Revistas
Revista:
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
ISSN:
1661-6596
Año:
2024
Vol.:
25
N°:
3
Págs.:
1721 - *
Plant-based food interventions are promising therapeutic approaches for non-alcoholic fatty liver disease (NAFLD) treatment, and microRNAs (miRNAs) have emerged as functional bioactive components of dietary plants involved in cross-kingdom communication. Deeper investigations are needed to determine the potential impact of plant miRNAs in NAFLD. This study aimed to identify plant miRNAs that could eventually modulate the expression of human metabolic genes and protect against the progression of hepatic steatosis. Plant miRNAs from the miRBase were used to predict human target genes, and miR8126-3p and miR8126-5p were selected as candidates for their potential role in inhibiting glucose and lipid metabolism-related genes. Human HepG2 cells were transfected with plant miRNA mimics and then exposed to a mixture of oleic and palmitic acids to mimic steatosis. miR8126-3p and miR8126-5p transfections inhibited the expression of the putative target genes QKI and MAPKAPK2, respectively, and had an impact on the expression profile of key metabolic genes, including PPARA and SREBF1. Quantification of intrahepatic triglycerides revealed that miR8126-3p and miR8126-5p attenuated lipid accumulation. These findings suggest that plant miR8126-3p and miR8126-5p would induce metabolic changes in human hepatocytes eventually protecting against lipid accumulation, and thus, they could be potential therapeutic tools for preventing and alleviating lipid accumulation.
Revista:
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
ISSN:
0141-8130
Año:
2023
Vol.:
249
Págs.:
126111
This study aims to provide a thorough characterization of Brij O2-stabilized gliadin nanoparticles to be used for the potential oral administration of various compounds. Different techniques were used in order to evaluate their physico-chemical features and then in vivo studies in rats were performed for the investigation of their biodistribution and gastrointestinal transit profiles. The results showed that the gliadin nanoparticles accumulated in the mucus layer of the bowel mucosa and evidenced their ability to move along the digestive systems of the animals. The incubation of the nanosystems with Caenorhabditis elegans, used as an additional in vivo model, confirmed the intake of the particles and evidenced their presence along the entire gastrointestinal tract of these nematodes. The gliadin nanoparticles influenced neither the egg-laying activity of the worms nor their metabolism of lipids up to 10 & mu;g/mL of nanoformulation. The systems decreased the content of the age-related lipofuscin pigment in the nematodes in a dose-dependent manner, demonstrating a certain antioxidant activity. Lastly, dihydroethidium staining showed the absence of oxidative stress upon incubation of the worms together with the formulations, confirming their safe profile. This data paves the way for the future application of the proposed nanosystems regarding the oral delivery of various bioactives.
Revista:
DIABETOLOGIA
ISSN:
0012-186X
Año:
2023
Vol.:
66
N°:
11
Págs.:
2117 - 2138
Aims/hypothesis Modulation of gut microbiota has emerged as a promising strategy to treat or prevent the development of different metabolic diseases, including type 2 diabetes and obesity. Previous data from our group suggest that the strain Pediococcus acidilactici CECT9879 (pA1c) could be an effective probiotic for regulating glucose metabolism. Hence, the objectives of this study were to verify the effectiveness of pA1c on glycaemic regulation in diet-induced obese mice and to evaluate whether the combination of pA1c with other normoglycaemic ingredients, such as chromium picolinate (PC) and oat beta-glucans (BGC), could increase the efficacy of this probiotic on the regulation of glucose and lipid metabolism. Methods Caenorhabditis elegans was used as a screening model to describe the potential synbiotic activities, together with the underlying mechanisms of action. In addition, 4-week-old male C57BL/6J mice were fed with a high-fat/high-sucrose diet (HFS) for 6 weeks to induce hyperglycaemia and obesity. Mice were then divided into eight groups (n=12 mice/group) according to dietary supplementation: control-diet group; HFS group; pA1c group (10(10) colony-forming units/day); PC; BGC; pA1c+PC+BGC; pA1c+PC; and pA1c+BGC. Supplementations were maintained for 10 weeks. Fasting blood glucose was determined and an IPGTT was performed prior to euthanasia. Fat depots, liver and other organs were weighed, and serum biochemical variables were analysed. Gene expression analyses were conducted by real-time quantitative PCR. Sequencing of the V3-V4 region of the 16S rRNA gene from faecal samples of each group was performed, and differential abundance for family, genera and species was analysed by ALDEx2R package. Results Supplementation with the synbiotic (pA1c+PC+BGC) counteracted the effect of the high glucose by modulating the insulin-IGF-1 signalling pathway in C. elegans, through the reversal of the glucose nuclear localisation of daf-16. In diet-induced obese mice, all groups supplemented with the probiotic significantly ameliorated glucose tolerance after an IPGTT, demonstrating the glycaemia-regulating effect of pA1c. Further, mice supplemented with pA1c+PC+BGC exhibited lower fasting blood glucose, a reduced proportion of visceral adiposity and a higher proportion of muscle tissue, together with an improvement in the brown adipose tissue in comparison with the HFS group. Besides, the effect of the HFS diet on steatosis and liver damage was normalised by the synbiotic. Gene expression analyses demonstrated that the synbiotic activity was mediated not only by modulation of the insulin-IGF-1 signalling pathway, through the overexpression of GLUT-1 and GLUT-4 mediators, but also by a decreased expression of proinflammatory cytokines such as monocyte chemotactic protein-1. 16S metagenomics demonstrated that the synbiotic combinations allowed an increase in the concentration of P. acidilactici, together with improvements in the intestinal microbiota such as a reduction in Prevotella and an increase in Akkermansia muciniphila. Conclusions/interpretation Our data suggest that the combination of pA1c with PC and BGC could be a potential synbiotic for blood glucose regulation and may help to fight insulin resistance, diabetes and obesity.
