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 RT-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 down- regulated 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
oxidation (P=0.008), TCA 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 metabolism
pathways, and could play a role in the susceptibility to weight gain in some individuals