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1.
J Ethnopharmacol ; 300: 115688, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36067838

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Chinese medicine, a long term of improper diet causes the Dampness and disturbs Zang-Fu's functions including Kidney deficiency. Atractylodes lancea (Atr) and Magnolia officinalis (Mag) as a famous herb pair are commonly used to transform Dampness, with kidney protection. AIM OF THE STUDY: To explore how Atr and Mag protected against insulin signaling impairment in glomerular podocytes induced by high dietary fructose feeding, a major contributor for insulin resistance in glomerular podocyte dysfunction. MATERIALS AND METHODS: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analyze constituents of Atr and Mag. Rat model was induced by 10% fructose drinking water in vivo, and heat-sensitive human podocyte cells (HPCs) were exposed to 5 mM fructose in vitro. Animal or cultured podocyte models were treated with different doses of Atr, Mag or Atr and Mag combination. Western blot, qRT-PCR and immunofluorescence assays as well as other experiments were performed to detect adiponectin receptor protein 1 (AdipoR1), protein kinase B (AKT), Sirt1, p53 and miR-221 levels in rat glomeruli or HPCs, respectively. RESULTS: Fifty-five components were identified in Atr and Mag combination. Network pharmacology analysis indicated that Atr and Mag combination might affect insulin signaling pathway. This combination significantly improved systemic insulin resistance and prevented glomerulus morphological damage in high fructose-fed rats. Of note, high fructose decreased IRS1, AKT and AdipoR1 in rat glomeruli and cultured podocytes. Further data from cultured podocytes with Sirt1 inhibitor/agonist, p53 agonist/inhibitor, or miR-221 mimic/inhibitor showed that high fructose downregulated Sirt1 to stimulate p53-driven miR-221, resulting in insulin signaling impairment. Atr and Mag combination effectively increased Sirt1, and decreased p53 and miR-221 in in vivo and in vitro models. CONCLUSIONS: Atr and Mag combination improved insulin signaling in high fructose-stimulated glomerular podocytes possibly through upregulating Sirt1 to inhibit p53-driven miR-221. Thus, the regulation of Sirt1/p53/miR-221 by this combination may be a potential therapeutic approach in podocyte insulin signaling impairment.


Assuntos
Atractylodes , Água Potável , Resistência à Insulina , Magnolia , MicroRNAs , Podócitos , Animais , Proteínas de Transporte/metabolismo , Cromatografia Líquida , Água Potável/metabolismo , Frutose/efeitos adversos , Humanos , Insulina/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Receptores de Adiponectina/metabolismo , Transdução de Sinais , Sirtuína 1/metabolismo , Espectrometria de Massas em Tandem , Proteína Supressora de Tumor p53/metabolismo
2.
Food Chem ; 400: 134107, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36087481

RESUMO

This study evaluated the inoculation of Meyerozyma guilliermondii and Bacillus licheniformis, separately or in co-culture, in wet-processed conilon coffee. Wet fermentation was conducted for 48 h. Mesophilic bacteria, lactic acid bacteria, yeasts, and filamentous fungi were counted during fermentation. The inoculation of B. licheniformis and M. guilliermondii stimulated the multiplication of lactic acid bacteria. Acetic, citric, lactic, oxalic, malic, succinic, tartaric acids, glucose, and fructose were identified in all treatments at different concentrations. Methyl salicylate, 2-heptanol, 2-nonanol, and heptanone were found during fermentation. Methylpyrazine, 2,6-dimethylpyrazine, 2,5-dimethylpyrazine, and 3-ethyl-2,5-dimethylpyrazine identified after roasting assigned notes of "almond" and "chocolate" to the beverages. All treatments were classified as "premium," with the B. licheniformis treatment receiving the highest score. Bacillus licheniformis obtained better performance in fermentation, increasing coffee score and producing volatile compounds that provided positive sensory notes to the beverage.


Assuntos
Coffea , Lactobacillales , Bactérias/genética , Café/microbiologia , Frutose , Glucose , Heptanol , Leveduras
3.
J Ethnopharmacol ; 301: 115806, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36216198