Revista:
FOOD & FUNCTION
ISSN:
2042-6496
Año:
2023
Vol.:
14
N°:
24
Págs.:
10855 - 10867
Due to the importance of the gut microbiota in the regulation of energy homeostasis, probiotics have emerged as an alternative therapy to ameliorate obesity-related disturbances, including cholesterol metabolism dysregulation, dyslipidemia and inflammation. Therefore, the objectives of this study were to evaluate the effect of the probiotic strain Pediococcus acidilactici (pA1c (R)) on the regulation of adiposity, cholesterol and lipid metabolism, inflammatory markers and gut microbiota composition in diet-induced obese rats. Twenty-nine four-week-old male Wistar rats were divided into three groups: rats fed a control diet (CNT group, n = 8), rats fed a high fat/high sucrose diet (HFS group, n = 11), and rats fed a HFS diet supplemented with pA1c (R) (pA1c (R) group, n = 10). Organs and fat depots were weighed, and different biochemical parameters were analysed in serum. Gene expression analyses in the adipose tissue were conducted using real-time quantitative-PCR. Faecal microbiota composition was evaluated using 16S metagenomics. Animals supplemented with pA1c (R) exhibited a lower proportion of visceral adiposity, a higher proportion of muscle, an improvement in the total-cholesterol/HDL-cholesterol ratio and a decrease in the total cholesterol, triglyceride and aspartate aminotransaminase (AST) serum levels, together with a decrease in several inflammation-related molecules. The expression of key genes related to adipose (Adipoq, Cebpa and Pparg) and glucose (Slc2a1 and Slc2a4) metabolism in the adipose tissue was normalized by pA1c (R). Moreover, it was demonstrated that pA1c (R) supplementation activated fatty acid beta-oxidation in the adipose tissue and the liver. Metagenomics demonstrated the presence of pA1c (R) in the faecal samples, an increase in alpha diversity, an increase in the abundance of beneficial bacteria, and a decrease in the abundance of harmful micro-organisms, including the Streptococcus genus. Thus, our data suggest the potential of pA1c (R) in the prevention of obesity-related disturbances including hypercholesterolemia, hypertriglyceridemia, inflammation and gut microbiota dysbiosis.
Revista:
FRONTIERS IN NUTRITION
ISSN:
2296-861X
Background: Edible plants can exert anti-inflammatory activities in humans, being potentially useful in the treatment of inflammatory diseases. Plant-derived microRNAs have emerged as cross-kingdom gene expression regulators and could act as bioactive molecules involved in the beneficial effects of some edible plants. We investigated the role of edible plant-derived microRNAs in the modulation of pro-inflammatory human genes.Methods: MicroRNAs from plant-derived foods were identified by next-generation sequencing. MicroRNAs with inflammatory putative targets were selected, after performing in silico analyses. The expression of candidate plant-derived miRNAs was analyzed by qPCR in edible plant-derived foods and their effects were evaluated in THP-1 monocytes differentiated to macrophages. The bioavailability of candidate plant miRNAs in humans was evaluated in feces and serum samples by qPCR.Results: miR482f and miR482c-5p are present in several edible plant-derived foods, such as fruits, vegetables, and cooked legumes and cereals, and fats and oils. Transfections with miR482f and miR482c-5p mimics decreased the gene expression of CLEC7A and NFAM1, and TRL6, respectively, in human THP-1 monocytes differentiated to macrophages, which had an impact on gene expression profile of inflammatory biomarkers. Both microRNAs (miR482f and miR482c-5p) resisted degradation during digestion and were detected in human feces, although not in serum.Conclusion: Our findings suggest that miR482f and miR482c-5p can promote an anti-inflammatory gene expression profile in human macrophages in vitro and their bioavailability in humans can be achieved through diet, but eventually restricted at the gut level.
Revista:
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
ISSN:
1422-0067
Año:
2022
Vol.:
23
N°:
5
Págs.:
2689
The increasing prevalence of metabolic syndrome-related diseases, including type-2 diabetes and obesity, makes it urgent to develop new alternative therapies, such as probiotics. In this study, we have used Caenorhabditis elegans under a high-glucose condition as a model to examine the potential probiotic activities of Pediococcus acidilactici CECT9879 (pA1c). The supplementation with pA1c reduced C. elegans fat accumulation in a nematode growth medium (NGM) and in a high-glucose (10 mM) NGM medium. Moreover, treatment with pA1c counteracted the effect of the high glucose by reducing reactive oxygen species by 20%, retarding the aging process and extending the nematode median survival (> 2 days in comparison with untreated control worms). Gene expression analyses demonstrated that the probiotic metabolic syndrome-alleviating activities were mediated by modulation of the insulin/IGF-1 signaling pathway (IIS) through the reversion of the glucose-nuclear-localization of daf-16 and the overexpression of ins-6 and daf-16 mediators, increased expression of fatty acid (FA) peroxisomal beta-oxidation genes, and downregulation of FA biosynthesis key genes. Taken together, our data suggest that pA1c could be considered a potential probiotic strain for the prevention of the metabolic syndrome-related disturbances and highlight the use of C. elegans as an appropriate in vivo model for the study of the mechanisms underlying these diseases.
