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1.
Proc Biol Sci ; 287(1931): 20201410, 2020 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-33043862

RESUMO

Joint friction has never previously been considered in the computation of mechanical and metabolic energy balance of human and animal (loco)motion, which heretofore included just muscle work to move the body centre of mass (external work) and body segments with respect to it. This happened mainly because, having been previously measured ex vivo, friction was considered to be almost negligible. Present evidences of in vivo damping of limb oscillations, motion captured and processed by a suited mathematical model, show that: (a) the time course is exponential, suggesting a viscous friction operated by the all biological tissues involved; (b) during the swing phase, upper limbs report a friction close to one-sixth of the lower limbs; (c) when lower limbs are loaded, in an upside-down body posture allowing to investigate the hip joint subjected to compressive forces as during the stance phase, friction is much higher and load dependent; and (d) the friction of the four limbs during locomotion leads to an additional internal work that is a remarkable fraction of the mechanical external work. These unprecedented results redefine the partitioning of the energy balance of locomotion, the internal work components, muscle and transmission efficiency, and potentially readjust the mechanical paradigm of the different gaits.


Assuntos
Extremidades , Articulações , Locomoção , Animais , Fricção , Humanos , Metabolismo , Estresse Mecânico
2.
Rev. Soc. Argent. Diabetes ; 54(2): 39-51, mayo-ago. 2020. tab, graf
Artigo em Espanhol | LILACS, BINACIS | ID: biblio-1119324

RESUMO

Introducción: dados los efectos pleiotrópicos de los glucocorticoides (GCs) sobre el metabolismo, los niveles excesivos y sostenidos de GCs circulantes tienen efectos deletéreos e incrementan la morbilidad y mortalidad cardiovascular. Objetivos: estudiar el efecto de la terapia antioxidante (con ácido lipoico o melatonina) sobre la hiperactivación del eje hipotálamo-hipófiso-adrenal (HHA) en animales alimentados con dieta rica en sacarosa (DRS). Materiales y métodos: se evaluó la actividad del eje HHA y se determinaron parámetros hormonales, de estrés oxidativo y de inflamación en la adenohipófisis de animales tratados con DRS durante tres semanas. Resultados: los animales del grupo DRS mostraron mayores niveles circulantes de hormona adrenocorticotropa (ACTH, por sus siglas en inglés) y corticosterona. En paralelo se detectó un aumento en la expresión del polipéptido precursor (proopiomelanocortina, POMC) y de ACTH en la adenohipófisis, donde también se observó un aumento de lipoperóxidos y proteínas nitradas en tirosina (daño oxidativo), un mayor número de macrófagos tisulares y un incremento en la producción de IL-1beta. El tratamiento antioxidante previno los cambios en estos parámetros. En particular la melatonina también normalizó la actividad del eje HHA y la expresión hipofisaria de POMC. Conclusiones: la sobrecarga metabólica inducida por la administración de DRS genera daño oxidativo e inflamación en la adenohipófisis. La activación de los macrófagos tisulares producida en consecuencia podría impactar sobre los corticotropos hipofisarios e inducir su hiperfunción. La melatonina podría utilizarse como herramienta terapéutica para normalizar la actividad del eje HHA en modelos de obesidad por dieta.


Introduction: given the pleiotropic effects of glucocorticoids (GCs) on metabolism, excessive and sustained levels of circulating GCs, have deleterious effects and increase cardiovascular morbidity and mortality. Objectives: to study the effect of antioxidant therapy on hyperactivation of the hypothalamic-pituitary-adrenal (HPA) axis in animals fed a sucrose-rich diet (SRD). Materials and methods: the activity of the HPA axis was evaluated and hormonal, oxidative stress and inflammation parameters were determined in the adenohypophysis of animals treated with SRD for trhee weeks. Results: animals from the SRD group showed higher circulating levels of adrenocorticotropic hormone (ACTH) and corticosterone. In parallel, an increase in the expression of the polypeptide precursors, POMC and ACTH were detected in the adenohypophysis. We also observed an increase in lipoperoxides and proteins nitrated in tyrosine (oxidative damage), a greater number of tissue macrophages and an increase in the production of IL-1beta. Antioxidant treatment prevented all these changes. In particular, melatonin also normalized the activity of the HPA axis and pituitary expression of POMC. Conclusions: the metabolic overload induced by the administration of SRD generates oxidative damage and inflammation in the adenohypophysis. Activation of tissue macrophages could affect, in turn, pituitary corticotrophs inducing their activation. Melatonin could be used as a therapeutic tool to normalize the activity of the HPA axis in diet obesity models.


