzyme inosine monophosphate dehydrogenase (IMPDH). Here, we demonstrated that primary MYChi human SCLC tumors also contained abundant guanosine nucleotides. We also found that elevated MYC in SCLCs with acquired chemoresistance rendered these otherwise recalcitrant tumors dependent on IMPDH. Unexpectedly, our data indicated that IMPDH linked the metabolic and protein synthesis outputs of oncogenic MYC. Coexpression analysis placed IMPDH within the MYC-driven ribosome program, and GTP depletion prevented RNA polymerase I (Pol I) from localizing to ribosomal DNA. Furthermore, the GTPases GPN1 and GPN3 were upregulated by MYC and directed Pol I to ribosomal DNA. Constitutively GTP-bound GPN1/3 mutants mitigated the effect of GTP depletion on Pol I, protecting chemoresistant SCLC cells from IMPDH inhibition. GTP therefore functioned as a metabolic gate tethering MYC-dependent ribosome biogenesis to nucleotide sufficiency through GPN1 and GPN3. IMPDH dependence is a targetable vulnerability in chemoresistant MYChi SCLC. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
46. Growth performance and metabolic responses to dietary protein/carbohydrate ratios in pacu (Piaractus mesopotamicus) juveniles.
- Author
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Pereira, Mayara de Moura, Nagata, Mariana Midori, Enes, Paula, Oliva‐Teles, Aires, Urbinati, Elisabeth Criscuolo, and Takahashi, Leonardo Susumu
- Subjects
- *
CARBOHYDRATES , *BLOOD sugar , *PYRUVATE kinase , *GLUCOSE-6-phosphate dehydrogenase , *PROTEINS , *GLYCEMIC index , *CARBOHYDRATE content of food - Abstract
Proper inclusion of carbohydrates in aquafeeds can increase protein and lipid retention preventing the catabolism of these nutrients for energy purposes. This research aimed to evaluate performance, metabolic and enzymatic indicators in pacu (Piaractus mesopotamicus) juveniles fed diets with 350 or 400 g/kg starch (S) and 190 or 210 g/kg digestible protein (P) (diets S35P19, S35P21, S40P19 and S40P21 respectively). Overall, the best growth performance was achieved with diet S35P21. Dietary protein and starch levels had no effect on feed intake, feed conversion ratio and protein efficiency ratio. The lowest whole‐body protein content was recorded in fish fed the S35P19 diet, while fish fed diet S40P21 presented the highest whole‐body lipid content. Regardless of dietary protein level, S40 diets led to higher plasma glucose and triglycerides levels, and higher liver glycogen content. No differences were observed on hepatosomatic index or muscle lipids content. Increasing dietary starch level led to an increase in mesenteric fat index and in liver glucokinase activity, while higher dietary protein promoted a decrease in liver lipid content. Fish fed diet S40P21 showed higher liver glucose‐6‐phosphate dehydrogenase activity than fish fed the S35P21 and S40P19 diets. Dietary protein and starch levels had no effect on pyruvate kinase and fructose‐1,6‐bisphosphatase activity. Overall, dietary starch enhanced glycolytic and lipogenic pathways but did not depress gluconeogenic pathway. The results of this study indicate that a diet with 350 g/kg starch and 210 g/kg digestible protein was the most adequate for pacu in terms of growth performance and feed utilization. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
47. Regulation of Osteoblast Metabolism by Wnt Signaling
- Author
-
Megan C. Moorer and Ryan C. Riddle
- Subjects
Wnt signaling ,Beta catenin ,Osteoblasts ,Intermediary metabolism ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
Wnt/β-catenin signaling plays a critical role in the achievement of peak bone mass, affecting the commitment of mesenchymal progenitors to the osteoblast lineage and the anabolic capacity of osteoblasts depositing bone matrix. Recent studies suggest that this evolutionarily-conserved, developmental pathway exerts its anabolic effects in part by coordinating osteoblast activity with intermediary metabolism. These findings are compatible with the cloning of the gene encoding the low-density lipoprotein related receptor-5 (LRP5) Wnt co-receptor from a diabetes-susceptibility locus and the now well-established linkage between Wnt signaling and metabolism. In this article, we provide an overview of the role of Wnt signaling in whole-body metabolism and review the literature regarding the impact of Wnt signaling on the osteoblast's utilization of three different energy sources: fatty acids, glucose, and glutamine. Special attention is devoted to the net effect of nutrient utilization and the mode of regulation by Wnt signaling. Mechanistic studies indicate that the utilization of each substrate is governed by a unique mechanism of control with β-catenin-dependent signaling regulating fatty acid β-oxidation, while glucose and glutamine utilization are β-catenin-independent and downstream of mammalian target of rapamycin complex 2 (mTORC2) and mammalian target of rapamycin complex 1 (mTORC1) activation, respectively. The emergence of these data has provided a new context for the mechanisms by which Wnt signaling influences bone development.