Revista:
INTERNATIONAL JOURNAL OF OBESITY
ISSN:
0307-0565
Año:
2021
Vol.:
45
N°:
10
Págs.:
0307-0565
Background and aim Fecal microbiome disturbances are linked to different human diseases. In the case of obesity, gut microbiota seems to play a role in the development of low-grade inflammation. The purpose of the present study was to identify specific bacterial families and genera associated with an increased obesity-related inflammatory status, which would allow to build a regression model for the prediction of the inflammatory status of obese and overweight subjects based on fecal microorganisms. Methods A total of 361 volunteers from the Obekit trial (65 normal-weight, 110 overweight, and 186 obese) were classified according to four variables: waist/hip ratio (>= 0.86 for women and >= 1.00 for men), leptin/adiponectin ratio (LAR, >= 3.0 for women and >= 1.4 for men), and plasma C-reactive protein (>= 2 mg/L) and TNF levels (>= 0.85 pg/mL). An inflammation score was designed to classify individuals in low (those subjects who did exceed the threshold value in 0 or 1 variable) or high inflammatory index (those subjects who did exceed the threshold value in 2 or more variables). Fecal 16 S rRNA sequencing was performed for all participants, and differential abundance analyses for family and genera were performed using the MicrobiomeAnalyst web-based platform. Results Methanobacteriaceae, Christensenellaceae, Coriobacteriaceae, Bifidobacteriaceae, Catabacteriaceae, and Dehalobacteriaceae families, and Methanobrevibacter, Eggerthella, Gemmiger, Anaerostipes, and Collinsella gen
Autores:
Mendez, D. A.; Fabra, M. J.; Falcó, I.; et al.
Revista:
FOOD & FUNCTION
ISSN:
2042-650X
Año:
2021
Vol.:
12
N°:
16
Págs.:
7428 - 7439
In this work, a bioactive persimmon extract was produced from discarded fruits. A central composite design was used to evaluate the effect of different extraction parameters and ripeness stages of persimmon fruits on the total phenolic content and antioxidant activity of the resulting extracts. Significantly greater phenolic contents were obtained from immature persimmon (IP) fruits. The optimum IP extract with the conditions set by the experimental design was industrially up-scaled and its composition and functional properties were evaluated and compared with those obtained under lab-scale conditions. Both extracts contained significant protein (>20%) and phenolic contents (similar to 11-27 mg GA/g dry extract) and displayed significant antiviral activity against murine norovirus and hepatitis A virus. Moreover, the extract showed no toxicity and significantly reduced the fat content and the cellular ageing of Caenorhabditis elegans (C. elegans) without affecting the worm development. These effects were mediated by down-regulation of fat-7, suggesting an anti-lipogenic activity of this extract.
Revista:
EUROPEAN JOURNAL OF NUTRITION
ISSN:
1436-6207
Purpose Obesity has been related to intestinal dysbiosis and the modification of gut microbiota composition by dietary strategies becomes a promising strategy to help manage obesity. The aim of the current study was to evaluate the effect of two weight-loss diets on the composition and functional profile of gut microbiota. Methods 55 men and 124 women with BMI > 25 kg/m(2) were randomly assigned to moderately high-protein (MHP) or low-fat (LF) diet. Differences in fecal bacteria abundance (based on 16 s rRNA sequencing) between before and after 4 months of calorie restriction was analyzed using EdgeR tool in MicrobiomeAnalyst platform. Bacterial functional profile was predicted using Tax4Fun and metagenomeSeq analysis. Significant KEGG Orthology (KO) terms were selected for the metabolomic study using chromatography. Results After the intervention, MHP-men showed a significant decrease in Negativicutes, Selenomonadales, Dielma and Dielma fastidiosa. LF-men showed a significant increase in Bacilli, Lactobacillales, Christensenellaceae, Peptococcaceae, and Streptococcaceae, Peptococcus, Streptococcus and Christensenella, Duncaniella dubosii_CP039396_93.49%, Roseburia sp_AB744234_98.96% and Alistipes inops_KJ572413_99.57%. MHP-women increased Pasteurellales, Phascolarctobacterium succinatutens, Ruthenibacterium lactatiformans_LR215981_99.55% and decreased in Phascolarctobacterium succinatutens_NR112902_99.56%. Finally, LF-women presented a significant decrease in Bacteroides clarus and Erysipelothrix inopinata_CP060715_84.4%. Surprisingly, no matching bacterial changes were found between these four groups. A total of 42 KO, 10 metabolic pathways and 107 related metabolites related were found implicated in these bacterial changes. Seven metabolites were confirmed in plasma. Conclusion Weight-loss-related-changes in gut microbiome composition and the functional profile occur in a sex- and diet-related manner, showing that women and men could differentially benefit from the consumption of MHP and LF diets.
Revista:
NUTRIENTS
ISSN:
2072-6643
Año:
2021
Vol.:
13
N°:
11
Págs.:
3968
In recent years, food ingredients rich in bioactive compounds have emerged as candidates to prevent excess adiposity and other metabolic complications characteristic of obesity, such as low-grade inflammation and oxidative status. Among them, fungi have gained popularity for their high polysaccharide content and other bioactive components with beneficial activities. Here, we use the C. elegans model to investigate the potential activities of a Grifola frondosa extract (GE), together with the underlying mechanisms of action. Our study revealed that GE represents an important source of polysaccharides and phenolic compounds with in vitro antioxidant activity. Treatment with our GE extract, which was found to be nongenotoxic through a SOS/umu test, significantly reduced the fat content of C. elegans, decreased the production of intracellular ROS and aging-lipofuscin pigment, and increased the lifespan of nematodes. Gene expression and mutant analyses demonstrated that the in vivo anti-obesity and antioxidant activities of GE were mediated through the daf-2/daf-16 and skn-1/nrf-2 signalling pathways, respectively. Taken together, our results suggest that our GE extract could be considered a potential functional ingredient for the prevention of obesity-related disturbances.