Assuntos
Animais , Antioxidantes , Sacarose , Dieta , Hipotálamo , Inflamação , Melatonina , Metabolismo
3.
PLoS Genet ; 16(8): e1008984, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32857789

RESUMO

Mutations in human metabolic genes can lead to rare diseases known as inborn errors of human metabolism. For instance, patients with loss-of-function mutations in either subunit of propionyl-CoA carboxylase suffer from propionic acidemia because they cannot catabolize propionate, leading to its harmful accumulation. Both the penetrance and expressivity of metabolic disorders can be modulated by genetic background. However, modifiers of these diseases are difficult to identify because of the lack of statistical power for rare diseases in human genetics. Here, we use a model of propionic acidemia in the nematode Caenorhabditis elegans to identify genetic modifiers of propionate sensitivity. Using genome-wide association (GWA) mapping across wild strains, we identify several genomic regions correlated with reduced propionate sensitivity. We find that natural variation in the putative glucuronosyltransferase GLCT-3, a homolog of human B3GAT, partly explains differences in propionate sensitivity in one of these genomic intervals. We demonstrate that loss-of-function alleles in glct-3 render the animals less sensitive to propionate. Additionally, we find that C. elegans has an expansion of the glct gene family, suggesting that the number of members of this family could influence sensitivity to excess propionate. Our findings demonstrate that natural variation in genes that are not directly associated with propionate breakdown can modulate propionate sensitivity. Our study provides a framework for using C. elegans to characterize the contributions of genetic background in models of human inborn errors in metabolism.


Assuntos
Predisposição Genética para Doença , Glucuronosiltransferase/genética , Propionatos/farmacologia , Acidemia Propiônica/genética , Alelos , Animais , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Modelos Animais de Doenças , Estudo de Associação Genômica Ampla , Glucuronosiltransferase/deficiência , Humanos , Mutação com Perda de Função/genética , Metabolismo/genética , Propionatos/metabolismo
4.
Nat Commun ; 11(1): 3285, 2020 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-32620774

RESUMO

The early life human gut microbiota exerts life-long health effects on the host, but the mechanisms underpinning its assembly remain elusive. Particularly, the early colonization of Clostridiales from the Roseburia-Eubacterium group, associated with protection from colorectal cancer, immune- and metabolic disorders is enigmatic. Here, we describe catabolic pathways that support the growth of Roseburia and Eubacterium members on distinct human milk oligosaccharides (HMOs). The HMO pathways, which include enzymes with a previously unknown structural fold and specificity, were upregulated together with additional glycan-utilization loci during growth on selected HMOs and in co-cultures with Akkermansia muciniphila on mucin, suggesting an additional role in enabling cross-feeding and access to mucin O-glycans. Analyses of 4599 Roseburia genomes underscored the preponderance and diversity of the HMO utilization loci within the genus. The catabolism of HMOs by butyrate-producing Clostridiales may contribute to the competitiveness of this group during the weaning-triggered maturation of the microbiota.


Assuntos
Butiratos/metabolismo , Clostridiales/metabolismo , Leite Humano/metabolismo , Mucinas/metabolismo , Oligossacarídeos/metabolismo , Bifidobacterium/metabolismo , Clostridiales/genética , Colo/microbiologia , Eubacterium/metabolismo , Microbioma Gastrointestinal/fisiologia , Humanos , Lactente , Recém-Nascido , Metabolismo/fisiologia , Leite Humano/química , Polissacarídeos/metabolismo , Verrucomicrobia/metabolismo , Desmame
5.
BMC Bioinformatics ; 21(1): 327, 2020 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-32703160

RESUMO

BACKGROUND: Managing and organizing biological knowledge remains a major challenge, due to the complexity of living systems. Recently, systemic representations have been promising in tackling such a challenge at the whole-cell scale. In such representations, the cell is considered as a system composed of interlocked subsystems. The need is now to define a relevant formalization of the systemic description of cellular processes. RESULTS: We introduce BiPOm (Biological interlocked Process Ontology for metabolism) an ontology to represent metabolic processes as interlocked subsystems using a limited number of classes and properties. We explicitly formalized the relations between the enzyme, its activity, the substrates and the products of the reaction, as well as the active state of all involved molecules. We further showed that the information of molecules such as molecular types or molecular properties can be deduced by automatic reasoning using logical rules. The information necessary to populate BiPOm can be extracted from existing databases or existing bio-ontologies. CONCLUSION: BiPOm provides a formal rule-based knowledge representation to relate all cellular components together by considering the cellular system as a whole. It relies on a paradigm shift where the anchorage of knowledge is rerouted from the molecule to the biological process. AVAILABILITY: BiPOm can be downloaded at https://github.com/SysBioInra/SysOnto.


