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1.
Int J Food Microbiol ; 333: 108792, 2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-32707524

RESUMO

Gamma aminobutyric acid (GABA) is a non-protein amino acid that is widely distributed in nature and its physiological importance goes beyond its role as an inhibitory neurotransmitter of the central nervous system in mammals. Since microbial fermentation is one of the most promising methods to obtain GABA, the production of this metabolite by several strains of lactic acid bacteria isolated from quinoa and amaranth sourdoughs was investigated. Lactobacillus brevis CRL 2013 produced the highest GABA levels, reaching 265 mM when optimal culture conditions were set up. The fermentative profile showed that CRL 2013 was able to catabolize carbohydrates through the phosphoketolase pathway yielding variable amounts of lactic acid, acetate and ethanol, which depended on the type of carbon source available and the presence of external electron acceptors such as fructose. Enhanced growth parameters and low GABA synthesis were associated to pentose fermentation. This impairment on GABA production machinery was partially overpassed by the addition of ethanol to the culture media. These results support the potential use of L. brevis CRL 2013 as a starter culture for the manufacture of GABA-enriched functional foods and provide further insights to the understanding of the GAD system regulation in lactic acid bacteria.


Assuntos
Pão/microbiologia , Metabolismo dos Carboidratos/fisiologia , Fermentação/fisiologia , Lactobacillus brevis/metabolismo , Ácido gama-Aminobutírico/biossíntese , Acetatos/metabolismo , Amaranthus/microbiologia , Carboidratos , Chenopodium quinoa/microbiologia , Meios de Cultura/metabolismo , Etanol/metabolismo , Ácido Láctico/metabolismo
2.
PLoS One ; 15(4): e0231197, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32267865

RESUMO

Various factors including diet, age, geography, culture and socio-economic status have a role in determining the composition of the human gut microbiota. The human gut microbial composition is known to be altered in disease conditions. Considering the important role of the gut microbiome in maintaining homeostasis and overall health, it is important to understand the microbial diversity and the functional metagenome of the healthy gut. Here, we characterized the microbiota of 31 fecal samples from healthy individuals of Indian ethnic tribes from Ladakh, Jaisalmer and Khargone by shotgun metagenomic sequencing. Sequence analysis revealed that Bifidobacterium and Prevotella were the key microbes contributing to the differences among Jaisalmer, Khargone and Ladakh samples at the genus level. Our correlation network study identified carbohydrate-active enzymes and carbohydrate binding proteins that are associated with specific genera in the different Indian geographical regions studied. Network analysis of carbohydrate-active enzymes and genus abundance revealed that the presence of different carbohydrate-active enzymes is driven by differential abundance of genera. The correlation networks were different in the different geographical regions, and these interactions suggest the role of less abundant genera in shaping the gut environment. We compared our data with samples from different countries and found significant differences in taxonomic composition and abundance of carbohydrate-active enzymes in the gut microbiota as compared to the other countries.


Assuntos
Bifidobacterium/genética , Microbioma Gastrointestinal/genética , Metagenômica/métodos , Prevotella/genética , Adulto , Índice de Massa Corporal , Metabolismo dos Carboidratos/fisiologia , DNA Bacteriano/genética , Dieta , Ingestão de Alimentos , Fezes/microbiologia , Feminino , Voluntários Saudáveis , Humanos , Índia , Masculino , Filogenia , Sequenciamento Completo do Genoma
3.
PLoS Biol ; 18(2): e3000622, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32108181

RESUMO

Circadian (daily) regulation of metabolic pathways implies that food may be metabolized differentially over the daily cycle. To test that hypothesis, we monitored the metabolism of older subjects in a whole-room respiratory chamber over two separate 56-h sessions in a random crossover design. In one session, one of the 3 daily meals was presented as breakfast, whereas in the other session, a nutritionally equivalent meal was presented as a late-evening snack. The duration of the overnight fast was the same for both sessions. Whereas the two sessions did not differ in overall energy expenditure, the respiratory exchange ratio (RER) was different during sleep between the two sessions. Unexpectedly, this difference in RER due to daily meal timing was not due to daily differences in physical activity, sleep disruption, or core body temperature (CBT). Rather, we found that the daily timing of nutrient availability coupled with daily/circadian control of metabolism drives a switch in substrate preference such that the late-evening Snack Session resulted in significantly lower lipid oxidation (LO) compared to the Breakfast Session. Therefore, the timing of meals during the day/night cycle affects how ingested food is oxidized or stored in humans, with important implications for optimal eating habits.


