GRUP “LABORATORI DE BIOLOGIA MOLECULAR, NUTRICIÓ I BIOTECNOLOGIA – NUTRIGENÒMICA
Universitat de les Illes Balears (Illes Balears)

Director: Andreu Palou Oliver, Catedràtic d’Universitat
Adreça mail de contacte del grup de Recerca: andreu.palou@uib.es
Telèfon de contacte: (+34) 971 17 31 70
Web del grup: http://palou.uib.es

Actualització fitxa tècnica del grup: juliol 2017

MEMBRES DEL GRUP INVESTIGADOR

(Actualització de l’apartat: 20/07/2017)

ACTIVITATS I CAPACITATS DEL GRUP DE RECERCA

El grup de recerca “Nutrigenòmica i Obesitat” (NUO) dirigit pel Prof. Andreu Palou consta de una plantilla de 12 plaçes permanents o molt estables (inclosos 4 catedràtics, 3 professors titulars, un professor ajudant doctor, una investigadora Ramón i Cajal i 3 contractats CIBER), a mes de tècnics superiors i becaris predoctorals. Això permet una I+D amb un abordatge simultani de reptes en els àmbits bàsic i aplicat, incloent la transferència de tecnologia.

La recerca del grup es centra, des de fa anys, en l’estudi dels mecanismes moleculars fisiològics del control del pes corporal i les seves alteracions en l’obesitat i, en connexió amb això, en el control de la homeòstasi energètica per nutrients i les seves implicacions, abordant també aspectes relacionats amb seguretat i qualitat alimentaria, incloent els desenvolupaments en el camp dels Health Claims i Novel Foods en aliments, de màxim interès en l’àmbit europeu.

La trajectòria científica e investigadora del grup ha permès consolidar nombroses relacions de treball amb grups de recerca d’excel·lència d’àmbit nacional i internacional i amb empreses líders en el sector. Cal ressaltar que, recentment, el grup ha estat coordinador d’un projecte del 7è programa marc de la Unió Europea (BIOCLAIMS), amb vigència des de 2010 a 2015, i ha participat en altres 5 projectes europeus en els darrers 5 anys. Es també un grup adscrit al CIBER de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), i va ser membre fundador (i part del seu consell de govern) de la Xarxa de Recerca europea d’excel·lència científica “The European Nutrigenomics Organisation: linking genomics, nutrition and health research (NuGO) (2004-2010)”, que continua el seu camí en forma de consorci d’universitats i centres d’investigació.

LÍNIES DE RECERCA

  • Línia: Alimentació perinatal: programació metabòlica en etapes primerenques (gestació/lactància).Investigador principal: Andreu Palou Oliver
  • Línia: Cerca de biomarcadores nutrigenòmics de salut/malaltia. Investigador principal: Andreu Palou Oliver
  • Línia: Alimentació personalitzada: estudi d’interaccions genotipus/dieta. Investigador principal: Andreu Palou Oliver
  • Línia: Alimentació funcional: recerca de compostos bioactius amb propietats funcionals. Investigador principal: Andreu Palou Oliver
  • Línia: Declaracions nutricionals i de salut; seguretat i qualitat alimentària. Investigador principal: Andreu Palou Oliver

MILLORS PUBLICACIONS DEL GRUP

Sánchez J, Picó C, Ahrens W, Foraita R, Fraterman A, Moreno L, Russo P, Siani A, Palou A.
Transcriptome analysis in blood cells from children reveals potential early biomarkers of metabolic alterations.
Int J Obes (Lond). 2017.
PMID: 28584296.

Objectives: The development of effective strategies to prevent childhood obesity and its comorbidities requires new, reliable early biomarkers. Here, we aimed to identify in peripheral blood cells potential transcript-based biomarkers of unhealthy metabolic profile associated to overweight/obesity in children.
Methods: We performed a whole-genome microarray analysis in blood cells to identify genes differentially expressed between overweight and normal weight children to obtain novel transcript-based biomarkers predictive of metabolic complications.
Results: The most significant enriched pathway of differentially expressed genes was related to oxidative phosphorylation, for which most of genes were downregulated in overweight versus normal weight children. Other genes were involved in carbohydrate metabolism/glucose homoeostasis or in lipid metabolism (for example, TCF7L2, ADRB3, LIPE, GIPR), revealing plausible mechanisms according to existing biological knowledge. A set of differentially expressed genes was identified to discriminate in overweight children those with high or low triglyceride levels.
Conclusions: Functional microarray analysis has revealed a set of potential blood-cell transcript-based biomarkers that may be a useful approach for early identification of children with higher predisposition to obesity-related metabolic alterations.International Journal of Obesity advance online publication, 27 June 2017; doi:10.1038/ijo.2017.132.

