Caloric restriction combined with Linggui Zhugan Decoction improves palmitic acid-induced insulin resistance

• Caloric restriction (30 %) improved palmitic acid induced insulin resistance in vitro. • Linggui Zhugan decoction could enhance the protective effects of 30 % caloric restriction in vitro. • The potential mechanism related to the upregulation of AKT/p-AKT/AS160 signaling. To explore the effects and probable mechanisms of caloric restriction (CR) combined with Linggui Zhugan pharmaceutic serum on insulin resistance (IR). Sprague–Dawley rats were treated with Linggui Zhugan decoction (LGZGD) or equivalent amount of saline as blank control by gavage for one week, after which blood was collected from the abdominal aorta to prepare LGZGD pharmaceutic serum or control serum. HepG2 cells were incubated with normal control medium or 30 % CR culture medium supplemented with LGZGD pharmaceutic serum or control serum for 24 h and then exposed to 250 μM palmitic acid (PA) for another 24 h. Changes in cellular glucose uptake were detected to evaluate the improvements in insulin resistance, and changes in the expression changes of AKT, p-AKT, and AS160 were detected via western blotting and qPCR. Both simple caloric restriction (30 %) and LGZGD pharmaceutic serum treatment significantly improved the decrease in cellular glucose uptake and the downregulation of AKT/p-AKT/AS160 signaling induced by PA, and the combined intervention group had a significantly greater effect than the single intervention groups. Linggui Zhugan decoction can enhance the effects of CR on improving insulin resistance in HepG2 cells. The potential mechanism may be related to the modulation of AKT/p-AKT/AS160 signaling, which needs to be verified further with knock-down experiment and in vivo study.