Figure 8.

Schematic depicting the underlying mechanism by which endogenous n-3 PUFAs, especially DHA antagonize HF diet-induced insulin resistance. Mechanistically, PA, the main saturated fatty acid in HF diet inactivated AMPK and led to decreased GSK-3β phosphorylation, at least partially through reducing Akt activity, which ultimately blocked the Nrf2/Trx1 antioxidant pathway and induced TXNIP cytoplasm translocation and NLRP3 inflammasome activation, whereas DHA, the most abundant n-3 PUFA in fat-1 adipose tissue, reversed this process via inducing Akt activation. Blue arrow indicates the inhibitory activity of GSK-3β is weakened when GSK-3β (Ser9) is phosphorylated.