Imbalanced triacylglycerol metabolism in fat cells from estrogen-treated rats

Abstract

We investigated the effects of ethinyl estradiol (EE 2) on body weight, weights of fat depots, triglyceridemia and lipoprotein lipase (LPL) activity of fat cells isolated from the parametrial fat pads of female rats. LPL activity was assayed at the cell surface, using a suspension of intact fat cells as enzyme source. The cellular uptake of fatty acids liberated during hydrolysis was also evaluated. EE 2 was administered daily for 10 days by s.c. injections of 0.06 0.6 6.0 and 60 μg of hormone per animal. EE 2 at and above 0.6 jug/rat reduced body weight gain and weights of fat depots. Triglyceridemia increased at doses of EE 2 up to 6 μg and showed a relative reduction at 60 μg. In parallel, LPL activity assayed both as cell-bound and heparin-released enzyme and expressed relative to cell DNA, responded to the hormone according to a biphasic pattern: EE 2 increased LPL activity in the dose range 0.6-6.0 μg of EE 2, whereas a decrease occurred at higher doses. Fat cells incorporated as acylglycerol 56.5 ± 6.2% (mean + SD) of the amount of fatty acid liberated enzymatically during incubation, and this percentage was essentially unchanged by EE 2. EE 2 at 60 μg/rat caused decreases in triglyceridemia and LPL activity and, as a consequence, decreases in fat depots. By contrast, EE 2 at doses up to 6 μg created a paradoxical situation where concomitant increases in triglyceridemia and LPL activity, which should have favoured fat deposition, coexisted with fat depletion. Estrogen hormones at doses below toxicity increase the secretion of triglyceride-rich lipoproteins by liver. Whereas the increase in LPL activity oberved in this study at low doses of EE 2 may reflect the LPL responses to liver-borne hypertriglyceridemia, the mechanism for the concomitant fat depletion is unclear. These data emphasize the complex effects of estrogen hormones on lipid metabolism.