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Qushi Huayu Decoction (QHD) is a traditional Chinese medicine formula consisting of five herbs, which has been used for non-alcoholic fatty liver disease (NAFLD) treatment in clinic for decades in China and validated in several NAFLD animal models. The hepatic de novo lipogenesis (DNL) is enhanced greatly to contribute to steatosis in NAFLD. The spliced form of X-box binding protein 1 (XBP1s) initiates DNL independently of sterol regulatory element-binding protein (SREBP) and carbohydrate-responsive element-binding protein (ChREBP). AIM OF THE STUDY: To disclose the mechanism of inhibition on hepatic DNL by QHD and the responsible compounds. METHODS: The effects of QHD on hepatic DNL were evaluated in mice induced by high-fructose diet (HFru). The effects of the serum-absorbed compounds of QHD on XBP1s were evaluated in HepG2 cells induced by tunicamycin. Hepatic histology, triglyceride (TG) and nonesterified fatty acids were observed. Hepatic apolipoprotein B100 and very low-density lipoprotein were measured to reflect lipid out-transport. The mRNA expression of XBP1s and its target genes were detected by real-time polymerase chain reaction. The protein expression of TG synthetases and DNL enzymes, and inositol requirement enzyme 1 alpha (IRE1α), phosphorylated IRE1α and XBP1s were detected in liver tissue and HepG2 cells by western-blot. The binding activity of SREBP1, protein expression of ChREBP and XBP1s were detected in the nuclear extracts of liver tissue. RESULTS: Dynamical observing suggested feeding with HFru for 2 weeks was sufficient to induce hepatic lipogenesis and XBP1s. QHD ameliorated liver steatosis without enhancing out-transport of lipids, accompanied with more inhibitory effects on DNL enzymes than TG synthetases. QHD inhibits the nuclear XBP1s without affecting ChREBP and SREBP1. In QHD, chlorogenic acid, geniposide and polydatin inhibit lipogenesis initiated by XPB1s. CONCLUSION: QHD probably decreases hepatic DNL by inhibiting XBP1s independent of SREBP1 and ChREBP. Chlorogenic acid, geniposide and polydatin are the potential responsible compounds.


Assuntos
Lipogênese , Hepatopatia Gordurosa não Alcoólica , Animais , Camundongos , Ácido Clorogênico/farmacologia , Endorribonucleases/metabolismo , Endorribonucleases/farmacologia , Endorribonucleases/uso terapêutico , Frutose , Ligases/metabolismo , Ligases/farmacologia , Ligases/uso terapêutico , Fígado , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Proteínas Serina-Treonina Quinases , Triglicerídeos/metabolismo
4.
J Sci Food Agric ; 103(1): 339-348, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-35871484

RESUMO

BACKGROUND: Rare sugars have become promising 'sugar alternatives' because of their low calories and unique physiological functions. Among the family of rare sugars, d-allulose is one of the sugars attracting interest. Ketose 3-epimerases (KEase), including d-tagatose 3-epimerase (DTEase) and d-allulose 3-epimerase (DAEase), are mainly used for d-allulose production. RESULTS: In this study, a putative xylose isomerase from Caballeronia insecticola was characterized and identified as a novel DAEase. Caballeronia insecticola DAEase displayed prominent enzymatic properties, and 150 g L-1 d-allulose was produced from 500 g L-1 d-fructose in 45 min with a conversion rate of 30% and high productivity of 200 g L-1 h-1 . Furthermore, DAEase was employed in a phosphorylation-dephosphorylation cascade reaction, which significantly increased the conversion rate of d-allulose. Under optimized conditions, the conversion rate of d-allulose was approximately 100% when the concentration of d-fructose was 50 mmol L-1 . CONCLUSION: This research described a very beneficial and facile approach for d-allulose production based on C. insecticola DAEase. © 2022 Society of Chemical Industry.


Assuntos
Frutose , Racemases e Epimerases , Racemases e Epimerases/genética , Concentração de Íons de Hidrogênio , Frutose/química
5.
Food Chem ; 401: 134166, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36095997

RESUMO

To develop an analytical method for rapid quantification of starch in agricultural produce, we measured the Raman spectra of ripening banana fruit and compared the obtained data to those of standard starch, sugar, and fiber chemical samples. Standard starches exhibited distinctive Raman bands, which were similar to the spectral features in green banana before ripening. Moreover, these banana-derived Raman bands gradually weakened during 10 d of storage. Standard sugars (glucose, sucrose, and fructose) exhibited Raman bands in both solid and liquid states, whereas standard fibers exhibited broad spectra and no such bands. Although the sugar content increased, no sugar bands were observed in the banana fruit even after ripening. A correlation was found between the Raman bands and starch content obtained by chemical analysis. These results demonstrate that Raman spectroscopy can selectively provide information regarding starch in banana fruit and be applied as an analytical method for rapid starch quantification.