Assuntos
Ontologias Biológicas , Metabolismo , Bases de Dados Factuais , Enzimas/metabolismo , Bases de Conhecimento
6.
Nutrients ; 12(6)2020 May 31.
Artigo em Inglês | MEDLINE | ID: covidwho-437160

RESUMO

Nicotinamide riboside (NR) has recently become one of the most studied nicotinamide adenine dinucleotide (NAD+) precursors, due to its numerous potential health benefits mediated via elevated NAD+ content in the body. NAD+ is an essential coenzyme that plays important roles in various metabolic pathways and increasing its overall content has been confirmed as a valuable strategy for treating a wide variety of pathophysiological conditions. Accumulating evidence on NRs' health benefits has validated its efficiency across numerous animal and human studies for the treatment of a number of cardiovascular, neurodegenerative, and metabolic disorders. As the prevalence and morbidity of these conditions increases in modern society, the great necessity has arisen for a rapid translation of NR to therapeutic use and further establishment of its availability as a nutritional supplement. Here, we summarize currently available data on NR effects on metabolism, and several neurodegenerative and cardiovascular disorders, through to its application as a treatment for specific pathophysiological conditions. In addition, we have reviewed newly published research on the application of NR as a potential therapy against infections with several pathogens, including SARS-CoV-2. Additionally, to support rapid NR translation to therapeutics, the challenges related to its bioavailability and safety are addressed, together with the advantages of NR to other NAD+ precursors.


Assuntos
Suplementos Nutricionais , Niacinamida/análogos & derivados , Envelhecimento , Animais , Betacoronavirus , Disponibilidade Biológica , Doenças Cardiovasculares/terapia , Infecções por Coronavirus/terapia , Humanos , Longevidade , Metabolismo , Doenças Neurodegenerativas/terapia , Niacinamida/farmacocinética , Niacinamida/farmacologia , Pandemias , Pneumonia Viral/terapia
7.
PLoS One ; 15(6): e0234626, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32559239

RESUMO

The benefits of inhaling hydrogen gas (H2) have been widely reported but its pharmacokinetics have not yet been sufficiently analyzed. We developed a new experimental system in pigs to closely evaluate the process by which H2 is absorbed in the lungs, enters the bloodstream, and is distributed, metabolized, and excreted. We inserted and secured catheters into the carotid artery (CA), portal vein (PV), and supra-hepatic inferior vena cava (IVC) to allow repeated blood sampling and performed bilateral thoracotomy to collapse the lungs. Then, using a hydrogen-absorbing alloy canister, we filled the lungs to the maximum inspiratory level with 100% H2. The pig was maintained for 30 seconds without resuming breathing, as if they were holding their breath. We collected blood from the three intravascular catheters after 0, 3, 10, 30, and 60 minutes and measured H2 concentration by gas chromatography. H2 concentration in the CA peaked immediately after breath holding; 3 min later, it dropped to 1/40 of the peak value. Peak H2 concentrations in the PV and IVC were 40% and 14% of that in the CA, respectively. However, H2 concentration decay in the PV and IVC (half-life: 310 s and 350 s, respectively) was slower than in the CA (half-life: 92 s). At 10 min, H2 concentration was significantly higher in venous blood than in arterial blood. At 60 min, H2 was detected in the portal blood at a concentration of 6.9-53 nL/mL higher than at steady state, and in the SVC 14-29 nL/mL higher than at steady state. In contrast, H2 concentration in the CA decreased to steady state levels. This is the first report showing that inhaled H2 is transported to the whole body by advection diffusion and metabolized dynamically.


Assuntos
Hidrogênio/farmacocinética , Administração por Inalação , Animais , Coleta de Amostras Sanguíneas , Artérias Carótidas/metabolismo , Difusão , Hidrogênio/sangue , Metabolismo , Veia Porta/metabolismo , Suínos , Veia Cava Inferior/metabolismo
8.
Nutrients ; 12(6)2020 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-32486488