Revista:
NUTRIENTS
ISSN:
2072-6643
Ultra-processed foods (UPFs) consumption could affect gut microbiota diversity and profile. We aimed to evaluate the effects of UPFs on microbiota, considering the role of sex. The consumption of UPFs (using NOVA criteria) was assessed with a validated 137-item food-frequency questionnaire. Participants (n = 359) were classified into less than three servings per day (n = 96) of UPFs and more than five (n = 90). Women and men were subclassified following the same criteria. 16S rRNA sequencing was performed from DNA fecal samples, and differences in microbiota were analyzed using EdgeR. The relationship between UPFs and bacteria was assessed by Spearman correlation and comparison of tertiles of consumption. Women who consumed more than five servings/day of UPFs presented an increase in Acidaminococcus, Butyrivibrio, Gemmiger, Shigella, Anaerofilum, Parabacteroides, Bifidobacterium, Enterobacteriales, Bifidobacteriales and Actinobacteria and a decrease in Melainabacter and Lachnospira. Bifidobacterium, Bifidobacteriales and Actinobacteria was positively associated with pizza and Actinobacteria with industrially processed dairy in women. Men who consumed more than five servings/day presented an increase of Granulicatella, Blautia, Carnobacteriaceae, Bacteroidaceae, Peptostreptococcaceae, Bacteroidia and Bacteroidetes and a decrease of Anaerostipes and Clostridiaceae. Bacteroidia and Bacteroidetes correlated positively with industrially processed meat. This study suggests that UPFs may affect microbiota composition differently in women and men.
Revista:
ACTA PHARMACEUTICA SINICA B
ISSN:
2211-3835
Año:
2021
Vol.:
11
N°:
4
Págs.:
989 - 1002
The aim was to evaluate the potential of mucus-permeating nanoparticles for the oral administration of insulin. These nanocarriers, based on the coating of zein nanoparticles with a polymer conjugate containing PEG, displayed a size of 260 nm with a negative surface charge and an insulin payload of 77 µg/mg. In intestinal pig mucus, the diffusivity of these nanoparticles (PPA-NP) was found to be 20-fold higher than bare nanoparticles (NP). These results were in line with the biodistribution study in rats, in which NP remained trapped in the mucus, whereas PPA-NP were able to cross this layer and reach the epithelium surface. The therapeutic efficacy was evaluated in Caenorhabditis elegans grown under high glucose conditions. In this model, worms treated with insulin-loaded in PPA-NP displayed a longer lifespan than those treated with insulin free or nanoencapsulated in NP. This finding was associated with a significant reduction in the formation of ROS as well as an important decrease in the glucose and fat content in worms. These effects would be related with the mucus-permeating ability of PPA-NP that would facilitate the passage through the intestinal peritrophic-like dense layer of worms (similar to mucus) and, thus, the absorption of insulin.
Revista:
REVISTA ESPAÑOLA DE NUTRICION HUMANA Y DIETETICA
ISSN:
2173-1292
Año:
2021
Vol.:
25
Págs.:
20 - 21
Revista:
FOOD & FUNCTION
ISSN:
2042-6496
Año:
2020
Vol.:
11
N°:
5
Págs.:
4512 - 4524
The metabolic properties of omega-6 fatty acid consumption are being increasingly accepted. We had previously observed that supplementation with a borage seed oil (BSO), as a source of linoleic (18:2n-6; LA) and gamma-linolenic (18:3n-6; GLA) acids, reduces body weight and visceral adiposity and improves insulin sensitivity in a diet-induced obesity model of Wistar rats. Here, it was investigated whether the anti-obesogenic properties of BSO could be maintained in a pre-obese model of rats, and if these effects are enhanced by a combination with low doses of quercetin, together with its potential role in the regulation of the adipocyte biology. The combination of BSO and quercetin during 8 weeks was able to ameliorate glucose intolerance and insulin resistance, and to improve liver steatosis. Although no effects were observed on body weight, animals supplemented with this combination exhibited a lower proportion of visceral adiposity. In addition, in vitro differentiation of epididymal adipose-precursor cells of the BSO-treated animals exhibited a down-regulation of Fasn, Glut4, Pparg and Srebp1 genes, in comparison with the control group. Finally, in vitro evaluation of the components of BSO demonstrated that the anti-adipogenic activity of quercetin was significantly potentiated by the combination with both LA and GLA through the down-regulation of different adipogenesis-key genes in 3T3-L1 cells. All these data suggest that omega-6 fatty acids LA and GLA, and their natural sources such as BSO, could be combined with quercetin to potentiate their effects in the prevention of the excess of adiposity and the insulin resistance.
Autores:
Chase, A.; Score, J.; Lin, F.; et al.
Revista:
LEUKEMIA
ISSN:
0887-6924
Año:
2020
Vol.:
34
N°:
12
Págs.:
3206 - 3214
EZH2, a component of the polycomb repressive complex 2, catalyses the trimethylation of histone H3 lysine 27, a chromatin mark associated with transcriptional repression. EZH2 loss-of-function mutations are seen in myeloid neoplasms and are associated with an adverse prognosis. Missense mutations in the SET/CXC domain abrogate catalytic activity as assessed by in vitro histone methylation assays, but missense mutations clustering in the conserved DI and DII regions retain activity. To understand the role of DI and DII mutations, we initially developed a cell-based histone methylation assay to test activity in a cellular context. Murine induced pluripotent stem cells lacking EZH2 were transiently transfected with wild type or mutant EZH2 (n = 15) and any resulting histone methylation was measured by flow cytometry. All DI mutations (n = 5) resulted in complete or partial loss of methylation activity whilst 5/6 DII mutations retained activity. Next, we assessed the possibility of splicing abnormalities induced by exon 8 mutations (encoding DII) using RT-PCR from primary patient samples and mini-gene assays. Exon 8 mutations resulted in skipping of exon 8 and an out-of-frame transcript. We have therefore shown that mutations within regions encoding EZH2 domains DI and DII are pathogenic by loss of function and exon skipping, respectively.
