Salsalate alleviates hyperglycemia by inhibiting endoplasmic reticulum stress in high fat diet induced obese mice / 第二军医大学学报

ABSTRACT

Objective To explore the effect of salsalate on the glucose metabolism of obese mice induced with high fat diet (HFD). Methods Eight week-old male C57BL/6J mice were fed with HFD in combination with 0.5% of salsalate (SAL group, n＝5) or normal saline (control group, n＝5) for 40 days. The effect of salsalate on serum glucose level was examined by glucose tolerance test (GTT) and insulin tolerance test (ITT). The expressions of endoplasmic reticulumn related proteins, including CCAAT/enhancer-binding protein homologous protein (CHOP), endoplasmic reticulum-localized DnaJ 4 (ERDJ4), glucose regulated protein (GRP)78 and GRP94, were measured by qPCR and Western blotting. Results The random blood glucose level of obese mice were significantly lower in the SAL group than that in the control group (P0.05), and GTT showed that the mice in the SAL group had better glucose tolerance. However, there was no significant difference in fasting insulin level between the two groups. ITT showed there was no difference in the change of blood glucose after insulin stimulation between the two groups. The mRNA expressions of GRP78 and GRP94 and protein expressions of CHOP, ERDJ4, GRP78 and GRP94 were significantly lower in the SAL group than those in the control group (P0.05 or P0.01). Conclusion Salsalate can alleviate the hyperglycemia of obese mice induced with HFD by inhibiting endoplasmic reticulum stress, and the effect is independent of the insulin secretion.