Precision nutrition impact on metabolic health and quality of life in aging population after a 3-month intervention: A randomized intervention.

OBJECTIVES: Innovative precision dietary procedures are required to promote healthy aging. This study aimed to evaluate the effects of a personalised strategy based on the inclusion of individualised foods and digital tools on overall health status and quality of life within a follow-up of 3 months in older adults with overweight or obesity. METHODS: 127 men and women aged between 50 and 80 years with overweight/obesity participated in the study-between January 2020 and September 2020 at the Center for Nutrition Research-University of Navarra and IMDEA-ALIMENTACIÓN-and were randomly assigned to a usual-care group (standard recommendations) or precision group (precision nutrition strategy based on the inclusion of individualised foods and a mobile application). Anthropometry, body fat percentage, biochemical parameters, diet, and quality of life (SF-36 Health Survey) were assessed at baseline and after 3 months. RESULTS: Both strategies were found to improve overall metabolic health; however, the precision approach demonstrated significantly better outcomes. The precision strategy reduced body weight at 3 months (-4.3 kg; p < 0.001) with significant improvements in body fat percentage, blood pressure and general metabolic health (glycated haemoglobin; alanine aminotransferase; aspartate aminotransferase; hepatic steatosis index) in comparison with the standard recommendations. The precision approach significantly enhanced the quality of life (SF-36) of individuals, with additional improvements in emotional well-being (p = 0.024) and vitality (p = 0.008). Adherence to the Mediterranean diet was significantly associated with a higher quality of life and vitality. CONCLUSION: These results support the benefit of precision nutrition approaches for promoting healthy aging and emotional well-being, enhancing the quality of life in aging populations, during the COVID-19 pandemic.

Zein-based nanospheres and nanocapsules for the encapsulation and oral delivery of quercetin.

In this study, the ability of zein nanospheres (NS) and zein nanocapsules containing wheat germ oil (NC) to enhance the bioavailability and efficacy of quercetin was evaluated. Both types of nanocarriers had similar physico-chemical properties, including size (between 230 and 250 nm), spherical shape, negative zeta potential, and surface hydrophobicity. However, NS displayed a higher ability than NC to interact with the intestinal epithelium, as evidenced by an oral biodistribution study in rats. Moreover, both types of nanocarriers offered similar loading efficiencies and release profiles in simulated fluids. In C. elegans, the encapsulation of quercetin in nanospheres (Q-NS) was found to be two twice more effective than the free form of quercetin in reducing lipid accumulation. For nanocapsules, the presence of wheat germ oil significantly increased the storage of lipids in C. elegans; although the incorporation of quercetin (Q-NC) significantly counteracted the presence of the oil. Finally, nanoparticles improved the oral absorption of quercetin in Wistar rats, offering a relative oral bioavailability of 26% and 57% for Q-NS and Q-NC, respectively, compared to a 5% for the control formulation. Overall, the study suggests that zein nanocarriers, particularly nanospheres, could be useful in improving the bioavailability and efficacy of quercetin.

Oral administration of zein-based nanoparticles reduces glycemia and improves glucose tolerance in rats.

The aim was to evaluate the effect of zein-based nanoparticles on the glucose homeostasis, following oral administration to Wistar rats. For this purpose, bare nanoparticles (NP, with tropism for the upper intestinal regions) and poly(ethylene glycol)-coated nanoparticles (NP-PEG), with the capability to reach the ileum and cecum of animals, were evaluated. Both formulations were spherical in shape, displaying sizes around 200 nm and a negative surface zeta potential. The oral administration of a single dose of these nanoparticles to animals (50 mg/kg) induced a significant decrease of the glycemia, compared control rats and in animals treated with the free protein (p < 0.001). Moreover, these nanoparticles improved the glycemic control against an intraperitoneal glucose tolerance test; particularly NP-PEG. These findings would be due to an increased release of glucagon-like peptide-1 (GLP-1) by l-cells, which are more abundant in distal regions of the intestine. In fact, the GLP-1 blood levels of animals treated with nanoparticles were significantly higher than controls (about 40 % and 60 % for NP and NP-PEG groups, respectively). This higher capability of NP-PEG, with respect to NP, to increase the release of GLP-1 and control glycemia would be related to its ability to reach the distal areas of the small intestine.

