Aims. Non-Alcoholic Fatty Liver Disease (NAFLD) is the leading cause of chronic liver disease in adults and children. It is characterized by triglycerides (TG) over accumulation in hepatocytes and ranges from simple fatty liver (steatosis) to nonalcoholic steatohepatitis (NASH) and to cirrhosis. Here, we study the expression and function of AQP9, an aquaporin regulated by insulin and leptin mediating the entry of glycerol into hepatocytes, in the liver of obese women with NAFLD undergoing bariatric surgery. Methods. Obese women were classified into three groups: normoglycemia (NG; n=15), impaired glucose tolerance (IGT; n=13) and type 2 diabetes mellitus (T2DM; n=9). Blood assays were from plasma samples after an overnight fast. Liver biopsies were used to assess the levels of 1) AQP9 mRNA (qPCR) and protein (immunoblotting and immunohistochemistry), and 2) glycerol permeability (Pgly) by stopped flow light scattering. Results. The livers of obese IGT and T2DM patients showed considerably lower Pgly and AQP9 expression compared with NG women. Consistent with these data, the plasma levels of glycerol were significantly higher in the IGT and T2DM patients (T2DM >> IGT) than NG women. A similar scenario was observed in animal models of NAFLD. Conclusions. The AQP9 downregulation and consequent reduction in hepatic glycerol import may be a compensatory mechanism by which the liver contrasts further TG accumulation within its parenchyma as well as reduces hepatic gluconeogenesis.

Liver AQP9 and glycerol permeability are decreased in obese women with non-alcoholic fatty liver disease.

Gena P;SVELTO, Maria;CALAMITA, Giuseppe
2012

Abstract

Aims. Non-Alcoholic Fatty Liver Disease (NAFLD) is the leading cause of chronic liver disease in adults and children. It is characterized by triglycerides (TG) over accumulation in hepatocytes and ranges from simple fatty liver (steatosis) to nonalcoholic steatohepatitis (NASH) and to cirrhosis. Here, we study the expression and function of AQP9, an aquaporin regulated by insulin and leptin mediating the entry of glycerol into hepatocytes, in the liver of obese women with NAFLD undergoing bariatric surgery. Methods. Obese women were classified into three groups: normoglycemia (NG; n=15), impaired glucose tolerance (IGT; n=13) and type 2 diabetes mellitus (T2DM; n=9). Blood assays were from plasma samples after an overnight fast. Liver biopsies were used to assess the levels of 1) AQP9 mRNA (qPCR) and protein (immunoblotting and immunohistochemistry), and 2) glycerol permeability (Pgly) by stopped flow light scattering. Results. The livers of obese IGT and T2DM patients showed considerably lower Pgly and AQP9 expression compared with NG women. Consistent with these data, the plasma levels of glycerol were significantly higher in the IGT and T2DM patients (T2DM >> IGT) than NG women. A similar scenario was observed in animal models of NAFLD. Conclusions. The AQP9 downregulation and consequent reduction in hepatic glycerol import may be a compensatory mechanism by which the liver contrasts further TG accumulation within its parenchyma as well as reduces hepatic gluconeogenesis.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11586/30538
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