Progesterone effects on energy metabolism and insulin resistance in menopause

Abstract

The consumption of a high-fat diet contributes largely to the development of obesity, insulin resistance, type 2 diabetes (DM2) and cardiovascular diseases. It is possible to observe that cardiovascular diseases associated with metabolic complications, such as insulin resistance and obesity, are less prevalent in young women than in men of the same age or postmenopausal women. Several mechanisms are currently considered to cause insulin resistance, such as abnormal lipid metabolism and ectopic accumulation, mitochondrial dysfunction, in addition to inflammation and endoplasmic reticulum stress. In addition, another complication associated with metabolic diseases is Non-Alcoholic Fatty Liver Disease (NAFLD), which affects about 30% of adults and up to 10% of children in developed countries. In recent decades, clinical and experimental studies have revealed that estradiol (the most potent estrogen) contributes enormously to glycemic homeostasis, probably via its receptor isoform alpha (ERalpha). In fact, the reduction in estrogen concentration during menopause is associated with increased visceral fat and, in turn, metabolic diseases such as insulin resistance, DM2 and cardiovascular diseases. The same phenotype is observed in female rodents undergoing ovariectomy, with this phenotype reversed after hormonal treatment with estradiol. However, the same consensus does not exist in women during menopause, since, while some studies demonstrate the beneficial effects of hormone replacement during this period, other studies are unable to observe benefits. Based on what has been observed in clinical studies with menopausal women and knowing that most hormone replacement treatments are performed with the hormones estradiol and progesterone together, the main objective of this project is to investigate the effects of progesterone on energy metabolism and insulin resistance in an experimental menopause model (ovariectomized female mice) fed a high-fat diet. (AU)