Assuntos
Ritmo Circadiano/fisiologia , Metabolismo dos Lipídeos/fisiologia , Refeições/fisiologia , Índice de Massa Corporal , Desjejum , Metabolismo dos Carboidratos/fisiologia , Estudos Cross-Over , Comportamento Alimentar/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oxirredução , Troca Gasosa Pulmonar/fisiologia , Sono/fisiologia , Lanches
4.
Plant Sci ; 293: 110413, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32081262

RESUMO

Protein N-glycosylation plays key roles in protein folding, stability, solubility, biogenesis, and enzyme activity. Tomato (Solanum lycopersicum L.) is an important vegetable crop with abundant nutritional value, and the formation of tomato fruit qualities primarily occurs in the fruit ripening process. However, a large number of N-glycosylation-mediated mechanisms in regulating tomato fruit ripening have not been elucidated to date. In this study, western blot assays showed that the extents of mature N-glycoproteins were differentially expressed in mature green fruits (fruit start ripening) and ripe fruits (fruit stop ripening). Next, through performing a comparative N-glycoproteome analysis strategy, a total of 553 N-glycosites from 363 N-glycoproteins were identified in mature green fruits compared with ripe fruits. Among them, 252 N-glycosites from 191 N-glycoproteins were differentially expressed in mature green fruits compared with ripe fruits. The differentially expressed N-glycoproteins were mainly located in the chloroplast (30 %) and cytoplasm (16 %). Gene Ontology (GO) analysis showed that these N-glycoproteins were involved in various biological processes, cellular components and molecular functions. These N-glycoproteins participate in biological processes, such as metabolic processes, cellular processes and single-organism processes. These N-glycoproteins are also cellular components in biological process cells, membranes and organelles and have different molecular functions, such as catalytic activity and binding. Notably, these N-glycoproteins were enriched in starch and sucrose metabolism and galactose metabolism by KEGG pathway analysis. This community resource regarding N-glycoproteins is the first large-scale N-glycoproteome during plant fruit ripening. This study will contribute to understanding the function of N-glycosylation in regulating plant fruit ripening.


Assuntos
Metabolismo dos Carboidratos/fisiologia , Frutas/metabolismo , Lycopersicon esculentum/metabolismo , Proteoma , Metabolismo dos Carboidratos/genética , Frutas/genética , Frutas/crescimento & desenvolvimento , Regulação da Expressão Gênica no Desenvolvimento , Regulação da Expressão Gênica de Plantas , Glicosilação , Lycopersicon esculentum/genética , Reguladores de Crescimento de Planta/genética , Reguladores de Crescimento de Planta/fisiologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Transcriptoma
5.
Sci Rep ; 10(1): 1015, 2020 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-31974388

RESUMO

Nursing behaviour, also known as breastfeeding behaviour, is the feeding of juvenile individuals with nutrients or proteins from matures especially in mammals. As a hypothetical phenomenon in bamboo forests, mature bamboos have transferred photoassimilates to young bamboos for recovering and rebuilding their photosystems especially in winter. This process is accompanied by changes in the ability of photosystems and the mass fraction of non-structural carbohydrates (NSCs), structural carbohydrates (SCs), and lignin. We analysed carbohydrates and chlorophyll fluorescence to compare the physiological traits in mature (age 2, 3, 4) and immature (age 1) Moso bamboos (Phyllostachys edilus) during a year using the Portable Chlorophyll Fluorometer (PCF) and the Liquid Chromatographic (LC) method. The results showed that the mass fraction of total soluble carbohydrates (TSCs) and starch in the bottom of bamboo at age 1 was higher than other parts and ages in spring, whereas the mass fraction of TSCs, starch, and sucrose at age 3 was higher than other parts and ages in winter. The Fv/Fm, an indicator to reveal photosystems were functional or not, at age 1 dramatically dropped when the cold current attacked first time in October, and then quickly recovered in November. Our findings indicate that mature bamboos very possibly provide carbohydrates to immature bamboos and help them rebuild their photosystems when a bamboo forest resists cold stress.


Assuntos
Metabolismo dos Carboidratos/fisiologia , Resposta ao Choque Frio/fisiologia , Fotossíntese/fisiologia , Fenômenos Fisiológicos Vegetais , Poaceae/fisiologia , Carboidratos/química , Clorofila/metabolismo , Cloroplastos/metabolismo , Cromatografia Líquida , Temperatura Baixa , Fluorometria , Nutrientes/análise , Poaceae/metabolismo , Estações do Ano
6.
Aquat Toxicol ; 218: 105359, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31765944

