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The Mediterranean diet is a dietary pattern typical of the populations living in the Mediterranean basin during the 50s-60s of the last century. This diet has demonstrated beneficial effects in the prevention of several pathologies such as cardiovascular diseases, metabolic syndrome, or several cancer types, at least in part, due to its antioxidant compounds. Since the COVID-19 pandemic started, different authors have been studying the effects of certain dietary habits on the presence of COVID-19 and its severity, and the Mediterranean diet is one of them. This review gathers data from studies supporting the potential usefulness of the main phenolic compounds present in the Mediterranean diet, based on their antioxidant and anti-inflammatory effects, as preventive/therapeutic agents against COVID-19. The current evidence supports the potential benefits that hydroxytyrosol, resveratrol, flavonols such as quercetin, flavanols like catechins, and flavanones on the order of naringenin could have on COVID-19. This is due to the increase in the synthesis and translocations of Nrf-2, which increases the activity of antioxidant enzymes and thus reduces ROS production, the scavenging of free radicals, and the suppression of the activity of MMP-9, which is involved in the cytokine storm, and the inhibition of NF-κB.

Background: The molecular mechanisms underlying the potential health benefits of a ketogenic diet are unknown and could be mediated by epigenetic mechanisms. Objective: To identify the changes in the obesity-related methylome that are mediated by the induced weight loss or are dependent on ketosis in subjects with obesity underwent a very-low calorie ketogenic diet (VLCKD). Methods: Twenty-one patients with obesity (n ¼ 12 women, 47.9 ± 1.02 yr, 33.0 ± 0.2 kg/m2 ) after 6 months on a VLCKD and 12 normal weight volunteers (n ¼ 6 women, 50.3 ± 6.2 yrs, 22.7 ± 1.5 kg/m2 ) were studied. Data from the Infinium MethylationEPIC BeadChip methylomes of blood leukocytes were obtained at time points of ketotic phases (basal, maximum ketosis, and out of ketosis) during VLCKD (n ¼ 10) and at baseline in volunteers (n ¼ 12). Results were further validated by pyrosequencing in representative cohort of patients on a VLCKD (n ¼ 18) and correlated with gene expression. Results: After weight reduction by VLCKD, differences were found at 988 CpG sites (786 unique genes). The VLCKD altered methylation levels in patients with obesity had high resemblance with those from normal weight volunteers and was concomitant with a downregulation of DNA methyltransferases (DNMT)1, 3a and 3b. Most of the encoded genes were involved in metabolic processes, protein metabolism, and muscle, organ, and skeletal system development. Novel genes representing the top scoring associated events were identified, including ZNF331, FGFRL1 (VLCKD-induced weight loss) and CBFA2T3, C3orf38, JSRP1, and LRFN4 (VLCKD-induced ketosis). Interestingly, ZNF331 and FGFRL1 were validated in an independent cohort and inversely correlated with gene expression. Conclusions: The beneficial effects of VLCKD therapy on obesity involve a methylome more suggestive of normal weight that could be mainly mediated by the VLCKD-induced ketosis rather than weight loss. This work was supported by the PronoKal Group® and grants from the Fondo de Investigacion Sanitaria as well as PI17/01287, PI20/00628 and PI20/00650 research projects and CIBERobn from the Instituto de Salud Carlos III (ISCIII)-Subdireccion General de Evaluacion y Fomento de la Investigación; Fondo Europeo de Desarrollo Regional (FEDER) Ana B Crujeiras is funded by a research contract “Miguel Servet” (CP17/00088) from the ISCIII, co-financed by the European Regional Development Fund (FEDER) and Xunta de Galicia-GAIN (IN607B2020). The funding source had no involvement in the study design or interpretation of the results

BACKGROUND/OBJECTIVES: Survivin is an oncogene associated with a decrease in apoptosis, an increase in tumor growth, and poor clinical outcome of diverse malignancies. A correlation between obesity, cancer, and survivin is reported in the literature. To date, the impact of weight loss on change in survivin levels is understudied. This study was aimed at: (1) comparing survivin levels in adipose tissue (AT) from lean and obese animal models and evaluating changes after weight loss induced by energy restriction and/or exercise; (2) comparing survivin levels in normal weighted and obese humans and evaluating changes in survivin levels after weight loss induced by a very-low-calorie ketogenic diet (VLCKD) or bariatric surgery in AT and/or blood leukocytes (PBL/PBMCs). SUBJECTS/METHODS: Survivin expression was evaluated in subcutaneous (SAT) and visceral (VAT) AT derived from animal models of monogenic (Zucker rats) and diet-induced obesity (Sprague Dawley rats and C57BL/6J mice) and after a 4-week weight-loss protocol of energy restriction and/or exercise. Plasma was used to measure the inflammatory status. Survivin expression was also evaluated in PBMCs from patients with obesity and compared with normal weight, in PBLs after VLCKD, and in SAT and/or PBLs after bariatric surgery. RESULTS: Survivin expression was specifically higher in VAT from obese that lean animals, without differences in SAT. It decreased after weight loss induced by energy restriction and correlated with adiposity and inflammatory markers. In humans, the correlation between being obese and higher levels of survivin was confirmed. In obese subjects, survivin levels were reduced following weight loss after either VLCKD or bariatric surgery. Particularly, a decrease in PBMCs expression (not in SAT one) was found after surgery. CONCLUSIONS: Weight loss is effective in decreasing survivin levels. Also, PBL/PBMC should be regarded as appropriate mirror of survivin levels in VAT for the identification of an obesity-related protumoral microenvironment.

Infants born small for gestational age (SGA) are known to have increased risk of developing several pathologies, including the metabolic syndrome, when they grow up. It has been described that both the growth pattern of these children as well as the risk of their presenting future metabolic disorders can be influenced by the expression of adipokines. Among them, chemerin has demonstrated to be implicated in lipid and glucose metabolism, presenting higher circulating concentration in diabetic and obese subjects. Thus, the aim of this study was to analyze the association of anthropometric parameters and plasmatic biochemical parameters with circulating chemerin concentration in SGA children. This prospective, longitudinal study was carried out in plasma samples of Caucasian children born SGA at Hospital Universitario de Álava-Txagorritxu. Significant positive correlations were observed between chemerin concentrations at 3 months and insulin values at 3 months and also with triglyceride levels at 24 months. These associations were maintained after adjustment by anthropometric parameters. Therefore, we suggest that circulating chemerin concentration, measured at an early age, might be an indicator of future metabolic alterations in SGA children.

