Estudio de los efectos metabólicos y transcriptómicos de diferentes concentraciones de oxígeno para su aplicación en la obesidad: modelos in vivo e in vitro

Abstract

Obesity is a major public health problem that commonly leads to the initiation and development of a number of chronic diseases such as type 2 diabetes, cardiovascular diseases and different metabolic syndrome manifestations. Adipose tissue often becomes poorly oxygenated in obese subjects, and this feature may provide cellular mechanisms involving chronic inflammation processes such as the release of pro-inflammatory cytokines and macrophage infiltration. Hypoxia has been shown to reduce appetite and adipose tissue mass in humans at certain circumstances, while hyperoxia can ameliorate the hypoxic state and reduce local inflammation in some cell lines and organs. Thus, the purpose of the present study was to determine whether hypoxia and hyperoxia exposures could induce favorable changes in specific metabolic variables and gene expression pathways in both rats and 3T3-L1 adipocyte models. A cyclic hypoxia (8% O2) produced appetite suppression in rats, leading to a significant decrease in weight gain compared to control group. However, this weight reduction was accompanied by a loss of muscle mass. On the other hand, exposing rats to hyperoxia (40% O2) produced no relevant differences between groups concerning body weight and biochemical values measured after the treatment. In adipocytes exposed to 95% O2 a decrease of lactate production and an increase of glycerol release was found, along with a decrease in the expression of GLUT-1 and ANGPTL4 and an increase in PPAR-γ mRNA levels, suggesting that hyperoxia could exert a beneficial effect on the modulation of the metabolism of glucose and lipids, and may play an indirect role in improving insulin sensitivity.