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1.
Biomed Res Int ; 2021: 9942152, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34485530

RESUMO

Lipid deposition is an etiology of renal damage caused by lipid metabolism disorder in diabetic nephropathy (DN). Thus, reducing lipid deposition is a feasible strategy for the treatment of DN. Morroniside (MOR), an iridoid glycoside isolated from the Chinese herb Cornus officinalis Sieb. et Zucc., is considered to be an effective drug in inhibiting oxidative stress, reducing inflammatory response, and countering apoptosis. To explore the protective mechanism of MOR in attenuating renal lipotoxicity in DN, we investigated the effect of MOR on an in vitro model of lipid metabolism disorder of DN established by stimulating mouse renal tubular epithelial cells (mRTECs) with sodium palmitate (PA) or high glucose (HG). Oil Red O and filipin cholesterol staining assays were used to determine intracellular lipid accumulation status. Results revealed that PA or HG stimulation inhibited the expressions of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), liver X receptors (LXR), ATP-binding cassette subfamily A member 1 (ABCA1), ABCG1, and apolipoprotein E (ApoE) in mRTECs as evidenced by western blot and quantitative real-time PCR, resulting in increased intracellular lipid deposition. Interestingly, MOR upregulated expressions of PGC-1α, LXR, ABCA1, ABCG1, and ApoE, thus reducing cholesterol accumulation in mRTECs, suggesting that MOR might promote cholesterol efflux from mRTECs via the PGC-1α/LXR pathway. Of note, silencing PGC-1α reversed the promotive effect of MOR on PA- or HG-induced cellular cholesterol accumulation. In conclusion, our results suggest that MOR has a protective effect on mRTECs under high lipid or high glucose conditions, which may be related to the promotion of intracellular cholesterol efflux mediated by PGC-1α.


Assuntos
Glucose/administração & dosagem , Glicosídeos/farmacologia , Nefropatias/metabolismo , Túbulos Renais/efeitos dos fármacos , Transtornos do Metabolismo dos Lipídeos/tratamento farmacológico , Ácido Palmítico/farmacologia , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Animais , Linhagem Celular , Inibidores Enzimáticos/farmacologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Túbulos Renais/metabolismo , Túbulos Renais/patologia , Transtornos do Metabolismo dos Lipídeos/etiologia , Transtornos do Metabolismo dos Lipídeos/metabolismo , Transtornos do Metabolismo dos Lipídeos/patologia , Camundongos , Extratos Vegetais/farmacologia , Transdução de Sinais , Edulcorantes/farmacologia
2.
Int J Mol Sci ; 22(18)2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34576027

RESUMO

Despite having been tagged as safe and beneficial, recent evidence remains inconclusive regarding the status of artificial sweeteners and their putative effects on gut microbiota. Gut microorganisms are essential for the normal metabolic functions of their host. These microorganisms communicate within their community and regulate group behaviors via a molecular system termed quorum sensing (QS). In the present study, we aimed to study the effects of artificial sweeteners on this bacterial communication system. Using biosensor assays, biophysical protein characterization methods, microscale thermophoresis, swarming motility assays, growth assays, as well as molecular docking, we show that aspartame, sucralose, and saccharin have significant inhibitory actions on the Gram-negative bacteria N-acyl homoserine lactone-based (AHL) communication system. Our studies indicate that these three artificial sweeteners are not bactericidal. Protein-ligand docking and interaction profiling, using LasR as a representative participating receptor for AHL, suggest that the artificial sweeteners bind to the ligand-binding pocket of the protein, possibly interfering with the proper housing of the native ligand and thus impeding protein folding. Our findings suggest that these artificial sweeteners may affect the balance of the gut microbial community via QS-inhibition. We, therefore, infer an effect of these artificial sweeteners on numerous molecular events that are at the core of intestinal microbial function, and by extension on the host metabolism.