The main function of brown adipose tissue (BAT) is thermogenesis, a process mediated by uncoupling protein 1 (UCP1), which is located in the inner mitochondrial membrane and acts uncoupling oxidative phosphorylation from ATP production, thereby dissipating energy as heat. White adipose tissue can also express UCP1 positive cells due to a process known as browning. This phenomenon could also increase the thermogenic effect in the classical brown adipose depots. BAT thermogenesis depends, among other factors on both, nutritional conditions and food availability. Indeed, some studies have found that BAT recruitment and function are enhanced by some food components. The present study focuses on the effects of resveratrol and pterostilbene, two phenolic compounds belonging to the stilbene group, on BAT thermogenic activation and white adipose tissue browning process. The reported studies, carried out in cell cultures and animal models, show that both resveratrol and pterostilbene induce thermogenic capacity in interscapular BAT by increasing mitochondriogenesis, as well as enhancing fatty acid oxidation and glucose disposal. In addition, resveratrol seems to promote browning by activating peroxisome proliferator-activated receptor (PPAR), while the lack of changes in mitochondrial biogenesis suggests that probably the browning process occurs by direct resveratrol-mediated upregulation of ucp1 mRNA expression.

El objetivo de este trabajo es dar a conocer el origen y la trayectoria del equipo docente estructurado IKAsasun (edIKDit-18-2, equipo docente para la Enseñanza Multidisciplinar Biosanitaria). El equipo está compuesto por personal docente investigador adscrito a los Campus de Leioa (Facultad de Medicina y Enfermería) y de Vitoria-Gasteiz (Facultad de Farmacia) de la Universidad del País Vasco/Euskal Herriko Unibertsitatea (UPV/EHU). La docencia que se imparte comprende a distintas disciplinas de Grados mayoritariamente relacionados con las Ciencias de la Salud (Enfermería, Farmacia, Fisioterapia, Medicina, Nutrición Humana y Dietética, Odontología, Ciencia y Tecnología de los Alimentos y Ciencias Ambientales). Desde el inicio de la andadura como equipo docente en el año 2015, el grupo ha participado en dos Proyectos de Innovación Educativa (PIE) subvencionados por la UPV/EHU (PIE nº 40 y nº 96). Estos proyectos están dirigidos a ayudar al alumnado a desarrollar, de una manera eficaz, las competencias específicas y transversales propias de cada Grado y a conseguir que se involucren en su propio aprendizaje. En ambos proyectos se ha incidido en la importancia de trabajar en equipos multidisciplinares, apostando por la utilización de metodologías de aprendizaje activo. En el primero de ellos (PIE nº 40; 2015-2017), se planteó la participación activa del alumnado en la resolución de casos clínicos complejos que requieren un abordaje multidisciplinar para garantizar la asistencia integral al paciente. En el segundo proyecto (PIE nº 96; 2018-2020), se llevó a cabo un abordaje multidisciplinar de temas relacionados con la salud biomédica y científica desde distintos Grados, y posterior divulgación enfocada a diferentes sectores de la sociedad. Los resultados obtenidos tras el desarrollo de ambos proyectos han sido muy alentadores, y alumnado, profesorado y personas externas colaboradoras han valorado muy positivamente la experiencia, que ha quedado reflejada en varias publicaciones y comunicaciones a congresos. The aim of this work is to provide an insight into the origin and background of the IKAsasun structured teaching team (edIKDit-18-2, teaching team for Multidisciplinary Biosanitary Education). Team is formed by an interdisciplinary group of teachers and researchers that belongs to the Campuses of Leioa (Faculty of Medicine and Nursing) and Vitoria-Gasteiz (Faculty of Pharmacy) of the University of the Basque Country (UPV/EHU). The teaching activity of the group covers different disciplines of the Degrees mostly related to Health Sciences (Nursing, Pharmacy, Physiotherapy, Medicine, Human Nutrition and Dietetics, Dentistry, Environmental Sciences and Food Sciences and Technology). Since the beginning of the journey as a teaching team in 2015, the group has participated in two educational innovation projects (PIE) funded by the UPV/EHU (PIE no. 40 and 96) aimed at helping students to effectively develop the specific and transversal competences of each degree, and to get them involved in their own learning. Theseprojects have emphasized the importance of working in multidisciplinary teams, promoting the implementation of active learning methodologies. In the first project (2015-2017), we proposed the resolution of complex clinical cases that require a multidisciplinary approach to ensure integral patient care. In the second one (2018-2020), we proposed a multidisciplinary approach to issues related to biomedical and scientific health from different Degrees, and their subsequent dissemination focusing on different sectors of society. The results obtained after the development of both projects have been very encouraging and both students, teaching staff and external collaborators have valued the experience very positively, which has been reflected in several publications and communications to conferences.

The epidemiological evidence regarding the association of obesity with liver disease and possibly hepatocellular carcinoma highlights the need for investigations of whether obesity itself could induce the differential expression of genes commonly associated with the initial phase of liver tumorigenesis, and whether such phenomenon could be reversed after a weight loss intervention. In this study, obese Zucker rats were found to have dysregulated cell proliferation, antioxidative defenses, and tumor suppressor gene expression in association with liver dysfunction parameters, as well as oxidative stress and inflammation. Importantly, after a 4-week weight loss protocol of energy restriction and/or exercise, this effect on the liver carcinogenesis-related genes was reversed concomitantly with reductions in the fat mass, hepatic lipid content, oxidative stress, and inflammation. The findings indicate that the oxidative stress and inflammation associated with excess adiposity promote dysregulation of the genes involved in liver tumorigenesis. This is clinically relevant because these effects were detectable in the liver without evidence of a tumoral mass and were reversed after weight loss. Consequently, this study reveals the susceptibility of obese individuals to the initiation of a hepatocarcinogenic process, and how this can be prevented by achieving a healthy body weight.

Infants born small for gestational age (SGA) are at increased risk of perinatal morbidity, persistent short stature, and metabolic alterations in later life. Moreover, the post-natal growth pattern of SGA infants may be an important contributor to health outcomes later in life, which can be influenced by adipokines. The aims of this study were to compare plasma adipokine profiles (leptin, adiponectin, vaspin, chemerin, and nephroblastoma overexpressed (NOV/CCN3)) among SGA newborns aged 3 months, with low, normal, or high catch-up, to search for potential differences between males and females and to analyze the evolution of several adipokines in plasma from SGA newborns between 3 and 24 months. This prospective, longitudinal study was addressed in SGA Caucasian subjects at Hospital Universitario de Alava-Txagorritxu. We observed that infants with fast catch-up showed significantly lower birth weight than the other two groups. As far as adipokines are concerned, they could have an influence on catch-up type because differences among the three experimental groups were found. It may be proposed that health prognoses in infants with slow and fast catch-up are opposite, not only in adulthood but also during their first months. Finally, adipokine evolution patterns during the first 24 months of age differ, depending on the adipokine, and 24-month-old males show lower levels of leptin, adiponectin, and omentin than females.