Assuntos
Musa , Musa/química , Amido/química , Frutas/química , Análise Espectral Raman , Açúcares/análise , Sacarose/análise , Glucose/análise , Frutose/análise
6.
Gene ; 851: 147039, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36368573

RESUMO

The prevalence of non-alcoholic fatty liver diseases (NAFLD) has reached epidemic levels during recent years and a major driver of NAFLD are diets high in fat and fructose. A common practice in the treatment of NAFLD are life-style interventions including for example increased physical activity. The transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α) has been shown to be central in mediating the beneficial effects of exercise training by regulating the expression of key metabolic genes. However, the significance of hepatic PGC-1α for high fat high fructose (HFFD) induced changes in gene expression and metabolites associated with NAFLD has not been elucidated. Therefore the aim of the present study was to investigate the effect of hepatic PGC-1α on HFFD and exercise-induced changes in the hepatic transcriptome and metabolome in mice. Using gene-arrays and 1H NMR spectroscopy, the liver transcriptome and metabolome of liver-specific PGC-1α knock-out mice receiving either standard chow, HFFD or HFFD + exercise (HFFD + Ex) were determined. In total 122 genes were identified as differently expressed in mice receiving HFFD for 13 weeks compared to chow, while the loss of hepatic PGC-1α only had very minor effects on the transcriptome. The same was observed for the liver metabolome. The effect of 4 weeks exercise training in combination with 13 weeks of HFFD, had small effects on the transcriptome and metabolome compared to HFFD alone. Together our results highlight a minor regulatory effect of hepatic PGC-1α on the liver transcriptome during high fat high fructose diet and exercise training.


Assuntos
Frutose , Hepatopatia Gordurosa não Alcoólica , Camundongos , Animais , Frutose/metabolismo , Frutose/farmacologia , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/metabolismo , Transcriptoma , Fígado/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Camundongos Knockout , Metaboloma
7.
J Nutr Biochem ; 111: 109189, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36272691

RESUMO

Fat and fructose are the two major components over-represented in the Western diet. The aim of this study was to determine the combined effects of different types of dietary fat and fructose on the development of nonalcoholic fatty liver disease (NAFLD) in a murine model. Eight-week-old male C57BL/6J mice were fed with high-fat diet enriched with saturated fat (HSF), or omega-6 polyunsaturated fat (n6HUSF), or omega-3 polyunsaturated fat (n3HUSF) with 42% of calories derived from the fat. Fructose supplementation was given via 10% fructose (w/v) in the drinking water ad libitum for 20 weeks. While both HSF and n6HUSF fed mice developed obesity, HSF fed mice exhibited severe hepatic steatosis associated with hepatomegaly and liver injury. Fructose feeding promotes the development of liver fibrosis in HSF fed mice. n6HUSF fed mice were characterized with moderate hepatic steatosis, accompanied with hypertriglyceridemia and hyperlipidemia. Notably, fructose supplementation led to remarkable glucose intolerance in n6HUSF fed mice compared to controls. Hepatic lipidomic analysis revealed that the total saturated fatty acids and total monounsaturated fatty acids were significantly increased by fructose in the free fatty acid pool in HSF fed mice. Moreover, fructose supplementation increased hepatic and plasma cholesterol levels in the HSF fed mice. Our data suggest that excess energy from HSF intake results in fat storage in the liver, likely due to impaired triglyceride secretion; whereas excess energy from n6HUSF diet is stored in the periphery. Both effects are exacerbated by fructose supplementation. n3HUSF is beneficial, even consumed with fructose.


Assuntos
Frutose , Hepatopatia Gordurosa não Alcoólica , Camundongos , Masculino , Animais , Frutose/efeitos adversos , Frutose/metabolismo , Gorduras na Dieta/efeitos adversos , Gorduras na Dieta/metabolismo , Camundongos Endogâmicos C57BL , Dieta Hiperlipídica/efeitos adversos , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Fígado/metabolismo , Fenótipo
8.
Food Chem ; 401: 134199, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36115227

RESUMO

D-Allulose, as low-calorie rare sugar, possessed several notable biological activities and was biosynthesized by D-allulose 3-epimerase (DAEase). Here, CcDAE from Clostridium cellulolyticum was successfully immobilization via covalent attachment (RI-CcDAE), and Resin-SpyCatcher/SpyTag-CcDAE modular (DI-CcDAE). Both immobilized CcDAEs exhibited higher thermal and pH stabilities than the free form, and they maintained 80.0 % of relative activity after 7 consecutive cycles and 25 days of storage. Predominantly, DI-CcDAE represented superior catalytic efficiency with a 2.4-fold increase of kcat/Km, compared with RI-CcDAE (0.75 s-1 mM-1 vs 0.31 s-1 mM-1). The RI-CcDAE and DI-CcDAE were then applied in mixed fruit Jiaosu to convert D-fructose into D-allulose, which exhibited the productivity of D-allulose 1.08 g/Lh-1 and 1.57 g/Lh-1, respectively. This research provided a promising directional immobilization strategy for DAEase, and robust biocatalyst for production of functional foodstuff containing D-allulose.