Szostaczuk N, Priego T, Palou M, Palou A, Picó C.
Oral leptin supplementation throughout lactation in rats prevents later metabolic alterations caused by gestational calorie restriction.
Int J Obes (Lond). 2017; 41(3): 360-371.
PMID: 28028317.

Objectives: Calorie-restriction during gestation in rats has been seen to produce lasting detrimental effects in the offspring, affecting energy balance control and other related metabolic functions. Our aim was to assess whether leptin supplementation throughout lactation may prevent the dysmetabolic phenotype in adulthood associated with gestational calorie restriction.
Methods: Three groups of male Wistar rats were followed: the offspring of ad libitum fed dams (controls); the offspring of 20% calorie-restricted dams during gestation (CR); and CR rats supplemented with physiological doses of leptin throughout lactation (CR-Leptin). Pups were weaned with a standard diet (SD) until 4 months of age, and then half of the animals of each group were moved to a Western diet (WD) until 6 months of age. Body weight and food intake were recorded. Energy expenditure, locomotive activity, blood parameters, liver triglycerides (TG), and gene expression and specific proteins in liver and white adipose tissue (WAT) were measured in adulthood.
Results: Adult CR rats, but not CR-Leptin rats, displayed greater adiposity index and feed efficiency (both under SD) than controls, along with lower locomotive activity and energy expenditure, higher HOMA-IR index and greater circulating TG and leptin levels. CR animals also exhibited increased values of the respiratory exchange ratio and more severe signs of hepatic steatosis under WD than CR-Leptin animals. Gene expression analysis revealed that CR, but not CR-Leptin, animals displayed indicators of lower capacity for WAT expansion, along with decreased lipogenesis and lipolytic capacity under SD, and impaired lipogenic response of the liver to WD feeding, in accordance with diminished insulin sensitivity and WAT leptin signaling.
Conclusions: Oral leptin supplementation in physiological doses throughout lactation in rats prevents most of the detrimental effects on energy homeostasis and metabolic alterations in adulthood caused by inadequate fetal nutrition.

Chaplin A, Palou A, Serra F.
Methylation analysis in fatty-acid-related genes reveals their plasticity associated with conjugated linoleic acid and calcium supplementation in adult mice.
Eur J Nutr. 2017; 56(2): 879-891.
PMID: 26700221

Purpose: DNA methylation is one of the most extensively studied mechanisms within epigenetics, and it is suggested that diet-induced changes in methylation status could be involved in energy metabolism regulation. Conjugated linoleic acid (CLA) and calcium supplementation counteract body weight gain, particularly under a high-fat (HF) diet, in adult mice. The aim was to determine whether the modulation of DNA methylation pattern in target genes and tissues could be an underlying mechanism of action.
Methods: Mice (C57BL/6J) were divided into five groups according to diet and treatment: normal fat as the control group (12 % kJ content as fat), HF group (43 % kJ content as fat), HF + CLA (6 mg CLA/day), HF + calcium (12 g/kg of calcium) and HF with both compounds. Gene expression and methylation degree of CpG sites in promoter sequences of genes involved in fatty acid metabolism, including adiponectin (Adipoq), stearoyl-CoA desaturase (Scd1) and fatty acid synthase (Fasn), were determined by bisulphite sequencing in liver and epididymal white adipose tissue.
Results: Results showed that the methylation profile of promoters was significantly altered by dietary supplementation in a gene- and tissue-specific manner, whereas only slight changes were observed in the HF group. Furthermore, changes in specific CpG sites were also associated with an overall healthier metabolic profile, in particular for calcium-receiving groups.
Conclusions: Both CLA and calcium were able to modify the methylation pattern of genes involved in energy balance in adulthood, which opens a novel area for increasing efficiency in body weight management strategies.