RESUMO

Carbohydrate metabolism switches from aerobic to anaerobic (glycolysis) to supply energy in response to acute hypoxic stress. Acute hypoxic stress with dissolved oxygen (DO) levels of 1.2 ±â€¯0.1 mg/L for 24 h and 12 h re-oxygenation was used to investigate the response of the anaerobic glycolytic pathway in Micropterus salmoides muscle. The results showed that the glucose concentration was significantly lower in muscle, while the lactic acid and pyruvic acid concentrations tended to increase during hypoxic stress. No significant difference was observed in muscle glycogen, and ATP content fluctuated significantly. The activities of gluconeogenesis-related enzymes were slightly elevated, such as phosphoenolpyruvate carboxykinase (PEPCK). The activities of the glycolytic enzymes increased after the induction of hypoxia, such as hexokinase (HK), pyruvate kinase (PK), and lactate dehydrogenase (LDH). Curiously, phosphofructokinase (PFK) activity was significantly down-regulated within 4 h during hypoxia, although these effects were transient, and most indices returned to control levels after 12 h of re-oxygenation. Upregulated hif-1α, ampkα, hk, glut1, and ldh mRNA expression suggested that carbohydrate metabolism was reprogrammed under hypoxia. Lactate transport was regulated by miR-124-5p according to quantitative polymerase chain reaction and dual luciferase reporter assays. Our findings provide new insight into the molecular regulatory mechanism of hypoxia in Micropterus salmoides muscle.


Assuntos
Aclimatação/fisiologia , Bass/metabolismo , Hipóxia/metabolismo , Ácido Láctico/metabolismo , MicroRNAs/genética , Transportadores de Ácidos Monocarboxílicos/genética , Músculos/metabolismo , Simportadores/genética , Aclimatação/genética , Animais , Bass/genética , Metabolismo dos Carboidratos/genética , Metabolismo dos Carboidratos/fisiologia , Regulação da Expressão Gênica , Hipóxia/genética , Músculos/enzimologia , Oxigênio/metabolismo
7.
Int J Mol Sci ; 20(19)2019 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-31546675

RESUMO

The Fibroblast Growth Factor 21 (FGF21) is considered an attractive therapeutic target for obesity and obesity-related disorders due to its beneficial effects in lipid and carbohydrate metabolism. FGF21 response is essential under stressful conditions and its metabolic effects depend on the inducer factor or stress condition. FGF21 seems to be the key signal which communicates and coordinates the metabolic response to reverse different nutritional stresses and restores the metabolic homeostasis. This review is focused on describing individually the FGF21-dependent metabolic response activated by some of the most common nutritional challenges, the signal pathways triggering this response, and the impact of this response on global homeostasis. We consider that this is essential knowledge to identify the potential role of FGF21 in the onset and progression of some of the most prevalent metabolic pathologies and to understand the potential of FGF21 as a target for these diseases. After this review, we conclude that more research is needed to understand the mechanisms underlying the role of FGF21 in macronutrient preference and food intake behavior, but also in ß-klotho regulation and the activity of the fibroblast activation protein (FAP) to uncover its therapeutic potential as a way to increase the FGF21 signaling.


Assuntos
Fatores de Crescimento de Fibroblastos/metabolismo , Fígado/metabolismo , Obesidade/metabolismo , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/metabolismo , Animais , Metabolismo dos Carboidratos/fisiologia , Comportamento Alimentar , Fatores de Crescimento de Fibroblastos/genética , Homeostase/fisiologia , Humanos , Resistência à Insulina/genética , Metabolismo dos Lipídeos/fisiologia , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Transdução de Sinais
8.
Cell ; 178(4): 901-918.e16, 2019 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-31398343

RESUMO

Physiology and metabolism are often sexually dimorphic, but the underlying mechanisms remain incompletely understood. Here, we use the intestine of Drosophila melanogaster to investigate how gut-derived signals contribute to sex differences in whole-body physiology. We find that carbohydrate handling is male-biased in a specific portion of the intestine. In contrast to known sexual dimorphisms in invertebrates, the sex differences in intestinal carbohydrate metabolism are extrinsically controlled by the adjacent male gonad, which activates JAK-STAT signaling in enterocytes within this intestinal portion. Sex reversal experiments establish roles for this male-biased intestinal metabolic state in controlling food intake and sperm production through gut-derived citrate. Our work uncovers a male gonad-gut axis coupling diet and sperm production, revealing that metabolic communication across organs is physiologically important. The instructive role of citrate in inter-organ communication might be significant in more biological contexts than previously recognized.


Assuntos
Metabolismo dos Carboidratos/fisiologia , Drosophila melanogaster/metabolismo , Ingestão de Alimentos/fisiologia , Mucosa Intestinal/metabolismo , Caracteres Sexuais , Maturação do Esperma/fisiologia , Animais , Ácido Cítrico/metabolismo , Proteínas de Drosophila/metabolismo , Feminino , Expressão Gênica , Janus Quinases/metabolismo , Masculino , RNA-Seq , Fatores de Transcrição STAT/metabolismo , Transdução de Sinais , Açúcares/metabolismo , Testículo/metabolismo
9.
Cells ; 8(8)2019 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-31412683

RESUMO

Cells constantly adapt their metabolic pathways to meet their energy needs and respond to nutrient availability. During the last two decades, it has become increasingly clear that NAD+, a coenzyme in redox reactions, also mediates several ubiquitous cell signaling processes. Protein ADP-ribosylation is a post-translational modification that uses NAD+ as a substrate and is best known as part of the genotoxic stress response. However, there is increasing evidence that NAD+-dependent ADP-ribosylation regulates other cellular processes, including metabolic pathways. In this review, we will describe the compartmentalized regulation of NAD+ biosynthesis, consumption, and regeneration with a particular focus on the role of ADP-ribosylation in the regulation of glucose metabolism in different cellular compartments.


