Orchestrated downregulation of genes involved in oxidative metabolic pathways in obese vs. lean high-fat young male consumers

J Physiol Biochem. 2011 Mar;67(1):15-26. doi: 10.1007/s13105-010-0044-4. Epub 2010 Sep 30.


There are major variations in the susceptibility to weight gain among individuals under similar external influences (decreased physical activity and excessive calorie intake), depending on the genetic background. In the present study, we performed a microarray analysis and real-time PCR validations in order to find out differential gene expression in subcutaneous abdominal adipose tissue from two groups of subjects that despite living in similar environmental conditions such as a habitual high-fat dietary intake (energy as fat >40%) and similar moderate physical activity, some of them were successfully "resistant" (lean) to weight gain, while others were "susceptible" to fat deposition (obese). The classification of up- and downregulated genes into different categories, together with the analysis of the altered biochemical pathways, revealed a coordinated downregulation of catabolic pathways operating in the mitochondria: fatty acid β oxidation (P = 0.008), tricarboxylic acid cycle (P = 0.001), and electron transport chain (P = 0.012). At the same time, glucose metabolism (P = 0.010) and fatty acid biosynthesis (P = 0.011) pathways were also downregulated in obese compared to lean subjects. In conclusion, our data showed an orchestrated downregulation of nuclear-encoded mitochondrial gene expression. These genes are involved in cellular respiration and oxidative metabolic pathways and could play a role in the susceptibility to weight gain in some individuals.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • 3-Hydroxyacyl CoA Dehydrogenases / genetics
  • 3-Hydroxyacyl CoA Dehydrogenases / metabolism
  • Acyl-CoA Dehydrogenases / genetics
  • Acyl-CoA Dehydrogenases / metabolism
  • Adipose Tissue / metabolism*
  • Adult
  • Citric Acid Cycle / genetics
  • Dietary Fats / administration & dosage
  • Down-Regulation
  • Electron Transport / genetics
  • Electron-Transferring Flavoproteins / genetics
  • Electron-Transferring Flavoproteins / metabolism
  • Fatty Acid Synthases / genetics
  • Fatty Acid Synthases / metabolism
  • Fatty Acids / biosynthesis*
  • Gene Expression Regulation / genetics*
  • Genetic Predisposition to Disease / genetics
  • Humans
  • Iron-Sulfur Proteins / genetics
  • Iron-Sulfur Proteins / metabolism
  • Male
  • Mitochondria / genetics
  • Mitochondria / metabolism*
  • Obesity / genetics*
  • Oxidation-Reduction
  • Oxidative Phosphorylation
  • Oxidoreductases Acting on CH-NH Group Donors / genetics
  • Oxidoreductases Acting on CH-NH Group Donors / metabolism
  • Polymerase Chain Reaction / standards
  • Protein Array Analysis / standards*
  • Stearoyl-CoA Desaturase / genetics
  • Stearoyl-CoA Desaturase / metabolism
  • Thinness / genetics*


  • Dietary Fats
  • Electron-Transferring Flavoproteins
  • Fatty Acids
  • Iron-Sulfur Proteins
  • 3-Hydroxyacyl CoA Dehydrogenases
  • Stearoyl-CoA Desaturase
  • Acyl-CoA Dehydrogenases
  • Oxidoreductases Acting on CH-NH Group Donors
  • electron-transferring-flavoprotein dehydrogenase
  • Fatty Acid Synthases