Assuntos
Frutose , Racemases e Epimerases , Racemases e Epimerases/genética , Concentração de Íons de Hidrogênio
9.
Food Chem ; 402: 134068, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36126570

RESUMO

Steam-processed Polygonatum sibiricum (PS) has been used as food for thousands of years. However, fewer studies concentrated on the effects of polysaccharides (SPSP) from the steamed PS on the intestinal tract. With fermentation in vitro, we investigated the impact of SPSP on the fatty acids and microbiotas. Results showed significant increases in short-chain fatty acids (SCFAs) like acetic acid and propionic acid, and long-chain fatty acids (LCFAs) like cis, cis, cis-9,12,15-linolenic acid, cis-6-octadecenoic acid, and cis-9-octadecenoic acid after 12 h. The positive-associated beneficial microbiotas were observed with proliferation like Parabacteroides and Bifidobacterium. Harmful microbiota like Shigella showed decreased abundance. Further, a small molecule polysaccharide was separated from the SPSP with the structure of one glucose and ten fructose, which significantly increased SCFAs and LCFAs contents during fermentation. The potential benefits of SPSP were proved by the analysis of fatty acid levels and the intestinal microbiotas during fermentation.


Assuntos
Microbioma Gastrointestinal , Polygonatum , Polygonatum/química , Propionatos/farmacologia , Vapor , Ácido Oleico/farmacologia , Polissacarídeos/química , Glucose/química , Ácidos Graxos Voláteis , Frutose , Ácidos Linolênicos
10.
Food Chem ; 402: 134318, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36152559

RESUMO

As a potent aromatic compound, furfural may have adverse effects on sugarcane juice quality. In this study, simplified sugarcane juice models containing glucose, fructose and amino acids were used to explore the potential precursors and formation pathways of furfural. The changes of precursors and intermediates involved in furfural formation were quantified. The results indicated that fructose contributed more to furfural formation than glucose. Serine was the main amino acid precursor for furfural formation. Furfural could be generated through 3 pathways in sugarcane juice: 1) Streaker reaction of serine, 2) caramelization of glucose and fructose via 3-deoxyglucosone, 3) formed from reducing sugars (glucose or fructose) and serine via N-(1-Deoxy-d-fructos-1-yl)-l-serine intermediate, which further converted to 3-deoxyglucosone. At the first 10 min, furfural was mainly produced through the caramelization of fructose. Subsequently, furfural was produced in the above three ways. Furfural was more effectively formed by caramelization than Maillard reaction in sugarcane juice.


Assuntos
Furaldeído , Saccharum , Saccharum/metabolismo , Reação de Maillard , Frutose/química , Aminoácidos/química , Glucose/química , Grão Comestível/metabolismo , Serina
11.
Food Chem ; 402: 134141, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36155292

RESUMO

The formation and mitigation of furan in pumpkin puree (PP) were studied during the complete process of producing PP. The content of furan was determined using headspace solid-phase microextraction combined by GC-MS analysis. Various PP samples added with precursors (glucose, fructose, linoleic acid, linolenic acid, ß-carotene, ascorbic acid, glutamic acid, alanine, and serine) showed increased furan formation (30.81 âˆ¼ 94.45 µg/kg) compared with the control (30.81 µg/kg), with ß-carotene resulting in the formation of the largest amount of furan. The effects of antioxidants, such as caffeic acid, chlorogenic acid, quercetin, and butylated hydroxytoluene, on the reduction of furan in PP containing ß-carotene were also investigated. All antioxidants showed significant reduction of furan. During sterilizing, the content of furan was considerably affected by temperature but not heating time. Reheating PP samples using a microwave oven, water bath, or open pot, revealed that open-pot reheating was the most effective for reducing furan (10.28 âˆ¼ 11.72 µg/kg).


