Efecto de diferentes factores nutricionales sobre el estrés oxidativo en el tratamiento dietético de la obesidad

Abstract

NUTRITIONAL EFECTS OF ENERGY-RESTRICTION DIETS ON OXIDATIVE STRESS Ana B Crujeiras Martinez School of Sciences, University of Navarra (Spain). 2008 Obesity and associated comorbidities such as diabetes mellitus and cardiovascular diseases, constitutes a serious public health threat. Indeed, excessive weight is a metabolic disorder, which is characterized by abnormally increased fat content potentially involving several factors. This condition is accompanied free radicals overproduction as well as mitochondrial dysfunction driving to an increase in oxidative stress. Therefore, antioxidant-rich-food consumption included in a balanced hypocaloric diets designed for treating obesity could provide protection against oxidative stress besides the recognized effects of weight loss. According to these statements, the general aims of the present research project was to study the metabolic effect of hypocaloric diet based on selected food consumption with specific antioxidant properties to be applied to the nutritional treatment of the obesity. Moreover, the effect of the weight loss and the use of these diets on oxidative stress markers at both, circulating level and gene expression in circulating mononuclear cells (PBMC), in an attempt to finding nutrigenomics markers for the development of personalized therapeutic strategies, was evaluated. in this context, in addition to the expected weight loss (-6%), a 8-week fruit-enriched hypocaloric diet reduced the ratio prooxidants/antioxidants (-30%;p=0.046), while a balanced diet with moderate caloric restriction including 4 day/week legume servings decreased (p<0.05) plasma ox-LDL (-18%), plasma MDA (-13%) and urinary 8-iso-PGF2¿Á (-38%). Moreover, after the weight loss induced by a balanced hypocaloric diet, the postprandial changes in several oxidative stress circulating biomarkers were lower than at baseline. This finding was accompanied by changes in COX15 transcripts, an essential protein for the biogenesis of citochome c oxidase, and MGST2, an important factor against the oxidative injury. Furthermore, the ATP content in blood leukocytes increased (+13.6¡À42.2 pmol/mg prot.; p=0.043) while the 2-ceto [1-13C]isocaproate (KICA) tracer mitochondrial oxidation decreased (-2.2¡À3.9%13C:p=0.037) after a 8-weeks hypocaloric diet treatment. Also, the caloric restriction treatment was associated with an increase in two sirtuins family members, NAD-dependent protein deacetylases, SIRT1 and SIRT2 gene expression (1.5(0.5) and 1.8(0.5) fold change; p=0.013, respectively) depending on the baseline antioxidant status. Taking together, this work allowed reaching the following general conclusion: Hypocaloric diets for the obesity nutritional treatment can reduce oxidative stress through not only by means of the activation of molecular mechanisms induced by the caloric restriction and the weight loss per se, but also by including food with specific antioxidant capacity such as fruit and the legumes. In addition, this study showed that circulating mononuclear cells could constitute a source of easily available mRNA to assess the gene expression and the mitochondrial bioenergetics in response to energy-restriction in the same line that the tissue biopsies and in association with parameters of the mitochondrial oxidation estimated by means of the breath test with 2-ceto[l-13C]isocaproate (KICA). Indeed, this research offer complementary information by means of minimally-invasive tests, which could help to optimize the design of slimming strategies, as well as in the search of prognosis factors concerning the complications associated to obesity in relation to the mitochondrial function and with oxidative stress.