Assuntos
Proteínas de Bactérias/genética , Microbioma Gastrointestinal/efeitos dos fármacos , Percepção de Quorum/efeitos dos fármacos , Edulcorantes/efeitos adversos , Transativadores/genética , Aspartame/efeitos adversos , Técnicas Biossensoriais/métodos , Hidrolases de Éster Carboxílico/genética , Comunicação Celular/efeitos dos fármacos , Microbioma Gastrointestinal/genética , Bactérias Gram-Negativas/efeitos dos fármacos , Humanos , Simulação de Acoplamento Molecular , Sacarina/efeitos adversos , Sacarose/efeitos adversos , Sacarose/análogos & derivados , Edulcorantes/farmacologia
3.
Nutrients ; 13(7)2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-34371971

RESUMO

Although physiologically pain has a protective function, in many diseases, it is one of the most prominent symptoms. Today, new trends are focused on finding more natural alternatives to conventional treatments to alleviate it. Thereby, the purpose of this investigation was to obtain preclinical data of the antinociceptive properties of a lyophilized obtained from a newly designed maqui-citrus beverage alone and added with different sweeteners. To achieve this objective, maqui berry and citrus pharmacological activity were studied separately, as well as the interaction of both ingredients. In addition, due to the controversy generated regarding the intake of sugars, related to different metabolic diseases, the influence of different sweeteners (stevia, sucralose, or sucrose) was studied to determine their possible influence on the bioactive compounds of this product. For the attainment of our goals, a pharmacological evaluation, using the 1% formalin test, a nociceptive pain model in mice, was performed by using a sub-efficacious dosage of Maqui (25 mg/kg, i.p.) alone and combined with citrus, and then compared with the effects obtained in the presence of the different sweeteners. As a result, the antinociceptive response of the maqui was synergized in the presence of citrus in the neurogenic and inflammatory phases of the formalin test. However, this response was partially or totally reduced in the presence of the sweeteners. Our study gives preclinical evidence that a combination of maqui and citrus might exert beneficial actions to relieve pain, whereas the presence of sweeteners could reduce or avoid it.


Assuntos
Analgésicos/administração & dosagem , Citrus , Elaeocarpaceae , Frutas/química , Compostos Fitoquímicos/antagonistas & inibidores , Edulcorantes/farmacologia , Analgesia , Animais , Antocianinas/análise , Bebidas , Sinergismo Farmacológico , Flavanonas/análise , Masculino , Camundongos , Compostos Fitoquímicos/administração & dosagem , Compostos Fitoquímicos/análise , Stevia , Sacarose/análogos & derivados , Sacarose/farmacologia
4.
Nutrients ; 13(8)2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34444906

RESUMO

Diabetic kidney disease (DKD) has become a global health concern, with about 40% of people living with type 1 and type 2 diabetes mellitus developing DKD. Upregulation of vascular endothelial growth factor (VEGF) in the kidney is a significant pathology of DKD associated with increased glomerular vascular permeability. To date, however, current anti-VEGF therapies have demonstrated limited success in treating DKD. Recent studies have shown that artificial sweeteners exhibit anti-VEGF potential. The aim of this study was therefore to assess the effects of aspartame, saccharin, and sucralose on VEGF-induced leak using an in vitro model of the glomerular endothelium. Saccharin and sucralose but not aspartame protected against VEGF-induced permeability. Whilst the sweeteners had no effect on traditional VEGF signalling, GC-MS analysis demonstrated that the sweetener sucralose was not able to enter the glomerular endothelial cell to exert the protective effect. Chemical and molecular inhibition studies demonstrated that sweetener-mediated protection of the glomerular endothelium against VEGF is dependent on the sweet taste receptor, T1R3. These studies demonstrate the potential for sweeteners to exert a protective effect against VEGF-induced increased permeability to maintain a healthy endothelium and protect against vascular leak in the glomerulus in settings of DKD.


Assuntos
Permeabilidade Capilar/efeitos dos fármacos , Substâncias Protetoras/farmacocinética , Sacarina/farmacocinética , Sacarose/análogos & derivados , Edulcorantes/farmacologia , Aspartame/farmacocinética , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/metabolismo , Células Endoteliais , Endotélio Vascular/metabolismo , Humanos , Técnicas In Vitro , Rim/irrigação sanguínea , Microvasos/metabolismo , Sacarose/farmacocinética , Fatores de Crescimento do Endotélio Vascular/metabolismo
5.
Int J Mol Sci ; 22(14)2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34299151

