Dietary Lycium barbarum Polysaccharide Induces Nrf2ARE Pathway and Ameliorates Insulin Resistance Induced by High-Fat via Activation of PI3KAKT Signaling

Abstract EN

Lycium barbarum polysaccharide (LBP), an antioxidant from wolfberry, displays the antioxidative and anti-inflammatory effects on experimental models of insulin resistance in vivo.

However, the effective mechanism of LBP on high-fat diet-induced insulin resistance is still unknown.

The objective of the study was to investigate the mechanism involved in LBP-mediated phosphatidylinositol 3-kinase (PI3K)/AKT/Nrf2 axis against high-fat-induced insulin resistance.

HepG2 cells were incubated with LBP for 12 hrs in the presence of palmitate.

C57BL/6J mice were fed a high-fat diet supplemented with LBP for 24 weeks.

We analyzed the expression of nuclear factor-E2-related factor 2 (Nrf2), Jun N-terminal kinases (JNK), and glycogen synthase kinase 3β (GSK3β) involved in insulin signaling pathway in vivo and in vitro.

First, LBP significantly induced phosphorylation of Nrf2 through PI3K/AKT signaling.

Second, LBP obviously increased detoxification and antioxidant enzymes expression and reduced reactive oxygen species (ROS) levels via PI3K/AKT/Nrf2 axis.

Third, LBP also regulated phosphorylation levels of GSK3β and JNK through PI3K/AKT signaling.

Finally, LBP significantly reversed glycolytic and gluconeogenic genes expression via the activation of Nrf2-mediated cytoprotective effects.

In summary, LBP is novel antioxidant against insulin resistance induced by high-fat diet via activation of PI3K/AKT/Nrf2 pathway.