Nephroblastoma overexpressed protein, also called NOV/CCN3, is an adipokine which is present in various tissues and recently linked to obesity. The objective of the study was to determine the effect of resveratrol and pterostilbene on NOV/CCN3 in adipose tissue from rats fed an obesogenic diet. Thirty-six male Wistar rats were split into four groups (n = 9): fed a standard diet (CC), high-fat high-sucrose (HFS) diet supplemented with resveratrol (RSV; 30 mg/kg/day) or with pterostilbene (PT; 30 mg/kg/day), or without phenolic supplementation (HFS). Rats were sacrificed after 6 weeks of treatment, and adipose tissue (white and brown) from different anatomical locations were dissected. Then, Nov/ccn3 gene and protein expression and the adipogenic genes, Ucp-1 and Pgc-1a, expressions were studied. Increased weight of white adipose tissues was found in rats fed the HFS diet. Whereas resveratrol-treated rats showed reduced internal and total adipose tissue weights, pterostilbene-treated rats showed reduced subcutaneous, internal and total adipose depots. Nov/ccn3 gene expression decreased in epididymal and interscapular brown depot in rats fed HFS diet when compared with the control group. Regarding the phenolic compounds, resveratrol prompted a Nov/ccn3 gene expression increase in epididymal fat tissue, whereas pterostilbene reduced its protein expression compared with the obese group. However, these phenolic compounds did not affect NOV/CCN3 expression in brown depot. NOV/CCN3 seems to be involved in weight changes in epididymal adipose tissue under obesogenic feeding, but not in subcutaneous, acting as a protective mechanism counteracting the fattening effect of the diet. To our knowledge, this is the first study analyzing whether NOV/CCN3 is involved in the anti-obesity effect of resveratrol and pterostilbene. Our results suggest that this is not the case.

Resveratrol and its 2-methoxy derivative pterostilbene are two phenolic compounds that occur in foodstuffs and feature hepato-protective effects. This study is devoted to analysing and comparing the metabolic effects of pterostilbene and resveratrol on gut microbiota composition in rats displaying NAFLD induced by a diet rich in saturated fat and fructose. The associations among changes induced by both phenolic compounds in liver status and those induced in gut microbiota composition were also analysed. For this purpose, fifty Wistar rats were distributed in five experimental groups: a group of animals fed a standard diet (CC group) and four additional groups fed a high-fat high-fructose diet alone (HFHF group) or supplemented with 15 or 30 mg/kg bw/d of pterostilbene (PT15 and PT30 groups, respectively) or 30 mg/kg bw/d of resveratrol (RSV30 group). The dramatic changes induced by high-fat high-fructose feeding in the gut microbiota were poorly ameliorated by pterostilbene or resveratrol. These results suggest that the specific changes in microbiota composition induced by pterostilbene (increased abundances of Akkermansia and Erysipelatoclostridium, and lowered abundance of Clostridum sensu stricto 1) may not entirely explain the putative preventive effects on steatohepatitis. This research was funded by Ministerio de Economía y Competitividad-Fondo Europeo de Desarrollo Regional (grant number AGL-2015-65719-R MINECO/FEDER, UE), Instituto de Salud Carlos III CIBERobn (grant number CB12/03/30007); University of the Basque Country (grant number GIU 18/173).

The use of phenolic compounds as a new therapeutic approach against NAFLD has emerged recently. In the present study, we aim to study the effect of pterostilbene in the prevention of liver steatosis developed as a consequence of high-fat (saturated) high-fructose feeding, by analysing the changes induced in metabolic pathways involved in triglyceride accumulation. Interestingly, a comparison with the anti-steatotic effect of its parent compound resveratrol will be made for the first time. Rats were distributed into 5 experimental groups and fed either a standard laboratory diet or a high-fat high-fructose diet supplemented with or without pterostilbene (15 or 30 mg per kg per d) or resveratrol (30 mg per kg per d) for 8 weeks. Serum triglyceride, cholesterol, NEFA and transaminase levels were quantified. Liver histological analysis was carried out by haematoxylin-eosin staining. Different pathways involved in liver triglyceride metabolism, including fatty acid synthesis, uptake and oxidation, triglyceride assembly and triglyceride release, were studied. Pterostilbene was shown to partially prevent high-fat high-fructose feeding induced liver steatosis in rats, demonstrating a dose-response pattern. In this dietary model, it acts mainly by reducing de novo lipogenesis and increasing triglyceride assembly and release. Improvement in mitochondrial functionality was also appreciated. At the same dose, the magnitude of pterostilbene and resveratrol induced effects, as well as the involved mechanisms of action, were similar.

This article belongs to the Special Issue Food Bioactive Compounds as Functional Ingredient., MicroRNAs (miRNAs) represent important tools in medicine and nutrition as new biomarkers, and can act as mediators of nutritional and pharmacological interventions. The aim of the present study was to analyse the effect of grape pomace supplementation on the expression of seven selected miRNAs and their potential relationship with the observed positive effect on glycaemic control, in order to shed light on the mechanism underlying the beneficial effect of this dietary intervention. For this purpose, plasma samples were obtained from 49 subjects with metabolic syndrome. After supplementation with grape pomace (6 weeks), these subjects were categorised as responders (n = 23) or non-responders (n = 26) according to the changes in their fasting insulin rate. MiRNA expression at baseline and at the end of the supplementation was analysed by RT-PCR, and the MiRecords Database was used to identify potential target genes for the studied miRNAs. The increase observed in miR-23a in the whole cohort was present in both subgroups of participants. The increase in miR-181a was significant among non-responders but not responders. The decrease in miR-30c and miR-222 was found in the responders, but not in the non-responders. No changes were observed in miR-10a, miR-151a, miR-181a, and miR-let-7a expressions. After analysing these results, a potential involvement of the reduced expression of miR-30c and miR-222, two microRNAs associated with insulin resistance and diabetes, in the improvement of glycaemic control produced by grape pomace administration, can be proposed. Further research is needed to confirm the involvement of glycolytic enzymes, PI3K, AMPK, and IRS-1 in the effect of grape pomace, as suggested by the changes induced in microRNAs., This research was funded by the Spanish Ministry of Economy and Competitiveness (MINECO-FEDER), grant number AGL2014-55102-JIN and AGL2017-83599-R; University of the Basque Country, grant number GIU18-173) and Carlos III Research Institute (CIBERobn).