RESUMO

Nicotinamide riboside (NR) has recently become one of the most studied nicotinamide adenine dinucleotide (NAD+) precursors, due to its numerous potential health benefits mediated via elevated NAD+ content in the body. NAD+ is an essential coenzyme that plays important roles in various metabolic pathways and increasing its overall content has been confirmed as a valuable strategy for treating a wide variety of pathophysiological conditions. Accumulating evidence on NRs' health benefits has validated its efficiency across numerous animal and human studies for the treatment of a number of cardiovascular, neurodegenerative, and metabolic disorders. As the prevalence and morbidity of these conditions increases in modern society, the great necessity has arisen for a rapid translation of NR to therapeutic use and further establishment of its availability as a nutritional supplement. Here, we summarize currently available data on NR effects on metabolism, and several neurodegenerative and cardiovascular disorders, through to its application as a treatment for specific pathophysiological conditions. In addition, we have reviewed newly published research on the application of NR as a potential therapy against infections with several pathogens, including SARS-CoV-2. Additionally, to support rapid NR translation to therapeutics, the challenges related to its bioavailability and safety are addressed, together with the advantages of NR to other NAD+ precursors.


Assuntos
Suplementos Nutricionais , Niacinamida/análogos & derivados , Envelhecimento , Animais , Betacoronavirus , Disponibilidade Biológica , Doenças Cardiovasculares/terapia , Infecções por Coronavirus/terapia , Humanos , Longevidade , Metabolismo , Doenças Neurodegenerativas/terapia , Niacinamida/farmacocinética , Niacinamida/farmacologia , Pandemias , Pneumonia Viral/terapia
9.
Nat Commun ; 11(1): 2821, 2020 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-32499584

RESUMO

Altered metabolism is associated with many human diseases. Human genome-scale metabolic models (GEMs) were reconstructed within systems biology to study the biochemistry occurring in human cells. However, the complexity of these networks hinders a consistent and concise physiological representation. We present here redHUMAN, a workflow for reconstructing reduced models that focus on parts of the metabolism relevant to a specific physiology using the recently established methods redGEM and lumpGEM. The reductions include the thermodynamic properties of compounds and reactions guaranteeing the consistency of predictions with the bioenergetics of the cell. We introduce a method (redGEMX) to incorporate the pathways used by cells to adapt to the medium. We provide the thermodynamic curation of the human GEMs Recon2 and Recon3D and we apply the redHUMAN workflow to derive leukemia-specific reduced models. The reduced models are powerful platforms for studying metabolic differences between phenotypes, such as diseased and healthy cells.


Assuntos
Genoma Humano , Metabolismo/genética , Modelos Biológicos , Biomassa , Vias Biossintéticas , Meios de Cultura , Humanos , Redes e Vias Metabólicas/genética , Reprodutibilidade dos Testes , Estatística como Assunto , Termodinâmica
10.
Horm Metab Res ; 52(7): 540-546, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32599638

RESUMO

The severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) pandemic affects people around the world. However, there have been striking differences in the number of infected individuals and deaths in different countries. Particularly, within Central Europe in countries that are similar in ethnicity, age, and medical standards and have performed similar steps of containment, such differences in mortality rates remain inexplicable. We suggest to consider and explore environmental factors to explain these intriguing variations. Countries like Northern Italy, France, Spain, and UK have suffered from 5 times more deaths from the corona virus infection than neighboring countries like Germany, Switzerland, Austria, and Denmark related to the size of their respective populations. There is a striking correlation between the level of environmental pollutants including pesticides, dioxins, and air pollution such as NO2 known to affect immune function and healthy metabolism with the rate of mortality in COVID-19 pandemic in these European countries. There is also a correlation with the use of chlorination of drinking water in these regions. In addition to the improvement of environmental protective programs, there are possibilities to lower the blood levels of these pollutants by therapeutic apheresis. Furthermore, therapeutic apheresis might be an effective method to improve metabolic inflammation, altered vascular perfusion, and neurodegeneration observed as long-term complications of COVID-19 disease.


Assuntos
Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/metabolismo , Meio Ambiente , Poluição Ambiental/efeitos adversos , Halogenação , Metabolismo , Pneumonia Viral/epidemiologia , Pneumonia Viral/metabolismo , Abastecimento de Água , Suscetibilidade a Doenças , Humanos , Pandemias
11.
Biochim Biophys Acta Bioenerg ; 1861(10): 148251, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32598881

