GRUP DE RECERCA NUTRIGENÒMICA

Universitat Rovira i Virgili (Tarragona)

Director: Lluís Arola Ferré, Catedràtic d’Universitat

sdbio@urv.cat

(+34) 977 55 95 21

(+34) 977 55 82 32

http://www.nutrigenomica.recerca.urv.cat/

Actualització fitxa tècnica del grup: setembre 2017

MEMBRES DEL GRUP INVESTIGADOR

Lluís Arola Ferrer, Coordinador del grup de Recerca /Catedràtic d’Universitat, Universitat Rovira i Virgili, a/e: lluis.arola@urv.cat

Maria Cinta Bladé Segarra, Catedràtica d’Universitat, Universitat Rovira i Virgili, a/e: mariacinta.blade@urv.cat

Maria Josepa Salvadó Rovira, Catedràtica d’Universitat, Universitat Rovira i Virgili, a/e: mariajosepa.salvado@urv.cat

Maria Begoña Muguerza Marquínez, Professor Agregat, Universitat Rovira i Virgili, a/e: begona.muguerza@urv.cat

Anna Arola Arnal, Professor Agregat, Universitat Rovira i Virgili, a/e: anna.arola@urv.cat

Manuel Suárez Recio, Professor Lector, Universitat Rovira i Virgili, a/e: manuel.suarez@urv.cat

Gerard Aragonès Bargalló, Professor Lector visitant, Universitat Rovira i Virgili, a/e: gerard.aragones@urv.cat

Francisca Isabel Bravo Vázquez, Professor Lector visitant, Universitat Rovira i Virgili, a/e: franciscaisabel.bravo@urv.cat

Niurka Llópiz Janer, Tècnic, Universitat Rovira i Virgili, a/e: niurkadaniela.llopiz@urv.cat

Maria Ibars Serra, Investigadora predoctoral, Universitat Rovira i Virgili, a/e: maria.ibars@urv.cat

Andrea Ardid Ruiz, Investigadora predoctoral, Universitat Rovira i Virgili, a/e: andrea.ardid@urv.cat

Anna Mas Capedevilla, Investigadora predoctoral, Universitat Rovira i Virgili, a/e: anna.mas@urv.cat

Lisard Iglesias Carres, Investigador predoctoral, Universitat Rovira i Virgili, a/e: lisard.iglesias@urv.cat

Albert Gibert Ramos, Investigador predoctoral, Universitat Rovira i Virgili, a/e: albert.gibert@urv.cat

Cristina Domènech Coca, Investigadora predoctoral, Universitat Rovira i Virgili, a/e: cristina.domenech@urv.cat

Héctor Palacios Jordan, Investigador predoctoral, Universitat Rovira i Virgili, a/e: hector.palacios@urv.cat

Andreu Gual Grau, Investigador predoctoral, Universitat Rovira i Virgili, a/e: andreu.gual@urv.cat

Miguel Martín González, Investigador predoctoral, Universitat Rovira i Virgili, a/e: miguel.martin@urv.cat

Maria Guirro Castellnou, Investigadora predoctoral, Universitat Rovira i Virgili, a/e: maria.guirro@urv.cat

(Actualització de l’apartat: 08/09/2017)

ACTIVITATS I CAPACITATS DEL GRUP DE RECERCA

L’objectiu principal del grup de Nutrigenòmica és crear coneixements bàsics sobre compostos bioactius d’aliments i aplicar aquest coneixement per dissenyar aliments funcionals per prevenir i/o alleujar malalties metabòliques com l’obesitat, la diabetis, la hipertensió i la síndrome metabòlica. A més, el grup Nutrigenòmica també se centra en l’obtenció d’ingredients funcionals a partir de subproductes derivats de la industria alimentària, per tal d’augmentar el seu valor i donar un ús a aquests productes de rebuig de les empreses alimentàries.

Els objectius específics del grup inclouen la recerca d’excel·lència, la internacionalització així com la transferència de coneixements a empreses agroalimentàries i als ciutadans. Específicament són:

  • Augmentar el coneixement sobre l’efectivitat dels compostos bioactius. Aquest objectiu està vinculat a l’actual projecte finançat pel Ministeri d’Economia i Competitivitat “Estudi de la interacció del ritme circadià i temporal amb l’eficacia d’ingredients funcionals (AGL2016-77105-R)” que estarà en funcionament fins al desembre de 2019. L’objectiu general d’aquesta proposta és investigar si els ritmes biològics determinen els efectes beneficiosos descrits pels compostos bioactius.
  • Augmentar les relacions i el finançament internacionals. El grup de Nutrigenòmica és membre del Consorci “NutriEpiHealth” que inclou 90 investigadors de 23 països del món. El nostre objectiu participant en aquest consorci és unir-nos a investigadors que estan interessats en els efectes epigenètics de la dieta, per tal de trobar sinèrgies per augmentar el coneixement i el finançament internacional.
  • Incrementar la transferència de coneixement a les empreses alimentàries i augmentar la sostenibilitat del “Camp de Tarragona”. El grup de recerca és molt actiu transferint el coneixement a les empreses alimentàries. De fet, la majoria dels membres del grup de recerca han gestionat projectes de transferència de tecnologia. El grup de recerca transfereix el seu coneixement a través de la “UTNS-Eurecat-Reus” i la “Fundació URV”.