Assuntos
Adenosina Difosfato Ribose/metabolismo , Glucose/metabolismo , NAD/metabolismo , Organelas/metabolismo , ADP-Ribosilação , Animais , Metabolismo dos Carboidratos/fisiologia , Linhagem Celular , Dano ao DNA/fisiologia , Humanos , Redes e Vias Metabólicas/fisiologia , Camundongos
10.
PLoS One ; 14(8): e0220877, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31415611

RESUMO

INTRODUCTION: Vegetable oil is an important source of fatty acids, and as palm oil being the highest consumed vegetable oil in many countries, its high saturated fatty acid content has led many concerns on cardiometabolic health. Dietary fatty acids has also been linked to affect glucose metabolism and insulin sensitivity. This systematic review is aimed at critically evaluating the available evidence on the association of palm oil with the biomarkers of glucose metabolism as compared to other vegetable oils. METHODS: We systemically searched PubMed, CENTRAL and Scopus up to June 2018. We searched for published interventional studies on biomarkers of glucose metabolism (defined as fasting glucose, fasting insulin, HOMA, 2-hour post prandial glucose and HbA1C) that compared palm oil- or palm olein-rich diets with other edible vegetable oils (such as olive oil, canola oil and soybean oil). Two reviewers independently extracted data and assessed study risks of bias. Mean differences of outcomes were pooled for the meta-analysis. RESULTS: We identified 1921 potentially eligible articles with only eight included studies. Seven randomised cross-over trials and one parallel trial were included. Study population were among young to middle-aged, healthy, non-diabetic, and normal weight participants. Intervention duration ranged from three to seven weeks, and fat substitution ranged from 15% to 20% energy. There were insignificant differences in fasting glucose when compared to partially hydrogenated soybean oil [-0.15mmol/L (-0.46,0.16) P = 0.33, I2 = 48%], soybean oil [0.05mmol/L (-0.09,0.18) P = 0.49, I2 = 0%] and olive oil [0.04mmol/L (-0.09,0.17) P = 0.76, I2 = 0%]. Insignificant effects were also seen on fasting insulin when compared to partially hydrogenated soybean oil [1.72pmol/L (-11.39,14.84) P = 0.80, I2 = 12%] and olive oil diet [-0.14pmol/L (-4.87,4.59) P = 0.95, I2 = 0%]. CONCLUSION: Current evidence on the effects of palm oil consumption on biomarkers of glucose metabolism is poor and limited to only healthy participants. We conclude that little or no additional benefit will be obtained by replacing palm oil with other oils rich in mono or polyunsaturated fatty acids for changes in glucose metabolism.


Assuntos
Glicemia/análise , Metabolismo dos Carboidratos/fisiologia , Gorduras na Dieta , Resistência à Insulina/fisiologia , Insulina/sangue , Óleo de Palmeira , Humanos
11.
Am J Physiol Endocrinol Metab ; 317(3): E483-E493, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31265327

RESUMO

While the triple tracer isotope dilution method has enabled accurate estimation of carbohydrate turnover after a mixed meal, use of the simple carbohydrate glucose as the carbohydrate source limits its translational applicability to everyday meals that typically contain complex carbohydrates. Hence, utilizing the natural enrichment of [13C]polysaccharide in commercially available grains, we devised a novel tracer method to measure postprandial complex carbohydrate turnover and indices of insulin action and ß-cell function and compared the parameters to those obtained after a simple carbohydrate containing mixed meal. We studied healthy volunteers after either rice (n = 8) or sorghum (n = 8) and glucose (n = 16) containing mixed meals and modified the triple tracer technique to calculate carbohydrate turnover. All meals were matched for calories and macronutrient composition. Rates of meal glucose appearance (2,658 ± 736 vs. 4,487 ± 909 µM·kg-1·2 h-1), endogenous glucose production (-835 ± 283 vs. -1,123 ± 323 µM·kg-1·2 h-1) and glucose disappearance (1,829 ± 807 vs. 3,606 ± 839 µM·kg-1·2 h-1) differed (P < 0.01) between complex and simple carbohydrate containing meals, respectively. Interestingly, there were significant increase in indices of insulin sensitivity (32.5 ± 3.5 vs. 25.6 ± 3.2 10-5 (dl·kg-1·min-2)/pM, P = 0.006) and ß-cell responsivity (disposition index: 1,817 ± 234 vs. 1,236 ± 159 10-14 (dl·kg-1·min-2)/pM, P < 0.005) with complex than simple carbohydrate meals. We present a novel triple tracer approach to estimate postprandial turnover of complex carbohydrate containing mixed meals. We also report higher insulin sensitivity and ß-cell responsivity with complex than with simple carbohydrates in mixed meals of identical calorie and macronutrient compositions in healthy adults.