RESUMO

Coagulopathies common to patients with diabetes and chronic kidney disease (CKD) are not fully understood. Fibrin deposits in the kidney suggest the local presence of clotting factors including tissue factor (TF). In this study, we investigated the effect of glucose availability on the synthesis of TF by cultured human kidney tubular epithelial cells (HTECs) in response to activation of protease-activated receptor 2 (PAR2). PAR2 activation by peptide 2f-LIGRLO-NH2 (2F, 2 µM) enhanced the synthesis and secretion of active TF (~45 kDa) which was blocked by a PAR2 antagonist (I-191). Treatment with 2F also significantly increased the consumption of glucose from the cell medium and lactate secretion. Culturing HTECs in 25 mM glucose enhanced TF synthesis and secretion over 5 mM glucose, while addition of 5 mM 2-deoxyglucose (2DOG) significantly decreased TF synthesis and reduced its molecular weight (~40 kDa). Blocking glycosylation with tunicamycin also reduced 2F-induced TF synthesis while reducing its molecular weight (~36 kDa). In conclusion, PAR2-induced TF synthesis in HTECs is enhanced by culture in high concentrations of glucose and suppressed by inhibiting either PAR2 activation (I-191), glycolysis (2DOG) or glycosylation (tunicamycin). These results may help explain how elevated concentrations of glucose promote clotting abnormities in diabetic kidney disease. The application of PAR2 antagonists to treat CKD should be investigated further.


Assuntos
Células Epiteliais/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Glucose/farmacologia , Túbulos Renais/metabolismo , Receptor PAR-2/metabolismo , Tromboplastina/metabolismo , Células Epiteliais/efeitos dos fármacos , Humanos , Túbulos Renais/efeitos dos fármacos , Receptor PAR-2/genética , Edulcorantes/farmacologia
6.
Behav Processes ; 191: 104462, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34284086

RESUMO

In three experiments thirsty rats were given exposure to a sweet solution (saccharin in some experiments, sucrose in others) prior to consuming a compound of the sweet substance and almond flavoring. Preference for that flavor, in a choice test of almond vs. water, was then assessed. In some cases the rats were hungry, in others they were not. When the sweetener used was saccharin, preexposure reduced the magnitude of the preference obtained on test in both hungry and nonhungry rats. When the sweetener was sucrose, preexposure had this effect only when the rats were hungry. The effects produced after preexposure to saccharin are interpreted as being the result of habituation to its sensory features that reduces the ability of these features to engage in subsequent learning. These effects will occur whether the animal is hungry or not. The results for sucrose are interpreted in terms of the fact that it possesses both sensory and nutritional properties, the role of the latter being dependent on the motivational state of subject. It is suggested that the sensory features of sucrose do not undergo habituation, but that an effect of preexposure can be obtained in hungry rats when the source of the learned preference will depend on learning about the nutritive consequences of the sucrose.


Assuntos
Adoçantes não Calóricos , Animais , Aromatizantes , Preferências Alimentares , Adoçantes não Calóricos/farmacologia , Ratos , Sacarina , Sacarose/farmacologia , Edulcorantes/farmacologia , Paladar
7.
Int J Mol Sci ; 22(10)2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-34063332

RESUMO

Artificial sweeteners (AS) are synthetic sugar substitutes that are commonly consumed in the diet. Recent studies have indicated considerable health risks which links the consumption of AS with metabolic derangements and gut microbiota perturbations. Despite these studies, there is still limited data on how AS impacts the commensal microbiota to cause pathogenicity. The present study sought to investigate the role of commonly consumed AS on gut bacterial pathogenicity and gut epithelium-microbiota interactions, using models of microbiota (Escherichia coli NCTC10418 and Enterococcus faecalis ATCC19433) and the intestinal epithelium (Caco-2 cells). Model gut bacteria were exposed to different concentrations of the AS saccharin, sucralose, and aspartame, and their pathogenicity and changes in interactions with Caco-2 cells were measured using in vitro studies. Findings show that sweeteners differentially increase the ability of bacteria to form a biofilm. Co-culture with human intestinal epithelial cells shows an increase in the ability of model gut bacteria to adhere to, invade and kill the host epithelium. The pan-sweet taste inhibitor, zinc sulphate, effectively blocked these negative impacts. Since AS consumption in the diet continues to increase, understanding how this food additive affects gut microbiota and how these damaging effects can be ameliorated is vital.


