The mulberry-derived 1-deoxynojirimycin (DNJ) inhibits high-fat diet (HFD)-induced hypercholesteremia and modulates the gut microbiota in a gender-specific manner

Abstract

1-Deoxynojirimycin (DNJ) is an effective anti-diabetic agent with potent α-glucosidase-inhibiting activity. Here we show that DNJ exhibits gender-specific modulating effects on hypercholesteremia and gut microbiota. Oral administration of DNJ for 12 weeks significantly inhibited bodyweight gain, decreased serum cholesterol, and improved oral glucose tolerance in high-fat diet (HFD)-induced hypercholesteremic female mice but not in male mice. Microbiological analysis also revealed that DNJ showed less influence on gut microbes in male mice but markedly shifted the gut microbiota structure in female ones. DNJ significantly decreased the relative abundance of Fimicutes, which mainly attributed to the decline of the genera Allobaculum, Turicibacter, Lactobacillus, Lachnoclostridium and Roseburia, and increased Verrucomicrobia especially Akkermansia, a beneficial genus with obesity- and diabetes-alleviating effects. Together, these data revealed gender-specific anti-hypercholesteremic and gut microbiota-modulating effects of DNJ, providing a potential utility of DNJ for the treatment of hypercholesteremia.