[The role of GSK3β in adipose tissue inflammation induced by bisphenol-A in high fat diet fed mice].

OBJECTIVE

To study the effect of glycogen synthase kinase 3β(GSK3β) in BPA-induced adipose tissue inflammation in high fat diet(HFD) fed mice.

METHODS

Four-week-old male C57 BL/6 mice were randomly divided into normal diet(ND) group, HFD group, HFD + GSK3β inhibitor group, HFD + 1000 nmol/L BPA group, HFD+1000 nmol/L BPA+GSK3β inhibitor group. The mice were exposed to BPA via drinking water. From the 14 th week of BPA exposure to the end of 16 weeks, the GSK3β inhibitor group was intraperitoneally injected with 21. 5 mg/kg lithium chloride(Li Cl) every two days for a total of 10 times. At the end of 16 weeks, the mice were sacrificed after anesthesia, and the epididymal fat tissue was taken aseptically. The pathological changes were observed by H&E staining. The expressions of interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α) were detected by immunohistochemistry(IHC). The expression of GSK3β protein and its S9 serine(GSK3β-S9) phosphorylation were detected by western blot.

RESULTS

Compared with the ND group, the body weight [(34. 97±1. 91) g]and epididymal fat pad coefficient [(3. 25±0. 39) %]of HFD group was significantly up-regulated(P < 0. 05), the adipose tissue inflammatory cell infiltration was increased, the expression of TNF-α(F = 73. 157, P < 0. 05) and IL-1β(F = 42. 788, P < 0. 05) was significantly enhanced, and the phosphorylation degree of GSK3β-S9(F = 57. 991, P < 0. 05) was decreased. The inflammatory cell infiltration of adipose tissue in the HFD+1000 nmol/L BPA group was significantly increased, the body weight [(38. 49±1. 34) g]and epididymal fat pad coefficient [(4. 41±0. 33) %] of the mice were significantly increased, the phosphorylation of GSK3β-S9(F = 57. 991, P <0. 05) was significantly down-regulated, and the expression of TNF-α(F = 73. 157, P <0. 05) and IL-1β(F = 42. 788, P <0. 05) was significantly enhanced compared with that in the HFD group. Compared with the HFD + 1000 nmol/L BPA group, the HFD + 1000 nmol/L BPA+GSK3 inhibitor group was decreased inflammatory cell infiltration in adipose tissue, significantly decreased body weight [(32. 61 ± 3. 34) g] and epididymal fat pad coefficient [(3. 33±0. 66) %], significantly increased GSK3-S9(F = 57. 991, P < 0. 05)phosphorylation, and significantly decreased TNF-α(F = 73. 157, P < 0. 05) and IL-1β(F = 42. 788, P<0. 05) expression.

CONCLUSION

GSK3β inhibitor can down-regulate BPA-induced adipose tissue inflammation, inflammatory cytokine expression and upregulate GSK3β-S9 phosphorylation in HFD-fed mice, suggesting that BPA exposure may regulate the expression of inflammatory cytokines mediating adipose tissue inflammation by affecting the degree of phosphorylation of GSK3β-S9.