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1.
Int J Mol Sci ; 23(7)2022 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-35409244

RESUMO

Sugars, which are critical osmotic compounds and signalling molecules in plants, and Sugars Will Eventually be Exported Transporters (SWEETs), which constitute a novel family of sugar transporters, play central roles in plant responses to multiple abiotic stresses. In the present study, a member of the SWEET gene family from cucumber (Cucumis sativus L.), CsSWEET2, was identified and characterized. Histochemical analysis of ß-glucuronidase expression in transgenic Arabidopsis plants showed that CsSWEET2 is highly expressed in the leaves; subcellular localization indicated that CsSWEET2 proteins are localized in the plasma membrane and endoplasmic reticulum. Heterologous expression assays in yeast demonstrated that CsSWEET2 encodes an energy-independent hexose/H+ uniporter that can complement both glucose and fructose transport deficiencies. Compared with wild-type Arabidopsis plants, transgenic Arabidopsis plants overexpressing CsSWEET2 had much lower relative electrolyte leakage levels and were much more resistant to cold stress. Sugar content analysis showed that glucose and fructose levels in the transgenic Arabidopsis plants were significantly higher than those in the wild-type plants. Taken together, our results suggest that, by mediating sugar metabolism and compartmentation, CsSWEET2 plays a vital role in improving plant cold tolerance.


Assuntos
Arabidopsis , Cucumis sativus , Arabidopsis/genética , Arabidopsis/metabolismo , Resposta ao Choque Frio , Cucumis sativus/metabolismo , Frutose/metabolismo , Regulação da Expressão Gênica de Plantas , Glucose/metabolismo , Hexoses/metabolismo , Proteínas de Transporte de Monossacarídeos/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/genética
2.
Microb Cell Fact ; 21(1): 63, 2022 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-35440084

RESUMO

BACKGROUND: D-allulose, a hexulose monosaccharide with low calorie content and high sweetness, is commonly used as a functional sugar in food and nutrition. However, enzyme preparation of D-allulose from D-frutose was severely hindered by the non-enzymatic browning under alkaline and high-temperature, and the unnecessary by-products further increased the difficulties in separation and extraction for industrial applications. Here, to address the above issue during the production process, a tandem D-allulose 3-epimerase (DPEases) isomerase synergistic expression strategy and an auto-inducible promoter engineering were levered in Bacillus subtilis 168 (Bs168) for efficient synthesis of D-allulose under the acidic conditions without browning. RESULTS: First, based on the dicistron expression system, two DPEases with complementary functional characteristics from Dorea sp. CAG:317 (DSdpe) and Clostridium cellulolyticum H10 (RCdpe) were expressed in tandem under the promoter HpaII in one cell. A better potential strain Bs168/pMA5-DSdpe-RCdpe increases enzyme activity to 18.9 U/mL at acidic conditions (pH 6.5), much higher than 17.2 and 16.7 U/mL of Bs168/pMA5-DSdpe and Bs168/pMA5-RCdpe, respectively. Subsequently, six recombinant strains based on four constitutive promoters were constructed in variable expression cassettes for improving the expression level of protein. Among those engineered strains, Bs168/pMA5-PspoVG-DSdpe-PsrfA-RCdpe exhibited the highest enzyme activity with 480.1 U/mL on fed-batch fermentation process in a 5 L fermenter at pH 6.5, about 2.1-times higher than the 228.5 U/mL of flask fermentation. Finally, the maximum yield of D-allulose reached as high as 163.5 g/L at the fructose concentration (50% w/v) by whole-cell biocatalyst. CONCLUSION: In this work, the engineered recombinant strain Bs168/pMA5-PspoVG-DSdpe-PsrfA-RCdpe was demonstrated as an effective microbial cell factory for the high-efficient synthesis of D-allulose without browning under acidic conditions. Based on the perspectives from this research, this strategy presented here also made it possible to meet the requirements of the industrial hyper-production of other rare sugars under more acidic conditions in theory.


