Poster Topical Area: Obesity
Location: Hall D
Poster Board Number: 728
Objectives. The subcutaneous adipose tissue (SAT) is a fat depot that contains cells capable of generate heat through diverse stimuli such as cold. This phenomenon is called browning and recently has gained attention as a possible new strategy for the treatment of obesity because it is related with beneficial metabolic effects. Experiments in humans and mice have shown that obesity impairs browning but the mechanisms involved are not clear yet. Recently, the peptide Angiotensin-(1-7)[Ang1-7] and its target, the Mas receptor, have been reported as a new mechanism for the induction of browning, therefore we decided to study if the Ang-1-7/Receptor Mas axis is altered in obese mice fed a high fat-sucrose diet (HFSD).
Methods/Results. Mice were fed with a control diet (CD) based on the recommendations of the American Institute of Nutrition (AIN93 Diet) and a HFSD for 16 weeks. HFSD mice gained more weight and more fat mass compared with the CD mice. Also HFSD mice had a reduced glucose tolerance, lean mass and had less energy expenditure compared with the CD mice. Additionally, HFSD mice had less Ang1-7 concentration in plasma. Other groups of mice were implanted with osmotic pumps in order to infuse Ang1-7 and saline for 3 days. In CD mice, the treatment with 300 mg/kg*min of Ang1-7 induced browning based on two evidences, Ang1-7 increased the oxygen consumption (VO2) measured by indirect calorimetry and increased the gene expression of the uncoupling protein 1 (Ucp1), the gold standard of browning, and some specific beige gene markers such as Cited1 and Tbx1 in the subcutaneous adipose tissue compared with the saline treated group. In HFSD mice, the treatment of 600 mg/kg*min of Ang1-7 (double dose compared to CD mice) also increased the VO2, but the effect was moderate compared with CD mice and the gene expression of the browning markers did not change compared with the saline treated group. This suggests that obesity impairs the Mas receptor pathway because exogenous Ang1-7 at a double dose was not able to reproduce the effect observed in lean mice.
Conclusions. Obesity induced by a HFSD reduces the concentration of Ang1-7 and also impairs the Mas receptor pathway that activates the browning program. This suggests that the Ang1-7/Mas receptor axis could be an attractive target for the treatment of metabolic disorders.
Mexico City, Distrito Federal, Mexico