Assuntos
Metabolismo dos Carboidratos/fisiologia , Carboidratos da Dieta/metabolismo , Polissacarídeos , Compostos Radiofarmacêuticos , Adulto , Algoritmos , Isótopos de Carbono , Feminino , Glucose/metabolismo , Glucose/farmacocinética , Voluntários Saudáveis , Humanos , Resistência à Insulina , Células Secretoras de Insulina/metabolismo , Masculino , Refeições , Oryza , Período Pós-Prandial , Sorghum , Adulto Jovem
12.
BMC Microbiol ; 19(1): 146, 2019 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-31253082

RESUMO

BACKGROUND: Enterococcus faecalis is a major clinically relevant nosocomial bacterial pathogen frequently isolated from polymicrobial infections. The biofilm forming ability of E. faecalis attributes a key role in its virulence and drug resistance. Biofilm cells are phenotypically and metabolically different from their planktonic counterparts and many aspects involved in E. faecalis biofilm formation are yet to be elucidated. The strain E. faecalis SK460 used in the present study is esp (Enterococcal surface protein) and fsr (two-component signal transduction system) negative non-gelatinase producing strong biofilm former isolated from a chronic diabetic foot ulcer patient. We executed a label-free quantitative proteomic approach to elucidate the differential protein expression pattern at planktonic and biofilm stages of SK460 to come up with potential determinants associated with Enterococcal biofilm formation. RESULTS: The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of proteomic data revealed that biofilm cells expressed higher levels of proteins which are associated with glycolysis, amino acid biosynthesis, biosynthesis of secondary metabolites, microbial metabolism in diverse environments and stress response factors. Besides these basic survival pathways, LuxS-mediated quorum sensing, arginine metabolism, rhamnose biosynthesis, pheromone and adhesion associated proteins were found to be upregulated during the biofilm transit from planktonic stages. The selected subsets were validated by quantitative real-time PCR. In silico functional interaction analysis revealed that the genes involved in upregulated pathways pose a close molecular interaction thereby coordinating the regulatory network to thrive as a biofilm community. CONCLUSIONS: The present study describes the first report of the quantitative proteome analysis of an esp and fsr negative non gelatinase producing E. faecalis. Proteome analysis evidenced enhanced expression of glycolytic pathways, stress response factors, LuxS quorum signaling system, rhamnopolysaccharide synthesis and pheromone associated proteins in biofilm phenotype. We also pointed out the relevance of LuxS quorum sensing and pheromone associated proteins in the biofilm development of E. faecalis which lacks the Fsr quorum signaling system. These validated biofilm determinants can act as potential inhibiting targets in Enterococcal infections.


Assuntos
Biofilmes/crescimento & desenvolvimento , Enterococcus faecalis/genética , Enterococcus faecalis/metabolismo , Proteômica , Aminoácidos/metabolismo , Aminoácidos/fisiologia , Arginina/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Metabolismo dos Carboidratos/genética , Metabolismo dos Carboidratos/fisiologia , Regulação Bacteriana da Expressão Gênica , Humanos , Proteínas de Membrana , Redes e Vias Metabólicas/genética , Redes e Vias Metabólicas/fisiologia , Dobramento de Proteína , Percepção de Quorum/genética , Percepção de Quorum/fisiologia , Ramnose/biossíntese
13.
Nat Commun ; 10(1): 2756, 2019 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-31227702

RESUMO

Flight loss in birds is as characteristic of the class Aves as flight itself. Although morphological and physiological differences are recognized in flight-degenerate bird species, their contributions to recurrent flight degeneration events across modern birds and underlying genetic mechanisms remain unclear. Here, in an analysis of 295 million nucleotides from 48 bird genomes, we identify two convergent sites causing amino acid changes in ATGLSer321Gly and ACOT7Ala197Val in flight-degenerate birds, which to our knowledge have not previously been implicated in loss of flight. Functional assays suggest that Ser321Gly reduces lipid hydrolytic ability of ATGL, and Ala197Val enhances acyl-CoA hydrolytic activity of ACOT7. Modeling simulations suggest a switch of main energy sources from lipids to carbohydrates in flight-degenerate birds. Our results thus suggest that physiological convergence plays an important role in flight degeneration, and anatomical convergence often invoked may not.