Revista:
PHARMACEUTICALS
ISSN:
1424-8247
Año:
2020
Vol.:
13
N°:
11
Págs.:
355
Supplementation with bioactive compounds capable of regulating energy homeostasis is a promising strategy to manage obesity. Here, we have screened the ability of different phenolic compounds (myricetin, kaempferol, naringin, hesperidin, apigenin, luteolin, resveratrol, curcumin and epicatechin), and phenolic acids (p-coumaric, ellagic, ferulic, gallic and vanillic acids) regulating C. elegans fat accumulation. Resveratrol exhibited the strongest lipid-reducing activity, which was accompanied by the improvement of lifespan, oxidative stress and ageing, without affecting worm development. Whole-genome expression microarrays demonstrated that resveratrol affected fat mobilization, fatty acid metabolism, and unfolded protein response of the endoplasmic reticulum (UPRER), mimicking the response to calorie restriction. Apigenin induced the oxidative stress response and lipid mobilization, while vanillic acid affected the unfolded-protein response in ER. In summary, our data demonstrates that phenolic compounds exert a lipid-reducing activity in C. elegans through different biological processes and signaling pathways, including those related with lipid mobilization and fatty acid metabolism, oxidative stress, ageing and UPR-ER response. These findings open the door to the possibility of combining them in order to achieve complementary activity against obesity-related disorders.
Revista:
JOURNAL OF FUNCTIONAL FOODS
ISSN:
1756-4646
Año:
2019
Vol.:
59
Págs.:
319 - 328
Brassicaceae contain bioactive compounds with potential positive effects on metabolic syndrome. Here, we evaluated the eventual anti-obesity properties of an ethanolic broccoli extract (BE), selected by a tested ability to reduce Caenorhabditis elegans fat content. Two doses (14 and 140 mg/kg animal) of BE were evaluated in a diet-induced obesity (DIO) Wistar rat model.
After 10 weeks of BE supplementation, animals exhibited reduced body weight gain and food efficiency, decreased atherogenic index of plasma and improved glucose tolerance in comparison with non-supplemented rats. BE also reduced the retroperitoneal fat mass and adipocyte size, all associated to down-regulation of Cebpa, Srebp1, Fasn and Adipoq expression in adipocytes. Finally, BE significantly decreased liver steatosis, accompanied by the up-regulation of Acot8 and Acox1, and the down-regulation of Fasn, Fatp4 and Srebf1 expression in hepatocytes. Our data provides new knowledge about the potential role of broccoli components in the prevention of metabolic syndrome.
Revista:
FOOD & FUNCTION
ISSN:
2042-6496
Año:
2019
Vol.:
10
N°:
8
Págs.:
4811 - 4822
Cocoa polyphenols exhibit high antioxidant activity and have been proposed as a potential adjuvant for the treatment of metabolic disturbances. Here, we demonstrate that supplementation with low doses (14 and 140 mg per kg per rat) of a complete cocoa extract induces metabolic benefits in a diet-induced obesity (DIO) model of Wistar rats. After 10 weeks, cocoa extract-supplemented animals exhibited significantly lower body weight gain and food efficiency, with no differences in energy intake. Cocoa significantly reduced visceral (epididymal and retroperitoneal) and subcutaneous fat accumulation accompanied by a significant reduction in the adipocyte size, which was mediated by downregulation of the adipocyte-specific genes Cebpa, Fasn and Adipoq. Additionally, cocoa extract supplementation reduced the triacylglycerol/high density lipoprotein (TAG/HDL) ratio, decreased hepatic triglyceride accumulation, improved insulin sensitivity by reducing HOMA-IR, and significantly ameliorated glucose tolerance after an intraperitoneal glucose tolerance test. Finally, no adverse effect was observed in an in vivo toxicity evaluation of our cocoa extract at doses up to 500 mg kg -1 day -1. Our data demonstrate that low doses of cocoa extract supplementation (14 and 140 mg kg -1 day -1) are safe and sufficient to counteract obesity and type-2 diabetes in rats and provide new insights into the potential application of cocoa supplements in the management of the metabolic syndrome.
Revista:
MOLECULES
ISSN:
1420-3049
Año:
2019
Vol.:
24
N°:
6
Págs.:
1 - 21
Phenolic compounds might modulate adiposity. Here, we report our observation that polyphenols and phenolic acids inhibit adipogenesis in 3T3-L1 with different intensity depending on the family and the stage of differentiation. While quercetin and resveratrol inhibited lipid accumulation along the whole process of differentiation, apigenin and myricetin were active during the early and latest stages, but not intermediate, contrary to hesperidin. The activity of phenolic acids was limited to the early stages of the differentiation process, except p-coumaric and ellagic acids. This anti-adipogenic effect was accompanied by down-regulation of Scd1 and Lpl. Molecular docking analysis revealed that the inhibitory activity of these phenolic compounds over the early stages of adipogenesis exhibits a significant correlation (r = 0.7034; p = 0.005) with their binding affinity to the ligand-binding domain of PPAR¿. Results show that polyphenols and phenolic acids would interact with specific residues of the receptor, which could determine their potential anti-adipogenic activity during the early stages of the differentiation. Residues Phe264, His266, Ile281, Cys285 and Met348 are the most frequently involved in these interactions, which might suggest a crucial role for these amino acids modulating the activity of the receptor. These data contribute to elucidate the possible mechanisms of phenolic compounds in the control of adipogenesis.
Autores:
Navarro-Herrera, D.; Aranaz, Paula; Eder-Azanza, L.; et al.