Assuntos
Bacillus subtilis , Racemases e Epimerases , Bacillus subtilis/genética , Bacillus subtilis/metabolismo , Fermentação , Frutose/metabolismo , Racemases e Epimerases/metabolismo
3.
Food Funct ; 13(9): 4941-4953, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35437549

RESUMO

Recently, the protective effects of a methionine-rich diet on hepatic oxidative stress and fibrosis have been suggested but not adequately studied. We, therefore, hypothesized that L-methionine supplementation would ameliorate the progression of hepatic injury in a diet-induced non-alcoholic steatohepatitis (NASH) model and aimed to investigate the underlying mechanism. NASH was developed in male Sprague Dawley rats by feeding them with a high-fat-fructose diet (HFFrD) for 10 weeks. The results demonstrated that L-methionine supplementation to NASH rats for 16 weeks improved the glycemic, lipid, and liver function profiles in NASH rats. Histological analysis of liver tissue revealed a remarkable improvement in the three classical lesions of NASH: steatosis, inflammation, and ballooning. Besides, L-methionine supplementation ameliorated the HFFrD-induced enhanced lipogenesis and lipid peroxidation. An anti-inflammatory effect of L-methionine was also observed through the inhibition of the release of proinflammatory cytokines. Furthermore, the hepatic SIRT1/AMPK signaling pathway was associated with the beneficial effects of L-methionine. This study demonstrates that L-methionine supplementation in HFFrD-fed rats improves their liver pathology via regulation of lipogenesis, inflammation, and the SIRT1/AMPK pathway, thus encouraging its clinical evaluation for the treatment of NASH.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Dieta Hiperlipídica/efeitos adversos , Suplementos Nutricionais , Modelos Animais de Doenças , Fibrose , Frutose/metabolismo , Inflamação/metabolismo , Metabolismo dos Lipídeos , Fígado/metabolismo , Masculino , Metionina/metabolismo , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Ratos , Ratos Sprague-Dawley , Sirtuína 1/genética , Sirtuína 1/metabolismo
4.
Plant Physiol Biochem ; 181: 12-22, 2022 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-35421745

RESUMO

Pomegranate (Punica granatum), an important fruit tree in the world, is rich in bioactive substances and has broad prospects for development. In this study, gene expression levels and the concentrations of metabolites involved in the metabolism of soluble sugars and organic acids were investigated in sweet and sour pomegranate cultivars at the S1 (July 25) stage, S2 (August 26) stage, and S3 (September 24) stage. The results showed that glucose, fructose, citric acid, and malic acid were predominantly present in pomegranate. The expression of invertase 2 (INV2), INV1, FRK2, FRK7, PFK2, PFK7, and HK1 was closely correlated with the fructose and glucose contents during different developmental stages, whereas the expression of sucrose synthase 3 (SUS3) and INV1 was negatively correlated with the sucrose content. The expression of MDH (c28468_g3) and WRKY42 (c20711_g1) genes were closely related to the content of sucrose, malic acid, citric acid, and succinic acid during different developmental stages. Gene expression and metabolite concentrations varied between the two cultivars. The results provide valuable information for gene discovery, marker-assisted selection, and investigation of metabolism mechanisms in pomegranate fruits.


Assuntos
Romã (Fruta) , Açúcares , Ácidos/metabolismo , Carboidratos , Ácido Cítrico/metabolismo , Frutose/metabolismo , Frutas/metabolismo , Glucose/metabolismo , Metabolômica , Compostos Orgânicos , Sacarose/metabolismo , Açúcares/metabolismo , Transcriptoma
5.
J Nutr Biochem ; 104: 108976, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35245653

RESUMO

Maternal high-fat diet (HFD) is associated with metabolic disturbances in the offspring. Fructose is a highly consumed lipogenic sugar; however, it is unknown whether skeletal muscle of maternal HFD offspring respond differentially to a fructose overload. Female Wistar rats received standard diet (STD: 9% fat) or isocaloric high-fat diet (HFD: 29% fat) during 8 weeks before mating until weaning. After weaning, male offspring received STD and, from 120 to 150 days-old, they drank water or 15% fructose in water (STD-F and HFD-F). At 150th day, we collected the oxidative soleus and glycolytic extensor digitorum longus (EDL) muscles. Fructose-treated groups exhibited hypertriglyceridemia, regardless of maternal diet. Soleus of maternal HFD offspring showed increased triglycerides and monounsaturated fatty acid content, independent of fructose, with increased fatty acid transporters and lipogenesis markers. The EDL exhibited unaltered triglycerides content, with an apparent equilibrium between lipogenesis and lipid oxidation markers in HFD, and higher lipid uptake (fatty acid-binding protein 4) accompanied by enhanced monounsaturated fatty acid in fructose-treated groups. Mitochondrial complexes proteins and Tfam mRNA were increased in the soleus of HFD, while uncoupling protein 3 was decreased markedly in HFD-F. In EDL, maternal HFD increased ATP synthase, while fructose decreased Tfam predominantly in STD offspring. Maternal HFD and fructose induced mitochondria ultrastructural damage, intensified in HFD-F in both muscles. Thus, alterations in molecular markers of lipid metabolism and mitochondrial function in response to fructose are modified by an isocaloric and moderate maternal HFD and are fiber-type specific, representing adaptation/maladaptation mechanisms associated with higher skeletal muscle fructose-induced mitochondria injury in adult offspring.


