Dydrogesterone and norethisterone regulate expression of lipoprotein lipase and hormone-sensitive lipase in human subcutaneous abdominal adipocytes

Abstract

Aim: In premenopausal women, hyperandrogenicity is associated with central obesity and an increased cardiovascular risk. The aim of this study was to investigate the effects of dydrogesterone (DYD) (a non-androgenic progestogen) and norethisterone (NET) (an androgenic progestogen) on lipoprotein lipase (LPL), hormone-sensitive lipase (HSL) and glycerol release in adipocytes isolated from subcutaneous abdominal adipose tissue.

Methods: Adipose tissue was obtained from 12 non-diabetic women, mean age 51 years (range 37-78) and mean body mass index 25.4 kg/m(2) (range 20.3-26.4). Adipocytes were treated with increasing doses of DYD and NET for 48 h prior to protein extraction. Effects on lipogenesis and lipolysis were assessed using western blotting to determine the expression of key enzymes, LPL (56 kDa) and HSL (84 kDa) respectively. Measurement of glycerol release into the medium provided an assessment of lipolytic activity.

Results: Expression of LPL was increased by DYD and NET (mean protein expression relative to control +/- s.e.), with greatest effect at 10(-8) M for DYD: 2.32 +/- 0.51 (p < 0.01) and 10(-8) M for NET: 2.06 +/- 0.19 (p < 0.01). In contrast, HSL expression was reduced by all concentrations of DYD, with maximal effect at 10(-9) M : 0.49 +/- 0.02 (p < 0.001). NET reduced HSL expression at all concentrations from 10(-9) M : 0.62 +/- 0.06 (p < 0.001) to 10(-7) M : 0.69 +/- 0.08 (p < 0.001). Glycerol measurements supported the HSL expression studies although they were not statistically significant (p > 0.05).

Conclusions: DYD and NET significantly increased LPL expression relative to control, while significantly reducing HSL expression. At the concentrations studied, similar effects were observed with the androgenic NET and the non-androgenic DYD despite differing effects on the lipid profile when taken orally in combination with oestrogen. Further work examining the effects of different progestogens on body fat distribution may enable progestogen use to be tailored to maximize benefits and minimize potential harm.