Susceptibilidad o resistencia al desarrollo de obesidad inducida por la dieta en humanosidentificación de genes del tejido adiposo implicados mediante tecnología microarray

Resumen

Susceptibilidad o resistencia al desarrollo de obesidad inducida por la dieta en humanos: identificación de genes del tejido adiposo implicado mediante tecnología microarray. Susceptibility or resistance to diet induced obesity in humans: identification of implicated genes from adipose tissue by microarray technology The aim of this doctoral thesis was to look for genetic and metabolic differences determining the predisposition or resistance to develop obesity and metabolic syndrome in two groups of young subjects (21 to 35 year old) that despite having habitual similar energy intake (with similar high proportion of energy as fat >40%) and similar patterns of physical activity, one group of volunteers remained lean, whereas the other group developed obesity and higher risk of developing the metabolic syndrome. The postpandrial measurements after a lipid rich meal study revealed that obese subjects presented a reduced thermogenic effect of food as well as a more positive fat balance compared with lean individuals. Using oligonucleotide microarray technology, we found 151 down-regulated and 85 up-regulated genes in subcutaneous abdominal adipose tissue from obese vs. lean subjects. The pathway analysis revealed a down regulation of catabolic pathways operating in the mitochondria (fatty acid946; 61472; oxidation, TCA cycle and electron transport chain). Furthermore, obese subjects showed a dysregulation of genes involved lipolysis, mRNA levels o ZAG, a lipolytic adipokine, were lower in obese subjects. In contrast, CES1 gene expression, an adipocyte lipase, was up regulated in the obese and associated with higher risk for cardiovascular disease. Moreover, a dysregulation in genes involved in the cholesterol transport and triglyceride storage in the adipocyte, was observed in obese subjects. These data together with the down regulation of AQP7 gene reinforce the hypothesis of impaired regulation in the mechanism controlling adipose tissue buffering capacity in obese subjects which has been proposed as a triggering mechanism of inflammation and the development of metabolic syndrome. In fact, our results revealed that genes involved in biological process of inflammation, extracellular remodelling and angiogenesis were differentially upregulated in subcutaneous adipose tissue of obese subjects. Taking all data together, our results suggest that a genetic background favouring chronic disturbance of metabolic homeostasis could ead to a major predisposition to become obese.