Vitamina D y enfermedad de hígado graso no alcohólico: nexo de unión y suplementación nutricional

Introducción: la enfermedad de hígado graso no alcohólico (EHGNA) es la patología hepática con mayor prevalencia en la población, caracterizada por la acumulación lipídica e inflamación en los hepatocitos. La vitamina D podría tener un papel beneficioso en EHGNA a través de sus propiedades antiinflamatorias y antifibróticas. Objetivo: revisar la relación entre los niveles sanguíneos de vitamina D y el desarrollo de EHGNA, evaluar los efectos de la suplementación nutricional de vitamina D en los marcadores de afectación hepática y analizar los suplementos y productos alimenticios con vitamina D disponibles en España. Material y Métodos: utilización de la base de datos PubMed como principal fuente bibliográfica mediante la metodología PRISMA, así como la herramienta BotPlus para los complementos alimenticios. Resultados: los pacientes con EHGNA presentan menores niveles sanguíneos de vitamina D en sangre que la población general. La suplementación nutricional con vitamina D ayuda a normalizar sus niveles y disminuye los niveles de marcadores de inflamación (IL-6 y TNF-α), pero no los de enzimas hepáticas. Se observan 455 complementos alimenticios con vitamina D en España, de los cuales un 70% son multivitamínicos, 25% son productos alimenticios y 5% suplementos exclusivos de vitamina D. Conclusiones: la vitamina D podría ser un factor nutricional a considerar en EHGNA, incluyendo la suplementación como una medida adicional a las estrategias nutricionales ya establecidas para esta patología.Introduction: non-alcoholic fatty liver disease (NAFLD) is the most prevalent hepatic pathology in population, characterized by lipid accumulation and inflammation in hepatocytes. Vitamin D could have a beneficial role in NAFLD through anti- inflammatory and antifibrotic features in the liver. Aim: Review the relationship between vitamin D blood levels and NAFLD, evaluate the effects of vitamin D supplementation and hepatic biomarkers and analyse the supplements and nutritional products with vitamin D available in Spain. Material & Methods: Use of database PubMed as the main bibliographic source using PRISMA methodology, as well as BotPlus tool for nutritional products. Results: patients with NAFLD show lower vitamin D blood levels than healthy people. Vitamin D supplementation lowers the levels of inflammatory biomarkers (IL-6 and TNF-α), but not the levels of hepatic enzymes. Conclusions: vitamin D could be a nutritional factor to consider in NAFLD, including supplementation as an additional measure to the nutritional strategies already established for this pathology

Avances en nutrición molecular: nutrigenómica y/o nutrigenética

La aplicación de las técnicas de la biología molecular y el éxito del Proyecto Genoma Humano ha abierto una nueva era tanto en Medicina como en Nutrición. Hasta la fecha, al menos, 1.000 genes humanos causantes de enfermedades han sido identificados y parcialmente caracterizados, el 97% de los cuales sabemos ahora que son causantes de enfermedades monogénicas. Sin embargo, otras patologías como la obesidad, enfermedad cardiovascular, diabetes, cáncer se deben a complejas interacciones entre diversos genes y factores ambientales. A pesar de los numerosos estudios de asociación, más de 600 publicados desde 2002, la base molecular de las enfermedades crónicas es todavía incierta. La información sobre polimorfismos de nucleótidos y mapas de haplotipos son recursos adicionales para identificar genes involucrados en enfermedades. El desarrollo genómico se aproxima, sin embargo, no se conocen con precisión algunos componentes de la dieta y sus mecanismos, que influyen de forma importante en la expresión de la información genética y en las alteraciones patológicas. La industria alimentaria tiene la oportunidad de utilizar los componentes bioactivos de los alimentos para mejorar la salud y evitar las enfermedades teniendo en cuenta la constitución genética de los consumidores. Esta nueva era de la nutrición molecular —interacciones genes-nutrientes— puede crecer en diversas direcciones, aunque hay dos esenciales. De una parte, el estudio de la influencia de los nutrientes sobre la expresión de genes (nutrigenómica) y de otra conocer la influencia de las variaciones genéticas en la respuesta del organismo a los nutrientes (nutrigenética)

Down-regulation of heart HFABP and UCP2 gene expression in diet-induced (cafeteria) obese rats.

