Liver glycerol permeability and Aquaporin-9 are dysregulated in a murine model of Non-Alcoholic Fatty Liver Disease
One form of liver steatosis, namely Non-Alcoholic Fatty Liver Disease (NAFLD), is a worrisome health problem worldwide<br />characterized by intrahepatic triacylglycerol (TG) overaccumulation. NAFLD is a common feature of metabolic syndrome<br />being often associated with obesity, dysli...
| Autores: | , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2013 |
| País: | Argentina |
| Institución: | Consejo Nacional de Investigaciones Científicas y Técnicas |
| Repositorio: | CONICET Digital (CONICET) |
| Idioma: | inglés |
| OAI Identifier: | oai:ri.conicet.gov.ar:11336/516 |
| Acceso en línea: | http://hdl.handle.net/11336/516 |
| Access Level: | acceso abierto |
| Palabra clave: | Aquaporin-9 glycerol NAFLD liver https://purl.org/becyt/ford/3 https://purl.org/becyt/ford/3.1 |
| Sumario: | One form of liver steatosis, namely Non-Alcoholic Fatty Liver Disease (NAFLD), is a worrisome health problem worldwide<br />characterized by intrahepatic triacylglycerol (TG) overaccumulation. NAFLD is a common feature of metabolic syndrome<br />being often associated with obesity, dyslipidemia and diabetes and mostly closely linked to insulin resistance. The<br />mechanism of NAFLD pathogenesis is object of intense investigation especially regarding complex systems ultimately<br />resulting in excessive TG deposition in hepatocytes. However, scarce is the attention about the relevance of hepatic import<br />of glycerol, the other primary source (as glycerol-3-phosphate) of increased TG in hepatocytes. Obese leptin-deficient (ob/<br />ob) mice, an animal model of NAFLD, were used to evaluate the functional involvement of Aquaporin-9 (AQP9), the major<br />pathway of liver glycerol entry, in hepatosteatosis. By RT-PCR and qPCR, the level of Aqp9 mRNA in the liver of starved obese<br />mice was comparable with the corresponding control lean littermates. By immunoblotting, the AQP9 protein at the<br />hepatocyte sinusoidal plasma membrane of obese mice was markedly lower (33%) than lean mice, a finding fully confirmed<br />by immunohistochemistry. By stopped-flow light scattering, the liver glycerol permeability of ob/ob mice was significantly<br />lower (53%) than lean mice, a finding consistent with both the observed down-regulation of AQP9 protein and increased<br />level of plasma glycerol characterizing obese mice. In summary, our results suggest implication of AQP9 in liver steatosis.<br />The reduction of hepatocyte AQP9 and, consequently, glycerol permeability might be a defensive mechanism to counteract<br />further fat infiltration in liver parenchyma. |
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