Assuntos
Enterococcus faecalis/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Edulcorantes/farmacologia , Aspartame/administração & dosagem , Aspartame/farmacologia , Aderência Bacteriana/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Células CACO-2 , Relação Dose-Resposta a Droga , Enterococcus faecalis/patogenicidade , Escherichia coli/patogenicidade , Microbioma Gastrointestinal/fisiologia , Hemólise/efeitos dos fármacos , Humanos , Sacarina/administração & dosagem , Sacarina/farmacologia , Sacarose/administração & dosagem , Sacarose/análogos & derivados , Sacarose/farmacologia , Edulcorantes/administração & dosagem
8.
Int J Mol Sci ; 22(5)2021 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-33801335

RESUMO

Mosquito-borne Zika virus (ZIKV) became a real threat to human health due to the lack of vaccine and effective antiviral treatment. The virus has recently been responsible for a global outbreak leading to millions of infected cases. ZIKV complications were highlighted in adults with Guillain-Barré syndrome and in newborns with increasing numbers of congenital disorders ranging from mild developmental delays to fatal conditions. The ability of ZIKV to establish a long-term infection in diverse organs including the kidneys has been recently documented but the consequences of such a viral infection are still debated. Our study aimed to determine whether the efficiency of ZIKV growth in kidney cells relates to glucose concentration. Human kidney HK-2 cells were infected with different ZIKV strains in presence of normal and high glucose concentrations. Virological assays showed a decrease in viral replication without modifying entry steps (viral binding, internalization, fusion) under high glucose conditions. This decrease replication was associated with a lower virus progeny and increased cell viability when compared to ZIKV-infected HK-2 cells in normal glucose concentration. In conclusion, we showed for the first time that an elevated glucose level influences ZIKV replication level with an effect on kidney cell survival.


Assuntos
Glucose/farmacologia , Rim/efeitos dos fármacos , Replicação Viral , Infecção por Zika virus/prevenção & controle , Zika virus/crescimento & desenvolvimento , Células Cultivadas , Humanos , Rim/virologia , Edulcorantes/farmacologia , Ligação Viral , Zika virus/efeitos dos fármacos , Zika virus/isolamento & purificação , Infecção por Zika virus/virologia
9.
Arch Biochem Biophys ; 701: 108810, 2021 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-33600787

RESUMO

As currently defined, the exposome represents the lifetime exposure measure of an individual to all potential external genetic influences and their impact on health. Although intentionally added chemicals (e.g., food additives) and food contact materials (e.g., packaging, pesticides) have been assessed for safety to some degree, the full extent to which they can affect health and reproduction has not been reported. The aim of this study was to determine the in vitro and in vivo effects of food additives on the male rat brain and sperm/testes, particularly through oxidative stress. Results from our in vitro study demonstrated that the administration of the common food additive, stevioside, a major component of the common sweetener stevia, as well as the preservatives, diphenyl and orthophenyl phenol (OPP), induced reactive oxygen species (ROS) production in sperm, and led to sperm dysfunction. These effects were inhibited by the addition of the antioxidant α-tocopherol. Moreover, OPP treatment (1/10,000 of no observed adverse effect) induced ROS production in sperm and lipid peroxidation in the epididymis and hippocampus after two weeks in vivo. Furthermore, 4-hydroxynonenal-positive cells, indicating ROS-generated protein modifications, were detected in spermatocytes in the testes and granular cell layer of the dentate gyrus in the brain. Treatment with α-tocopherol significantly improved oxidative stress. Our study suggests that certain food additives may affect sperm function and induce oxidative stress in the testes and brain, resulting in infertility and short-term memory loss, and some antioxidants may improve these dysfunctions.


Assuntos
Hipocampo/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Espermatócitos/metabolismo , Stevia/química , Edulcorantes/efeitos adversos , Testículo/metabolismo , Animais , Hipocampo/patologia , Infertilidade Masculina/induzido quimicamente , Infertilidade Masculina/metabolismo , Infertilidade Masculina/patologia , Masculino , Ratos , Ratos Wistar , Espermatócitos/patologia , Edulcorantes/química , Edulcorantes/farmacologia , Testículo/patologia
10.
Cell Metab ; 33(2): 225-226, 2021 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-33535094

RESUMO

The lack of appropriate comparator can lead to incorrect interpretation of results regarding low-calorie sweeteners. The result of a re-analysis of the study by Dalenberg et al. shows that the impairment of insulin sensitivity by sucralose in combination with carbohydrate may be explained by the carbohydrate component rather than the low-calorie sweetener.