Long-term exposure to hypercaloric high fat diet induced marked tissue fatty acid accumulation and may influence cell function. Previous results in our laboratory showed that uncoupling proteins (UCPs) and fatty acid-binding protein (FABP) gene expression are changed in adipose tissue and skeletal muscle tissue in diet-induced (cafeteria) obese animals. The aim of this study was to examine heart FABP (HFABP) and UCP2 gene expressions in dietary obese rats. Rats fed on a high-fat diet for 65 days had significantly higher fat stores and body weight than control rats. Interestingly, we found that both HFABP and UCP2 mRNA levels were significantly reduced in cafeteria-obese rats when compared to control animals. Moreover, a statistically significant correlation was observed between the two gene expression levels. The down-regulation of heart HFABP and UCP2 parallels the lower lipid utilization which may account for an enhanced fat deposition. It is plausible that these two genes are regulated by the same family of transcription factors

Biomarcadores del estado inflamatorio: nexo de unión con la obesidad y complicaciones asociadas

El objetivo de este trabajo ha consistido en realizar una revisión de los biomarcadores que actualmente se proponen como el nexo de unión entre la inflamación, la obesidad y complicaciones asociadas, seleccionando los estudios llevados a cabo y las cuestiones pendientes. Cada vez hay mayor evidencia científica de que la inflamación puede jugar un papel importante en la etiología de diversas enfermedades crónicas de gran relevancia para la salud pública. En los últimos años, distintos estudios han sugerido que la obesidad podría ser un desorden inflamatorio. Asimismo, el estrés oxidativo se ha propuesto como un potencial inductor de la inflamación y de la susceptibilidad a la obesidad y patología asociadas. Entre los biomarcadores relacionados con la obesidad, la resistencia insulínica, las enfermedades cardiovasculares y el síndrome metabólico se encuentran: el factor de necrosis tumoral alfa, interleuquinas 6 y 18, angiotensinógeno, factor de crecimiento TGF-beta, inhibidor de la activación del plasminógeno, leptina, resistina, proteína C reactiva, amiloide A, ácido siálico, marcadores de disfunción endotelial (factor von Willebrand, ICAMs, vCAMs) factor 3 del sistema del complemento, haptoglobina, glicoproteína zinc-alfa2, eotaxina, visfatina, apelina, alfa1-antitripsina, vaspina, omentina, proteína transportadora de retinol 4, ceruloplasmina, adiponectina y desnutrina. Algunos de estos biomarcadores son buenos predictores de riesgo cardiovascular (inhibidor de la activación de plasminógeno 1, angiotensinógeno, fibrinógeno, ácido siálico, factor 3 del complemento y proteína C reactiva), adiposidad (leptina, visfatina, resistina, haptoglobina) y/o resistencia insulínica (ácido siálico, proteína C reactiva, inhibidor de la activación de plasminógeno 1, factor von Willebrand). Sin embargo, todavía queda por dilucidar el papel de muchos de ellos en la etiología de la obesidad y comorbilidades asociadas en humanos, así como los factores implicados en su regulación

Factors Associated with Sarcopenia and 7-Year Mortality in Very Old Patients with Hip Fracture Admitted to Rehabilitation Units: A Pragmatic Study