Assuntos
Antioxidantes , Cucurbita , Antioxidantes/análise , Ácido Linoleico , Ácido alfa-Linolênico , Ácido Glutâmico , beta Caroteno , Hidroxitolueno Butilado , Quercetina , Ácido Clorogênico , Furanos/análise , Ácido Ascórbico/análise , Esterilização , Frutose/análise , Glucose/análise , Alanina , Serina , Água
12.
Sci Rep ; 12(1): 20227, 2022 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-36418417

RESUMO

The aim of the present study was to investigate the effect of etanercept (ETA)-an anti-tumor necrosis factor α (TNF-α) monoclonal antibody-on metabolic disorders such as obesity, hypertension, dyslipidemia, and insulin resistance associated with the metabolic syndrome (MS). MS was induced in rats via high-fat high-fructose (HFHF) administration for 8 weeks. Rats were divided into three groups: negative control, HFHF model, and ETA-treated groups [HFHF + ETA (0.8 mg/kg/twice weekly, subcutaneously) administered in the last 4 weeks]. ETA effectively diminished the prominent features of MS via a significant reduction in the percent body weight gain along with the modulation of adipokine levels, resulting in a significant elevation of serum adiponectin consistent with TNF-α and serum leptin level normalization. Moreover, ETA enhanced dyslipidemia and the elevated blood pressure. ETA managed the prominent features of MS and its associated complications via the downregulation of the hepatic inflammatory pathway that induces nonalcoholic steatohepatitis (NASH)-from the expression of Toll-like receptor 4, nuclear factor kappa B, and TNF-α until that of transforming growth factor-in addition to significant improvements in glucose utilization, insulin sensitivity, and liver function parameter activity and histopathological examination. ETA was effective for the treatment of all prominent features of MS and its associated complications, such as type II diabetes mellitus and NASH.


Assuntos
Diabetes Mellitus Tipo 2 , Dislipidemias , Resistência à Insulina , Síndrome Metabólica , Hepatopatia Gordurosa não Alcoólica , Ratos , Animais , Síndrome Metabólica/tratamento farmacológico , Frutose/efeitos adversos , Etanercepte/farmacologia , Etanercepte/uso terapêutico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Citocinas , Fator de Necrose Tumoral alfa/metabolismo , Dieta Hiperlipídica/efeitos adversos
13.
Biomolecules ; 12(11)2022 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-36358897

RESUMO

d-Allulose is the corresponding epimer of d-fructose at the C-3 position, which exhibits a similar taste and sweetness to sucrose. As a low-calorie sweetener, d-allulose has broad application prospects in the fields of medicine, food, and so on. Currently, the production method of d-allulose is mainly the enzymatic conversion of d-fructose by d-allulose 3-epimerase (DAEase). However, the limited specific activity and thermal stability of DAEase restrict its industrial application. Herein, an ultrahigh-throughput screening assay based on the transcription factor PsiR was extensively optimized from the aspects of culture medium components, screening plasmid, and expression host, which enhanced the correction between the fluorescent readout and the enzyme activity. Then, the error-prone PCR (epPCR) library of Clostridium cellulolyticum H10 DAEase (CcDAEase) was screened through the above optimized method, and the variant I228V with improved specific activity and thermal stability was obtained. Moreover, after combining two beneficial substitutions, D281G and C289R, which were previously obtained by this optimized assay, the specific activity of the triple-mutation variant I228V/D281G/C289R reached up to 1.42-fold of the wild type (WT), while its half-life (T1/2) at 60 °C was prolonged by 62.97-fold. The results confirmed the feasibility of the optimized screening assay as a powerful tool for the directed evolution of DAEase.


Assuntos
Frutose , Racemases e Epimerases , Racemases e Epimerases/genética , Concentração de Íons de Hidrogênio , Frutose/metabolismo , Engenharia de Proteínas
14.
Cells ; 11(21)2022 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-36359843

RESUMO

Pituitary gonadotropins directly govern ovarian functions, which are in turn regulated by the ovarian steroid hormones. The precise interplay of gonadotropins and steroid hormones is critical for follicle growth and differentiation. Furthermore, autophagy regulates ovarian follicle differentiation. However, how the high-fat-high fructose (HFD-HF) diet regulates gonadotropins and facilitates autophagy-mediated follicular differentiation in the ovary is obscure. We fed prepubertal rats (PND 25) an HFD-HF diet until PND 90. The results showed diminished adenohypophyseal GnRHR, PR, and aromatase expression, whereas AR, ERα, PRLR, and inhibin were augmented, resulting in gonadotropins decline. Interestingly, autophagy biomarkers, Beclin-1, ATG5, ATG12, LC3-II, and LAMP1 were reduced but SQSTM1/p62 was augmented in the ovaries of HFD-HF-fed rats, causing autolysosome to aggregation. The diet altered T, E2, P4, PRL, and their receptors status in the ovary, disturbed estrous cyclicity, and delayed vaginal opening. Ovarian histomorphology exhibited numerous cystic and atretic follicles, along with disturbed follicular maturation and ovulation. Moreover, the reduction of FSHR; steroidogenic proteins; receptor proteins AR, ERß, PR; and signaling proteins Wnt2 and ß-catenin was also noticed in the ovary, whereas PRLR, inhibin, and pGSK3ß were augmented. In conclusion, exposure to a prepubertal HFD-HF diet leads to hypogonadotropism and the autophagy-mediated defective differentiation of ovarian follicles, abating fertility in adult rats.