[Scope]: Dietary polyphenols have shown promising effects in mechanistic and preclinical studies on the regulation of cardiometabolic alterations. Nevertheless, clinical trials have provided contradictory results, with high inter-individual variability. This study explores the role of gut microbiota and microRNAs (miRNAs) as factors contributing to the inter-individual variability in polyphenol response., [Methods and Results]: 49 subjects with at least two factors of metabolic syndrome are divided between responders (n = 23) or non-responders (n = 26), depending on the variation rate in fasting insulin after grape pomace supplementation (6 weeks). The populations of selected fecal bacteria are estimated from fecal deoxyribonucleic acid (DNA) by quantitative real-time polymerase chain reaction (qPCR), while the microbial-derived short-chain fatty acids (SCFAs) are measured in fecal samples by gas chromatography. MicroRNAs are analyzed on a representative sample, followed by targeted miRNA analysis. Responder subjects show significantly lower (p < 0.05) Prevotella and Firmicutes levels, and increased (p < 0.05) miR-222 levels., [Conclusion]: After evaluating the selected substrates for Prevotella and target genes of miR-222, these variations suggest that responders are those subjects exhibiting impaired glycaemic control. This study shows that fecal microbiota and miRNA expression may be related to inter-individual variability in clinical trials with polyphenols., This study was funded by the Spanish Ministry of Economy and Competitiveness (MINNECO-FEDER, grants AGL2014-55102-JIN and AGL2017-83599-R, and graduate fellowship to M.H.: BES2014-068592) University of the Basque Country, grant: GIU18-173 and Carlos III Research Institute (CIBERobn).

Isoflavones are phenolic compounds with a chemical structure similar to that of estradiol. They are present in several vegetables, mainly in legumes such as soy, white and red clover, alfalfa and beans. The most significant food source of isoflavones in humans is soy-derived products. Isoflavones could be used as an alternative therapy for pathologies dependent on hormonal disorders such as breast and prostate cancer, cardiovascular diseases, as well as to minimize menopausal symptoms. According to the results gathered in the present review, it can be stated that there is scientific evidence showing the beneficial effect of isoflavones on bone health and thus in the prevention and treatment of osteoporosis on postmenopausal women, although the results do not seem entirely conclusive as there are discrepancies among the studies, probably related to their experimental designs. For this reason, the results should be interpreted with caution, and more randomized clinical trials are required. By contrast, it seems that soy isoflavones do not lead to a meaningful protective effect on cardiovascular risk. Regarding cancer, scientific evidence suggests that isoflavones could be useful in reducing the risk of suffering some types of cancer, such as breast and endometrial cancer, but further studies are needed to confirm these results. Finally, isoflavones could be useful in reducing hot flushes associated with menopause. However, a limitation in this field is that there is still a great heterogeneity among studies. Lastly, with regard to isoflavone consumption safety, it seems that they are safe and that the most common adverse effect is mild and occurs at the gastrointestinal level. This study was supported by Instituto de Salud Carlos III (CIBERobn) under Grant CB12/03/30007, Basque Government under Grant PA20/04 and the University of the Basque Country under Grant GIU18-173

This review deals with the relationship among nutrition, the immune system, and coronavirus disease 2019 (COVID-19). The influence of nutrients and bioactive molecules present in foodstuffs on immune system activity, the influence of COVID-19 on the nutritional status of the patients, and the dietary recommendations for hospitalized patients are addressed. Deficient nutritional status is probably due to anorexia, nausea, vomiting, diarrhea, hypoalbuminemia, hypermetabolism, and excessive nitrogen loss. There is limited knowledge regarding the nutritional support during hospital stay of COVID-19 patients. However, nutritional therapy appears as first-line treatment and should be implemented into standard practice. Optimal intake of all nutrients, mainly those playing crucial roles in immune system, should be assured through a diverse and well-balanced diet. Nevertheless, in order to reduce the risk and consequences of infections, the intakes for some micronutrients may exceed the recommended dietary allowances since infections and other stressors can reduce micronutrient status. In the case of critically ill patients, recently published guidelines are available for their nutritional management. Further, several natural bioactive compounds interact with the angiotensin-converting enzyme 2 (ACE2) receptor, the gateway for severe acute respiratory syndrome (SARS) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Natural bioactive compounds can also reduce the inflammatory response induced by SARS-CoV-2. These compounds are potential beneficial tools in the nutritional management of COVID-19 patients. This research was supported by Instituto de Salud Carlos III (CIBERobn) and University of the Basque Country (GIU18-173).

Macroalgae have attracted great interest for their potential applications in nutraceutical and pharmaceutical industries as source of bioactive medicinal products and food ingredients. This review gathers data from in vitro and in vivo studies addressing the anti-obesity effects of macroalgae. Great consensus exists in all reported in vitro studies concerning the reduction induced by seaweed extracts in the expression of transcriptional factors controlling adipogenesis. In animals, macroalgae reduced body fat accumulation and prevented other obesity features, such as dyslipidemia, insulin resistance and fatty liver. These effects are not due to food intake reduction, since few studies have reported such event. Indeed, the effects on metabolic pathways in target tissues/organs seem to play a more relevant role. Macroalgae can reduce de novo lipogenesis, limiting fatty acid availability for triglyceride synthesis in white adipose tissue. This effect has been observed in both cell cultures and adipose tissue from animals treated with macroalgae extracts. In addition, increased fatty acid oxidation and thermogenic capacity, as well as a shift towards healthier gut microbiota composition may contribute to the body fat-lowering effect of macroalgae. Studies in humans are needed to determine whether macroalgae can represent a feasible tool to prevent and/or manage overweight and obesity. This study has been supported by grants from the Government of the Basque Country (ELKARTEK) under grant KK-2019/00031, Instituto de Salud Carlos III (CIBERobn) under Grant CB12/03/30007 and University of the Basque Country under Grant GIU18-173. M.G.-A. is a fellow from the University of the Basque Country.