Díaz-Rúa R, van Schothorst EM, Keijer J, Palou A, Oliver P.
Isocaloric high-fat feeding directs hepatic metabolism to handling of nutrient imbalance promoting liver fat deposition.
Int J Obes (Lond). 2016; 40(8): 1250-9.
PMID: 27089994

Background/objectives: Consumption of fat-rich foods is associated with obesity and related alterations. However, there is a group of individuals, the metabolically obese normal-weight (MONW) subjects, who present normal body weight but have metabolic features characteristic of the obese status, including fat deposition in critical tissues such as liver, recognized as a major cause for the promotion of metabolic diseases. Our aim was to better understand metabolic alterations present in liver of MONW rats applying whole genome transcriptome analysis.
Methods: Wistar rats were chronically fed a high-fat diet isocaloric relative to Control animals to avoid the hyperphagia and overweight and to mimic MONW features. Liver transcriptome analysis of both groups was performed.
Results: Sustained intake of an isocaloric high-fat diet had a deep impact on the liver transcriptome, mainly affecting lipid metabolism. Although serum cholesterol levels were not affected, circulating triacylglycerols were lower, and metabolic adaptations at gene expression level indicated adaptation toward handling the increased fat content of the diet, an increased triacylglycerol and cholesterol deposition in liver of MONW rats was observed. Moreover, gene expression pointed to increased risk of liver injury. One of the top upregulated genes in this tissue was Krt23, a marker of hepatic disease in humans that was also increased at the protein level.
Conclusion: Long-term intake of a high-fat diet, even in the absence of overweight/obesity or increase in classical blood risk biomarkers, promotes a molecular environment leading to hepatic lipid accumulation and increasing the risk of suffering from hepatic diseases.

Petrov PD, Granados N, Chetrit C, Martínez-Puig D, Palou A, Bonet ML.
Synergistic Effects of a Mixture of Glycosaminoglycans to Inhibit Adipogenesis and Enhance Chondrocyte Features in Multipotent Cells.
Cell Physiol Biochem. 2015; 37(5): 1792-806.
PMID: 26584280

Background/aims: Multipotent mesenchymal stem cells affect homeostasis of adipose and joint tissues. Factors influencing their differentiation fate are of interest for both obesity and joint problems. We studied the impact of a mixture of glycosaminoglycans (GAGs) (hyaluronic acid: dermatan sulfate 1:0.25, w/w) used in an oral supplement for joint discomfort (Oralvisc™) on the differentiation fate of multipotent cells.
Methods: Primary mouse embryo fibroblasts (MEFs) were used as a model system. Post-confluent monolayer MEF cultures non-stimulated or hormonally stimulated to adipogenesis were chronically exposed to the GAGs mixture, its individual components or vehicle. The appearance of lipid laden cells, lipid accumulation and expression of selected genes at the mRNA and protein level was assessed.
Results: Exposure to the GAGs mixture synergistically suppressed spontaneous adipogenesis and induced the expression of cartilage extracellular matrix proteins, aggrecan core protein, decorin and cartilage oligomeric matrix protein. Hormonally-induced adipogenesis in the presence of the GAGs mixture resulted in decreased adipogenic differentiation, down-regulation of adipogenic/lipogenic factors and genes for insulin resistance-related adipokines (resistin and retinol binding protein 4), and up-regulation of oxidative metabolism-related genes. Adipogenesis in the presence of dermatan sulfate, the minor component of the mixture, was not impaired but resulted in smaller lipid droplets and the induction of a more complete brown adipocyte-related transcriptional program in the cells in the adipose state.
Conclusions: The Oralvisc™ GAGs mixture can tip the adipogenic/chondrogenic fate balance of multipotent cells away from adipogenesis while favoring chondrocyte related gene expression. The mixture and its dermatan sulfate component also have modulatory effects of interest on hormonally-induced adipogenesis and on metabolic and secretory capabilities of adipose cells.

INSTITUCIONS QUE RECONEIXEN AL GRUP DE RECERCA

  • Universitat de les Illes Balears
  • Govern de les Illes Balears
  • Govern Espanyol (varis ministeris): Ministerio de Sanidad, Servicios Sociales e Igualdad – Agencia Española de Consumo, Seguridad alimentaria y Nutrición (AECOSAN); Ministerio de Economía, Industria y Competititividad – Instituto de Salud Carlos III
  • CIBER de Fisiopatologia de la Obesidad y Nutrición (CIBEROBN)
  • Institut d’Investigació Sanitària Illes Balears (IdISBa)
  • Comissió Europea – European Food Safety Authority (EFSA)