Assuntos
Evolução Biológica , Aves/fisiologia , Metabolismo Energético/genética , Voo Animal/fisiologia , Genoma/genética , Animais , Metabolismo dos Carboidratos/fisiologia , Genômica/métodos , Lipase/genética , Lipase/metabolismo , Lipólise/fisiologia , Palmitoil-CoA Hidrolase/genética , Palmitoil-CoA Hidrolase/metabolismo , Filogenia
14.
Orv Hetil ; 160(25): 973-979, 2019 Jun.
Artigo em Húngaro | MEDLINE | ID: mdl-31203640

RESUMO

Progranulin is a recently recognized multifunctional glycopeptide shown to be related to obesity and diabetes mellitus. Progranulin is an endogenous antagonist of tumor necrosis factor-α by competitively binding to its receptor, therefore, it exerts anti-inflammatory activity. Paradoxically, previous studies have shown that serum levels of progranulin were elevated in patients with diabetes and associated to its complications including micro- and macroangiopathies, macroalbuminuria or reduced renal function. Moreover, hyperprogranulinemia may be involved in the pathogenesis of obesity-associated insulin resistance. The review summarizes the currently available data on progranulin as a novel marker of the carbohydrate metabolism and inflammation. Orv Hetil. 2019; 160(25): 973-979.


Assuntos
Metabolismo dos Carboidratos/fisiologia , Progranulinas/sangue , Biomarcadores/sangue , Humanos , Inflamação/sangue , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Prognóstico
15.
Plant Sci ; 285: 224-229, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31203887

RESUMO

Why evergreen fruit tree species accumulate starch in the ovary during flower bud differentiation in spring, as deciduous species do during flower bud dormancy, is not fully understood. This is because in evergreen species carbon supply is assured by leaves during flower development. We suggest the existence of an autonomous mechanism in the flowers which counteracts the competition for photoassimilates with new leaves, until they become source organs. Our hypothesis is that starch accumulated during Citrus ovary ontogeny originates from 1) its own photosynthetic capacity and 2) the mobilization of reserves. Through defoliation experiments, we found that ovaries accumulate starch during flower ontogeny using a dual mechanism: 1) the autotrophic route of source organs activating Rubisco (RbcS) genes expression, and 2) the heterotrophic route of sink organs that hydrolyze sucrose in the cytosol. Defoliation 40 days before anthesis did not significantly reduce ovary growth, flower abscission or starch concentration up to 20 days after anthesis (i.e. 60 days later). Control flowers activated the energy depletion signaling system (i.e. SnRK1) and RbcS gene expression around athesis. Defoliation accelerated and boosted both activities, increasing SPS gene expression (sucrose synthesis), and SUS1, SUS3 and cwINV (sucrose hydrolysis) to maintain a glucose threshold which satisfied its need to avoid abscission.


Assuntos
Metabolismo dos Carboidratos/fisiologia , Citrus/crescimento & desenvolvimento , Flores/fisiologia , Frutas/crescimento & desenvolvimento , Citrus/metabolismo , Citrus/fisiologia , Flores/crescimento & desenvolvimento , Flores/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Transcriptoma
16.
Proc Natl Acad Sci U S A ; 116(23): 11299-11308, 2019 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-31110021

RESUMO

Skeletal muscle plays a central role in the control of metabolism and exercise tolerance. Analysis of muscle enhancers activated after exercise in mice revealed the orphan nuclear receptor NURR1/NR4A2 as a prominent component of exercise-responsive enhancers. We show that exercise enhances the expression of NURR1, and transgenic overexpression of NURR1 in skeletal muscle enhances physical performance in mice. NURR1 expression in skeletal muscle is also sufficient to prevent hyperglycemia and hepatic steatosis, by enhancing muscle glucose uptake and storage as glycogen. Furthermore, treatment of obese mice with putative NURR1 agonists increases energy expenditure, improves glucose tolerance, and confers a lean phenotype, mimicking the effects of exercise. These findings identify a key role for NURR1 in governance of skeletal muscle glucose metabolism, and reveal a transcriptional link between exercise and metabolism. Our findings also identify NURR1 agonists as possible exercise mimetics with the potential to ameliorate obesity and other metabolic abnormalities.