Assuntos
Resistência à Insulina , Adoçantes não Calóricos , Humanos , Adoçantes não Calóricos/farmacologia , Sacarose/análogos & derivados , Açúcares , Edulcorantes/farmacologia
11.
Diabetes Obes Metab ; 23(6): 1311-1321, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33565706

RESUMO

AIM: To determine whether a dose-dependent effect in the stimulation of gut hormone release (plasma cholecystokinin [CCK], active glucagon-like peptide-1 [aGLP-1] and peptide tyrosine tyrosine [PYY]) is found for the natural sweetener erythritol. MATERIALS AND METHODS: Twelve healthy, lean volunteers received solutions with 10, 25 or 50 g erythritol, or tap water enriched with 13 C-sodium acetate on four study days via a nasogastric tube in this randomized (active treatments), placebo-controlled, double-blind, cross-over trial. Blood samples and breath samples (13 C-sodium acetate method for measurement of gastric emptying [GE]) were taken at regular intervals, and sensations of appetite and gastrointestinal symptoms were rated. RESULTS: We found (a) a dose-dependent stimulation of CCK, aGLP-1 and PYY, and slowing of GE, (b) no effect on blood glucose, insulin, motilin, glucagon or glucose-dependent insulinotropic polypeptide, (c) no effect on blood lipids and uric acid, and (d) no abdominal pain, nausea or vomiting. CONCLUSIONS: Solutions with 10 and 50 g of erythritol stimulated gut hormone release. Emptying of erythritol-containing solutions from the stomach was slower compared with placebo. There was no effect on plasma glucose, insulin, glucagon, blood lipids or uric acid. All doses were well tolerated.


Assuntos
Esvaziamento Gástrico , Hormônios Gastrointestinais , Glicemia , Colecistocinina , Estudos Cross-Over , Método Duplo-Cego , Eritritol , Glucagon , Humanos , Insulina , Edulcorantes/farmacologia
12.
Biochim Biophys Acta Gen Subj ; 1865(6): 129881, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33617932

RESUMO

BACKGROUND: The yeast Saccharomyces cerevisiae senses extracellular glucose levels through the two paralogous glucose sensing receptors Rgt2 and Snf3, which appear to sense high and low levels of glucose, respectively. METHODS: Western blotting and qRT-PCR were used to determine expression levels of the glucose sensing receptors. RESULTS: Rgt2 and Snf3 are expressed at different levels in response to different glucose concentrations. SNF3 expression is repressed by high glucose, whereas Rgt2 is turned over in response to glucose starvation. As a result, Rgt2 is predominant in cells grown on high glucose, whereas Snf3 is more abundant of the two paralogs in cells grown on low glucose. When expressed from a constitutive promoter, however, Snf3 behaves like Rgt2, being able to transduce the high glucose signal that induces HXT1 expression. Of note, constitutively active Rgt2 does not undergo glucose starvation-induced endocytic downregulation, whereas signaling defective Rgt2 is constitutively targeted for vacuolar degradation. These results suggest that glucose protects Rgt2 from endocytic degradation and reveal a previously unknown function of glucose as a signaling molecule that regulates the stability of its receptor. CONCLUSION: Expression of Rgt2 and Snf3 is regulated by different mechanisms: Rgt2 expression is highly regulated at the level of protein stability; Snf3 expression is mainly regulated at the level of transcription. GENERAL SIGNIFICANCE: The difference in the roles of Rgt2 and Snf3 in glucose sensing is a consequence of their cell surface abundance rather than a result of the two paralogous proteins having different functions.