Background: Admitted bedridden older patients are at risk of the development of sarcopenia during hospital stay (incident sarcopenia). The objective of this study was to assess the factors associated with sarcopenia (incident and chronic) and its impact on mortality in older people with hip fracture. Methods: A multicenter, pragmatic, prospective observational study was designed. Older subjects with hip fracture admitted to two rehabilitation units were included. Sarcopenia was assessed at admission and at discharge according to the revised EWGSOP (European Working Group on Sarcopenia in Older People) consensus definition. The mortality was evaluated after 7 years of follow-up. Results: A total of 187 subjects (73.8% women) age 85.2 ± 6.3 years were included. Risk factors associated to incident and chronic sarcopenia were undernutrition (body mass index-BMI and Mini Nutritional Assessment-Short Form-MNA-SF), hand-grip strength and skeletal muscle index. During follow-up 114 patients died (60.5% sarcopenic vs. 39.5% non-sarcopenic, p = 0.001). Cox regression analyses showed that factors associated to increased risk of mortality were sarcopenia (HR: 1.67, 95% CI 1.11-2.51) and low hand-grip strength (HR: 1.76, 95% CI 1.08-2.88). Conclusions: Older patients with undernutrition have a higher risk of developing sarcopenia during hospital stay, and sarcopenic patients have almost two times more risk of mortality than non-sarcopenic patients during follow-up after hip fracture

Higher baseline irisin concentrations are associated with greater reductions in glycemia and insulinemia after weight loss in obese subjects

Irisin is assumed to be a relevant link between muscle and weight maintenance as well as to mediate exercise benefits on health. The aim of this study was to assess the possible associations between irisin levels and glucose homeostasis in obese subjects with metabolic syndrome (MetS) following an energy-restricted treatment. Ninety-six adults with excessive body weight and MetS features underwent a hypocaloric dietary pattern for 8 weeks, within the RESMENA randomized controlled trial (www.clinicaltrials.gov; NCT01087086). After the intervention, dietary restriction significantly reduced body weight and evidenced a dietary-induced decrease in circulating levels of irisin in parallel with improvements on glucose homeostasis markers. Interestingly, participants with higher irisin values at baseline (above the median) showed a greater reduction on glucose (P=0.022) and insulin (P=0.021) concentrations as well as on the homeostasis model assessment index (P=0.008) and triglycerides (P=0.006) after the dietary intervention, compared with those presenting low-irisin baseline values (below the median). Interestingly, a positive correlation between irisin and carbohydrate intake was found at the end of the experimental period. In conclusion, irisin appears to be involved in glucose metabolism regulation after a dietary-induced weight loss

Oxidized LDL levels decreases after the consumption of ready-to-eat meals supplemented with cocoa extract within a hypocaloric diet

Background and aims Cocoa flavanols are recognised by their favourable antioxidant and vascular effects. This study investigates the influence on health of the daily consumption of ready-to-eat meals supplemented with cocoa extract within a hypocaloric diet, on middle-aged overweight/obese subjects. Methods and results Fifty healthy male and female middle-aged volunteers [57.26 ± 5.24 years and body mass index (BMI) 30.59 ± 2.33 kg/m2] were recruited to participate in a 4 week randomised, parallel and double-blind study. After following 3 days on a low-polyphenol diet, 25 volunteers received meals supplemented with 1.4 g of cocoa extract (645.3 mg of polyphenols) and the other 25 participants received control meals, within a 15% energy restriction diet. On the 4th week of intervention individuals in both dietary groups improved (p < 0.05) anthropometric, body composition, blood pressure and blood biochemical measurements. Oxidised LDL cholesterol (oxLDL), showed a higher reduction (p = 0.030) in the cocoa group. Moreover, myeloperoxidase (MPO) levels decreased only in the cocoa supplemented group (p = 0.007). Intercellular Adhesion Molecule-1 (sICAM-1) decreased significantly in both groups, while Vascular Cell Adhesion Molecule-1 (sVCAM-1) did not present differences after the 4 weeks of intervention. Interestingly, cocoa intake showed a different effect by gender, presenting more beneficial effects in men. Conclusions The consumption of cocoa extract as part of ready-to-eat meals and within a hypocaloric diet improved oxidative status (oxLDL) in middle-aged subjects, being most remarkable in males

Changes in lysophospholipids and liver status after weight loss: the RESMENA study