LÍNIES DE RECERCA

Línia: Ritmes biològics
Investigador principal: Maria Cinta Bladé Segarra/ Lluís Arola

Línia: Senyalització de la leptina
Investigador principal: Gerard Aragonès / Maria Cinta Bladé / Manuel Suárez

Línia: Metabolòmica
Investigador principal: Maria Cinta Bladé / Lluís Arola / Manuel Suárez

Línia: Biodisponibilitat de compostos bioactius
Investigador principal: Anna Arola Arnal / Begoña Muguerza Marquínez

Línia: Funció endotelial
Investigador principal: Anna Arola Arnal / Begoña Muguerza Marquínez / Francisca Isabel Bravo

Línia: Metabolisme energètic
Investigador principal: Begoña Muguerza Marquínez / Gerard Aragonès

Línia: Microbiota
Investigador principal: Lluís Arola

Línia: Adipogènesi
Investigador principal: Maria Josepa Salvadó

MILLORS PUBLICACIONS DEL GRUP (DARRERS 2 ANYS)

Baselga L, Blade C, Ribas A, Casanova E, Suárez M, Torres JL, Salvadó MJ, Arola L, Arola-Anal A.
Resveratrol and EGCG bind directly and distinctively to miR-33a and miR-122 and modulate divergently their levels in hepatic cells.
Nucleic Acids Res 2014; 42(2): 882-892.
PMID: 24165878
Abstract:
Modulation of miR-33 and miR-122 has been proposed to be a promising strategy to treat dyslipidemia and insulin resistance associated with obesity and metabolic syndrome. Interestingly, specific polyphenols reduce the levels of these mi(cro)RNAs. The aim of this study was to elucidate the effect of polyphenols of different chemical structure on miR-33a and miR-122 expression and to determine whether direct binding of the polyphenol to the mature microRNAs (miRNAs) is a plausible mechanism of modulation. The effect of two grape proanthocyanidin extracts, their fractions and pure polyphenol compounds on miRNA expression was evaluated using hepatic cell lines. Results demonstrated that the effect on miRNA expression depended on the polyphenol chemical structure. Moreover, miR-33a was repressed independently of its host-gene SREBP2. Therefore, the ability of resveratrol and epigallocatechin gallate to bind miR-33a and miR-122 was measured using (1)H NMR spectroscopy. Both compounds bound miR-33a and miR-122 and differently. Interestingly, the nature of the binding of these compounds to the miRNAs was consistent with their effects on cell miRNA levels. Therefore, the specific and direct binding of polyphenols to miRNAs emerges as a new posttranscriptional mechanism by which polyphenols could modulate metabolism.

Aragonès G, Suárez M, Ardid-Ruiz A, Vinaixa M, Rodríguez MA, Correig X, Arola L, Bladé C.
Dietary proanthocyanidins boost hepatic NAD + metabolism and SIRT1 expression and activity in a dose-dependent manner in healthy rats.
Sci Rep 2016; 6, 24977.
PMID: 27102823
Abstract:
Proanthocyanidins (PACs) have been reported to modulate multiple targets by simultaneously controlling many pivotal metabolic pathways in the liver. However, the precise mechanism of PAC action on the regulation of the genes that control hepatic metabolism remains to be clarified. Accordingly, we used a metabolomic approach combining both nuclear magnetic resonance and mass spectrometry analysis to evaluate the changes induced by different doses of grape-seed PACs in the liver of healthy rats. Here, we report that PACs significantly increased the hepatic nicotinamide adenine dinucleotide (NAD(+)) content in a dose-dependent manner by specifically modulating the hepatic concentrations of the major NAD(+) precursors as well as the mRNA levels of the genes that encode the enzymes involved in the cellular metabolism of NAD(+). Notably, Sirtuin 1 (Sirt1) gene expression was also significantly up-regulated in a dose-response pattern. The increase in both the NAD(+) availability and Sirt1 mRNA levels, in turn, resulted in the hepatic activation of SIRT1, which was significantly associated with improved protection against hepatic triglyceride accumulation. Our data clearly indicates that PAC consumption could be a valid tool to enhance hepatic SIRT1 activity through the modulation of NAD(+) levels.

