Sulfated glucuronomannan hexasaccharide G6S1 enhanced lipolysis and lipophagy via PPARα pathway

Nonalcoholic fatty liver disease (NAFLD) is considered as the hepatic manifestation of metabolic syndrome, ranging from benign steatosis to severe non-alcoholic steatohepatitis. Recently, it has been found that lipophagy plays a pivotal role in lipid turnover, which can alleviate NAFLD in hepatocytes. In this study, we found that a highly sulfated glucuronomannan hexamer G6S1 has the ability to enhance lipophagy. When treated with G6S1, the number and the size of lipid droplet (LD) decreased significantly on hepatocytes AML12 cells. Western blot results showed that the expressions of the lipolysis-related proteins increased, while the expressions of proteins that is responsible for lipid transportation and synthesis exhibited no significant change. Immunofluorescence assay and electron microscopy results showed an increase of autophagy related protein expression level and lysosome number in hepatocytes treated with G6S1, suggesting that G6S1 could also promote lipophagy. A significant increase of peroxisome proliferator-activated receptor alpha (PPAR alpha) expression level was detected in G6S1 treated cells, suggesting that G6S1 may promote autophagy via enhancing the expression of PPAR alpha. In addition, these effects could be inhibited after treatment with autophagy inhibitor 3-methyladenine (3-MA) and PPAR alpha inhibitor MK-886. These findings indicate that G6S1 can promote lipophagy via enhanced PPAR alpha expression and can result in a slowdown of lipids accumulation.

Automated summary

The highly sulfated glucuronomannan hexamer G6S1 was found to enhance lipophagy in hepatocytes, reducing the number and size of lipid droplets. It increased the expression of lipolysis-related proteins and promoted lipid turnover by enhancing PPAR alpha expression. These effects were inhibited by autophagy inhibitor 3-MA and PPAR alpha inhibitor MK-886, suggesting that G6S1 promotes lipophagy through PPAR alpha activation.