Gibel gantzatsu ez-alkoholikoa (GGEA) espektro zabaleko gaixotasuna da, zeinak gaixotasun-multzo bat hartzen duen barne, gibel esteatositik hasita gibel-minbizia izatera arte iritsi daitekeena. Bere garapenerako arrisku faktore garrantzitsuenak obesitatea eta intsulinarekiko erresistentzia dira, gaur egun osasun-arazo pandemikoa izatera iritsi direnak. Populazioaren %25ak gibel-esteatosia pairatzen duela uste da, datu hauek gutxi gorabeherakoak direlarik gaixotasuna asintomatikoa izanik duen diagnosi zaila dela eta. Prebalentzia altuko gaixotasuna bada ere, nabarmentzekoa da gaur egun ez dagoela oraindik tratamendu estandarizaturik, ez eta hura hasteko momentu onenari buruzko akordiorik ere. Hala ere, bi dira gaur egun gehien erabiltzen diren tratamenduak: farmakologikoa, non intsulinarekiko erresistentzia hobetzen duten eta pisu galera eragiten duten farmakoak erabiltzen diren, eta dietetikoa, energia murrizketa delarik estrategiarik erabiliena. Bestetik, GGEAren tratamenduan konposatu fenolikoak erabilgarriak izan daitezkeela frogatu da in vitro eta in vivo egindako ikerketetan. Hala ere, entsegu klinikoetan lortutako emaitzek argi uzten duten bezala, oraindik ere ikerketa gehiagoren beharra dago konposatu fenolikoak gizakietan GGEAren tratamendu gisa erabili ahal izateko.; Non-alcoholic fatty liver disease (NAFL) is a wide spectrum illness which is comprised of different hepatic alterations, from steatosis to hepatocellular carcinoma. In this development, obesity and insulin resistance, two health alterations that currently have reached pandemic proportions, are considered as the main risk factors. It is believed that the 25% of the population suffers from hepatic steatosis, although these data is a mere stimation, due to the fact that the illness is asymptomatic and hard to diagnose. In spite of being such a prevalent illness, still today there are neither a standarized treatment nor a consensus regarding the best moment to start treating the illness. Nevertheless, there are two treatment strategies that are mainly used nowadays: the pharmacological treatment (based on the usage of drugs that ameliorate insulin resistance and enhance body weight reduction) and diet (being energy restricted diets the most commonly used ones). Moreover, in vitro and in vivo performed studies have demonstrated that phenolic compounds could also be useful for hepatic steatosis treatment. However, taking into account the results obtained in clinical trials, there is still more research to do in order to use these compounds as a therapeutic tool for hepatic steatosis treatment in humans.

This study aimed at identifying seaweed species with optimal characteristics to develop multifunctional foods for metabolic syndrome (MetS) management. Mass spectrometry chemical characterization and bioactive profile evaluation of methanolic extracts from seven commonly consumed seaweeds were compared. Monomeric sugars namely mannitol, fucitol, xylitol and their sulphated analogs as well as lipids (phosphatidic acid, octadecenoic acid, and prostaglandin 2α) were detected in seaweeds. Himanthalia elongata showed the highest phenolic content (24.04 µmol GAE/g), and antioxidant activity. This species was the only one showing angiotensin converting enzyme-I inhibitory activity (IC = 65 µg/mL). U. pinnatifida and H. elongata extracts were notably more effective reducing pro-inflammatory molecules in lipopolysaccharide-induced RAW 264.7 macrophages. Finally, Ulva spp., Palmaria palmata, U. pinnatifida and H. elongata significantly inhibited triglyceride accumulation in mature 3T3-L1 adipocytes (43–52% inhibition). Among seaweeds, H. elongata showed the highest potential to be used as ingredient in the development of new functional foods for MetS management., This study has been supported by the National Institute for Agricultural and Food Research and Technology of Spain (INIA: RTA2014-0037-C02).

The prevalence of obesity has been increasing in recent decades and is reaching epidemic proportions. The current options for overweight and obesity management are energy restriction and physical activity. However, compliance with these treatments is frequently poor and less successful than expected. Therefore, the scientific community is interested in active biomolecules, which may be useful in body weight management. Among them, resveratrol (3,5,4'-trihydroxy-trans-stilbene) has generated great interest as an antiobesity agent. The focus of this report is the mechanisms of action of resveratrol on several tissues (i.e., white and brown adipose tissues, liver, and skeletal muscle). Resveratrol blunts fat accumulation through decreasing adipogenesis and/or de novo lipogenesis in white adipose tissue. The effects on lipolysis are controversial. Regarding brown adipose tissue, resveratrol increases the capacity for adaptive thermogenesis. As far as liver and skeletal muscle is concerned, resveratrol increases lipid oxidation in both tissues. Therefore, in rodents, there is a general consensus concerning the effect of resveratrol on reducing body fat accumulation. By contrast, in humans, the studies are scarce, and no clear antiobesity action has been revealed so far.

The anti-obesity effects of resveratrol shown in rodents are not transposed into an efficient therapy of human obesity. Consequently, the search for molecules mimicking or surpassing resveratrol actions is ongoing. The natural phenolic compound pterostilbene exhibits beneficial health effects and has the capacity to limit fat mass in animal models. In this study, we tested whether pterostilbene modulates triacylglycerol accumulation/breakdown. Prolonged exposure to pterostilbene or resveratrol inhibited adipocyte differentiation in 3T3-F442A preadipocytes. Acute effects on lipolysis, antilipolysis and lipogenesis were determined for pterostilbene in mouse adipocytes, and compared with resveratrol. Pterostilbene was also tested on glycerol release and glucose uptake in subcutaneous human adipocytes. Dose–response analyses did not reveal a clear lipolytic effect in both species. The antilipolytic effect of insulin was improved by pterostilbene at 1–10 μM in mouse fat cells only, while at 1 mM, the phenolic compound was antilipolytic in human fat cells in a manner not additive to insulin. Pterostilbene dose-dependently inhibited glucose incorporation into lipids similarly to resveratrol and caffeine. However, only the former did not inhibit insulin-stimulated glucose uptake. Indeed, pterostilbene abolished the insulin lipogenic effect without inhibiting its antilipolytic action and rapid activation of glucose uptake. Pterostilbene therefore exhibits a unique panel of direct interactions with adipocytes that relies on its reported anti-obesity and antidiabetic properties. Copyright © 2017 John Wiley & Sons, Ltd.

Several studies have observed that gut microbiota can play a critical role in nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) development. The gut microbiota is influenced by different environmental factors, which include diet. The aim of the present review is to summarize the information provided in the literature concerning the impact of changes in gut microbiota on the effects which dietary fat has on liver steatosis in rodent models. Most studies in which high-fat feeding has induced steatosis have reported reduced microbiota diversity, regardless of the percentage of energy provided by fat. At the phylum level, an increase in Firmicutes and a reduction in Bacteroidetes is commonly found, although widely diverging results have been described at class, order, family, and genus levels, likely due to differences in experimental design. Unfortunately, this fact makes it difficult to reach clear conclusions concerning the specific microbiota patterns associated with this feeding pattern. With regard to the relationship between high-fat feeding-induced changes in liver and microbiota composition, although several mechanisms such as alteration of gut integrity and increased permeability, inflammation, and metabolite production have been proposed, more scientific evidence is needed to address this issue and thus further studies are needed. This research was funded by MINECO (AGL-2015-65719-R-MINECO/FEDER, UE) and Instituto de Salud Carlos III (CIBERobn, CB12/03/30007)