Revista:
FOOD & FUNCTION
ISSN:
2042-6496
Año:
2018
Vol.:
9
N°:
8
Págs.:
4340 - 4351
Obesity is a medical condition with increasing prevalence, characterized by an accumulation of excess fat that could be improved using some bioactive compounds. However, many of these compounds with in vitro activity fail to respond in vivo, probably due to the sophistication of the physiological energy regulatory networks. In this context, C. elegans has emerged as a plausible model for the identification and characterization of the effect of such compounds on fat storage in a complete organism. However, the results obtained in such a simple model are not easily extrapolated to more complex organisms such as mammals, which hinders its application in the short term. Therefore, it is necessary to obtain new experimental data about the evolutionary conservation of the mechanisms of fat loss between worms and mammals. Previously, we found that some omega-6 fatty acids promote fat loss in C. elegans by up-regulation of peroxisomal fatty acid Ã-oxidation in an omega-3 independent manner. In this work, we prove that the omega-6 fatty acids¿ effects on worms are also seen when they are supplemented with a natural omega-6 source (borage seed oil, BSO). Additionally, we explore the anti-obesity effects of two doses of BSO in a diet-induced obesity rat model, validating the up-regulation of peroxisomal fatty acid Ã-oxidation. The supplementation with BSO significantly reduces body weight gain and energy efficiency and prevents white adipose tissue accumulation without affecting food
Revista:
INTERNATIONAL JOURNAL OF PHARMACEUTICS
ISSN:
0378-5173
Año:
2018
Vol.:
547
N°:
1 - 2
Págs.:
97 - 105
The aim of this work was to prepare and evaluate cyclodextrins-modified poly(anhydride) nanoparticles to enhance the oral administration of glibenclamide. A conjugate polymer was synthesized by incorporating hydroxypropyl-beta-cyclodextrin to the backbone of poly(methylvinyl ether-co-maleic anhydride) via Steglich reaction. The degree of substitution of anhydride rings by cyclodextrins molecules was calculated to be 4.9% using H-NMR spectroscopy. A central composite design of experiments was used to optimize the preparative process. Under the optimal conditions, nanoparticles displayed a size of about 170 nm, a surface charge of - 47 mV and a drug loading of 69 mu g GB/mg. X-ray diffraction studies confirmed the loss of the crystalline structure of GB due to its dispersion into the nanoparticles, either included into cyclodextrin cavities or entrapped in the polymer chains. Glibenclamide was mainly release by Fickian-diffusion in simulated intestinal fluid. GB-loaded nanoparticles produced a hypolipidemic effect over C. elegans N2 wild-type and daf-2 mutant. The action mechanism included daf-2 and daf-28 genes, both implicated in the insulin signaling pathway of C. elegans. In summary, the covalent linkage of cyclodextrin to the poly(anhydride) backbone could be an interesting strategy to prepare nanoparticles for the oral administration of glibenclamide.
Autores:
Navarro Herrera, D.; Aranaz, Paula; Eder-Azanza, L.; et al.
Revista:
FOOD & FUNCTION
ISSN:
2042-6496
Año:
2018
Vol.:
9
N°:
3
Págs.:
1621 - 1637
Bioactive compounds, including some fatty acids (FAs), can induce beneficial effects on body fat-content and metabolism. In this work, we have used C. elegans as a model to examine the effects of several FAs on body fat accumulation. Both omega-3 and omega-6 fatty acids induced a reduction of fat content in C. elegans, with linoleic, gamma-linolenic and dihomo-gamma-linolenic acids being the most effective ones. These three FAs are sequential metabolites especially in omega-6 PUFA synthesis pathway and the effects seem to be primarily due to dihomo-gamma-linolenic acid, and independent of its transformation into omega-3 or arachidonic acid. Gene expression analyses suggest that peroxisomal beta oxidation is the main mechanism involved in the observed effect. These results point out the importance of further analysis of the activity of these omega-6 FAs, due to their potential application in obesity and related diseases.
Revista:
FOOD & FUNCTION
ISSN:
2042-6496
Obesity and type 2-diabetes are becoming a worldwide health problem, remarking the importance of alternative therapies to tackle their progression. Here, we hypothesized that supplementation of diet with 6 % w/w of a freeze-dried strawberry-blueberry (5:1) powder (FDSB) could exert beneficial metabolic effects in Wistar rats. FDSB-supplemented animals experienced significantly reduced body weight gain, food efficiency and visceral adiposity accumulation in two independent experiments. FDSB supplementation also contributed to lower area under the curve after an intraperitoneal GTT and reduced serum insulin levels and insulin resistance index (IR-HOMA) in HFS diet-fed animals, together with reduced plasma MCP-1 inflammation marker concentrations. Gene expression analysis in retroperitoneal adipocytes from experiment 1 and 3T3-L1 cells showed that FDSB inhibited adipogenesis and lipogenesis through down-regulation of Pparg, Cebpa, Lep, Fasn, Scd-1 and Lpl gene expression. Untargeted metabolomics identified the cis isomer ofresveratrol-3-glucoside-sulphate as a metabolite differentially increased in FDSB-treated serum samples, which corresponds to a strawberry metabolite that could be considered a serum biomarker of FDSB-intake. Our results suggest that FDSB powder might be useful for treatment/prevention of obesity-related diseases.
Revista:
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
ISSN:
0939-6411
Año:
2017
Vol.:
121
Págs.:
104 - 112
The aim of this work was to evaluate the capability of zein nanoparticles as oral carriers for glibenclamide (GB). Nanoparticles were prepared by a desolvation procedure in the presence of lysine as stabilizer. A central composite design was used to optimize this preparative process. Under the selected conditions, nanoparticles displayed a size of about 190 nm, a surface charge of -37 mV and a payload of 45 mu g GB/mg. Small-angle neutron scattering and X-ray diffraction techniques suggested an internal fractal-like structure, based on the repetition of spherical blocks of zein units (about 20 nm) grouped to form the nanoparticles. This structure, stabilized by lysine molecules located at the surface, would determine the release of GB (molecularly trapped into the nanoparticles) by a pure diffusion mechanism. Moreover, GB-loaded nanoparticles induced a significant hypolipidemic effect with a reduction of about 15% in the fat content of C. elegans worms. In addition, did not induce any significant modification in the lifespan of worms. In summary, the employment of zein nanoparticles as delivery systems of glibenclamide may be an interesting approach to develop new oral formulations of this antidiabetic drug.
Revista:
HAEMATOLOGICA
ISSN:
0390-6078
Año:
2017
Vol.:
102
N°:
8
Págs.:
e328 - e331
Revista:
BIOTECHNIQUES
ISSN:
0736-6205
Año:
2014
Vol.:
56
N°:
6
Págs.:
327 - 329
When studying mutations in DNA samples, determining whether novel sequence changes are somatic mutations or germline polymorphisms can be difficult. Here we describe a novel and very simple approach for identification of somatic mutations and loss of heterozygosity (LoH) events in DNA samples where no matched tissue sample is available. Our method makes use of heterozygous polymorphisms that are located near the putative mutation to trace both germinal alleles.