Ibars M, Ardid-Ruiz A, Suárez M, Muguerza B, Bladé C, Aragonès, G.
Proanthocyanidins potentiate hypothalamic leptin/STAT3 signalling and Pomc gene expression in rats with diet-induced obesity.
Int J Obes 2017; 41(1): 129-136.
PMID: 27677620
Abstract:
OBJECTIVE: Dietary obesity is usually linked with hypothalamic leptin resistance, in which the primary impact is an interference in the homeostatic control of body weight and appetite. Notably, proanthocyanidins (PACs), which are the most abundant phenolic compounds present in human diet, modulate adiposity and food intake. The aim of this study was to assess whether PACs could re-establish appropriate leptin signalling in both the hypothalamus and peripheral tissues.
DESIGN: Male Wistar rats were fed either a standard chow diet (STD group, n=7) or a cafeteria diet (CD) for 13 weeks. The CD-fed rats were treated with either grape-seed PAC extract (GSPE) at 25 mg  per kg of body weight per day (CD+GSPE group, n=7) or with the vehicle (CD group, n=7) for the last 21 days of the study period. Specific markers for intracellular leptin signalling, inflammation and endoplasmic reticulum stress in the hypothalamus, liver, mesenteric white adipose tissue and skeletal muscle were analysed using immunoblotting and quantitative PCR.
RESULTS: GSPE treatment significantly reduced the food intake but did not reverse the hyperleptinemia and body wt gain assessed. However, the animals treated with GSPE exhibited greater hypothalamic activation of signal transducer and activator of transcription-3, which was associated with a rise in the Pomc mRNA levels compared with the CD group. In addition, this restoration of leptin responsiveness was accompanied by lower local inflammation and increased Sirt1 gene expression. The effects of the GSPE treatment in the peripheral tissues were not as evident as those in the hypothalamus, although the GSPE treatment significantly restored the mRNA levels of Socs3 and Ptp1b in the skeletal muscle.
CONCLUSIONS: The use of GSPE reduces hyperphagia and improves the central and peripheral leptin resistance associated with diet-induced obesity. Our results suggest that GSPE could exert these effects partially by increasing Sirt1 expression and preventing hypothalamic inflammation.

Margalef M, Iglesias-Carres L, Pons Z, Bravo FI, Muguerza B, Arola-Arnal, A.
Age related differences in the plasma kinetics of flavanols in rats.
J Nutr Biochem 2016; 29: 90-96.
PMID: 26895669
Abstract:
Dietary flavanols produce beneficial health effects; once absorbed, they are recognized as xenobiotics and undergo Phase-II enzymatic detoxification. However, flavanols with a degree of polymerization greater than 2 reach the colon, where they are subjected to microbial metabolism and can be further absorbed and undergo Phase-II reactions. In this sense, flavanols’ health-promoting properties are mainly attributed to their metabolic products. Several age-related physiological changes have been evidenced, and it is known that flavanols’ bioavailability is affected by internal factors. Therefore, this study aimed to elucidate whether animals of different ages, specifically young and adult rats, exhibit differences in their flavanol metabolism and plasma bioavailability. To accomplish this, an acute dose of a grape seed polyphenol extract was administered to male rats; after 2, 4, 7, 24 and 48 h, flavanols and their Phase-II and microbial metabolites were quantified by HPLC-ESI-MS/MS in plasma. The results indicated important age-related quantitative differences in plasma flavanol metabolites. Interestingly, adult rats presented a remarkable reduction in flavanol absorption and Phase-II flavanol metabolism. Consequently, microbial-derived flavanol metabolism is triggered by higher flavanol affluence in the colonic tract. Furthermore, young rats presented a faster metabolic profile than adult rats. Hence, our results indicate that the physiological bioactivities of flavanols may depend on age.

Ribas-Latre A, Del Bas JM, Baselga-Escudero L, Casanova E, Arola-Arnal A, Salvadó MJ, Arola L, Bladé C.
Dietary proanthocyanidins modulate melatonin levels in plasma and the expression pattern of clock genes in the hypothalamus of rats.
Mol Nutr Food Res 2015; 59(5): 865-878.
PMID: 25677201
Abstract:
SCOPE: Circadian rhythms allow organisms to anticipate and adapt to environmental changes, and food components can adjust internal rhythms. Proanthocyanidins improve cardiovascular risk factors that exhibit circadian oscillations. Therefore, the aim of the current study was to determine whether proanthocyanidins can modulate body rhythms.
METHODS AND RESULTS: Male Wistar rats were orally gavaged with 250 mg grape seed proanthocyanidin extract (GSPE)/kg body weight at zeitgeber time (ZT) 0 (light on). Phenotypic biorhythm was evaluated by measuring the concentration of plasma melatonin and metabolites, using MNR-metabolomics, at several ZT. Remarkably, GSPE treatment maintained nocturnal melatonin levels at ZT3 and altered the oscillations of some metabolites in plasma. Quantification of expression of clock-core (Clock, Bmal1, Per2, Rorα, Rev-erbα) and clock-controlled (Nampt) genes in the hypothalamus by RT-PCR showed that this phenotypic alteration was concomitant with the modulation of the expression pattern of Bmal1 and Nampt. However, GSPE did not modulate the nocturnal expression of clock genes when administered at ZT12 (light off).
CONCLUSION: PAs could have chronobiological properties, although their activity depends largely on the time of administration.

INSTITUCIONS QUE RECONEIXEN AL GRUP DE RECERCA

Generalitat de Catalunya

Universitat Rovira i Virgili

Institut de Salut Pere Virgili