About half of Brazilian adults are obese or overweight, and excess weight gain during pregnancy is one of the most important risk factors for the development of obesity in women. In addition to excessive weight gain during pregnancy, gestational diabetes is another metabolic problem often faced by pregnant women. Despite recent advances in understanding the physiological components that regulate energy balance, little is known about the molecular mechanisms involved in fat deposition and insulin resistance during pregnancy. It is known that pregnant women have leptin resistance. In addition, some studies have shown that expression of hypothalamic proteins known as cytokine suppressive signal (SOCS) is increased in pregnant women, in particular SOCS3. Among other effects, increased SOCS3 expression in the hypothalamus inhibits intracellular signaling induced by insulin and leptin. However, the possible involvement of SOCS3 in the etiology of leptin resistance caused by pregnancy has not yet been investigated. Thus, this project aims to generate and validate a model of genetically engineered mouse that has SOCS3 gene inactivation exclusively in cells that express the leptin receptor. Subsequently, we will investigate the role of SOCS3 in the etiology of leptin resistance observed during pregnancy. Accordingly, females with conditional deletion of SOCS3 in cells that express the leptin receptor will be mated and changes in body weight, food intake, adiposity, glycemic control, sensitivity to leptin, insulin resistance and gene expression will be evaluated throughout pregnancy. Thus, this project has the potential to reveal the molecular mechanisms involved in metabolic disorders more common during pregnancy (weight gain and insulin resistance). Furthermore, this knowledge can contribute to understanding the pathophysiology of obesity and type 2 diabetes mellitus.
News published in Agência FAPESP Newsletter about the scholarship: