Gender specific regulation of hepatic aquaporin‐9 and glycerol kinase expression in starved rats

Abstract

Glycerol is known as a product of lipolysis and an important precursor for hepatic gluconeogenesis. Nevertheless, the regulation of hepatic glycerol metabolism is far from fully elucidated. Aquaporin-9 (AQP9) has been linked to the hepatic uptake of glycerol, and inside the cell glyceriol is converted to glycerol-3-phosphate by glycerol kinase (GK). We investigated the effect of starvation on the initial hepatic glycerol metabolism and found that the hepatic AQP9 and GK are regulated in a gender specific manner. Starved male rats increased the expression of both AQP9 and GK by ~ 2-fold, whereas no changes were observed in females. The glycerol permeability of basolateral membranes from hepatocytes of starved rats was higher in males than in females. A corresponding increase in plasma glycerol levels was observed specifically in female rats. Starvation of ovariectomized rats resulted in increased expression of AQP9 as in starved males, whereas GK abundance remained unchanged. By contrast, orchiectomy decreased the abundance of GK and slightly increased AQP9 expression. Taken together, the results demonstrate that sexual dimorphism exists in the initial hepatic glycerol handling. Moreover, the results suggest that ovary derived factors are crucial for the regulation of hepatic AQP9 expression whereas testicular factors govern the expression of hepatic GK. Supported by the Danish National Research Foundation.