Autores:
Eder Azanza, L.; Navarro Herrera, D.; Aranaz, Paula; et al.
Revista:
LEUKEMIA
ISSN:
0887-6924
Año:
2014
Vol.:
28
N°:
10
Págs.:
2106 - 2109
Revista:
LEUKEMIA AND LYMPHOMA
ISSN:
1042-8194
Año:
2013
Vol.:
54
N°:
2
Págs.:
428 - 431
Revista:
BRITISH JOURNAL OF HAEMATOLOGY
ISSN:
0007-1048
Año:
2013
Vol.:
163
N°:
2
Págs.:
235 - 239
Whole exome sequencing was performed in a patient with myelodysplastic syndrome before and after progression to acute myeloid leukaemia. Mutations in several genes, including SETBP1, were identified following leukaemic transformation. Screening of 328 patients with myeloid disorders revealed SETBP1 mutations in 14 patients (4 center dot 3%), 7 of whom had -7/del(7q) and 3 had i(17)(q10), cytogenetic markers associated with shortened overall survival and increased risk of leukaemic evolution. SETBP1 mutations were frequently acquired at the time of leukaemic evolution, coinciding with increase of leukaemic blasts. These data suggest that SETBP1 mutations may play a role in MDS and chronic myelomonocytic leukaemia disease progression.
Revista:
Haematologica-journal of Hematology
ISSN:
1138-0381
Año:
2012
Vol.:
97
N°:
8
Págs.:
1234 -1241
Revista:
Leukemia & Lymphoma
ISSN:
1042-8194
Año:
2011
Vol.:
53
N°:
6
Págs.:
1230-1233
Revista:
Leukemia Research
ISSN:
0145-2126
Año:
2011
Vol.:
35
N°:
11
Págs.:
1537 - 1539
Revista:
CANCER GENETICS AND CYTOGENETICS
ISSN:
0165-4608
Año:
2010
Vol.:
199
N°:
1
Págs.:
1 - 8
BCR/ABL1-negative chronic myeloproliferative neoplasms (CMPNs) are a heterogeneous group of clonal hematological malignancies. Over recent years, some genetic events in tyrosine lcinase (TK) genes have been described as causal events of these diseases. To identify new genetic aberrations underlying these diseases, we used denaturing high performance liquid chromatography and fluorescence in situ hybridization (FISH) to analyze 17 genes from two receptor-TK families (III and IV) and from three cytoplasmic-TK families (Syk, Abl, and Jak) on samples from 44 BCR/ABL1-negative and JAK2(V617F)-negative CMPN patients with different clinical phenotypes. Although screening by FISH did not reveal novel chromosomal aberrations, several sequence changes were detected. None of them were frequent events, but we identified a new potential activating mutation in the FERM domain of JAK2(R340Q). None of the germline JAK2(V617F) singlenucleotide polymorphisms detected differed in distribution between patients and control subjects. In summary, data presented here show that these genes are not frequently mutated or rearranged in CMPNs, suggesting that molecular events causing these disorders must be located in other genes.
Revista:
LEUKEMIA AND LYMPHOMA
ISSN:
1042-8194
Año:
2010
Vol.:
51
N°:
9
Págs.:
1720 - 1726
Hematological malignancies with eosinophilia are often associated with fusions in PDGFRA, PDGFRB, or FGFR1 genes. RT-PCR has proved to be useful for finding new PDGFRA gene fusions, but some studies have shown overexpression of the TK domain which cannot be explained by the existence of such aberrations. This fact could be related to the expression of alternative PDGFRA transcripts. We show that quantification of the expression of three different PDGFRA fragments discriminates between PDGFRA alternative transcripts and fusion genes, and we have tested this novel methodological approach in a group of eosinophilia cases. Our data show that alternative PDGFRA transcripts should be taken into account when screening for PDGFRA aberrations, such as gene fusions, by RT-PCR. Expression from an internal PDGFRA promoter seems to be a frequent event, in both normal and leukemic samples, and is probably related to physiological conditions, but it could have a role in other tumors. Even so, we show that our RQ-PCR methodology can discriminate expression of alternative transcripts from the presence of X-PDGFRA fusion genes.
Nacionales y Regionales
Título:
Residuos de Pleurotus como fuente Alternativa de NutrACEuticos Avanzados PANACEA
Investigador principal:
Paula Aranaz Oroz
Financiador:
CENTRO NACIONAL DE TECNOLOGÍA Y SEGURIDA ALIMENTARIA, LABORATORIO DEL EBRO
Convocatoria:
2023 CNTA Eatex Programa para el fomento de la colaboración en acciones de I+D+i entre Comunidades Autónomas
Fecha de inicio:
03/10/2023
Fecha fin:
02/10/2025
Importe concedido:
175.320,26€
Otros fondos:
-
Título:
Aplicación de agentes paraprobióticos y postbióticos en la prevención y tratamiento de la obesidad. Mecanismos implicados.