Assuntos
Regulação Fúngica da Expressão Gênica/efeitos dos fármacos , Glucose/farmacologia , Proteínas de Transporte de Monossacarídeos/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/metabolismo , Edulcorantes/farmacologia , Proteínas de Transporte de Monossacarídeos/genética , Saccharomyces cerevisiae/efeitos dos fármacos , Saccharomyces cerevisiae/crescimento & desenvolvimento , Proteínas de Saccharomyces cerevisiae/genética
13.
ISME J ; 15(7): 2117-2130, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33589766

RESUMO

Antimicrobial resistance (AMR) poses a worldwide threat to human health and biosecurity. The spread of antibiotic resistance genes (ARGs) via conjugative plasmid transfer is a major contributor to the evolution of this resistance. Although permitted as safe food additives, compounds such as saccharine, sucralose, aspartame, and acesulfame potassium that are commonly used as nonnutritive sweeteners have recently been associated with shifts in the gut microbiota similar to those caused by antibiotics. As antibiotics can promote the spread of antibiotic resistance genes (ARGs), we hypothesize that these nonnutritive sweeteners could have a similar effect. Here, we demonstrate for the first time that saccharine, sucralose, aspartame, and acesulfame potassium could promote plasmid-mediated conjugative transfer in three established conjugation models between the same and different phylogenetic strains. The real-time dynamic conjugation process was visualized at the single-cell level. Bacteria exposed to the tested compounds exhibited increased reactive oxygen species (ROS) production, the SOS response, and gene transfer. In addition, cell membrane permeability increased in both parental bacteria under exposure to the tested compounds. The expression of genes involved in ROS detoxification, the SOS response, and cell membrane permeability was significantly upregulated under sweetener treatment. In conclusion, exposure to nonnutritive sweeteners enhances conjugation in bacteria. Our findings provide insight into AMR spread and indicate the potential risk associated with the presence of nonnutritive sweeteners.


Assuntos
Adoçantes não Calóricos , Resistência Microbiana a Medicamentos , Transferência Genética Horizontal , Humanos , Filogenia , Plasmídeos/genética , Edulcorantes/farmacologia
14.
Anim Sci J ; 92(1): e13532, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33634929

RESUMO

The effects of dietary rebaudioside A inclusion on feed intake, digestion of nutrients, rumen fermentation, and blood biochemical parameters of goats were evaluated in a replicated 3 × 3 Latin square study. Nine adult goats during summer were fed a basal forage/concentrate-based diet and the forage was chopped rice straw. The three dietary treatments were 0, 350, and 700 mg rebaudioside A per kg chopped rice straw on a DM basis. No significant improvement was observed in dry matter intake (DMI) of forage and diet among treatments. Nutrient digestibility of DM and organic matter (OM) showed a significant trend (p < .10) across groups. Rebaudioside A inclusion significantly (p < .01) increased the concentration of total volatile fatty acids in the rumen, however, there were no differences in concentration of ruminal ammonia, and molar proportions of acetate, propionate, and butyrate. About blood metabolites, increasing rebaudioside A in the diet caused a quadratic response in glucose and total protein, and albumin concentrations. Under the conditions of this study, supplementation with rebaudioside A at 350 and 700 mg/kg forage did not improve consumption of rice straw-based diet in adult goats in summer. However, the responses in digestibility, rumen fermentation, and blood metabolites appear to indicate the potential of rebaudioside A as a bio-active substance in goats.


Assuntos
Dieta/veterinária , Suplementos Nutricionais , Digestão/efeitos dos fármacos , Diterpenos do Tipo Caurano/administração & dosagem , Diterpenos do Tipo Caurano/farmacologia , Ingestão de Alimentos/efeitos dos fármacos , Fermentação/efeitos dos fármacos , Cabras/metabolismo , Cabras/fisiologia , Nutrientes/metabolismo , Rúmen/metabolismo , Edulcorantes/farmacologia , Ração Animal , Animais , Análise Química do Sangue , Ácidos Graxos Voláteis/metabolismo , Glucose/metabolismo , Cabras/sangue , Temperatura Alta , Masculino , Proteínas/metabolismo , Estações do Ano , Albumina Sérica
15.
Nutrients ; 13(1)2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33429977

