Adiponectin regulates aquaglyceroporin expression in hepatic stellate cells altering their functional state

作者：Tardelli Matteo; Moreno Viedma Veronica; Zeyda Maximilian; Itariu Bianca K; Langer Felix B; Prager Gerhard; Stulnig Thomas M

来源：Journal of Gastroenterology and Hepatology, 2017, 32(1): 253-260.

DOI：10.1111/jgh.13415

<jats:title>Abstract</jats:title><jats:sec><jats:title>Background and Aim</jats:title><jats:p>Obesity is a major risk factor for liver fibrosis and tightly associated with low levels of adiponectin. Adiponectin has antifibrogenic activity protecting from liver fibrosis, which is mainly driven by activated hepatic stellate cells (HSC). Aquaporins are transmembrane proteins that allow the movement of water and, in case of aquaglyceroporins (AQPs), of glycerol that is needed in quiescent HSC for lipogenesis. Expression of various AQPs in liver is altered by obesity; however, the mechanisms through which obesity influences HSCs activation and AQPs expression remain unclear. This study aimed to identify obesity‐associated factors that are related to HSC AQPs expression activation and lipid storage.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Correlations between serum adipokine levels and hepatic AQPs gene expression were analyzed from a cohort of obese patients. AQP and fibrotic gene expression was determined in a HSC line (LX2) and in a hepatocyte cell line (HepG2) after stimulation with adiponectin using quantitative real‐time polymerase chain reaction.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>We found that serum adiponectin significantly correlated with liver AQP3, AQP7, AQP9 gene expressions. <jats:italic>In vitro</jats:italic>, adiponectin induced upregulation of AQP3 gene and AQP3 protein expression in human HSCs, but not in hepatocytes, while AQP7, AQP9 remained undetectable. Accordingly, HSC stimulated with adiponectin increased glycerol uptake, lipogenic gene expression, and lipid storage while downregulating activation/fibrosis markers.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>These findings demonstrate that adiponectin is a potent inhibitor of HSC activation and induces AQPs expression. Thus, low serum levels of adiponectin could be a mechanism how obesity affects the functional state of HSC, thereby contributing to obesity‐associated liver fibrosis.</jats:p></jats:sec>

• 出版日期2017-1