17β-estradiol lowers triglycerides in adipocytes via estrogen receptor α and it may be attenuated by inflammation.

BACKGROUND: Estrogen was reported to protect against obesity, however the mechanism remains unclear. We aimed to investigate the impact of 17β-estradiol (17β-E2) on triglyceride metabolism in adipocytes with or without lipopolysacchride (LPS) stimulating, providing novel potential mechanism for estrogen action.

METHODS: 3T3-L1 adipocytes were cultured and differentiated into mature adipocytes in vitro. The differentiated 3T3-L1 cells were divided into six groups: (i) control group, treated with 0.1% DMSO alone; (ii) 17β-E2 group, treated with 1, 0.1, or 0.001 μM 17β-E2 for 48 h; (iii) 17β-E2 plus MPP group, pre-treated with 10 μM MPP (a selective ERα receptor inhibitor) for 1 h, then incubated with 1 μM 17β-E2 for 48 h; (iv) 17β-E2 plus PHTPP group, pre-treated with 10 μM PHTPP (a selective ERβ receptor inhibitor), then incubated with 1 μM 17β-E2 for 48 h; (v) LPS group, pre-treated with 100 ng/mL LPS for 24 h, then cells were washed by PBS for 3 times and incubated with 0.1% DMSO alone for 48 h; (vi) 17β-E2 plus LPS group, pre-treated with 100 ng/mL LPS for 24 h, then cells were washed by PBS for 3 times and incubated with 1 μM 17β-E2 for 48 h. The levels of triglyceride and adipose triglyceride lipase (ATGL) in differentiated 3T3-L1 cells and the concentrations of interleukin-6 (IL-6) in culture medium were measured.

RESULTS: Comparing with control group, 1 μM and 0.1 μM 17β-E2 decreased the intracellular TG levels by about 20% and 10% respectively (all P < 0.05). The triglyceride-lowing effect of 17β-E2 in differentiated 3T3-L1 cells was abolished by ERα antagonist MPP but not ERβ antagonist PHTPP. Comparing with control group, the IL-6 levels were significantly higher in the culture medium of the cultured differentiated 3T3-L1 cells in LPS group and 17β-E2 + LPS group (all P < 0.05). And, the IL-6 levels were similar in LPS group and 17β-E2 + LPS group (P > 0.05). There was no significant difference in the triglyceride contents of differentiated 3T3-L1 cells among control group, LPS group and 17β-E2 + LPS group (all P > 0.05). ATGL expression in 17β-E2 group was significantly higher than control group (P < 0.05), which was abolished by ERα antagonist MPP or LPS.

CONCLUSIONS: 17β-E2 increased ATGL expression and lowered triglycerides in adipocytes but not in LPS stimulated adipocytes via estrogen ERα.