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

Eur J Nutr. 2009 Sep;48(6):341-7. doi: 10.1007/s00394-009-0019-9. Epub 2009 Apr 10.

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/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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers / blood
  • Caloric Restriction*
  • Female
  • Gene Expression Regulation, Enzymologic*
  • Humans
  • Leukocytes, Mononuclear / enzymology
  • Lipid Peroxidation
  • Male
  • Middle Aged
  • Mitochondria / enzymology*
  • Nutritional Status
  • Obesity / blood
  • Obesity / diet therapy
  • Obesity / metabolism
  • Overweight / blood
  • Overweight / diet therapy
  • Overweight / metabolism*
  • Oxidative Stress*
  • Postprandial Period
  • RNA, Messenger / metabolism
  • Statistics, Nonparametric
  • Tachyphylaxis*
  • Weight Loss
  • White People

Substances

  • Biomarkers
  • RNA, Messenger