- Published
- 2018
- Full Text
- View/download PDF
48. Metabolic responses to dietary carbohydrate/lipids ratios in neotropical hybrid catfish (♂Pseudoplatystoma corruscans×♀Pseudoplatystoma fasciatum)
- Author
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DANIEL OKAMURA, RODRIGO FORTES-SILVA, RENAN R. PAULINO, FELIPE G. DE ARAÚJO, DIEGO V. DA COSTA, RAQUEL T. PEREIRA, and PRISCILA V. ROSA
- Subjects
enzymes activity ,hepatic function ,intermediary metabolism ,hybrid catfish ,Surubim ,Science - Abstract
Abstract: The purpose of this study was to assess the effect of different carbohydrate and lipid (CHO/L) ratios on the performance and energy metabolism of hybrid catfish (♂Pseudoplatystoma corruscans × ♀ Pseudoplatystoma fasciatum). One hundred and sixty-eight fish (104.9±16.5 g BW) were distributed into 24 100-L tanks. The experiment was performed using a randomised block design with four CHO/L ratios (0.45, 1.00, 1.66 and 2.85) and six replications. Growth performance, protein content, glucose and triglycerides in plasma, muscle and liver, and the hepatic activity of the malic and glucose-6-phosphate dehydrogenase (G6PD) enzymes were measured after 60 feeding days. No significant differences were observed in growth performance, protein and triglycerides of plasma and muscle, hepatic protein or malic enzyme activity. CHO/L: 2.85 provided the highest plasma and liver glucose, while CHO/L: 0.45 showed high liver triglycerides. A linear effect was found for the hepatic activity of G6PD and dietary starch levels (R2=0.93). The hepatic activity of G6PD was greater in CHO/L=2.85 than for CHO/L: 0.45. In conclusion, the limit of dietary starch inclusion and lipids were 15% and 9.00%, respectively (CHO/L: 1.66), and this level did not affect the energy metabolism of the juvenile hybrid catfish.
- Published
- 2019
- Full Text
- View/download PDF
49. Effects of Artemisia annua methanolic extract on the enzymatic components of intermediary metabolism and the antioxidant system of Pseudococcus viburni Signoret
- Author
-
Samar Ramzi, Ali Seraji, Reza Azadi Gonbad, Kimia Mirhaghparast, and Zahra Mojib-Haghghadam
- Subjects
antioxidant response ,Artemisia annua ,intermediary metabolism ,methanolic extract ,Pseudococcus viburni ,Plant culture ,SB1-1110 - Abstract
Toxicity and physiological alterations were determined in Pseudococcus viburni nymphs treated with Artemisia annua methanolic extract. The leaf dipping bioassay showed LC50 values of 0.287% and 0.194% 24 and 48 hours post-exposure. Activities of general esterases were significantly higher in the control nymphs than in those which had been treated except for the 48 h time interval using α-naphtyl acetate. The activity of glutathione S-transferase using CDNB (1-chloro-2,4-dinitrobenzene) in the control nymphs, was significantly higher than in the control at both time intervals while no significant difference was observed after 24 h in addition to the higher enzymatic activity in the treated nymphs after 48 h. All three aminotransferases were significantly more active in the control nymphs except for time intervals of 24 h for γ-glutamyl transferase and 48 h for alanine aminotransferase. Higher activities of lactate dehydrogenase, acid- and alkaline phosphatase were found in the control nymphs than in treated nymphs for all time intervals. Activities of the enzymes involved in the antioxidant system including catalase, peroxidase, superoxide dismutase, ascorbate peroxidase and glucose-6-phosphate dehydrogenase was increased in the treated nymphs compared to the control. Results of the current study demonstrated toxic effects of A. annua methanolic extract on P. viburni nymphs causing mortality and physiological turbulences.
- Published
- 2018
- Full Text
- View/download PDF
50. HDAC inhibitors elicit metabolic reprogramming by targeting super-enhancers in glioblastoma models.
- Author
-
Trang Thi Thu Nguyen, Yiru Zhang, Enyuan Shang, Chang Shu, Torrini, Consuelo, Junfei Zhao, Bianchetti, Elena, Mela, Angeliki, Humala, Nelson, Mahajan, Aayushi, Harmanci, Arif O., Zhengdeng Lei, Maienschein-Cline, Mark, Quinzii, Catarina M., Westhoff, Mike-Andrew, Karpel-Massler, Georg, Bruce, Jeffrey N., Canoll, Peter, Siegelin, Markus D., and Nguyen, Trang Thi Thu
- Subjects
- *
SUPER enhancers , *PROTEIN metabolism , *CELL differentiation , *ENERGY metabolism , *RESEARCH , *AMIDASES , *DNA , *ANIMAL experimentation , *RESEARCH methodology , *GLIOMAS , *EVALUATION research , *MEDICAL cooperation , *COMPARATIVE studies , *CELLS , *RESEARCH funding , *ENZYME inhibitors , *GLYCOLYSIS , *MICE , *FATTY acids , *PHARMACODYNAMICS , *CHEMICAL inhibitors - Abstract
The Warburg effect is a tumor-related phenomenon that could potentially be targeted therapeutically. Here, we showed that glioblastoma (GBM) cultures and patients' tumors harbored super-enhancers in several genes related to the Warburg effect. By conducting a transcriptome analysis followed by ChIP-Seq coupled with a comprehensive metabolite analysis in GBM models, we found that FDA-approved global (panobinostat, vorinostat) and selective (romidepsin) histone deacetylase (HDAC) inhibitors elicited metabolic reprogramming in concert with disruption of several Warburg effect-related super-enhancers. Extracellular flux and carbon-tracing analyses revealed that HDAC inhibitors blunted glycolysis in a c-Myc-dependent manner and lowered ATP levels. This resulted in the engagement of oxidative phosphorylation (OXPHOS) driven by elevated fatty acid oxidation (FAO), rendering GBM cells dependent on these pathways. Mechanistically, interference with HDAC1/-2 elicited a suppression of c-Myc protein levels and a concomitant increase in 2 transcriptional drivers of oxidative metabolism, PGC1α and PPARD, suggesting an inverse relationship. Rescue and ChIP experiments indicated that c-Myc bound to the promoter regions of PGC1α and PPARD to counteract their upregulation driven by HDAC1/-2 inhibition. Finally, we demonstrated that combination treatment with HDAC and FAO inhibitors extended animal survival in patient-derived xenograft model systems in vivo more potently than single treatments in the absence of toxicity. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
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