RESUMO

Saponins are a diverse group of secondary plant metabolites, some of which display hemolytic toxicity due to plasma membrane permeabilization. This feature is employed in biological applications for transferring hydrophilic molecules through cell membranes. Widely used commercial saponins include digitonin and saponins from soap tree bark, both of which constitute complex mixtures of little definition. We assessed the permeabilization power of pure saponins towards cellular membranes in an effort to detect novel properties and to improve existing applications. In a respirometric assay, we characterized half-maximal permeabilization of the plasma membrane for different metabolites, of the mitochondrial outer membrane for cytochrome C and the full solubilization of mitochondrial inner membrane protein complexes. Beyond the complete list as repository for the field, we highlight several findings with direct applicability. First, we identified and validated α-chaconine as alternative permeabilization agent in respirometric assays of cultured cells and isolated synaptosomes, superior to digitonin in its tolerability for mitochondria. Second, we identified glycyrrhizic acid to form exceptionally small pores impermeable for adenosine diphosphate. Third, in a concentration dependent manner, tomatine proved to be able to selectively permeabilize the mitochondrial outer, but not inner membrane, allowing for novel states in which to determine cytochrome C oxidase activity. In summary, we provide a list of the permeabilization properties of 18 pure saponins. The identification of two saponins, namely tomatine and chaconine, with direct usability in improved or novel cell biological applications within this small subgroup demonstrates the tremendous potential for further functional screening of pure saponins.


Assuntos
Metabolismo/efeitos dos fármacos , Saponinas/farmacologia , Animais , Calorimetria , Permeabilidade da Membrana Celular/efeitos dos fármacos , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Células HEK293 , Humanos , Camundongos
12.
Chemosphere ; 256: 127080, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32450349

RESUMO

Bisphenol A (BPA) is an estrogenic contaminant linked to metabolic disruption. Developmental BPA exposure is of particular concern, as organizational effects may irreversibly disrupt metabolism at later life-stages. While BPA exposures in adult fish elicit metabolic perturbations similar to effects described in rodents, the metabolic effects of developmental BPA exposure in juvenile fish remain largely unknown. Following embryonic zebrafish exposure to BPA (0.1, 1 and 4 mg/L) and EE2 (10 ng/L) from 2 to 5 dpf, we assessed the metabolic phenotype in larvae (4-6 dpf) and juveniles (43-49 dpf) which had been divided into regular-fed and overfed groups at 29 dpf. Developmental BPA exposure in larvae dose-dependently reduced food-intake and locomotion and increased energy expenditure. Juveniles (29 dpf) exhibited a transient increase in body weight after developmental BPA exposure and persistent diet-dependent locomotion changes (43-49 dpf). At the molecular level, glucose and lipid metabolism-related transcript abundance clearly separated BPA exposed fish from controls and EE2 exposed fish at the larval stage, in juveniles on a regular diet and, to a lesser extent, in overfed juveniles. In general, the metabolic endpoints affected by BPA exposure were not mimicked by EE2 treatment. We conclude that developmental BPA exposure elicits acute metabolic effects in zebrafish larvae and fewer transient and persistent effects in juveniles and that these metabolic effects are largely independent of BPA's estrogenicity.


Assuntos
Compostos Benzidrílicos/toxicidade , Metabolismo/efeitos dos fármacos , Fenóis/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Larva/efeitos dos fármacos , Peixe-Zebra/embriologia
13.
Chemosphere ; 253: 126629, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32283422

RESUMO

Recent reports demonstrate that octopamine receptor (OR) agonists such as formamidine pesticides cause reproductive and developmental toxicity through endocrine disrupting effects in both humans and animals. Herein, we studied the effects of different sublethal concentrations of OR agonists, Amitraz and Chlordimeform, on growth, development, and reproduction of D. melanogaster from a genotype perspective view. As a result, the sublethal concentrations for both OR agonists delayed the developmental time including pupation and eclosion. It significantly reduced the lifespan, eclosion rate, and production of eggs. The mRNA expression of genes relevant for development and metabolism was significantly changed after exposure to sublethal concentrations of both OR agonists. Octopamine receptor in mushroom bodies (Oamb), trehalase enzyme (Treh), hemocyte proliferation (RyR), and immune response (IM4) genes were upregulated whereas, trehalose sugar (Tret1-1), mixed function oxidase enzyme (Cyp9f2), lifespan (Atg7), male mating behavior (Ple), female fertility (Ddc), and lipid metabolism (Sxe2) genes were downregulated. These results support the conclusion that OR agonists activate the octopamine receptor in D. melanogaster leading to an increase of trehalase enzyme activity and degradation of trehalose sugar into free glucose which results in rapid energy exhaustion, hyperexcitation, and disturbing of the octopaminergic system in D. melanogaster.


