Dendrobium huoshanense stem polysaccharide ameliorates high fructose-induced hepatocyte lipid accumulation through decreasing miR-429 to upregulate RIP2

Dendrobium huoshanense is an edible medicinal herb. Its stem polysaccharide (DHP) can alleviate hepatic injury, but the underlying mechanism is not fully understood. Receptor-interacting protein 2 (RIP2) is an important regulator in metabolic diseases. Here, we found that high fructose decreased RIP2 expression, and increased inositol-requiring enzyme-1α (IRE1α) and spliced X-box binding protein 1 (XBP1s) expression in cultured hepatocytes along with lipid accumulation, which were attenuated by DHP. RIP2 overexpression blocked high fructose-induced upregulation of IRE1α and XBP1s as well as hepatocyte lipid accumulation. RIP2 knockdown reversed amelioration effect of DHP on hepatocyte lipid accumulation. Furthermore, high fructose increased hepatocyte miR-429 expression targeting RIP2. MiR-429 inhibitor reversed high fructose-induced downregulation of RIP2 and lipid accumulation. Notably, DHP reduced miR-429 expression and increased RIP2 expression in its amelioration of lipid accumulation in this cell model. These results suggested that DHP protected against high fructose-induced hepatocyte lipid accumulation through downregulating miR-429 to upregulate RIP2 expression.