Possible metabolic interplay between quality of life and fecal microbiota in a presenior population: Preliminary results.

OBJECTIVES: The number of people aged ≥60 y is increasing worldwide, so establishing a relationship between lifestyle and health-associated factors, such as gut microbiota in an older population, is important. This study aimed to characterize the gut microbiota of a presenior population, and analyze the association between some bacteria and quality of life with the Short Form (SF) 36 questionnaire. METHODS: Participants were adult men and women ages 50 to 80 y (n = 74). In addition to the SF-36 questionnaire, fecal samples were collected in cryotubes, and 16S RNA gene sequencing was performed to characterize microbial features. Participants were classified into two groups according to SF-36 punctuation. Linear and logistic regression models were performed to assess the possible association between any bacterial bowl and SF-36 score. Receiver operating characteristics curves were fitted to define the relative diagnostic strength of different bacterial taxa for the correct determination of quality of life. RESULTS: A positive relationship was established between SF-36 score and Actinobacteria (P = 0.0310; R = 0.2510) compared with Peptostreptococcaceae (P = 0.0259; R = -0.2589), which increased with decreasing quality of life. Logistic regressions models and receiver operating characteristics curves showed that the relative abundance of Actinobacteria and Peptostreptococcaceae may be useful to predict quality of life in a presenior population (area under the curve: 0.71). CONCLUSIONS: Quality of life may be associated with the relative abundance of certain bacteria, especially Actinobacteria and Peptostreptococcaceae, which may have a specific effect on certain markers and health care, which is important to improve quality of life in older populations.

Grifola frondosa (Maitake) Extract Reduces Fat Accumulation and Improves Health Span in C. elegans through the DAF-16/FOXO and SKN-1/NRF2 Signalling Pathways.

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.

Both macronutrient food composition and fasting insulin resistance affect postprandial glycemic responses in senior subjects.

INTRODUCTION: Postprandial hyperglycemia is a risk factor for type 2 diabetes. Insulin resistance (IR) might affect metabolic responses in non-fasting states. Dietary intake and food composition influence postprandial glucose homeostasis. The aims of this study were to evaluate the effects of different test foods varying in the macronutrient composition on postprandial glycemic responses and whether these outcomes are conditioned by the basal glycemic status in senior subjects. METHODS: In a randomized, controlled crossover design, thirty-four adults consumed a test food, a high protein product (n = 19) or a high carbohydrate (CHO) product (n = 15), using the oral glucose tolerance test (OGTT) as a reference. Blood glucose and insulin were measured at fasting and at 15, 30, 45, 60, 90, and 120 min after starting the food intake. For each type of food, the incremental area under the curve (iAUC) for glucose and insulin was calculated. IR was measured using the Homeostatic Model Assessment of IR (HOMA-IR). RESULTS: Consumption of a high protein product significantly lowered the peak and Δ blood glucose concentrations compared to the high CHO product (p < 0.001). Concerning the insulin response, no significant differences between both foods were observed. Fasting glucose was positively correlated with the glucose iAUC only for the high protein product. Positive associations of both fasting insulin and HOMA-IR with the insulin iAUC for all the cases were observed. Linear regression models showed significant positive associations between the glucose iAUC and fasting glucose after adjusting for age and sex. Regarding the insulin iAUC, positive associations were found with fasting insulin and HOMA-IR. Regression models also evidenced that both food test consumptions were able to decrease the glucose and insulin iAUC values when compared with the OGTT product. CONCLUSION: Our research found that not only is the nutritional composition of foods important, but also the baseline glycemic state of individuals when assessing glycemic index estimations and addressing precision nutritional strategies to prevent and treat IR-associated disturbances.

In vivo testing of mucus-permeating nanoparticles for oral insulin delivery using Caenorhabditis elegans as a model under hyperglycemic conditions.