Assuntos
Proteínas de Drosophila/genética , Drosophila melanogaster/fisiologia , Octopamina/toxicidade , Amidinas , Animais , Proteína 7 Relacionada à Autofagia , Comportamento Animal , Drosophila melanogaster/efeitos dos fármacos , Feminino , Masculino , Metabolismo/genética , Receptores de Amina Biogênica , Toluidinas
14.
Arq. bras. med. vet. zootec. (Online) ; 72(2): 553-559, Mar./Apr. 2020. tab
Artigo em Português | LILACS, VETINDEX | ID: biblio-1128404

RESUMO

Durante o periparto, as vacas leiteiras são submetidas a uma grande demanda de energia, ao mesmo tempo em que reduzem sua ingestão de matéria seca. O balanço energético negativo, resultante dessa equação, acarreta severos transtornos metabólicos, à produção e, principalmente, à reprodução. O objetivo do presente estudo foi avaliar o efeito da colina protegida sobre os parâmetros metabólicos, o intervalo entre parto e concepção e a produção de leite em vacas no período de transição. Cinquenta e quatro vacas leiteiras foram divididas em três grupos: controle, suplementação com colina por 10 dias pré-parto (T10) e suplementação com colina por 20 dias pré-parto (T20). Após o parto, foram mensurados os teores de frutosamina, colesterol, ácidos graxos não esterificados (AGNE), beta-hidroxibutirato (BHB), aspartato aminotransferase (AST), gamaglutamiltransferase (GGT) e total de oxidantes (TOS), nos dias 10, 20 e 30. Ainda foram avaliadas produção de leite e intervalo entre parto e concepção. Não houve efeito da suplementação com colina sobre os parâmetros sanguíneos e a produção. O intervalo entre parto e concepção foi menor no grupo T20. A colina suplementada por 20 dias durante o pré-parto melhorou a performance reprodutiva de vacas leiteiras(AU)


During the periparturient dairy cows undergo a large energy demand, at the same time reducing their intake of dry matter. The negative energy balance resulting from this equation leads to severe metabolic disorders in production, and mainly in reproduction. The aim of this study was to evaluate the effect of protected choline on metabolic parameters, reproductive performance, and milk production in cows during the transition period. Fifty-four dairy cows were divided into three groups: control, supplementation with choline for 10 days prepartum (T10) and supplementation with choline for 20 days prepartum (T20). After delivery we measured fructosamine levels, cholesterol, non-esterified fatty acids (NEFA), beta-hydroxybutyrate (BHB), aspartate aminotransferase (AST), gamma glutamyltransferase (GGT), and total oxidant (TOS) on days 10, 20 and 30. We also evaluated milk production and interval between calving and conception. There was no effect of supplementation with choline on blood and production parameters. The interval between calving and conception was lower in the T20 group. Choline supplemented by 20 during the antepartum improved reproductive performance of dairy cows, although it did not change the metabolic profile.(AU)


Assuntos
Animais , Feminino , Gravidez , Bovinos , Comportamento Sexual Animal , Colina/administração & dosagem , Período Periparto/fisiologia , Metabolismo , Aspartato Aminotransferases , Colesterol , Ácido 3-Hidroxibutírico , Ácidos Graxos não Esterificados , gama-Glutamiltransferase
15.
Artigo em Inglês | MEDLINE | ID: mdl-32208989

RESUMO

Tryptophan catabolism through the kynurenine pathway generates a variety of bioactive metabolites. Physical exercise can modulate kynurenine pathway metabolism in skeletal muscle and thus change the concentrations of select compounds in peripheral tissues and in the central nervous system. Here we review recent advances in our understanding of how exercise alters tryptophan-kynurenine metabolism in muscle and its subsequent local and distal effects. We propose that the effects of kynurenine pathway metabolites on skeletal muscle, adipose tissue, immune system, and the brain suggest that some of these compounds could qualify as exercise-induced myokines. Indeed, some of the more recently discovered biological activities for kynurenines include many of the best-known benefits of exercise: improved energy homeostasis, promotion of an anti-inflammatory environment, and neuroprotection. Finally, by considering the tissue expression of the different membrane and cytosolic receptors for kynurenines, we discuss known and potential biological activities for these tryptophan metabolites.