Assuntos
Dieta Hiperlipídica , Doenças Sexualmente Transmissíveis , Animais , Dieta Hiperlipídica/efeitos adversos , Ácidos Graxos Monoinsaturados/metabolismo , Feminino , Frutose/efeitos adversos , Frutose/metabolismo , Metabolismo dos Lipídeos , Masculino , Músculo Esquelético/metabolismo , Ratos , Ratos Wistar , Doenças Sexualmente Transmissíveis/metabolismo , Triglicerídeos/metabolismo , Água/metabolismo
6.
Am J Physiol Regul Integr Comp Physiol ; 322(5): R347-R359, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35271385

RESUMO

Fructose metabolism and hyperuricemia have been shown to drive insulin resistance, metabolic syndrome, hepatic steatosis, hypertension, inflammation, and innate immune reactivity in experimental studies. We suggest that these adverse effects are at least in part the result of suppressed activity of sirtuins, particularly Sirtuin1. Deficiency of sirtuin deacetylations is a consequence of reduced bioavailability of its cofactor nicotinamide adenine dinucleotide (NAD+). Uric acid-induced inflammation and oxidative stress consume NAD+ and activation of the polyol pathway of fructose and uric acid synthesis also reduces the NAD+-to-NADH ratio. Variability in the compensatory regeneration of NAD+ could result in variable recovery of sirtuin activity that may explain the inconsistent benefits of treatments directed to reduce uric acid in clinical trials. Here, we review the pathogenesis of the metabolic dysregulation driven by hyperuricemia and their potential relationship with sirtuin deficiency. In addition, we discuss therapeutic options directed to increase NAD+ and sirtuins activity that may improve the adverse effects resulting from fructose and uric acid synthesis.


Assuntos
Resistência à Insulina , Sirtuínas , Frutose/efeitos adversos , Frutose/metabolismo , Humanos , NAD/metabolismo , Sirtuínas/metabolismo , Ácido Úrico
7.
Cancer Lett ; 534: 215617, 2022 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-35257833

RESUMO

Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide. Abundant metabolic fuels have been implicated as potential drivers of CRC. However, it remains unclear whether fructose, an ample sugar in daily diets, is essential for CRC growth. In the present study, we found that glucose levels were always insufficient in human CRC tissues. Compensating for this, fructose was flexibly utilized by tumor cells as an alternative energy source to maintain proliferation and exert chemotherapy resistance in vitro by upregulating GLUT5, a major fructose transporter encoded by SLC2A5. Mechanistically, in glucose-deprived but fructose-rich environments, GLUT5 could interact with ketohexokinase and inhibit its autophagy-dependent degradation, thus trapping fructose into glycolysis and tricarboxylic acid cycle for the malignant growth of CRC cells. In addition, reducing dietary fructose or pharmacological blockade of fructose utilization significantly reduced CRC growth and sensitized CRC cells to chemotherapy in vivo. Taken together, our findings highlight the role of elevated fructose utilization mediated by the GLUT5-KHK axis in governing CRC growth and imply that efforts to refine fructose intake or inhibit fructose-mediated actions may serve as potential therapeutic strategies.


Assuntos
Neoplasias Colorretais , Frutoquinases , Frutose , Transportador de Glucose Tipo 5 , Proliferação de Células , Neoplasias Colorretais/tratamento farmacológico , Frutoquinases/metabolismo , Frutose/metabolismo , Glucose , Transportador de Glucose Tipo 5/metabolismo , Humanos
8.
Nutrients ; 14(3)2022 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-35276876

RESUMO

Although epidemiological studies indicate a strong correlation between high sugar intake and metabolic diseases, the biological mechanisms underlying this link are still controversial. To further examine the modification and crosstalk occurring in enterocyte metabolism during sugar absorption, in this study we evaluate the diffusion and intestinal metabolism of glucose, fructose and sucrose, which were supplemented in equimolar concentration to Caco-2 cells grown on polyester membrane inserts. At different time points after supplementation, changes in metabolite concentration were evaluated in the apical and basolateral chambers by nuclear magnetic resonance (NMR) and gas-chromatography (GC). Sucrose was only minimally hydrolyzed by Caco-2 cells. Upon supplementation, we observed a faster uptake of fructose than glucose, the pentose sugar being also faster catabolized. Monosaccharide absorption was concomitant to the synthesis/transport of other metabolites, which occurred differently in glucose and fructose supplemented cells. Our results confirm the prominent role of intestinal cells in fructose metabolism and clearance after absorption, representing a further step forward in the understanding of the role of dietary sugars. Future research, including targeted analysis on specific transporters/enzymes and the use of labeled substrates, will be helpful to confirm the present results and their interpretation.