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-NPs) was found to be 20-fold higher than bare nanoparticles (NPs). These results were in line with the biodistribution study in rats, in which NPs remained trapped in the mucus, whereas PPA-NPs 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-NPs displayed a longer lifespan than those treated with insulin free or nanoencapsulated in NPs. This finding was associated with a significant reduction in the formation of reactive oxygen species (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-NPs that would facilitate the passage through the intestinal peritrophic-like dense layer of worms (similar to mucus) and, thus, the absorption of insulin.

Zein Nanoparticles Improve the Oral Bioavailability of Curcumin in Wistar Rats.

Curcumin is a natural compound obtained from turmeric root with high antioxidant and anti-inflammatory activities. However, clinical application of curcumin has been limited due to its low solubility and bioavailability and rapid metabolism and degradation. This study was conducted to evaluate the effect of curcumin incorporation in zein nanoparticles on the pharmacokinetic parameters of systemic curcumin in plasma. Wistar rats were administered a single oral dose of 250 mg/kg of standard curcumin (control) or nanocurcumin (zein-based nanoparticles, Nucaps). The proposed new formulation was also compared with two commercially available curcumin complexes. Blood samples were collected at different times, and plasma levels were determined using HPLC-MS/MS. Overall, nanocurcumin (Nucaps) formulation was well tolerated and showed a 9-fold increase in oral bioavailability when compared to the standard curcumin natural extract. In addition, the nanoparticles prepared in this study demonstrated a bioavailability profile superior to that of other bioavailability-enhanced curcumin complexes currently available in the marketplace. Thus, our nanoparticle-based formulation has shown great potential as a nutraceutical for the oral administration of curcumin.

Zein-based nanocarriers for the oral delivery of insulin. In vivo evaluation in Caenorhabditis elegans.

The aim was to evaluate the potential of nanocarriers, based on the coating of zein nanoparticles (ZNP) with a Gantrez® AN-PEG conjugate (GP), for the oral delivery of insulin. ZNP-GP displayed less negative surface charge and a 14-fold higher diffusion coefficient in pig intestinal mucus than ZNP. Both nanoparticles showed a spherical shape and an insulin load of 77.5 µg/mg. Under simulated gastric conditions, ZNP-GP released significantly lower amount of insulin than ZNP, while under simulated intestinal conditions, both types of nanoparticles displayed similar behaviour. In Caenorhabditis elegans wild-type N2, grown under high glucose conditions, insulin treatments reduced glucose and fat accumulation without altering the growth rate, the worm length, or the pumping rate. The effect was significantly greater (p < 0.001) when insulin was nanoencapsulated in ZNP-GP compared with that encapsulated in ZNP or formulated in solution. This would be related to the highest capability of ZNP-GP to diffuse in the dense peritrophic-like layer covering intestinal cells in worms. In daf-2 mutants, the effect on fat and glucose reduction by insulin treatment was suppressed, indicating a DAF-2 dependent mechanism. In summary, ZNP-GP is a promising platform that may offer new opportunities for the oral delivery of insulin and other therapeutic proteins.

Zein-Based Nanoparticles as Oral Carriers for Insulin Delivery.

Zein, the major storage protein from corn, has a GRAS (Generally Regarded as Safe) status and may be easily transformed into nanoparticles, offering significant payloads for protein materials without affecting their stability. In this work, the capability of bare zein nanoparticles (mucoadhesive) and nanoparticles coated with poly(ethylene glycol) (mucus-permeating) was evaluated as oral carriers of insulin (I-NP and I-NP-PEG, respectively). Both nanocarriers displayed sizes of around 270 nm, insulin payloads close to 80 µg/mg and did not induce cytotoxic effects in Caco-2 and HT29-MTX cell lines. In Caenorhabditis elegans, where insulin decreases fat storage, I-NP-PEG induced a higher reduction in the fat content than I-NP and slightly lower than the control (Orlistat). In diabetic rats, nanoparticles induced a potent hypoglycemic effect and achieved an oral bioavailability of 4.2% for I-NP and 10.2% for I-NP-PEG. This superior effect observed for I-NP-PEG would be related to their capability to diffuse through the mucus layer and reach the surface of enterocytes (where insulin would be released), whereas the mucoadhesive I-NP would remain trapped in the mucus, far away from the absorptive epithelium. In summary, PEG-coated zein nanoparticles may be an interesting device for the effective delivery of proteins through the oral route.