Assuntos
Sistema Nervoso Central/metabolismo , Cinurenina/metabolismo , Redes e Vias Metabólicas/fisiologia , Músculo Esquelético/metabolismo , Encéfalo/metabolismo , Encéfalo/fisiologia , Sistema Nervoso Central/fisiologia , Exercício Físico/fisiologia , Homeostase/genética , Homeostase/fisiologia , Humanos , Sistema Imunitário/metabolismo , Sistema Imunitário/fisiologia , Cinurenina/genética , Metabolismo/fisiologia , Músculo Esquelético/fisiologia , PPAR gama/genética , Triptofano/metabolismo
16.
J Athl Train ; 55(4): 336-342, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32196379

RESUMO

CONTEXT: Long-term eccentric exercise is known to promote muscle growth better than concentric exercise, but its acute effect on muscle is not well understood because of misinterpreted modeling and in situ and in vitro stretch protocols. Knowing if the initial bout of eccentric exercise promotes muscle growth and limits damage is critical to understanding the effect of this mode of exercise. OBJECTIVE: To directly evaluate the immediate effects of eccentric and concentric exercises on untrained muscle when fiber strains were physiological and exercise doses were comparable. DESIGN: Controlled laboratory study. SETTING: Laboratory. PATIENTS OR OTHER PARTICIPANTS: A total of 40 skeletally mature male Long-Evans rats (age = 16 weeks, mass = 452.1 ± 35.2 g) were randomly assigned to an eccentric exercise (downhill walking, n = 16), concentric exercise (uphill walking, n = 16), or control (no exercise, n = 8) group. INTERVENTION(S): Rats were exposed to a single 15-minute bout of eccentric or concentric exercise on a motorized treadmill and then were euthanized at 6 or 24 hours postexercise. We harvested the vastus lateralis muscle bilaterally. MAIN OUTCOME MEASURE(S): The percentage increase or decrease in protein abundance in exercised animals relative to that in unexercised control animals was evaluated as elevated phosphorylated p70S6k relative to total p70S6k. Fiber damage was quantified using immunoglobulin G permeability staining. One-way analysis of variance and post hoc Tukey tests were performed. RESULTS: Rats exposed to eccentric exercise and euthanized at 24 hours had higher percentage response protein synthesis rates than rats exposed to eccentric exercise and euthanized at 6 hours (P = .02) or to concentric exercise and euthanized at 6 (P = .03) or 24 (P = .03) hours. We assessed 9446 fibers for damage and found only 1 fiber was infiltrated (in the concentric exercise group euthanized at 6 hours). Furthermore, no between-groups differences in immunoglobulin G fluorescent intensity were detected (P = .94). CONCLUSIONS: Incorporating eccentric exercise is a simple, universally available therapeutic intervention for promoting muscle recovery. A single 15-minute dose of eccentric exercise to a novice muscle can better exert an anabolic effect than a comparable dose of concentric exercise, with very limited evidence of fiber damage.


Assuntos
Contração Muscular/fisiologia , Músculo Esquelético , Condicionamento Físico Animal/fisiologia , Serina-Treonina Quinases TOR/metabolismo , Animais , Teste de Esforço , Masculino , Metabolismo/fisiologia , Músculo Esquelético/lesões , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Ratos , Ratos Long-Evans , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo
17.
Am J Physiol Endocrinol Metab ; 318(4): E568-E578, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32101029

RESUMO

Fetal growth restriction (FGR) is associated with compromised growth and metabolic function throughout life. Intrauterine therapy of FGR with intra-amniotic insulin-like growth factor-1 (IGF1) enhances fetal growth and alters perinatal metabolism and growth in a sex-specific manner, but the adult effects are unknown. We investigated the effects of intra-amniotic IGF1 treatment of FGR on adult growth and body composition, adrenergic sensitivity, and glucose-insulin axis regulation. Placental embolization-induced FGR was treated with four weekly doses of 360 µg intra-amniotic IGF1 (FGRI) or saline (FGRS). Offspring were raised to adulthood (18 mo: FGRI, n = 12 females, 12 males; FGRS, n = 13 females, 10 males) alongside offspring from unembolized and untreated sheep (CON; n = 12 females, 21 males). FGRI females had increased relative lean mass compared with CON but not FGRS (P < 0.05; 70.6 ± 8.2% vs. 61.4 ± 8.2% vs. 67.6 ± 8.2%), decreased abdominal adipose compared with CON and FGRS (P < 0.05; 43.7 ± 1.2% vs. 49.3 ± 0.9% vs. 48.5 ± 1.0%), increased glucose utilization compared with FGRS but not CON (P < 0.05; 9.6 ± 1.0 vs. 6.0 ± 0.9 vs. 7.6 ± 0.9 mg·kg-1·min-1), and increased ß-hydroxybutyric acid:nonesterified fatty acid ratio in response to adrenaline compared with CON and FGRS (P < 0.05; 3.9 ± 1.4 vs. 1.1 ± 1.4 vs. 1.8 ± 1.4). FGRS males were smaller and lighter compared with CON but not FGRI (P < 0.05; 86.8 ± 6.3 vs. 93.5 ± 6.1 vs. 90.7 ± 6.3 kg), with increased peak glucose concentration (10%) in response to a glucose load but few other differences. These effects of intra-amniotic IGF1 therapy on adult body composition, glucose-insulin axis function, and adrenergic sensitivity could indicate improved metabolic regulation during young adulthood in female FGR sheep.