Assuntos
Dieta Hiperlipídica , Frutose , Folículo Ovariano , Animais , Feminino , Ratos , Autofagia , Dieta Hiperlipídica/efeitos adversos , Frutose/efeitos adversos , Frutose/metabolismo , Frutose/farmacologia , Gonadotropinas/metabolismo , Inibinas/metabolismo , Folículo Ovariano/metabolismo , Folículo Ovariano/patologia , Transtornos do Desenvolvimento Sexual
15.
Cells ; 11(21)2022 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-36359786

RESUMO

Nonalcoholic steatohepatitis (NASH) increases with fructose consumption and metabolic syndrome and has been recently linked with endogenous ethanol production, notably by high alcohol-producing Klebsiella pneumoniae (HiAlc Kpn). Candida yeasts are the main causes of auto-brewery syndromes but have been neglected in NASH. Here, the fecal ethanol and microbial content of 10 cases and 10 controls were compared. Ethanol was measured by gas chromatography-mass spectrometry. Species identification was performed by MALDI-TOF MS, and triglyceride production was assessed by a colorimetric enzymatic assay. The fecal ethanol concentration was four times higher in patients with NASH (median [interquartile range]: 0.13 [0.05-1.43] vs. 0.034 [0.008-0.57], p = 0.037). Yeasts were isolated from almost all cases but not from controls (9/10 vs. 0/10, p = 0.0001). Pichia kudriavzevii was the most frequent (four patients), while Candida glabrata, Candida albicans, and Galactomyces geotrichum were identified in two cases each. The concentration of ethanol produced by yeasts was 10 times higher than that produced by bacteria (median, 3.36 [0.49-5.60] vs. 0.32 [0.009-0.43], p = 0.0029). Using a 10% D-fructose restricted medium, we showed that NASH-associated yeasts transformed fructose in ethanol. Unexpectedly, yeasts isolated from NASH patients produced a substantial amount of triglycerides. Pichia kudriavzevii strains produced the maximal ethanol and triglyceride levels in vitro. Our preliminary human descriptive and in vitro experimental results suggest that yeasts have been neglected. In addition to K. pneumoniae, gut Pichia and Candida yeasts could be linked with NASH pathophysiology in a species- and strain-specific manner through fructose-dependent endogenous alcohol and triglyceride production.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Pichia , Humanos , Pichia/metabolismo , Etanol , Candida albicans , Candida glabrata/metabolismo , Triglicerídeos/metabolismo , Candida/metabolismo , Frutose/metabolismo
16.
Cells ; 11(21)2022 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-36359820

RESUMO

Both high-fat diet (HFD) alone and high-fructose plus HFD (HFr/HFD) cause diet-induced non-alcoholic fatty liver disease in murine models. However, the mechanisms underlying their impacts on inducing different levels of liver injury are yet to be elucidated. This study employed a proteomic approach to elucidate further on this issue. Adult male C57BL/6J mice were allocated to the HFD or the HFr/HFD group. After feeding for 12 weeks, all mice were euthanized and samples were collected. The proteomic profiles in liver tissues were analyzed using liquid chromatography-tandem mass spectrometry followed by canonical pathway analysis. We demonstrated that the mitochondrial oxidative phosphorylation (OXPHOS) pathway was the most significantly downregulated canonical pathway in the HFr/HFD group when compared with the HFD group. Within the OXPHOS pathway, the HFr/HFD group demonstrated significant downregulation of complexes I and III and significant upregulation of complex IV when compared with the HFD group. Moreover, the HFr/HFD group had lower protein levels of NADH: ubiquinone oxidoreductase subunits S3, S6, A5, and A12 in complex I (p < 0.001, =0.03, <0.001, and <0.001, respectively), lower protein level of cytochrome C in complex III (p < 0.001), and higher protein level of cytochrome C oxidase subunit 2 in complex IV (p = 0.002), when compared with the HFD group. To summarize, we have demonstrated that the hepatic mitochondrial OXPHOS pathway is significantly downregulated in long-term HFr/HFD feeding when compared with long-term HFD feeding. These data support the concept that the hepatic mitochondrial OXPHOS pathway should be involved in mediating the effects of HFr/HFD on inducing more severe liver injury than HFD alone.