Background: Obesity and comorbidities such as non-alcoholic fatty liver disease (NAFLD) are major public health burdens. Alterations in lipid metabolism are involved in hepatic diseases. The objective of this study was to assess the influence of weight loss on lysophospholipid (LP) metabolism and liver status in obese subjects as well as to provide new evidence regarding the interaction of LP metabolism as a key factor in the onset and management of obesity-related diseases such as liver damage. Methods: Thirty-three subjects from the RESMENA (Reduction of Metabolic Syndrome in Navarra, NCT01087086) study were selected based on their Fatty Liver Index (FLI). Plasma lipid species (lysophosphatidilcholine: LPC, lysophosphatidilethanolamines: LPE and lysophosphatidylinositols: LPI specifically) were determined by LC-MS, while waist circumference (WC) and other non-invasive liver markers such as, FLI and BAAT scores as well as dietary records, anthropometrical measurements, body composition by DXA and other metabolic determinants were analyzed before and after a six-month hypocaloric nutritional intervention. Results: Computed Z-scores of total LP (LPC, LPE, and LPI) were significantly decreased after 6-months of following a hypocaloric diet. Specifically, LPC14:0, LPC15:0, LPC16:1, LPC18:4, LPC20:4, showed clear relationships with weight loss. Changes in FLI score, WC and BAAT score revealed associations with general changes in LPC score. Interestingly the BAAT score was statistically associated with the LPC score after adjustment for weight loss. Conclusion: The lipidomic LPC profile analysis revealed a generalized decrease in circulating lysophospholipids after weight loss. The involvement of particular LP in liver metabolism and obesity merit further attention, as some of these specific non-invasive liver markers were reduced independently of weight loss

Dietary total antioxidant capacity and obesity in children and adolescents

Dietary antioxidant intake has been suggested to protect against oxidative damage and related clinical complications. The aim of this study was to assess the potential relationships between the dietary total antioxidant capacity (TAC) and obesity-related features in children and adolescents. Anthropometric variables from 369 children and adolescents were measured (184 obese and 185 control). A validated food-frequency questionnaire was used to calculate the TAC and the daily nutrient and energy intake. Dietary TAC showed positive associations with fiber, folic acid, magnesium, and vitamins A, C and E. BMI, SDS-BMI and total body fat were inversely associated with dietary TAC only in obese subjects. These data suggest that dietary TAC may be a potential indicator of the risk to develop obesity-related features and could be considered as a useful method in assessing antioxidant intake

DNA hypermethylation of the serotonin receptor type-2A gene is associated with a worse response to a weight loss intervention in subjects with metabolic syndrome

Understanding the regulation of gene activities depending on DNA methylation has been the subject of much recent study. However, although polymorphisms of the HTR2A gene have been associated with both obesity and psychiatric disorders, the role of HTR2A gene methylation in these illnesses remains uncertain. The aim of this study was to evaluate the association of HTR2A gene promoter methylation levels in white blood cells (WBC) with obesity traits and depressive symptoms in individuals with metabolic syndrome (MetS) enrolled in a behavioural weight loss programme. Analyses were based on 41 volunteers (mean age 49 ± 1 year) recruited within the RESMENA study. Depressive symptoms (as determined using the Beck Depression Inventory), anthropometric and biochemical measurements were analysed at the beginning and after six months of weight loss treatment. At baseline, DNA from WBC was isolated and cytosine methylation in the HTR2A gene promoter was quantified by a microarray approach. In the whole-study sample, a positive association of HTR2A gene methylation with waist circumference and insulin levels was detected at baseline. Obesity measures significantly improved after six months of dietary treatment, where a lower mean HTR2A gene methylation at baseline was associated with major reductions in body weight, BMI and fat mass after the treatment. Moreover, mean HTR2A gene methylation at baseline significantly predicted the decrease in depressive symptoms after the weight loss treatment. In conclusion, this study provides newer evidence that hypermethylation of the HTR2A gene in WBC at baseline is significantly associated with a worse response to a weight-loss intervention and with a lower decrease in depressive symptoms after the dietary treatment in subjects with MetS