Pterostilbene, a phenolic compound derived from resveratrol, possesses greater bioavailability than its parent compound due to the presence of two methoxyl groups. In this review, the beneficial effects of pterostilbene on diabetes, liver steatosis and dyslipidemia are summarized. Pterostilbene is a useful bioactive compound in preventing type 1 diabetes, insulin resistance and type 2 diabetes in animal models. Concerning type 1 diabetes, the main mechanisms described to justify the positive effects of this phenolic compound are increased liver glycogen content and hepatic glucokinase and phosphofructokinase activities, the recovery of pancreatic islet architecture, cytoprotection and a decrease in serum and pancreatic pro-inflammatory cytokines. As for type 2 diabetes, increased liver glucokinase and glucose-6-phosphatase and decreased fructose-1,6-biphosphatase activities are reported. When insulin resistance is induced by diets, a greater activation of insulin signaling cascade has been reported, increased cardiotrophin-1 levels and liver glucokinase and glucose- 6-phosphatase activities, and a decreased fructose-1,6-biphosphatase activity. Data concerning pterostilbene and liver steatosis are scarce so far, but the reduction in oxidative stress induced by pterostilbene may be involved since oxidative stress is related to the progression of steatosis to steatohepatitis. Finally, pterostilbene effectively reduces total cholesterol, LDL-cholesterol and serum triglyceride levels, while increases HDL-cholesterol in animal models of dyslipidemia.

Excessive fat accumulation within the liver is known as &ldquo, simple hepatic steatosis&rdquo, which is the most benign form of non-alcoholic fatty liver disease (NAFLD). The aim of the present study was to determine whether pterostilbene improves this hepatic alteration in Zucker (fa/fa) rats. Animals were distributed in two experimental groups (n = 10) and fed a standard laboratory diet. Rats in the pterostilbene group were given a dose of 30 mg/kg body weight/d for six weeks. After sacrifice, serum glucose, transaminase, and insulin concentrations were quantified and the liver triacylglycerol content and fatty acid profile was analyzed. Different pathways of triacylglycerol metabolism in liver were studied, including fatty acid synthesis and oxidation, triglyceride assembly, fatty acid uptake, and glucose uptake. With pterostilbene administration, a reduction in insulin concentrations (consequently in the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR)) and hepatic triacylglycerol content were observed. No effects were observed in pterostilbene-treated rats in the activity of de novo lipogenesis enzymes. An improvement in the fatty acid profile was observed in pterostilbene-treated rats. In conclusion, pterostilbene is a useful molecule to reduce liver steatosis. Its delipidating effect is due, at least in part, to reduced fatty acid availability and triacylglycerol synthesis, as well as to an increased very low-density lipoprotein assembly and fatty acid oxidation.

Quercetin is a phenolic compound belonging to the family of flavonoids and the group of flavonols, which is present in onions, apples, various types of berries, coffee, and tea. Numerous beneficial effects on health of this bioactive molecule have been reported in the literature. The present chapter focuses on the effects of quercetin on skeletal muscle mitochondria biogenesis and their consequences in terms of physical endurance and glycemic control in rodent models and human beings. Studies carried out on rodents show that quercetin is able to induce mitochondria biogenesis through increased mitochondrial DNA, genes that play a key role in this process (sirt-1, pparα, pgc-1α) and activity of oxidative enzymes. This effect leads to the enhancement of maximal exercise capacity. It has not been reproduced in human beings so far. In animal models showing insulin resistance induced by high-fat feeding, quercetin administration improved glycemic control.

The prevalence of obesity has increased rapidly during recent years and has reached epidemic proportions. As a result, the scientific community is interested in active biomolecules which are naturally present in plants and foodstuffs and may be useful in body weight management. In recent years, polyphenols have made up one of the most frequently studied groups among these molecules. Numerous studies have been carried out on animals to analyse the potential anti-obesity effects of resveratrol, a non-flavonoid polyphenol, and a general consensus concerning the body-fat-lowering effect of this compound exists. By contrast, studies in humans have been few so far. Moreover, in these studies, the effectiveness of resveratrol is low. The aims of the present review are to summarize the results reported so far on this topic and to justify the differences observed between animals and humans. It seems that the reduced response to resveratrol in humans cannot be attributed to the use of lower doses in humans because the doses that induce body-fat-lowering effects in rodents are in the same range as those used in human studies. With regard to the experimental period length, treatments were longer in animal studies than in human studies. This can be one of the reasons contributing to the reduced responses observed in humans. Moreover, animals used in the reported studies are young while volunteers participating in human studies are adults, suggesting that resveratrol may be more efficient in young individuals. In addition to differences in the experimental designs, metabolic differences between animals and human cannot be discarded.

The epigenetic mechanisms of action of resveratrol as an anti-obesity molecule have not been fully addressed so far. The aim of the present study was to assess changes produced by resveratrol in the microRNA (miRNA) profile in white adipose tissue (WAT) and to relate these changes to those induced in the expression of genes involved in triacylglycerol metabolism. Male Wistar rats were fed (6 weeks) an obesogenic diet: a control group and a group treated with resveratrol (30 mg kg(-1) d(-1)). A miRNA microarray was carried out in perirenal adipose tissue. The overexpression of miR-539-5p and miR-1224-5p was performed in 3T3-L1 cells. Protein expression was analysed by western-blot and gene expression by qRT-PCR. Associations between variables were assessed by Pearson's correlations. The microarray showed that 3 miRNAs were decreased and 13 were increased after resveratrol treatment. Among those miRNAs increased, miR-129, miR-328-5p and miR-539-5p showed predicted target genes relevant for triacylglycerol metabolism in WAT (pparγ: peroxisome proliferator-activated receptor gamma, hsl: hormone sensitive lipase and sp1: SP1 transcription factor) in the miRWalk database. Moreover, the literature shows that miR-1224, another miRNA up-regulated by resveratrol, can also regulate sp1. Among the three targets, only SP1 showed a reduction in protein expression. Correlation and overexpression studies revealed that the decrease in SP1 protein expression was only associated with the increase of miR-539-5p. In addition, significant reductions in SREBP1 protein expression and fasn gene expression were found in resveratrol-treated rats. In conclusion, the up-regulation of miR-539-5p is involved in the inhibition of de novo lipogenesis induced by resveratrol in WAT.