Phenolic Compounds Reduce the Fat Content in Caenorhabditis elegans by Affecting Lipogenesis, Lipolysis, and Different Stress Responses.

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 aging, 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, aging, 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.

A combination of borage seed oil and quercetin reduces fat accumulation and improves insulin sensitivity in obese rats.

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.

Casein nanoparticles in combination with 2-hydroxypropyl-ß-cyclodextrin improves the oral bioavailability of quercetin.

The aim of this work was to optimize the preparative process of quercetin loaded casein nanoparticles as well as to evaluate the pharmacokinetics of this flavonoid when administered orally in Wistar rats. Nanoparticles were obtained by coacervation after the incubation of casein, 2-hydroxypropyl-ß-cyclodextrin (HP-ß-CD) and quercetin in an aqueous environment. Then, nanoparticles were purified and dried. The resulting nanoparticles displayed a size of 200 nm with a negative zeta potential and a payload of about 32 µg/mg. Release studies showed a zero-order kinetic, suggesting a mechanism based on erosion of the nanoparticle matrix. For the pharmacokinetic study, quercetin was orally administered to rats as a single dose of 25 mg/kg. Animals treated with quercetin-loaded casein nanoparticles displayed higher plasma levels than those observed in animals receiving the solution of the flavonoid (control). Thus, the relative oral bioavailability of quercetin when administered as casein nanoparticles (close to 37%) was found to be about 9-times higher than the oral solution of the flavonoid in a mixture of PEG 400 and water. In summary, the combination of casein and 2-hydroxypropyl-ß-cyclodextrin produces nanoparticles that may be a good option to load quercetin for both nutraceutical and pharmaceutical purposes.

Low doses of cocoa extract supplementation ameliorate diet-induced obesity and insulin resistance in rats.

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.

Increased Oral Bioavailability of Resveratrol by Its Encapsulation in Casein Nanoparticles.

Resveratrol is a naturally occurring polyphenol that provides several health benefits including cardioprotection and cancer prevention. However, its biological activity is limited by a poor bioavailability when taken orally. The aim of this work was to evaluate the capability of casein nanoparticles as oral carriers for resveratrol. Nanoparticles were prepared by a coacervation process, purified and dried by spray-drying. The mean size of nanoparticles was around 200 nm with a resveratrol payload close to 30 µg/mg nanoparticle. In vitro studies demonstrated that the resveratrol release from casein nanoparticles was not affected by the pH conditions and followed a zero-order kinetic. When nanoparticles were administered orally to rats, they remained within the gut, displaying an important capability to reach the intestinal epithelium. No evidence of nanoparticle "translocation" were observed. The resveratrol plasma levels were high and sustained for at least 8 h with a similar profile to that observed for the presence of the major metabolite in plasma. The oral bioavailability of resveratrol when loaded in casein nanoparticles was calculated to be 26.5%, 10 times higher than when the polyphenol was administered as oral solution. Finally, a good correlation between in vitro and in vivo data was observed.

Borago officinalis seed oil (BSO), a natural source of omega-6 fatty acids, attenuates fat accumulation by activating peroxisomal beta-oxidation both in C. elegans and in diet-induced obese rats.

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 ß-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 ß-oxidation. The supplementation with BSO significantly reduces body weight gain and energy efficiency and prevents white adipose tissue accumulation without affecting food intake. Moreover, BSO also increases serum HDL-cholesterol levels, improves insulin resistance and promotes the down-regulation of Cebpa, an adipogenesis-related gene. Therefore, we conclude that the effects of omega-6 fatty acids are highly conserved between worms and obesity-induced mammals, so these compounds could be considered to treat or prevent obesity-related disorders.

Untargeted metabolomic on urine samples after α-lipoic acid and/or eicosapentaenoic acid supplementation in healthy overweight/obese women.