Assuntos
Frutose , Glucose , Células CACO-2 , Enterócitos/metabolismo , Frutose/metabolismo , Glucose/metabolismo , Humanos , Transportador 1 de Glucose-Sódio/metabolismo
9.
Mol Metab ; 58: 101451, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35123128

RESUMO

OBJECTIVE: Transmembrane 4 L six family member 5 (TM4SF5) is likely involved in non-alcoholic steatohepatitis, although its roles and cross-talks with glucose/fructose transporters in phenotypes derived from high-carbohydrate diets remain unexplored. Here, we investigated the modulation of hepatic fructose metabolism by TM4SF5. METHODS: Wild-type or Tm4sf5-/- knockout mice were evaluated via different diets, including normal chow, high-sucrose diet, or high-fat diet without or with fructose in drinking water (30% w/v). Using liver tissues and blood samples from the mice or hepatocytes, the roles of TM4SF5 in fructose-mediated de novo lipogenesis (DNL) and steatosis via a crosstalk with glucose transporter 8 (GLUT8) were assessed. RESULTS: Tm4sf5 suppression or knockout in both in vitro and in vivo models reduced fructose uptake, DNL, and steatosis. Extracellular fructose treatment of hepatocytes resulted in an inverse relationship between fructose-uptake activity and TM4SF5-mediated translocalization of GLUT8 through dynamic binding at the cell surface. Following fructose treatment, TM4SF5 binding to GLUT8 transiently decreased with translocation to the plasma membrane (PM), where GLUT8 separated and became active for fructose uptake and DNL. CONCLUSIONS: Overall, hepatic TM4SF5 modulated GLUT8 localization and activity through transient binding, leading to steatosis-related fructose uptake and lipogenesis. Thus, TM4SF5 and/or GLUT8 may be promising treatment targets against liver steatosis resulting from excessive fructose consumption.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Animais , Frutose/metabolismo , Proteínas Facilitadoras de Transporte de Glucose/metabolismo , Hepatócitos/metabolismo , Lipogênese , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos , Hepatopatia Gordurosa não Alcoólica/metabolismo
10.
J Mol Biol ; 434(7): 167480, 2022 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-35176290

RESUMO

FraR, a transcriptional repressor, was postulated to regulate the metabolism of the Amadori compound fructose-asparagine (F-Asn) in the foodborne pathogen Salmonella enterica. Here, the DNA- and inducer-binding affinities and stoichiometries of FraR were determined and cross-validated by electrophoretic mobility-shift assays (EMSAs) and online buffer exchange coupled to native mass spectrometry (OBE-nMS). We demonstrate the utility of OBE-nMS to characterize protein and protein-DNA complexes that are not amenable to offline exchange into volatile buffers. OBE-nMS complemented EMSAs by revealing that FraR binds to the operator DNA as a dimer and by establishing 6-phosphofructose-aspartate as the inducer that weakens DNA binding by FraR. These results provide insights into how FraR regulates the expression of F-Asn-catabolizing enzymes and add to our understanding of the intricate bacterial circuitry that dictates utilization of diverse nutrients.


Assuntos
Proteínas de Bactérias , Salmonella enterica , Fatores de Transcrição , Asparagina/metabolismo , Proteínas de Bactérias/metabolismo , DNA/metabolismo , Frutose/metabolismo , Espectrometria de Massas/métodos , Salmonella enterica/metabolismo , Fatores de Transcrição/metabolismo
11.
Int J Mol Sci ; 23(4)2022 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-35216187