Assuntos
Homeostase/fisiologia , Músculo Esquelético/metabolismo , Membro 2 do Grupo A da Subfamília 4 de Receptores Nucleares/metabolismo , Animais , Metabolismo dos Carboidratos/fisiologia , Metabolismo Energético/fisiologia , Fígado Gorduroso/metabolismo , Glucose/metabolismo , Glicogênio/metabolismo , Humanos , Hiperglicemia/metabolismo , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/metabolismo , Condicionamento Físico Animal/fisiologia , Transcrição Genética/fisiologia , Regulação para Cima/fisiologia
17.
Cell Mol Life Sci ; 76(21): 4319-4340, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31062073

RESUMO

The human gut microbiota, which underpins nutrition and systemic health, is compositionally sensitive to the availability of complex carbohydrates in the diet. The Bacteroidetes comprise a dominant phylum in the human gut microbiota whose members thrive on dietary and endogenous glycans by employing a diversity of highly specific, multi-gene polysaccharide utilization loci (PUL), which encode a variety of carbohydrases, transporters, and sensor/regulators. PULs invariably also encode surface glycan-binding proteins (SGBPs) that play a central role in saccharide capture at the outer membrane. Here, we present combined biophysical, structural, and in vivo characterization of the two SGBPs encoded by the Bacteroides ovatus mixed-linkage ß-glucan utilization locus (MLGUL), thereby elucidating their key roles in the metabolism of this ubiquitous dietary cereal polysaccharide. In particular, molecular insight gained through several crystallographic complexes of SGBP-A and SGBP-B with oligosaccharides reveals that unique shape complementarity of binding platforms underpins specificity for the kinked MLG backbone vis-à-vis linear ß-glucans. Reverse-genetic analysis revealed that both the presence and binding ability of the SusD homolog BoSGBPMLG-A are essential for growth on MLG, whereas the divergent, multi-domain BoSGBPMLG-B is dispensable but may assist in oligosaccharide scavenging from the environment. The synthesis of these data illuminates the critical role SGBPs play in concert with other MLGUL components, reveals new structure-function relationships among SGBPs, and provides fundamental knowledge to inform future (meta)genomic, biochemical, and microbiological analyses of the human gut microbiota.


Assuntos
Bacteroides/fisiologia , Grão Comestível/metabolismo , Trato Gastrointestinal/metabolismo , Trato Gastrointestinal/microbiologia , Proteínas de Membrana/fisiologia , Polissacarídeos/metabolismo , beta-Glucanas/metabolismo , Bacteroides/genética , Bacteroides/metabolismo , Metabolismo dos Carboidratos/fisiologia , Sequência de Carboidratos , Fibras na Dieta/metabolismo , Microbioma Gastrointestinal/fisiologia , Regulação Bacteriana da Expressão Gênica , Loci Gênicos , Glicosídeo Hidrolases/genética , Glicosídeo Hidrolases/metabolismo , Humanos , Proteínas de Membrana/metabolismo
18.
Psychoneuroendocrinology ; 107: 59-69, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31108306

RESUMO

BACKGROUND: Major depressive disorder (MDD) is a pathophysiologically uncharacterized mental illness with complex etiology and clinical manifestations. Rodent depression-like models have been widely used to mimic the morbid state of depression. However, research on emotional disorders can also benefit from the use of models in non-human primates, which share a wide range of genetic and social similarities with humans. METHODS: To investigate the pathophysiological mechanisms of depression, we established two models, naturally occurring depression cynomolgus (NOD) and social plus visual isolation-induced depression cynomolgus (SVC), imitating chronic mild or acute intense stress, respectively. We used i-TRAQ (isobaric tags for relative and absolute quantitation)-based quantitative proteomics and shotgun proteomics to identify differentially expressed proteins in cerebrospinal fluid (CSF) of the two monkey models and human MDD patients. We also used DAVID and ingenuity pathway analysis (IPA) for further bioinformatic investigation. RESULTS: In behavioral tests, NOD monkeys achieved higher scores in depression-like and anxiety-like behavioral measures, and spent more time on ingesting, thermoregulatory, and locomotive actions than SVC monkeys. A total of 902 proteins were identified by i-TRAQ, and 40 differentially expressed proteins were identified in each of the NOD-CON1 and SVC-CON2 groups. Application of DAVID revealed dysregulation of energy metabolism in the NOD group, whereas lipid metabolism and inflammatory response pathways were significantly altered in the SVC group. Use of IPA and Cytoscape showed that the oxygen species metabolic process glycolysis I/gluconeogenesis I, accompanied by downregulation of tubulin beta 3 class III (TUBB3), RAC-alpha serine/threonine-protein kinase (AKT1), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), was the most significantly affected pathway in the NOD group. Furthermore, 152 differentially expressed proteins in human MDD patients also revealed disruption of glucose energy metabolism. Significantly aberrant energy metabolism in various brain regions and the plasma and liver of chronic unpredictable mild stress rodent samples were also observed in a previous study. CONCLUSIONS: Our results reveal for the first time the overall CSF protein profiles of two cynomolgus monkey models of depression. We propose that chronic mild stress may affect the disruption of glucose energy metabolism in NOD cynomolgus monkeys and rodents. These findings promote our understanding of the pathophysiology of MDD and may help to identify novel therapeutic targets.