Nephroblastoma overexpressed protein, also called NOV/CCN3, is an adipokine which is present in various tissues and recently linked to obesity. The objective of the study was to determine the effect of resveratrol and pterostilbene on NOV/CCN3 in adipose tissue from rats fed an obesogenic diet. Thirty-six male Wistar rats were split into four groups (n = 9): fed a standard diet (CC), high-fat high-sucrose (HFS) diet supplemented with resveratrol (RSV; 30 mg/kg/day) or with pterostilbene (PT; 30 mg/kg/day), or without phenolic supplementation (HFS). Rats were sacrificed after 6 weeks of treatment, and adipose tissue (white and brown) from different anatomical locations were dissected. Then, Nov/ccn3 gene and protein expression and the adipogenic genes, Ucp-1 and Pgc-1a, expressions were studied. Increased weight of white adipose tissues was found in rats fed the HFS diet. Whereas resveratrol-treated rats showed reduced internal and total adipose tissue weights, pterostilbene-treated rats showed reduced subcutaneous, internal and total adipose depots. Nov/ccn3 gene expression decreased in epididymal and interscapular brown depot in rats fed HFS diet when compared with the control group. Regarding the phenolic compounds, resveratrol prompted a Nov/ccn3 gene expression increase in epididymal fat tissue, whereas pterostilbene reduced its protein expression compared with the obese group. However, these phenolic compounds did not affect NOV/CCN3 expression in brown depot. NOV/CCN3 seems to be involved in weight changes in epididymal adipose tissue under obesogenic feeding, but not in subcutaneous, acting as a protective mechanism counteracting the fattening effect of the diet. To our knowledge, this is the first study analyzing whether NOV/CCN3 is involved in the anti-obesity effect of resveratrol and pterostilbene. Our results suggest that this is not the case.

Infants born small for gestational age (SGA) are at increased risk of perinatal morbidity, persistent short stature, and metabolic alterations in later life. Moreover, the post-natal growth pattern of SGA infants may be an important contributor to health outcomes later in life, which can be influenced by adipokines. The aims of this study were to compare plasma adipokine profiles (leptin, adiponectin, vaspin, chemerin, and nephroblastoma overexpressed (NOV/CCN3)) among SGA newborns aged 3 months, with low, normal, or high catch-up, to search for potential differences between males and females and to analyze the evolution of several adipokines in plasma from SGA newborns between 3 and 24 months. This prospective, longitudinal study was addressed in SGA Caucasian subjects at Hospital Universitario de Álava-Txagorritxu. We observed that infants with fast catch-up showed significantly lower birth weight than the other two groups. As far as adipokines are concerned, they could have an influence on catch-up type because differences among the three experimental groups were found. It may be proposed that health prognoses in infants with slow and fast catch-up are opposite, not only in adulthood but also during their first months. Finally, adipokine evolution patterns during the first 24 months of age differ, depending on the adipokine, and 24-month-old males show lower levels of leptin, adiponectin, and omentin than females.

Aquaglyceroporins (AQPs) are transmembrane channels that mediate glycerol release and glycerol uptake. They are involved in fat metabolism, with implications in obesity. The aim was to determine whether the administration of resveratrol and pterostilbene during the six weeks of the experimental period would modify AQPs expression in white and brown adipose tissues from Wistar rats fed an obesogenic diet, and to establish a potential relationship with the delipidating properties of these compounds. Consequently, thirty-six rats were divided into four groups: (a) group fed a standard diet, and three more groups fed a high-fat high-sucrose diet: (b) high-fat high-sucrose group: (c) pterostilbene-treated group (30 mg/kg/d): (d) resveratrol-treated group (30 mg/kg/d). Epididymal, subcutaneous white adipose tissues and interscapular brown adipose tissue were dissected. AQPs gene expression (RT-PCR) and protein expression (western-blot) were measured. In white adipose tissue, pterostilbene reduced subcutaneous adipose tissue weight and prevented the decrease in AQP9 induced by obesogenic feeding, and thus glycerol uptake for triglyceride accumulation. Resveratrol reduced epididymal adipose tissue weight and avoided the decrease in AQPs related to glycerol release induced by high-fat high-sucrose feeding, suggesting the involvement of lipolysis in its body-fat lowering effect. Regarding brown adipose tissue, AQP7 seemed not to be involved in the previously reported thermogenic activity of both phenolic compounds.

Nonalcoholic fatty liver disease (NAFLD) is a term that covers a disease spectrum ranging from simple triacylglycerol accumulation in hepatocytes (hepatic steatosis; NAS), in the absence of excessive alcohol consumption, through, hepatic steatosis with inflammation and fibrosis (steatohepatitis, NASH), to cirrhosis. The “two-hit” model has been proposed to explain the progression of NAFLD. In the “first hit,” there is an accumulation of triacylglycerols as lipid droplets within the cytoplasm of hepatocytes (steatosis). The disease does not progress unless additional cellular events, such as oxidative stress, occur (the “second hit”). Resveratrol (3,4′,5-trihydroxy-trans-stilbene), a nonflavonoid phenolic compound, belonging to the group of stilbenes, which is naturally present in some foodstuffs (grapes, wine, peanuts, and berries) has been reported to have beneficial effects in steatosis prevention and treatment. The present chapter summarizes reported studies showing the antisteatotic effects of resveratrol in relation to its antioxidant action in animal models and clinical studies.

Phenolic compounds make up a wide group of different substances that can be grouped together by its chemical structure. They are synthesized by plants as sec-ondary metabolites in response to aggressions such as ultraviolet radiation, pathogens, oxidative damage and rough climatic conditions. For this reason, they can be found in plant based foodstuffs, such as fruits, vegetables, nuts, oils, teas and wines. The major-ity of the phenolic compounds present on food are found as esters, glycosides or polymers, which have to be hydrolyzed in the gut before being absorbed. By the action of the so called phase II enzymes, the phenolic compounds are metabolized in the small bowel and in the liver. Some of the metabolites produced in the liver are secreted to the small bowel through the bile duct, where they will be either deconjugated to be reab-sorbed or reach the colon. Once in the large bowel, the phenolic compounds are further metabolized by the gut microbiota. As a consequence of all these processes, the bioa-vailability of the phenolic compounds is low. The excretion of the phenolic compounds and their metabolites is basically done through the urine. They are bioactive com-pounds with high antioxidant capacity. In the last years, different beneficial effects against the development of some illnesses (cancer, cardiovascular and neurodegenera-tive diseases) were attributed to these compounds, in part because of their antioxidant effect, and also due to other different mechanisms.; Konposatu fenolikoak, egitura kimikoaren arabera sailkatu daitezkeen zenbait sustantziaz osatutako talde zabal bat dira. Landareek ekoizten dituzte bigarren mailako metabolito gisa, erantzun modura erradiazio ultramorea, patogenoak, kalte oxidatiboa eta ingurumen baldintza zailak bezalako erasoei aurre egiteko. Hori dela eta, modu naturalean daude landare jatorriko elikagaietan, hala nola frutetan, barazkie-tan, fruitu lehorretan, olioetan, tean eta ardoan. Konposatu fenoliko gehienak ester, glu-kosido edo polimero gisa aurkitzen dira elikagaietan, eta ondorioz hestean hidrolizatu behar dira xurgatuak izan baino lehen. Gibelean eta heste meharrean konposatu fenoli-koak metabolizatzen dira II faseko entzimen eraginez. Gibelean eratzen diren metabo-litoen zati bat, heste meharrera jariatuko da behazun bideetatik, eta bertan berriro xur-gatuak izateko dekonjugatu egingo dira, edota kolonerako bidea jarraituko dute. Behin heste lodian, hesteko mikrobiotak konposatu fenolikoak metabolizatuko ditu. Prozesu hauen ondorioz, konposatu fenolikoen bioerabilgarritasuna txikia da. Konposatu fe-nolikoen eta beren metabolitoen iraizpena, gernu bidez gertatzen da nagusiki. Antio-xidazio-ahalmen handia duten konposatu bioaktiboak dira. Azken urteetan, eragiten dituzten antioxidazio efektuengatik, eta beste mekanismo batzuengatik, hainbat gaixo-tasunen garapenaren aurkako efektu onuragarriak egotzi zaizkie: minbizia, gaixotasun kardiobaskularrak eta neuroendekapenezko gaixotasunak.