RESUMO

Sugar consumption is associated with a whole range of negative health effects and should be reduced and the natural sweetener xylitol might be helpful in achieving this goal. The present study was conducted as a randomized, placebo-controlled, double-blind, cross-over trial. Twelve healthy, lean volunteers received intragastric solutions with 7, 17 or 35 g xylitol or tap water on four separate days. We examined effects on: gut hormones, glucose, insulin, glucagon, uric acid, lipid profile, as well as gastric emptying rates, appetite-related sensations and gastrointestinal symptoms. We found: (i) a dose-dependent stimulation of cholecystokinin (CCK), active glucagon-like peptide-1 (aGLP-1), peptide tyrosine tyrosine (PYY)-release, and decelerated gastric emptying rates, (ii) a dose-dependent increase in blood glucose and insulin, (iii) no effect on motilin, glucagon, or glucose-dependent insulinotropic peptide (GIP)-release, (iv) no effect on blood lipids, but a rise in uric acid, and (v) increased bowel sounds as only side effects. In conclusion, low doses of xylitol stimulate the secretion of gut hormones and induce a deceleration in gastric emptying rates. There is no effect on blood lipids and only little effect on plasma glucose and insulin. This combination of properties (low-glycemic sweetener which stimulates satiation hormone release) makes xylitol an attractive candidate for sugar replacement.


Assuntos
Esvaziamento Gástrico/efeitos dos fármacos , Hormônios Gastrointestinais/metabolismo , Edulcorantes/farmacologia , Xilitol/farmacologia , Adulto , Glicemia/metabolismo , Colecistocinina/sangue , Estudos Cross-Over , Dipeptídeos/sangue , Método Duplo-Cego , Feminino , Polipeptídeo Inibidor Gástrico/sangue , Hormônios Gastrointestinais/sangue , Glucagon/sangue , Peptídeo 1 Semelhante ao Glucagon/sangue , Humanos , Insulina/sangue , Lipídeos/sangue , Masculino , Edulcorantes/administração & dosagem , Ácido Úrico/sangue , Xilitol/administração & dosagem , Adulto Jovem
16.
PLoS One ; 16(1): e0244988, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33411772

RESUMO

The virulence of Clostridioides difficile (formerly Clostridium difficile) is mainly caused by its two toxins A and B. Their formation is significantly regulated by metabolic processes. Here we investigated the influence of various sugars (glucose, fructose, mannose, trehalose), sugar derivatives (mannitol and xylitol) and L-lactate on toxin synthesis. Fructose, mannose, trehalose, mannitol and xylitol in the growth medium resulted in an up to 2.2-fold increase of secreted toxin. Low glucose concentration of 2 g/L increased the toxin concentration 1.4-fold compared to growth without glucose, while high glucose concentrations in the growth medium (5 and 10 g/L) led to up to 6.6-fold decrease in toxin formation. Transcriptomic and metabolic investigation of the low glucose effect pointed towards an inactive CcpA and Rex regulatory system. L-lactate (500 mg/L) significantly reduced extracellular toxin formation. Transcriptome analyses of the later process revealed the induction of the lactose utilization operon encoding lactate racemase (larA), electron confurcating lactate dehydrogenase (CDIF630erm_01321) and the corresponding electron transfer flavoprotein (etfAB). Metabolome analyses revealed L-lactate consumption and the formation of pyruvate. The involved electron confurcation process might be responsible for the also observed reduction of the NAD+/NADH ratio which in turn is apparently linked to reduced toxin release from the cell.


Assuntos
Proteínas de Bactérias/metabolismo , Toxinas Bacterianas/metabolismo , Clostridioides difficile/metabolismo , Glucose/farmacologia , Ácido Láctico/farmacologia , Metaboloma/efeitos dos fármacos , Clostridioides difficile/efeitos dos fármacos , Clostridioides difficile/crescimento & desenvolvimento , Edulcorantes/farmacologia
17.
Biochim Biophys Acta Mol Basis Dis ; 1867(5): 166036, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33508421

RESUMO

High consumption of fructose has paralleled an explosion in metabolic disorders including obesity and type 2 diabetes. Even more problematic, sustained consumption of fructose is perceived as a threat for brain function and development of neurological disorders. The action of fructose on peripheral organs is an excellent model to understand how systemic physiology impacts the brain. Given the recognized action of fructose on liver metabolism, here we discuss mechanisms by which fructose can impact the brain by interacting with liver and other organs. The interaction between peripheral and central mechanisms is a suitable target to reduce the pathophysiological consequences of neurological disorders.