RESUMO

Sugar consumption can readily lead to obesity and metabolic diseases such as liver steatosis. We previously demonstrated that a novel hypothalamic neuropeptide, neurosecretory protein GL (NPGL), promotes fat accumulation due to the ingestion of sugar by rats. However, differences in lipogenic efficiency of sugar types by NPGL remain unclear. The present study aimed to elucidate the obesogenic effects of NPGL on mice fed different sugars (i.e., sucrose or fructose). We overexpressed the NPGL-precursor gene (Npgl) in the hypothalamus of mice fed a medium-fat/medium-sucrose diet (MFSD) or a medium-fat/medium-fructose diet (MFFD). Food intake and body mass were measured for 28 days. Body composition and mRNA expression of lipid metabolic factors were measured at the endpoint. Npgl overexpression potently increased body mass with fat accumulation in the white adipose tissue of mice fed MFFD, although it did not markedly affect food intake. In contrast, we observed profound fat deposition in the livers of mice fed MFFD but not MFSD. In the liver, the mRNA expression of glucose and lipid metabolic factors was affected in mice fed MFFD. Hence, NPGL induced liver steatosis in mice fed a fructose-rich diet.


Assuntos
Fígado Gorduroso/metabolismo , Frutose/metabolismo , Fígado/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Tecido Adiposo Branco/metabolismo , Animais , Composição Corporal/fisiologia , Dieta Hiperlipídica/métodos , Sacarose na Dieta/metabolismo , Metabolismo Energético/fisiologia , Comportamento Alimentar/fisiologia , Glucose/metabolismo , Hipotálamo/metabolismo , Insulina/metabolismo , Metabolismo dos Lipídeos/fisiologia , Lipogênese/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neuropeptídeos/metabolismo , Obesidade/metabolismo
12.
Microbiol Spectr ; 10(1): e0122121, 2022 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-35171023

RESUMO

We describe the genomic characteristics of Vibrio cholerae strain PS-4 that is unable to ferment sucrose on a thiosulfate citrate bile salt sucrose (TCBS) agar medium. This bacterium was isolated from the skin mucus of a freshwater pufferfish. The genome of strain PS-4 was sequenced to understand the sucrose nonfermenting phenotype. The gene encoding the sucrose-specific phosphotransferase system IIB (sucR) was absent, resulting in the defective sucrose fermenting phenotype. In contrast, genes encoding the glucose-specific transport system IIB (ptsG) and fructose-specific transport system IIB (fruA) showed acid production while growing with respective sugars. The overall genome relatedness indices (OGRI), such as in silico DNA-DNA hybridization (isDDH), average nucleotide identity (ANI), and average amino acid identity (AAI), were above the threshold value, that is, 70% and 95 to 96%, respectively. Phylogenomic analysis based on genome-wide core genes and the nonrecombinant core genes showed that strain PS-4 clustered with Vibrio cholerae ATCC 14035T. Further, genes encoding cholera toxin (ctx), zonula occludens toxin (zot), accessory cholera enterotoxin (ace), toxin-coregulated pilus (tcp), and lipopolysaccharide biosynthesis (rfb) were absent. PS-4 showed hemolytic activity and reacted strongly to the R antibody. Therefore, the Vibrio cholerae from the pufferfish adds a new ecological niche of this bacterium. IMPORTANCE Vibrio cholerae is native of aquatic environments. In general, V. cholerae ferments sucrose on thiosulfate citrate bile salt sucrose (TCBS) agar and produces yellow colonies. V. cholerae strain PS-4 described in this study is a sucrose nonfermenting variant associated with pufferfish skin and does not produce yellow colonies on TCBS agar. Genes encoding sucrose-specific phosphotransferase system IIB (sucR) were absent. The observed phenotype in the distinct metabolic pathway indicates niche-specific adaptive evolution for this bacterium. Our study suggests that the nonfermenting phenotype of V. cholerae strains on TCBS agar may not always be considered for species delineation.


Assuntos
Reservatórios de Doenças/microbiologia , Sacarose/metabolismo , Tetraodontiformes/microbiologia , Vibrio cholerae/metabolismo , Animais , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Cólera/microbiologia , Endotoxinas/metabolismo , Fermentação , Frutose/metabolismo , Genoma Bacteriano , Glucose/metabolismo , Humanos , Fosfotransferases/genética , Fosfotransferases/metabolismo , Rios/microbiologia , Pele/microbiologia , Vibrio cholerae/genética , Vibrio cholerae/isolamento & purificação
13.
Mol Nutr Food Res ; 66(7): e2101115, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35124887

