Effect of glucocorticoids on glyceroneogenesis in adipose tissue: A systematic review

Glyceroneogenesis is important for the maintenance of fat content in white adipose tissue (WAT). An increase in WAT, and especially the pattern of fat distribution, specifically in visceral depots, potentially contributes to cardiovascular and metabolic diseases, such as type 2 diabetes mellitus, myocardial infarction and hypertension. Recent studies have shown important differences in glyceroneogenesis of different fat sites under the administration of glucocorticoids (GCs). Such differences need to be analysed with criteria evidencing the parameter studied, the type of corticoid, the form of administration and also the tissue studied. PubMed, Scopus and Virtual Health Library were used to search for articles that analysed the effect of GCs on glyceroneogenesis in different sites of adipose tissue in mammals and primary cultures. GCs decrease the glyceroneogenesis in epididymal WAT (EWAT) and also decrease the expression of the mRNA, content and activity of phosphoenolpyruvate carboxykinase (PEPCK-C), key enzyme of glyceroneogenesis. However, in retroperitoneal WAT (RWAT), although there is no consensus about the effect of GCs on PEPCK mRNA, GCs increase PEPCK-C activity and glyceroneogenesis flux. In inguinal WAT (IWAT) an in vitro study showed an increase in the PEPCK mRNA induced by dexamethasone. However, prednisolone does not change glyceroneogenesis flux. In interscapular brown adipose tissue (IBAT) prednisolone or dexamethasone does not change PEPCK-C activity in control diet-fed rats but led to a decrease in PEPCK-C activity in fasted- or high-fat/low-carbohydrate diet-fed rats, as well as in suckling rats. Despite that fact that GCs have different potencies, the same dose of dexamethasone reduces PEPCK-C activity in EWAT, but not in RWAT and IBAT from control-diet fed rats. In summary, the data presented in this article show that GCs differentially regulate glyceroneogenesis in different sites of adipose tissue. Further experiments are needed to firmly establish our hypothesis and clarify the mechanisms involved.