CONICET | Buscador de Institutos y Recursos Humanos

One form of liver steatosis, namely Non-Alcoholic Fatty Liver Disease (NAFLD), is a worrisome health problem worldwidecharacterized by intrahepatic triacylglycerol (TG) overaccumulation. NAFLD is a common feature of metabolic syndromebeing often associated with obesity, dyslipidemia and diabetes and mostly closely linked to insulin resistance. Themechanism of NAFLD pathogenesis is object of intense investigation especially regarding complex systems ultimatelyresulting in excessive TG deposition in hepatocytes. However, scarce is the attention about the relevance of hepatic importof glycerol, the other primary source (as glycerol-3-phosphate) of increased TG in hepatocytes. Obese leptin-deficient (ob/ob) mice, an animal model of NAFLD, were used to evaluate the functional involvement of Aquaporin-9 (AQP9), the majorpathway of liver glycerol entry, in hepatosteatosis. By RT-PCR and qPCR, the level of Aqp9 mRNA in the liver of starved obesemice was comparable with the corresponding control lean littermates. By immunoblotting, the AQP9 protein at thehepatocyte sinusoidal plasma membrane of obese mice was markedly lower (33%) than lean mice, a finding fully confirmedby immunohistochemistry. By stopped-flow light scattering, the liver glycerol permeability of ob/ob mice was significantlylower (53%) than lean mice, a finding consistent with both the observed down-regulation of AQP9 protein and increasedlevel of plasma glycerol characterizing obese mice. In summary, our results suggest implication of AQP9 in liver steatosis.The reduction of hepatocyte AQP9 and, consequently, glycerol permeability might be a defensive mechanism to counteractfurther fat infiltration in liver parenchyma.