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

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Abstract

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/m2) 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.

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Abbreviations

AOP:

Serum total antioxidant capacity

BMI:

Body mass index (kg/m2)

COX15:

Cytochrome c oxidase assembly protein

CR:

Caloric restriction

GPx:

Glutathione peroxidase

MDA:

Malondialdehyde

MGST2:

Microsomal glutathione S-transferase

NDUFS2:

NADH-Coenzyme Q reductase

NO:

Nitric oxide

NT:

Nitrotyrosine

Ox-LDL:

Oxidized-LDL

PBMC:

Peripheral blood mononuclear cell

TNFAIP8L1:

Tumor necrosis factor alfa-related gen

UA:

Uric acid

UV:

Ultraviolet visible

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Acknowledgments

Thanks are given to Linea Especial about Nutrition, Obesity and Health (University of Navarra LE/97) and IBERCAJA for financial support as well as to Friends of University of Navarra and CAIXANOVA that supports AB Crujeiras with a fellowship. We also wish to thank our physician Blanca E Martínez de Morentin, our nurse Salomé Pérez, our dietician María Hernandez and our technicians Ana Lorente and Verónica Ciaurriz, for excellent clinical and technical assistance. We also thank Paul Miller from the Foreign Language Institute at the University of Navarra for careful reading of the last version of this manuscript for English grammar and style.

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Correspondence to J. Alfredo Martínez.

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Crujeiras, A.B., Parra, D., Goyenechea, E. et al. Tachyphylaxis effects on postprandial oxidative stress and mitochondrial-related gene expression in overweight subjects after a period of energy restriction. Eur J Nutr 48, 341–347 (2009). https://doi.org/10.1007/s00394-009-0019-9

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  • DOI: https://doi.org/10.1007/s00394-009-0019-9

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