Assuntos
Depressão/metabolismo , Metabolismo Energético/fisiologia , Glucose/metabolismo , Adulto , Animais , Comportamento Animal , Metabolismo dos Carboidratos/fisiologia , Depressão/líquido cefalorraquidiano , Transtorno Depressivo Maior/líquido cefalorraquidiano , Transtorno Depressivo Maior/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Macaca fascicularis/líquido cefalorraquidiano , Macaca fascicularis/metabolismo , Masculino , Proteômica/métodos , Isolamento Social , Estresse Psicológico/metabolismo , Estresse Psicológico/fisiopatologia
19.
Acta Diabetol ; 56(9): 1013-1022, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30989379

RESUMO

AIM: More than 40% of pancreatic ductal adenocarcinoma (PDAC) patients have glucose intolerance or diabetes. The association has led to two hypotheses: PDAC causes diabetes or diabetes shares risk factors for the development of PDAC. In order to elucidate the relationship between diabetes and PDAC, we investigated the glucose metabolism during tumorigenesis in the LSL-KrasG12D/+; LSL-Trp53R172H/+; and Pdx-1-Cre (KPC) mouse, a genetically engineered model of PDAC. METHODS: Male and female KPCs have been fed with standard diet (SD) or high-fat diet (HFD). The imaging-based 4-class tumor staging was used to follow pancreatic cancer development. Not fasting glycemia, 4-h fasting glycemia, insulin, C-peptide, glucose tolerance after OGTT and abdominal fat volume were measured during tumorigenesis. RESULTS: PDAC development did not lead to an overt diabetic phenotype or to any alterations in glucose tolerance in KPC fed with SD. Consumption of HFD induced higher body weight/abdominal fat volume and worsened glucose homeostasis both in control CRE mice and only in early tumorigenesis stages of the KPC mice, excluding that the cancer development itself acts as a trigger for the onset of dysmetabolic features. CONCLUSION: Our data demonstrate that carcinogenesis in KPC mice is not associated with paraneoplastic diabetes.


Assuntos
Metabolismo dos Carboidratos/fisiologia , Carcinogênese/metabolismo , Glucose/metabolismo , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Animais , Metabolismo dos Carboidratos/genética , Carcinogênese/genética , Carcinoma Ductal Pancreático/metabolismo , Modelos Animais de Doenças , Feminino , Proteínas de Homeodomínio/genética , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Estadiamento de Neoplasias , Neoplasias Pancreáticas/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Transativadores/genética , Proteína Supressora de Tumor p53/genética
20.
Tuberculosis (Edinb) ; 115: 161-170, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30948172

RESUMO

Tuberculosis (TB) protein biomarkers are urgently needed for the development of point-of-care diagnostics, new drugs and vaccines. Mycobacterium tuberculosis extracellular and secreted proteins play an important role in host-pathogen interactions. Antibodies produced against M. tuberculosis proteins before the onset of clinical symptoms can be used in proteomic studies to identify their target proteins. In this study, M. tuberculosis F15/LAM4/KZN strain phage secretome library was screened against immobilized polyclonal sera from active TB patients (n = 20), TST positive individuals (n = 15) and M. tuberculosis uninfected individuals (n = 20) to select and identify proteins recognized by patients' antibodies. DNA sequence analysis from randomly selected latent TB and active TB specific phage clones revealed 118 and 96 ORFs, respectively. Proteins essential for growth, virulence and metabolic pathways were identified using different TB databases. The identified active TB specific biomarkers included five proteins, namely, TrpG, Alr, TreY, BfrA and EspR, with no human homologs, whilst latent TB specific biomarkers included NarG, PonA1, PonA2 and HspR. Future studies will assess potential applications of identified protein biomarkers as TB drug or vaccine candidates/targets and diagnostic markers with the ability to discriminate LTBI from active TB.


Assuntos
Tuberculose Latente/diagnóstico , Mycobacterium tuberculosis/isolamento & purificação , Adulto , Aminoácidos/metabolismo , Antígenos de Bactérias/metabolismo , Proteínas de Bactérias/imunologia , Proteínas de Bactérias/metabolismo , Biomarcadores/metabolismo , Metabolismo dos Carboidratos/fisiologia , Parede Celular/metabolismo , Diagnóstico Precoce , Metabolismo Energético/fisiologia , Feminino , Ontologia Genética , Genes Bacterianos/genética , Genoma Bacteriano , Biblioteca Genômica , Humanos , Imunidade Celular/fisiologia , Ferro/metabolismo , Tuberculose Latente/imunologia , Metabolismo dos Lipídeos/fisiologia , Masculino , Redes e Vias Metabólicas/fisiologia , Mycobacterium tuberculosis/imunologia , Virulência/fisiologia , Fatores de Virulência/metabolismo
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