Kate luzeko omega-3 gantz-azido poliasegabeak, azido eikosapentaenoikoa (EPA) eta azido dokosahexaenoikoa (DHA) kasurako, kantitate handitan aurkitzen dira arrain koipetsuetan eta haietatik eratorritako arrain-olioan, zeina elikadura-osagarri gisa erabiltzen den (nutrazeutiko gisa, alegia). EPA zein DHA mintz zelularren fosfolipidoei gehitzen zaizkio, non lipooxigenasa eta ziklooxigenasa entzimen bidez jaria dai- tezkeen, eta zelula babesten duten hanturen kontrako produktuak eratu. Hainbat ikerketaren arabera, EPA eta DHA kontsumitzea baliagarria da zenbait gaixotasun ekiditeko edota haien tratamendurako, hantura-prozesuak eragindako gaixotasunetan bereziki. Hain zuzen ere, EPA eta DHAk hanturaren kontrako propietateak dituzte, bai erresolbina gisako hanturaren kontrako eragileak ekoiztuz, edota hantura eragileak blokeatuz. Ebidentzia zientifiko honen arabera, kate luzeko omega-3 gantz-azidoek zenbait aplikazio izan patologia kliniko edo nutrizional ezberdinen tratamenduan nahiz edota prebentzioan. Alabaina, gaur egun gantz-azido aseen kontsumoa zeharo hazi da, eta lipido onuragarrien kontsumoa, berriz, jaitsi egin da; era honetan, populazioaren atal handi batek omega-3 gantz-azidoen gabezia aurkezten du. Frogatu da egoera honek eragin handia duela endekapenezko gaixotasunen garapenean esaterako, gaixotasun kardiobaskularrak, minbizia, hantura-prozesuak eta bereziki ikusmenaren eta nerbio sistema zentralaren osasunean eta garapenean, non DHA kontzentrazio handiak dauden; Omega-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFA) eicosap-entaenoic acid (EPA) and docosahexaenoic acid (DHA) are found in significant amounts in fatty fish and especially in the oil obtained from these species, which is actually used as a nutritional supplement (nutraceutical). After ingestion, both EPA and DHA are rapidly incorporated into cellular membrane phospholipids where they can be released by lipooxygenases and cyclooxygenases enzymes and transformed in powerful bioactive products which have cytoprotective and especially anti-inflamma-tory activities. Clinical and epidemiological evidence have firmly established that consumption of EPA and DHA may contribute to the prevention and/or treatment of a number of diseases, especially those where inflammation process plays a remarkable role in its development. EPA and DHA exhibit potent anti-inflammatory properties, either via the generation of anti-inflammatory products, such as resolvins, or by block-ing inflammatory agents. The evidence suggests that omega-3 LC-PUFA may have promising applications in the prevention and/or treatment of different clinical and nu-tritional pathologies. However, nowadays the consumption of foods rich in saturated fats has increased drastically to the detriment of healthy fatty acids, thus much of the population has a deficiency in omega-3 fatty acids. This has a great impact on the de-velopment of degenerative diseases such as cardiovascular diseases, cancer, processes with a strong inflammatory component, and especially on the development and health of the vision and central nervous system, where there is a high concentration of DHA in particular.

The present review focuses on the role of miRNAs in the control of white adipose tissue browning, a process which describes the recruitment of adipocytes showing features of brown adipocytes in white adipose tissue. MicroRNAs (miRNAs) are a class of short non-coding RNAs (19-22 nucleotides) involved in gene regulation. Although the main effect of miRNAs is the inhibition of the translational machinery, thereby preventing the production of the protein product, the activation of protein translation has also been described in the literature. In addition to modifying translation, miRNAs binding to its target mRNAs also trigger the recruitment and association of mRNA decay factors, leading to mRNA destabilization, degradation, and thus to the decrease in expression levels. Although a great number of miRNAs have been reported to potentially regulate genes that play important roles in the browning process, only a reduced number of studies have demonstrated experimentally an effect on this process associated to changes in miRNA expressions, so far. These studies have shown, by using either primary adipocyte cultures or experimental models of mice (KO mice, mice overexpressing a specific miRNA), that miR-196a, miR-26, and miR-30 are needed for browning process development. By contrast, miR-155, miR-133, miR-27b, and miR-34 act as negative regulators of this process [corrected]. Further studies are needed to fully describe the miRNA network-involved white adipose tissue browning regulation.

This study aims to determine whether pterostilbene improves glycaemic control in rats showing insulin resistance induced by an obesogenic diet. Rats were divided into 3 groups: the control group and two groups treated with either 15 mg kg(-1) d(-1) (PT15) or 30 mg kg(-1) d(-1) of pterostilbene (PT30). HOMA-IR was decreased in both pterostilbene-treated groups, but this reduction was greater in the PT15 group (-45% and -22% respectively vs. the control group). The improvement of glycaemic control was not due to a delipidating effect of pterostilbene on skeletal muscle. In contrast, GLUT4 protein expression was increased (+58% and +52% vs. the control group), suggesting an improved glucose uptake. The phosphorylated-Akt/total Akt ratio was significantly enhanced in the PT30 group (+25%), and therefore a more efficient translocation of GLUT4 is likely. Additionally, in this group the amount of cardiotrophin-1 was significantly increased (+65%). These data suggest that the effect of pterostilbene on Akt is mediated by this cytokine. In the liver, glucokinase activity was significantly increased only in the PT15 group (+34%), and no changes were observed in glucose-6-phosphatase activity. The beneficial effect of pterostilbene on glycaemic control was more evident with the lower dose, probably because in the PT15 group both the muscle and the liver were contributing to this effect, but in the PT30 group only the skeletal muscle was responsible. In conclusion, pterostilbene improves glycaemic control in rats showing insulin resistance induced by an obesogenic diet. An increase in hepatic glucokinase activity, as well as in skeletal muscle glucose uptake, seems to be involved in the anti-diabetic effect of this phenolic compound.