Aims 

Non-Alcoholic Fatty Liver Disease (NAFLD) is an emerging health problem worldwide characterized by exceedingly accumulation of triglycerides (TG) within hepatocytes. Here, we evaluate whether AQP9, an aquaglyceroporin regulated by insulin that facilitates the entry of glycerol into hepatocytes, has pathophysiological relevance in NAFLD.

Methods 

Human liver biopsies were from 12 volunteers morbidly obese patients with NAFLD associated with insulin resistance and type 2 diabetes mellitus undergoing bariatric surgery. Mice fed a high fat diet (HFD) and ob/ob mice were used as animal models of NAFLD. Liver AQP9 levels were assessed by qPCR, high-density oligonucleotide microarray, immunoblotting and immunocytochemistry. The glycerol permeability (P_gly) of vesicles prepared from hepatocyte basolateral plasma membranes was assessed by stopped flow light scattering.

Results 

Both the AQP9 levels and Pgly extent in the fatty livers of ob/ob and HFD mice were significantly lower than in the control counterparts. Most AQP9 downregulation occurred at a post-translational level. Similar AQP9 dysregulation was also seen in liver biopsies by morbidly obese patients.

Conclusions 

The observed AQP9 downregulation and consequent reduction in hepatocyte glycerol permeability may be a compensatory mechanism aimed to avoiding further TG accumulation within the liver parenchima. AQP9 may prove to be a novel therapeutic target to treat a severe form of metabolic syndrome such as NAFLD.