Estrogen upregulates hepatic apolipoprotein M expression via the estrogen receptor

Abstract

Apolipoprotein M (apoM) is present predominantly in high-density lipoprotein (HDL) in human plasma, thus possibly involved in the regulation of HDL metabolism and the process of atherosclerosis. Although estrogen replacement therapy increases serum levels of apoAI and HDL, it does not seem to reduce the cardiovascular risk in postmenopausal women. Therefore, we investigated the effects of estrogen on apoM expression in vitro and in vivo. HepG2 cells were incubated with different concentrations of estrogen with or without the estrogen receptor antagonist, fulvestrant, and apoM expression in the cells was determined. Hepatic apoM expression and serum levels of apoM were also determined in normal and in ovariectomized rats treated with either placebo or estradiol benzoate, using sham operated rats as controls. Estrogen significantly increased mRNA levels of apoM and apoAI in HepG2 cell cultures in a dose-and time-dependent manner; the upregulation of both apolipoproteins was fully abolished by addition of estrogen receptor antagonist. In normal rats, estrogen treatment led to an increase in plasma lipid levels including HDL cholesterol, a marked upregulation of apoM mRNA and a significant increase in serum levels of apoM. The same pattern of regulation was found in ovariectomized rats treated with estrogen. Thus, estrogen upregulates apoM expression both in vivo and in vitro by mechanism(s) involving the estrogen receptor.

The Effects of Short-term Circuit Resistance Training with Supplementation of Milk, Cheese Juice, Whey Protein on Resting Level Apolipoprotein M- HDL Total Cholesterol, Lipid Profile, Gastric Inhibitory Polypeptide and Plasma Estradiol in Untrained Young Men

“…Although in the present study the levels of leptin were not measured, the reduced leptin levels might have happened as a reduction mechanism of Apo-M. However, the study reported that estrogen in vivo and in vitro conditions by a series of mechanisms upregulated the Apo-M (Wei et al, 2011). In this study, one of the possible reasons for low levels of Apo-M may be the decreased estrogen levels; So, the reduction of Apo-M in exercise and milk consumption group may be associated with estradiol further reduction.…”

Effect of menopause and exercise training on plasma apolipoprotein M and sphingosine-1-phosphate

“…This observation does not prove a link between apoM and menopause, but the study supports the notion that apoM concentrations could be dependent on hormone levels, as the positive correlation with age is seen for women only. Few studies have addressed the effect of sex hormones on apoM, but it has been shown that estrogen upregulates apoM expression in vitro and in vivo in rats (44). This suggests that plasma apoM concentrations should be higher in pre-than postmenopausal women, which was not the case in the present study.…”

17-β-estradiol up-regulates apolipoprotein genes expression during osteoblast differentiation <i>in vitro </i>

“…Estrogen up-regulates ApoE gene expression by increasing ApoE mRNA in the translating pool via the estrogen receptor alpha-mediated pathway (53). Estrogen up-regulates ApoM gene expression via the estrogen receptor in HepG2 cells (54). No previous studies have examined the effect of estrogen on the expression of the ApoD, ApoF, and ApoH genes.…”