BACKGROUND: Eicosapentaenoic acid (EPA) and α-lipoic acid (α-LA) have been investigated for their beneficial effects on obesity and cardiovascular risk factors. In the current research, the goal was to evaluate metabolomic changes following the dietary supplementation of these two lipids, alone or combined in healthy overweight/obese sedentary women following an energy-restricted diet. For this purpose, an untargeted metabolomics approach was conducted on urine samples using liquid chromatography coupled with time of flight mass spectrometry (HPLC-TOF-MS). METHODS: This is a short-term double blind placebo-controlled study with a parallel nutritional design that lasted 10 weeks. Participants were assigned to one of the 4 experimental groups [Control, EPA (1.3 g/d), α-LA (0.3 g/d) and EPA+α-LA (1.3 g/d + 0.3 g/d)]. All intervention groups followed an energy-restricted diet of 30% less than total energy expenditure. Clinically relevant biochemical measurements were analyzed. Urine samples (24 h) were collected at baseline and after 10 weeks. Untargeted metabolomic analysis on urine samples was carried out, and principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) were performed for the pattern recognition and characteristic metabolites identification. RESULTS: Urine samples were scattered in the PCA scores plots in response to the supplementation with α-LA. Totally, 28 putative discriminant metabolites in positive ionization, and 6 in negative ionization were identified among groups clearly differentiated according to the α-LA administration. Remarkably is the presence of an ascorbate intermediate metabolite (one of the isomers of trihydroxy-dioxohexanoate, or dihydroxy-oxohexanedionate) in the groups supplemented with α-LA. This fact might be associated with antioxidant properties of both α-LA and ascorbic acid. Correlations between phenotypical parameters and putative metabolites of provided additional information on whether there is a direct or inverse relationship between them. Especially interesting are the negative correlation between ascorbate intermediate metabolite and asymmetric dimethylarginine (ADMA) and the positive one between superoxide dismutase (SOD) and α-LA supplementation. CONCLUSIONS: This metabolomic approach supports that the beneficial effects of α-LA administration on body weight reduction may be partly explained by the antioxidant properties of this organosulfur carboxylic acid mediated by isomers of trihydroxy-dioxohexanoate, or dihydroxy-oxohexanedionate. TRIAL REGISTRATION: Clinicaltrials.gov NCT01138774 .

Dihomo-gamma-linolenic acid induces fat loss in C. elegans in an omega-3-independent manner by promoting peroxisomal fatty acid ß-oxidation.

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.

Coencapsulation of cyclodextrins into poly(anhydride) nanoparticles to improve the oral administration of glibenclamide. A screening on C. elegans.

This work describes the feasibility of poly(anhydride) nanoparticles as carriers for the oral administration of glibenclamide (GB) as well as the in vivo evaluation of their hypolipidemic effect in a C. elegans model. For this purpose, and in order to increase the GB payload, the drug was encapsulated in nanoparticles in presence of cyclodextrins (either ßCD or HPßCD). The optimized nanoparticles displayed a size of about 220 nm and a negative zeta potential (-40 mV), with a drug loading up to 52 µg/mg. Small-angle neutron scattering studies suggested an internal fractal-like structure, based on the repetition of spherical blocks of polymeric units (about 5 nm) grouped to form the nanoparticle. X-ray diffraction study confirmed the absence of crystalline GB molecules due to its dispersion into the nanoparticles, either entrapped in the polymer chains and/or included into cyclodextrin cavities. GB-loaded nanoparticles induced a significant reduction in the fat content of C. elegans. This hypolipidemic effect was slightly higher for the nanoparticles prepared with coencapsulated HPßCD (8.2%) than for those prepared with ßCD (7.9%) or in the absence of cyclodextrins (7.0%). In summary, the coencapsulation of cyclodextrins into poly(anhydride) nanoparticles could be an interesting strategy to develop new oral formulations of glibenclamide.

Freeze-dried strawberry and blueberry attenuates diet-induced obesity and insulin resistance in rats by inhibiting adipogenesis and lipogenesis.

Obesity and type 2-diabetes are becoming a worldwide health problem, reiterating 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 on 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 an 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 of resveratrol-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.