Assuntos
Encefalopatias/etiologia , Sacarose na Dieta/efeitos adversos , Frutose/efeitos adversos , Doenças Metabólicas/patologia , Plasticidade Neuronal , Encefalopatias/patologia , Humanos , Doenças Metabólicas/induzido quimicamente , Fenômenos Fisiológicos do Sistema Nervoso , Edulcorantes/farmacologia
18.
Sci Rep ; 11(1): 603, 2021 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-33436691

RESUMO

While numerous techniques can be used to measure and analyze insulin secretion in isolated islets in culture, assessments of insulin secretion in vivo are typically indirect and only semiquantitative. The CpepSfGFP reporter mouse line allows the in vivo imaging of insulin secretion from individual islets after a glucose stimulation, in live, anesthetized mice. Imaging the whole pancreas at high resolution in live mice to track the response of each individual islet over time includes numerous technical challenges and previous reports were only limited in scope and non-quantitative. Elaborating on this previous model-through the development of an improved methodology addressing anesthesia, temperature control and motion blur-we were able to track and quantify longitudinally insulin content throughout a glucose challenge in up to two hundred individual islets simultaneously. Through this approach we demonstrate quantitatively for the first time that while isolated islets respond homogeneously to glucose in culture, their profiles differ significantly in vivo. Independent of size or location, some islets respond sharply to a glucose stimulation while others barely secrete at all. This platform therefore provides a powerful approach to study the impact of disease, diet, surgery or pharmacological treatments on insulin secretion in the intact pancreas in vivo.


Assuntos
Glucose/farmacologia , Secreção de Insulina/efeitos dos fármacos , Insulina/metabolismo , Ilhotas Pancreáticas/metabolismo , Imagem Molecular/métodos , Edulcorantes/farmacologia , Animais , Ilhotas Pancreáticas/citologia , Ilhotas Pancreáticas/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL
19.
J Food Sci ; 86(2): 540-545, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31042819

RESUMO

Sucralose (SUC) has been used in the food industry for nearly 30 years since it was first allowed as an artificial sweetener at the end of the 20th century. However, its effects on the body remain not incontrovertible. This work aimed to investigate the influence of SUC exposure on sweetness receptors and glucose absorption and to explore the relationship between them. Mice were exposed with different concentration of SUC (from 0.27 to 0.47 g/L) for 12 weeks. Long-term treatment with SUC resulted in impaired glucose metabolism, manifested in the decrease of glucose tolerance and the increase of sweet taste receptors, glucose transporters, and glucose absorption. This study also provides a method to quantify the glucose absorptivity. In detail, with increasing concentration of SUC, the glucose absorptivities in the dodecadactylon of mice were added 1.48, 1.56, 1.71, and 1.71 times, respectively, showing wide interindividual variation compared with the control group. PRACTICAL APPLICATION: The artificial sweetener, sucralose, has physiological influences of changing glucose metabolism. The small bowel is the main location for glucose metabolism and absorbs the ingested proteins and carbohydrates. And, this study provides a method to quantify the glucose absorptivity of intestine.


Assuntos
Duodeno/efeitos dos fármacos , Duodeno/metabolismo , Glucose/metabolismo , Sacarose/análogos & derivados , Edulcorantes/farmacologia , Paladar/fisiologia , Animais , Regulação da Expressão Gênica/efeitos dos fármacos , Hexoses , Camundongos , Sacarose/farmacologia , Paladar/genética
20.
Food Chem ; 343: 128538, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33183872

RESUMO

In this study, we present a framework comprises of several independent modules which are built upon data based (structure activity relationship and classification model) and structure (molecular docking) based for identifying possible sweeteners from a vast database of natural molecules. A large database, Universal Natural Products Database (UNPD) consisting of 213,210 compounds was screened using the developed framework. At first, 10,184 molecules structurally similar to the known sweeteners were identified in the database. Further, 1924 molecules from these screened molecules were classified as sweet molecules. The shortlisted 1354 molecules were subjected to ADMET analysis. Finally, 60 molecules were arrived at with no toxicity and acceptable oral bioavailability as potential sweetener candidates. Further, molecular docking of these molecules on sweet taste receptor performed to obtain their binding energy, binding sites and correlation with sweetness index. The developed framework offers a convenient route for fast screening of molecules prior to synthesis and testing.


Assuntos
Simulação por Computador , Bases de Dados de Produtos Farmacêuticos , Simulação de Acoplamento Molecular , Edulcorantes/química , Edulcorantes/metabolismo , Sítios de Ligação , Humanos , Receptores Acoplados a Proteínas G/metabolismo , Relação Estrutura-Atividade , Edulcorantes/farmacologia
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