Código de expediente:
0011-1383-2022-000015 (PC128-129 PARABIOTICS
Investigador principal:
Paula Aranaz Oroz
Financiador:
GOBIERNO DE NAVARRA
Convocatoria:
2022 GN Proyectos Colaborativos
Fecha de inicio:
01/12/2022
Fecha fin:
30/11/2024
Importe concedido:
251.608,88€
Otros fondos:
-
Título:
Metabolitos postbióticos: papel en obesidad y síndrome metabólico, su aplicación y personalización
Código de expediente:
PID2022-141766OB-I00
Investigador principal:
Paula Aranaz Oroz, Fermín Ignacio Milagro Yoldi
Financiador:
AGENCIA ESTATAL DE INVESTIGACION
Convocatoria:
2022 AEI Proyectos de Generación del Conocimiento
Fecha de inicio:
01/09/2023
Fecha fin:
31/08/2026
Importe concedido:
200.000,00€
Otros fondos:
Fondos FEDER
Título:
Encapsulación de probióticos hasta estudio de intervención nutricional (PROCAPS)
Código de expediente:
0011-1365-2023-000192
Investigador principal:
Santiago Navas Carretero
Financiador:
GOBIERNO DE NAVARRA
Convocatoria:
2023 GN I+D Transferencia del conocimiento (empresas)
Fecha de inicio:
01/09/2023
Fecha fin:
31/07/2025
Importe concedido:
113.012,58€
Otros fondos:
Fondos FEDER
Título:
DESARROLLO, EVALUACIÓN FUNCIONAL Y APLICABILIDAD INDUSTRIAL DE NUEVOS DERIVADOS DE PROTEÍNA VEGETAL
Código de expediente:
0011-1411-2023-000103
Investigador principal:
Paula Aranaz Oroz
Financiador:
GOBIERNO DE NAVARRA
Convocatoria:
2023 GN PROYECTOS ESTRATEGICOS DE I+D 2023-2026
Fecha de inicio:
01/07/2023
Fecha fin:
31/12/2025
Importe concedido:
396.416,15€
Otros fondos:
-
Título:
USO DE LA BIOTECNOLOGÍA PARA LA OBTENCIÓN DE INGREDIENTES Y ALIMENTOS BENEFICIOSOS PARA LA SALUD (BIOFOOD)
Código de expediente:
0011-1411-2019-000031
Investigador principal:
Fermín Ignacio Milagro Yoldi
Financiador:
GOBIERNO DE NAVARRA
Convocatoria:
2019 GN PROYECTOS ESTRATEGICOS DE I+D 2019-2021
Fecha de inicio:
01/07/2019
Fecha fin:
30/11/2021
Importe concedido:
238.952,30€
Otros fondos:
-
Título:
PREDISMET Estudio de la potencial aplicación de una combinación de probióticos, prebióticos y postibióticos para la prevención y tratamiento de la disbiosis intestintal caracterísstica del síndrome metabólico.
Código de expediente:
0011-1383-2020-000010 PC173 predismet
Investigador principal:
Paula Aranaz Oroz
Financiador:
GOBIERNO DE NAVARRA
Convocatoria:
2020 GN Proyectos Colaborativos
Fecha de inicio:
01/06/2020
Fecha fin:
30/11/2022
Importe concedido:
296.051,13€
Otros fondos:
-
Título:
MICROLIVER La mircobiota intestintal y los probióticos como nuevos abordajes de la esteatosis hepática, gracias al desarrollo de un dispositivio para el análisis de microbiota en las diferentes zonas del tracto digestivo.
Código de expediente:
0011-1383-2020-000010 PC131 MICROLIVER
Investigador principal:
Fermín Ignacio Milagro Yoldi
Financiador:
GOBIERNO DE NAVARRA
Convocatoria:
2020 GN Proyectos Colaborativos
Fecha de inicio:
01/06/2020
Fecha fin:
30/11/2022
Importe concedido:
408.589,75€
Otros fondos:
-
Título:
DISEÑO DE ALIMENTOS E INGREDIENTES SALUDABLES Y SOSTENIBLES A PARTIR DE LA APLICACIÓN DE ECONOMÍA CIRCULAR (ALISSEC)
Código de expediente:
0011-1411-2021-000100
Investigador principal:
Fermín Ignacio Milagro Yoldi
Financiador:
GOBIERNO DE NAVARRA
Convocatoria:
2021 GN PROYECTOS ESTRATEGICOS DE I+D 2021-2024
Fecha de inicio:
01/05/2021
Fecha fin:
31/12/2023
Importe concedido:
372.686,84€
Otros fondos:
-
Título:
MODULACIÓN PERSONALIZADA DE LA MICROBIOTA MEDIANTE EL DISEÑO INTELIGENTE DE ALIMENTOS E INGREDIENTES A PARTIR DEL DIAGNÓSTICO BASADO EN ENTEROTIPOS (NUTRIBIOTA)
Código de expediente:
0011-1411-2018-000040
Investigador principal:
Fermín Ignacio Milagro Yoldi
Financiador:
GOBIERNO DE NAVARRA
Convocatoria:
2018 GN PROYECTOS ESTRATEGICOS DE I+D 2018-2020
Fecha de inicio:
01/05/2018
Fecha fin:
30/11/2020
Importe concedido:
477.778,14€
Otros fondos:
-
Título:
OBTENCIÓN DE BIOACTIVOS DE APLICACIÓN EN LA PREVENCIÓN DE LA OBESIDAD Y EL SÍNDROME METABÓLICO MEDIANTE FRACCIONAMIENTO BIOGUIADO DE EXTRACTOS NATURALES
Código de expediente:
0011-1383-2018-000005
Investigador principal:
Carlos Javier González Navarro
Financiador:
GOBIERNO DE NAVARRA
Convocatoria:
2018 GN Centros
Fecha de inicio:
01/02/2018
Fecha fin:
30/11/2018
Importe concedido:
86.968,48€
Otros fondos:
-
Título:
Mecanismos por los que la microbiota intestinal previene el riesgo de obesidad: posbióticos y miRNAs de origen microbiano y alimentario
Código de expediente:
RTI2018-102205-B-100
Investigador principal:
José Ignacio Riezu Boj, Fermín Ignacio Milagro Yoldi
Financiador:
MINISTERIO DE CIENCIA, INNOVACIÓN Y UNIVERSIDADES
Convocatoria:
2018 AEI - MCIU - Retos Investigación
Fecha de inicio:
01/01/2019
Fecha fin:
30/09/2022
Importe concedido:
121.000,00€
Otros fondos:
Fondos FEDER