Assuntos
Dieta Hiperlipídica , Frutose , Camundongos , Masculino , Animais , Dieta Hiperlipídica/efeitos adversos , Frutose/metabolismo , Fosforilação Oxidativa , Proteômica , Camundongos Endogâmicos C57BL , Fígado/metabolismo
17.
Int J Mol Sci ; 23(21)2022 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-36361617

RESUMO

Demand for healthy diets has led researchers to explore new saccharide as sucrose alternatives. ᴅ-Psicose, the C-3 epimer of ᴅ-fructose, has a similar sweetness intensity to sucrose but contributes fewer calories. This study proposes a disaccharide with a stable structure derived from ᴅ-psicose. The compound with a spiro-tricyclic core was generated at 32% conversion via caramelization of ᴅ-psicose under acidic anhydrous conditions. The compound was identified by high-resolution mass spectrometry and multi-dimensional nuclear magnetic resonance (NMR). The molecular formula was established as C12H20O10 from the molecular weight of m/z 324.1055. Twelve signals were observed by the 13C NMR spectrum. This compound, denoted di-ᴅ-psicose anhydride (DPA), exhibited a lower water solubility (40 g/L) and higher thermal stability (peak temperature = 194.7 °C) than that of ᴅ-psicose (peak temperature = 126.5 °C). The quantitatively evaluated metal ion scavenging ability of DPA was the best in magnesium (average 98.6 ± 1.1%). This synthesis methodology can provide disaccharides with high stability-reducing heavy metals.


Assuntos
Anidridos , Frutose , Frutose/química , Sacarose , Glicoconjugados
18.
Molecules ; 27(21)2022 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-36364023

RESUMO

Species in the fungal genus Rhizopus are able to convert simple sugars into primary metabolites such as fumaric acid, lactic acid, citric acid, and, to a lesser extent, malic acid in the presence of specific carbon and nitrogen sources. This ability has been linked to plant pathogenicity. Rhizopus stolonifer causes hull rot disease in almonds, symptoms of which have been previously associated with the fungus's production of fumaric acid. Six isolates of R. stolonifer taken from infected almond hulls were grown in artificial media amended with one of four carbon sources (glucose, fructose, sucrose, and xylose) and two nitrogen sources (asparagine and ammonium sulphate) chosen based on almond hull composition and used in industry. Proton nuclear magnetic resonance (1H NMR)-based metabolomics identified that R. stolonifer could metabolise glucose, fructose, sucrose, and to a lesser extent xylose, and both nitrogen sources, to produce three metabolites, i.e., fumaric acid, lactic acid, and ethanol, under in vitro conditions. Sugar metabolisation and acid production were significantly influenced by sugar source and isolates, with five isolates depleting glucose most rapidly, followed by fructose, sucrose, and then xylose. The maximum amounts of metabolites were produced when glucose was the carbon source, with fumaric acid produced in higher amounts than lactic acid. Isolate 19A-0069, however, preferred sucrose as the carbon source, and Isolate 19A-0030 produced higher amounts of lactic acid than fumaric acid. This is the first report, to our knowledge, of R. stolonifer producing lactic acid in preference to fumaric acid. Additionally, R. stolonifer isolate 19-0030 was inoculated into Nonpareil almond fruit on trees grown under high- and low-nitrogen and water treatments, and hull compositions of infected and uninfected fruit were analysed using 1H NMR-based metabolomics. Glucose and asparagine content of uninfected hulls was influenced by the nitrogen and water treatments provided to the trees, being higher in the high-nitrogen and water treatments. In infected hulls, glucose and fructose were significantly reduced but not sucrose or xylose. Large amounts of both fumaric and lactic acid were produced, particularly under high-nitrogen treatments. Moreover, almond shoots placed in dilute solutions of fumaric acid or lactic acid developed leaf symptoms very similar to the 'strike' symptoms seen in hull rot disease in the field, suggesting both acids are involved in causing disease.