RESUMO

SCOPE: The aim of this study is to delineate the contribution of dietary saturated fatty acids (FA) versus liquid fructose to fatty liver and hypertriglyceridemia. METHODS AND RESULTS: Three groups of female rats are maintained for 3 months in standard chow (CT); High-fat diet (46.9% of fat-derived calories, rich in palmitic and stearic FA, HFD); and HFD with 10% w/v fructose in drinking water (HFHFr). Zoometric parameters, plasma biochemistry, and liver Oil-Red O (ORO) staining, lipidomics, and expression of proteins involved in FA metabolism are analyzed. Both diets increase ingested calories without modifying body weight. Only the HFHFr diet increases liver triglycerides (x11.0), with hypertriglyceridemia (x1.7) and reduces FA ß-oxidation (x0.7), and increases liver FA markers of DNL (de novo lipogenesis). Whereas HFD livers show a high content of ceramides, HFHFr samples show unchanged ceramides, and an increase in diacylglycerols. Only the HFHFr diet leads to a marked increase in the expression of enzymes involved in DNL and triglyceride metabolism, such as carbohydrate response element binding protein ß (ChREBPß, x3.2), a transcription factor that regulates DNL, and patatin-like phospholipase domain-containing 3 (PNPLA3, x2.6), a lipase that mobilizes stored triglycerides for VLDL secretion. CONCLUSION: The addition of liquid-fructose to dietary FA is determinant in liver steatosis and hypertriglyceridemia production, through increased DNL and PNPLA3 expression, and reduced FA catabolism.


Assuntos
Fígado Gorduroso , Hipertrigliceridemia , Animais , Dieta Hiperlipídica/efeitos adversos , Feminino , Frutose/efeitos adversos , Frutose/metabolismo , Hipertrigliceridemia/etiologia , Lipogênese/fisiologia , Fígado/metabolismo , Ratos , Fatores de Transcrição/metabolismo , Triglicerídeos
15.
Neurosci Lett ; 772: 136476, 2022 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-35085689

RESUMO

Fructose ingestion elicits a diversity of brain alterations, but it is unknown how it affects N-methyl-D-Aspartate receptors (NMDAr). Here, we analyzed the expression of NMDAr subunits and protein kinases after the long-term dietary fructose intake. Since NMDAr are related to epileptogenesis, we also examined whether fructose increases the susceptibility to seizures after the microinjection of kainic acid (KA) in the rat hippocampus. Wistar rats were randomly divided into water (control) and fructose groups. For twelve weeks, groups had ad libitum access to water or fructose solution (10% w/v). After treatment, hippocampal protein expression of NMDAr subunits and protein kinases involved in NMDAr regulation were analyzed. Additionally, electroencephalographic and behavioral changes related to seizures were evaluated after the microinjection of a sub-convulsive dose of KA in the hippocampus. Fructose induced the decrease of NR1 and, conversely, the increase of NR2A subunits expression in the hippocampus. Also, the phosphorylation of protein kinase C alpha (PKCα) and c-Src increased significantly. No electroencephalographic or behavioral patterns related to convulsive motor seizures were observed in the control group. However, all the rats that ingested fructose showed stage 3 seizures (forelimb clonus) and a significant increase in the number of wet-dog shakes. Moreover, electroencephalographic recordings revealed pronounced epileptiform activity and increased total spectral power at 30 and 60 min after the microinjection of KA. This study shows for the first time that fructose intake exacerbates the seizures induced by KA. Therefore, we propose that this proconvulsant effect could be mediated by changes in NMDAr subunits expression and increased activation of kinases modulating NMDAr function.


Assuntos
Frutose/metabolismo , Xarope de Milho Rico em Frutose/efeitos adversos , Receptores de N-Metil-D-Aspartato/metabolismo , Convulsões/metabolismo , Animais , Ingestão de Alimentos , Frutose/administração & dosagem , Xarope de Milho Rico em Frutose/administração & dosagem , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Ácido Caínico/toxicidade , Masculino , Proteína Quinase C/metabolismo , Ratos , Ratos Wistar , Receptores de N-Metil-D-Aspartato/genética , Convulsões/etiologia , Quinases da Família src/metabolismo
16.
Am J Physiol Gastrointest Liver Physiol ; 322(3): G295-G309, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-34984925

