Tachyphylaxis effects on postprandial oxidative stress and mitochondrial-related gene expression in overweight subjects after a period of energy restriction.

BACKGROUND Postprandially induced oxidative stress can cause damage to mitochondrial components and initiate cellular degradative processes; which are related to obesity comorbidities. AIM OF THE STUDY This trial sought to determine whether weight loss induced by caloric restriction provides antioxidant protection to reduce the postprandial response of mitochondrial function and oxidative stress markers. METHODS A group of overweight/obese volunteers (n = 17; 39 +/-7 years, 32.5 +/- 4.8 kg/m(2)) followed an 8-week hypocaloric diet. Volunteers provided blood samples at fasting and 2-h after a test drink (CHO: 95% E, PROT: 5% E and containing antioxidants) and these were examined for postprandial oxidative stress responses, before and after the nutritional intervention. The expression of four mitochondrial-related genes, COX15, NDUFS2, MGST2 and TNF-alfa, was measured in peripheral blood mononuclear cells (PBMC) by quantitative RT-PCR. Lipid peroxidation and nitrosative stress biomarkers, total antioxidant capacity (AOP), uric acid and glutathione peroxidase were also determined. RESULTS Before nutritional treatment, the test drink induced a postprandial increase in lipid peroxidation and nitrosative stress biomarkers with a concomitant increase in the AOP. The increase in postprandial oxidative stress biomarkers was accompanied by a decrease in PBMC COX15 mRNA levels. Interestingly, after the weight loss period (-5.8 +/- 2.3%), the postprandial-induced changes were lower than at the beginning of the study and involved oxidative stress biomarkers and the COX15 and MGST2 transcripts. This finding suggests the occurrence of a tachyphylactic process. CONCLUSIONS We demonstrate for the first time that the well-known effect of energy restriction on oxidative stress is accompanied by a tolerance mechanism on the postprandial oxidative stress response and mitochondrial function-related genes. Indeed, the COX15 and MGST2 gene expression assays in PBMC emerged as valuable nutrigenomic biomarkers of the oxidative response under energy-restriction conditions.