Non-Alcoholic Fatty Liver Disease (NAFLD), a pathology caused by excessive accumulation of triglycerides (TG) within hepatocytes, is recognized as the leading cause of chronic liver disease in adults and children worldwide. NAFLD is often associated with obesity and diabetes and mostly closely linked to insulin resistance. Investigation into NAFLD pathogenesis has increased exponentially in the last years. Main pathways include increased visceral adipose tissue and insulin resistance, altered hepatic fatty acid export, oxidation, and desaturation within the liver, and the initiation and subsequent effects of lipotoxicity. Altered uptake of glycerol by hepatocytes is also a major intersecting component, however, the underlying mechanism has begun to be understood only recently after Aquaporin-9 (AQP9), an aquaglyceroporin regulated by insulin and leptin, was found to mediate liver glycerol permeability. AQP9 is dysregulated in the liver of morbidly obese patients with NAFLD associated with insulin resistance and diabetes and in animal models of NAFLD. The reduction in AQP9 expression and consequent decrease of glycerol influx into steatotic hepatocytes is hypothesized to be a compensatory mechanism to avoid further infiltration of TGs in liver parenchyma. Besides being a new important player in metabolic homeostasis AQP9 may prove a novel target to treat therapeutically NAFLD, a common feature of metabolic syndrome.
Hepatic uptake of glycerol and Aquaporin-9 are altered in Non-Alcoholic Fatty Liver Disease
CALAMITA, Giuseppe
2013-01-01
Abstract
Non-Alcoholic Fatty Liver Disease (NAFLD), a pathology caused by excessive accumulation of triglycerides (TG) within hepatocytes, is recognized as the leading cause of chronic liver disease in adults and children worldwide. NAFLD is often associated with obesity and diabetes and mostly closely linked to insulin resistance. Investigation into NAFLD pathogenesis has increased exponentially in the last years. Main pathways include increased visceral adipose tissue and insulin resistance, altered hepatic fatty acid export, oxidation, and desaturation within the liver, and the initiation and subsequent effects of lipotoxicity. Altered uptake of glycerol by hepatocytes is also a major intersecting component, however, the underlying mechanism has begun to be understood only recently after Aquaporin-9 (AQP9), an aquaglyceroporin regulated by insulin and leptin, was found to mediate liver glycerol permeability. AQP9 is dysregulated in the liver of morbidly obese patients with NAFLD associated with insulin resistance and diabetes and in animal models of NAFLD. The reduction in AQP9 expression and consequent decrease of glycerol influx into steatotic hepatocytes is hypothesized to be a compensatory mechanism to avoid further infiltration of TGs in liver parenchyma. Besides being a new important player in metabolic homeostasis AQP9 may prove a novel target to treat therapeutically NAFLD, a common feature of metabolic syndrome.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