RESUMO

Mice exposed in gestation to maternal high-fat/high-sucrose (HF/HS) diet develop altered bile acid (BA) homeostasis. We hypothesized that these reflect an altered microbiome and asked if microbiota transplanted from HF/HS offspring change hepatic BA and lipid metabolism to determine the directionality of effect. Female mice were fed HF/HS or chow (CON) for 6 wk and bred with lean males. 16S sequencing was performed to compare taxa in offspring. Cecal microbiome transplantation (CMT) was performed from HF/HS or CON offspring into antibiotic-treated mice fed chow or high fructose. BA, lipid metabolic, and gene expression analyses were performed in recipient mice. Gut microbiomes from HF/HS offspring segregated from CON offspring, with increased Firmicutes to Bacteriodetes ratios and Verrucomicrobial abundance. After CMT was performed, HF/HS-recipient mice had larger BA pools, increased intrahepatic muricholic acid, and decreased deoxycholic acid species. HF/HS-recipient mice exhibited downregulated hepatic Mrp2, increased hepatic Oatp1b2, and decreased ileal Asbt mRNA expression. HF/HS-recipient mice exhibited decreased cecal butyrate and increased hepatic expression of Il6. HF/HS-recipient mice had larger livers and increased intrahepatic triglyceride versus CON-recipient mice after fructose feeding, with increased hepatic mRNA expression of lipogenic genes including Srebf1, Fabp1, Mogat1, and Mogat2. CMT from HF/HS offspring increased BA pool and shifted the composition of the intrahepatic BA pool. CMT from HF/HS donor offspring increased fructose-induced liver triglyceride accumulation. These findings support a causal role for vertical transfer of an altered microbiome in hepatic BA and lipid metabolism in HF/HS offspring.NEW & NOTEWORTHY We utilized a mouse model of maternal obesogenic diet exposure to evaluate the effect on offspring microbiome and bile acid homeostasis. We identified shifts in the offspring microbiome associated with changes in cecal bile acid levels. Transfer of the microbiome from maternal obesogenic diet-exposed offspring to microbiome-depleted mice altered bile acid homeostasis and increased fructose-induced hepatic steatosis.


Assuntos
Ácidos e Sais Biliares , Microbioma Gastrointestinal , Animais , Ácidos e Sais Biliares/metabolismo , Dieta Hiperlipídica , Feminino , Frutose/metabolismo , Microbioma Gastrointestinal/fisiologia , Homeostase , Metabolismo dos Lipídeos/genética , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , RNA Mensageiro/metabolismo , Triglicerídeos/metabolismo
17.
Mol Biol Rep ; 49(4): 2839-2845, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35067813

RESUMO

BACKGROUND: Hepatic fibrosis is one of the main reasons for mortality in the world. Hepatic stellate cells (HSCs) activate during chronic liver injury, express more Transforming growth factor beta (TGF-ß), Collagen1α (COLA1) and actin-alpha smooth muscle (αSMA) that lead to hepatic fibrosis. Quercetin is a flavonoid in vegetables and fruits that has shown hepatoprotective potential, but little is known about its effects on HSCs activation. In this study, we investigated the antifibrotic activity of Quercetin on fructose-activated human HSCs and its underlying mechanism in vitro. METHODS: First, the human HSCs were treated with fructose (25 mM) for 48 h and then with Quercetin for 24 h. Total RNAs were extracted, reversely transcribed into cDNA, Quantitative Real-time PCR and western blot were performed. RESULTS: The results showed that the levels of mRNA expression of TGF-ß, αSMA, Collagen1 genes, and phosphorylated smad3 protein were significantly reduced in fructose-activated HSCs after treatment with Quercetin compared to fructose-activated HSCs. CONCLUSION: Quercetin is effective in reducing the expression of fibrogenic genes in fructose-activated human HSCs through downregulation of the TGF-ß/smad3 signaling pathway. Therefore, Quercetin possesses significant antifibrotic properties in hepatic fibrosis.


Assuntos
Células Estreladas do Fígado , Quercetina , Frutose/metabolismo , Frutose/farmacologia , Células Estreladas do Fígado/metabolismo , Humanos , Cirrose Hepática/patologia , Quercetina/farmacologia , Fator de Crescimento Transformador beta/metabolismo , Fator de Crescimento Transformador beta1/metabolismo
18.
Int J Mol Sci ; 23(1)2022 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-35008925