Assuntos
Prunus dulcis , Xilose , Xilose/metabolismo , Asparagina/metabolismo , Rhizopus/metabolismo , Ácido Láctico/metabolismo , Nitrogênio/metabolismo , Glucose/metabolismo , Ácidos/metabolismo , Carbono/metabolismo , Sacarose/metabolismo , Frutose/metabolismo
19.
Drug Saf ; 45(12): 1517-1527, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36318419

RESUMO

INTRODUCTION: The US FDA required a Risk Evaluation and Mitigation Strategy (REMS) for phentermine/topiramate, an anti-obesity medication, to prevent congenital malformations. No REMS is required for single-ingredient topiramate, which may be used off-label for the same purpose. OBJECTIVE: The aim of this study was to evaluate the impact of phentermine/topiramate approval in 2012 on subsequent topiramate use among patients with obesity. METHODS: We used a national insurance claims database to conduct an interrupted time-series study (2009-2015). Enrollees aged 18-65 years in each examined calendar quarter had full insurance benefits during that quarter and the preceding 6 months. We required patients to have an obesity diagnosis and no other conditions warranting topiramate use. We calculated topiramate or comparator drug (atorvastatin, metformin) initiation rates and evaluated changes in trends before and after 2012 (transition period). RESULTS: Among topiramate users, 80% were female, and demographic characteristics remained consistent during the study period. Between 2009 and 2011, the topiramate initiation rate (95% confidence interval) among patients with obesity was 0.85 (0.73-0.98) per 1000 patients, with no significant upward or downward trend. In the first quarter of 2013, this rate had increased more than 2.5-fold (change: + 1.36 [1.19-1.52]). Metformin and atorvastatin initiation rates did not change. Topiramate initiation rates were threefold higher than phentermine/topiramate rates during the post-approval period. CONCLUSION: Phentermine/topiramate approval was associated with increased topiramate use among patients with obesity. Prescribers are encouraged to enhance patient education and monitoring in such clinical use since topiramate prescribing information, compared with REMS for phentermine/topiramate, has less emphasis on preventing prenatal exposure.


Assuntos
Fármacos Antiobesidade , Metformina , Gravidez , Humanos , Feminino , Masculino , Fentermina/efeitos adversos , Topiramato/uso terapêutico , Reposicionamento de Medicamentos , Atorvastatina , Frutose/efeitos adversos , Fármacos Antiobesidade/efeitos adversos , Obesidade/tratamento farmacológico , Obesidade/epidemiologia , Metformina/uso terapêutico , Aprovação de Drogas
20.
Artigo em Inglês | MEDLINE | ID: mdl-36429936

RESUMO

Germinated millet (Pennisetum glaucum (L.) R. Br.) is a source of phenolic compounds that has potential prebiotic action. This study aims at evaluating the action of germinated pearl millet on gut function and its microbiota composition in Wistar rats fed with a high-fat high-fructose (HFHF) diet. In the first stage, lasting eight weeks, the experiment consisted of two groups: AIN-93M (n = 10) and HFHF group (n = 20). In the second stage, which lasted ten weeks, the animals of the AIN-93M group (n = 10) were kept, while the HFHF group was dismembered into HFHF (HFHF diet, n = 10) and HFHF + millet (HFHF added 28.6% of germinated millet flour, n = 10) groups. After the 18th week, the urine of the animals was collected for the analysis of lactulose and mannitol intestinal permeability by urinary excretion. The histomorphometry was analyzed on the proximal colon and the fecal pH, concentration of short-chain fatty acids (SCFA), and sequencing of microbiota were performed in cecum content. The Mothur v.1.44.3 software was used for data analysis of sequencing. Alpha diversity was estimated by Chao1, Shannon, and Simpson indexes. Beta diversity was assessed by PCoA (Principal Coordinate Analysis). The functional predictive analysis was performed with PICRUSt2 software (version 2.1.2-b). Functional traits attributed to normalized OTU abundance were determined by the Kyoto Encyclopedia of Genes and Genomes (KEGG). In the results, germinated millet flour reduced Oscillibacter genus and Desulfobacterota phylum, while increasing the Eggerthellaceae family. Furthermore, germinated millet flour: increased beta diversity, cecum weight, and cecum/body weight ratio; improved gut histological parameters by increasing the depth and thickness of the crypt and the goblet cell count (p < 0.05); reduced (p < 0.05) the fecal pH and mannitol urinary excretion; increased (p < 0.05) the propionate short-chain fatty acid concentration. Thus, germinated millet has the potential to improve the composition of gut microbiota and the intestinal function of rats fed with an HFHF diet.


Assuntos
Microbioma Gastrointestinal , Pennisetum , Ratos , Animais , Farinha/análise , Milhetes , Frutose , Ratos Wistar , Dieta Hiperlipídica , Ácidos Graxos Voláteis , Grão Comestível/química , Manitol/análise
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