Assuntos
Composição Corporal/efeitos dos fármacos , Retardo do Crescimento Fetal/tratamento farmacológico , Fator de Crescimento Insulin-Like I/uso terapêutico , Metabolismo/efeitos dos fármacos , Ácido 3-Hidroxibutírico/metabolismo , Absorciometria de Fóton , Animais , Epinefrina/metabolismo , Ácidos Graxos não Esterificados/metabolismo , Feminino , Desenvolvimento Fetal/efeitos dos fármacos , Glucose/metabolismo , Injeções , Insulina/metabolismo , Fator de Crescimento Insulin-Like I/administração & dosagem , Gravidez , Caracteres Sexuais , Ovinos , Embolização da Artéria Uterina , Útero
18.
Mil Med ; 185(Suppl 1): 311-318, 2020 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-32074311

RESUMO

INTRODUCTION: Current pharmacological treatments of post-traumatic stress disorder (PTSD) have limited efficacy. Although the diagnosis is based on psychopathological criteria, it is frequently accompanied by somatic comorbidities and perhaps "accelerated biological aging," suggesting widespread physical concomitants. Such physiological comorbidities may affect core PTSD symptoms but are rarely the focus of therapeutic trials. METHODS: To elucidate the potential involvement of metabolism, inflammation, and mitochondrial function in PTSD, we integrate findings and mechanistic models from the DOD-sponsored "Systems Biology of PTSD Study" with previous data on these topics. RESULTS: Data implicate inter-linked dysregulations in metabolism, inflammation, mitochondrial function, and perhaps the gut microbiome in PTSD. Several inadequately tested targets of pharmacological intervention are proposed, including insulin sensitizers, lipid regulators, anti-inflammatories, and mitochondrial biogenesis modulators. CONCLUSIONS: Systemic pathologies that are intricately involved in brain functioning and behavior may not only contribute to somatic comorbidities in PTSD, but may represent novel targets for treating core psychiatric symptoms.


Assuntos
Distúrbios de Guerra/tratamento farmacológico , Microbioma Gastrointestinal/efeitos dos fármacos , Inflamação/tratamento farmacológico , Metabolismo/efeitos dos fármacos , Distúrbios de Guerra/fisiopatologia , Microbioma Gastrointestinal/fisiologia , Humanos , Inflamação/fisiopatologia , Metabolismo/fisiologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Fenômenos Farmacológicos/fisiologia
19.
JAMA ; 323(5): 482, 2020 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-32016300
20.
Diabetes ; 69(5): 893-901, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32086288

RESUMO

An aging global population combined with sedentary lifestyles and unhealthy diets has contributed to an increasing incidence of obesity and type 2 diabetes. These metabolic disorders are associated with perturbations to nitric oxide (NO) signaling and impaired glucose metabolism. Dietary inorganic nitrate, found in high concentration in green leafy vegetables, can be converted to NO in vivo and demonstrates antidiabetic and antiobesity properties in rodents. Alongside tissues including skeletal muscle and liver, white adipose tissue is also an important physiological site of glucose disposal. However, the distinct molecular mechanisms governing the effect of nitrate on adipose tissue glucose metabolism and the contribution of this tissue to the glucose-tolerant phenotype remain to be determined. Using a metabolomic and stable-isotope labeling approach, combined with transcriptional analysis, we found that nitrate increases glucose uptake and oxidative catabolism in primary adipocytes and white adipose tissue of nitrate-treated rats. Mechanistically, we determined that nitrate induces these phenotypic changes in primary adipocytes through the xanthine oxidoreductase-catalyzed reduction of nitrate to NO and independently of peroxisome proliferator-activated receptor-α. The nitrate-mediated enhancement of glucose uptake and catabolism in white adipose tissue may be a key contributor to the antidiabetic effects of this anion.


Assuntos
Tecido Adiposo Branco/efeitos dos fármacos , Tecido Adiposo Branco/metabolismo , Glucose/metabolismo , Nitratos/farmacologia , Óxido Nítrico/metabolismo , Xantina Desidrogenase/metabolismo , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Animais , Células Cultivadas , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Regulação Enzimológica da Expressão Gênica/fisiologia , Masculino , Metabolismo , Nitratos/administração & dosagem , Oxirredução , Ratos , Ratos Wistar
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