RESUMO

Non-alcoholic steatohepatitis (NASH) is characterized by steatosis, lobular inflammation, and enlargement of the diameter of hepatocytes (ballooning hepatocytes), with or without fibrosis. It affects 20% of patients with non-alcoholic fatty liver disease (NAFLD). Due to liver dysfunction and the numerous metabolic changes that commonly accompany the condition (obesity, insulin resistance, type 2 diabetes, and metabolic syndrome), the secretion of organokines is modified, which may contribute to the pathogenesis or progression of the disease. In this sense, this study aimed to perform a review of the role of organokines in NASH. Thus, by combining descriptors such as NASH, organokines, oxidative stress, inflammation, insulin resistance, and dyslipidemia, a search was carried out in the EMBASE, MEDLINE-PubMed, and Cochrane databases of articles published in the last ten years. Insulin resistance, inflammation and mitochondrial dysfunction, fructose, and intestinal microbiota were factors identified as participating in the genesis and progression of NASH. Changes in the pattern of organokines secretion (adipokines, myokines, hepatokines, and osteokines) directly or indirectly contribute to aggravating the condition or compromise homeostasis. Thus, further studies involving skeletal muscle, adipose, bone, and liver tissue as endocrine organs are essential to better understand the modulation of organokines involved in the pathogenesis of NASH to advance in the treatment of this disease.


Assuntos
Adipocinas/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Proteínas Morfogenéticas Ósseas/metabolismo , Dislipidemias , Frutose/metabolismo , Microbioma Gastrointestinal , Humanos , Inflamação , Resistência à Insulina , Mitocôndrias/metabolismo , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/microbiologia , Osteocalcina/metabolismo
19.
Plant J ; 109(5): 1183-1198, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34888978

RESUMO

Fructose (Fru) content is a key determinant of fruit sweetness and quality. An F1 hybrid population of the apple cultivars 'Honeycrisp' × 'Qinguan' was used to investigate the quantitative trait locus (QTL) regions and genes controlling Fru content in fruit. A stable QTL on linkage group (LG) 01 in 'Honeycrisp' was detected on the single nucleotide polymorphism (SNP) genetic linkage maps. In this region, a sorbitol dehydrogenase (SDH) gene, MdSDH2, was detected and showed promoter variations and differential expression patterns between 'Honeycrisp' and 'Qinguan' fruits as well as their hybrids. A SNP variant (A/G) in the MdSDH2 promoter region (SDH2p-491) affected the binding ability of the transcription factor MdABI3, which can affect the expression of MdSDH2. Promoter sequences with an A nucleotide at SDH2p-491 had stronger binding affinity for MdABI3 than those with a G. Among 27 domesticated apple cultivars and wild relatives, this SNP (A/G) was associated with Fru content. Our results indicate that MdSDH2 can alter Fru content as the major regulatory gene and that ABA signaling might be involved in Fru content accumulation in apple fruit.


Assuntos
Malus , Frutose/metabolismo , Frutas/metabolismo , L-Iditol 2-Desidrogenase/genética , Malus/genética , Malus/metabolismo , Regiões Promotoras Genéticas/genética , Sorbitol/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
20.
J Sci Food Agric ; 102(7): 2855-2863, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34741307

RESUMO

BACKGROUND: Pea sprouts are considered a healthy food. Sucrose is a key nutritional factor affecting taste and flavor. Meanwhile, selenium (Se) is an essential micronutrient that plays multiple roles in wide variety of physiological processes and improves crop quality and nutritional value. Nonetheless, the effects of the combination of sucrose and Se treatment on growth, quality, and sugar metabolism of pea sprouts have not been explored. RESULTS: The results revealed that sucrose at 10 mg L-1 obviously increased fresh weight, vitamin C, soluble protein, soluble sugar, fructose, glucose, and sucrose contents. Se treatments also improved nutritional quality, but higher Se (2.5 mg L-1 ) significantly inhibited the growth of seedlings. Interestingly, the combined application of sucrose (10 mg L-1 ) and Se (1.25 mg L-1 ) could effectively promote vitamin C, sucrose, and fructose contents, especially the Se content, compared with Se application alone. Additionally, there were significant differences in the regulation of sugar metabolism between Se alone and combined application of sucrose and Se. Acid invertase and neutral invertase play a pivotal role in the accumulation of soluble sugar under Se treatments alone, and acid invertase might be the key enzyme to limit sugar accumulation under combined application of sucrose and Se. CONCLUSION: The moderate combined application of sucrose (10 mg L-1 ) and Se (1.25 mg L-1 ) more effectively regulated sugar metabolism and improved nutritional quality than Se application alone did. © 2021 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.


Assuntos
Selênio , Sacarose , Ácido Ascórbico , Metabolismo dos Carboidratos , Carboidratos , Frutose/metabolismo , Ervilhas/metabolismo , Selênio/metabolismo , Sacarose/metabolismo , Açúcares , beta-Frutofuranosidase/metabolismo
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