title: Liver glycerol permeability and aquaporin-9 are dysregulated in a murine model of Non-Alcoholic Fatty Liver Disease.
abstract: 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.
authors.affiliation: Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari Aldo Moro, Bari, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Gena
authors.forename: Maria
authors.initials: M
authors.lastname: Mastrodonato
authors.forename: Piero
authors.initials: P
authors.lastname: Portincasa
authors.forename: Elena
authors.initials: E
authors.lastname: Fanelli
authors.forename: Donatella
authors.initials: D
authors.lastname: Mentino
authors.forename: Amaia
authors.initials: A
authors.lastname: Rodríguez
authors.forename: Raúl A
authors.initials: RA
authors.lastname: Marinelli
authors.forename: Catherine
authors.initials: C
authors.lastname: Brenner
authors.forename: Gema
authors.initials: G
authors.lastname: Frühbeck
authors.forename: Maria
authors.initials: M
authors.lastname: Svelto
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Calamita
mesh_terms: D000818:Animals; D020346:Aquaporins / Q000378:metabolism*; D005234:Fatty Liver / Q000401:mortality*; D005990:Glycerol / Q000378:metabolism*; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D065626:Non-alcoholic Fatty Liver Disease
chemical_list: D020346:Aquaporins; D005990:Glycerol