Liver glycerol permeability and Aquaporin-9 are dysregulated in a murine model of Non-Alcoholic Fatty Liver Disease

• Autores: Gena, Patrizia; Mastrodonato, María; Portincasa, Piero; Fanelli, Elena; Mentino, Donatella; Rodríguez, Amaia; Marinelli, Raul Alberto; Brenner, Catherine; Frühbeck, Gema; Svelto, María; Calamita, Giuseppe
• Año de publicación: 2013
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: Aquaporin-9; glycerol; NAFLD; liver
• Institución: Consejo Nacional de Investigaciones Científicas y Técnicas

One form of liver steatosis, namely Non-Alcoholic Fatty Liver Disease (NAFLD), is a worrisome health problem worldwide
characterized by intrahepatic triacylglycerol (TG) overaccumulation. NAFLD is a common feature of metabolic syndrome
being often associated with obesity, dyslipidemia and diabetes and mostly closely linked to insulin resistance. The
mechanism of NAFLD pathogenesis is object of intense investigation especially regarding complex systems ultimately
resulting in excessive TG deposition in hepatocytes. However, scarce is the attention about the relevance of hepatic import
of 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 major
pathway of liver glycerol entry, in hepatosteatosis. By RT-PCR and qPCR, the level of Aqp9 mRNA in the liver of starved obese
mice was comparable with the corresponding control lean littermates. By immunoblotting, the AQP9 protein at the
hepatocyte sinusoidal plasma membrane of obese mice was markedly lower (33%) than lean mice, a finding fully confirmed
by immunohistochemistry. By stopped-flow light scattering, the liver glycerol permeability of ob/ob mice was significantly
lower (53%) than lean mice, a finding consistent with both the observed down-regulation of AQP9 protein and increased
level 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 counteract
further fat infiltration in liver parenchyma.
Fil: Gena, Patrizia. Department of Biosciences. Biotechnologies and Biopharmaceutics. University of Bari Aldo Moro; Italy;
Fil: Mastrodonato, María. Department of Biology. University of Bari Aldo Moro; Italy;
Fil: Portincasa, Piero. Department of Biomedical Sciences and Human Oncology. University of Bari Aldo Moro; Italy;
Fil: Fanelli, Elena. Department of Biosciences. Biotechnologies and Biopharmaceutics. University of Bari Aldo Moro; Italy;
Fil: Mentino, Donatella. Department of Biology. University of Bari Aldo Moro; Italy;
Fil: Rodríguez, Amaia. Metabolic Research Laboratory. Clıínica Universidad de Navarra. The Spanish Biomedical Research Centre in Physiopathology of Obesity and Nutrition; Spain;
Fil: Marinelli, Raul Alberto. Consejo Nacional de Invest.cientif.y Tecnicas. Centro Cientifico Tecnol.conicet - Rosario. Instituto de Fisiologia Experimental (i);
Fil: Brenner, Catherine. Institut National de la Sante et de la Recherche Medicale U769. LabEx LERMIT. Universite Paris-Sud. France;
Fil: Frühbeck, Gema. Metabolic Research Laboratory. Clıínica Universidad de Navarra. The Spanish Biomedical Research Centre in Physiopathology of Obesity and Nutrition; Spain;
Fil: Svelto, María. Department of Biosciences. Biotechnologies and Biopharmaceutics. University of Bari Aldo Moro; Italy; Centro di Eccellenza di Genomica in campo Biomedico ed Agrario; Italy.;
Fil: Calamita, Giuseppe. Network of Apulian Public Research Laboratories ‘‘WAFITECH’’; Italy.;