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Dehydroepiandrosterone reduces proliferation and differentiation of 3T3-L1 preadipocytes
Y R Lea-Currie1, P Wen, M K McIntosh
1Department of Nutrition, School of Environmental Health Sciences, University of North Carolina at Greensboro 27402-6170, USA.
Abstract:
The purpose of these studies was to determine whether the antiobesity actions of dehydroepiandrosterone (DHEA) and DHEA-sulfate (DHEAS) observed in vivo are due to an influence on proliferation and/or differentiation in monolayer cultures of 3T3-L1 preadipocytes. For the proliferation study (Exp. 1), cells were grown in plating medium containing DHEA at 0, 5, 25, 50, or 100 microM for 1-4 d. DHEAS was added at the 100 microM level only. For the differentiation study (Exp. 2), cultures were grown in plating medium containing DHEA at 0, 5, 30, 60, 120, or 240 microM for 2-6 d. DHEAS was added at the 240 microM level only. In Exp. 3, the effect of DHEA on mature adipocytes was determined by exposing adipocytes grown in plating medium to DHEA at 0, 75, 125, and 250 microM for 1-4 d. In Exp. 1, preadipocyte proliferation decreased as the level of DHEA increased in cultures of 3T3-L1 cells. DHEAS had no effect on preadipocyte proliferation. The antiproliferative effect of DHEA was partially reversed by the addition of 1 microM mevalonic acid to proliferating cultures containing 25 microM DHEA. In Exp. 2, preadipocyte differentiation decreased as the level of DHEA in the cultures increased. In contrast, neither DHEAS nor mevalonic acid treatment influenced preadipocyte differentiation decreased as the level and duration of DHEA treatment increased in cultures of mature adipocytes. These data support the hypothesis that DHEA, but not DHEAS, is the active form of the steroid that attenuates obesity via altering preadipocyte proliferation and differentiation. The addition of 1 microM mevalonic acid to cultures of 3T3-L1 preadipocytes partially reversed DHEA's antiproliferative effects.
Insights
Dehydroepiandrosterone (DHEA) reduces obesity by inhibiting preadipocyte proliferation and differentiation. Dehydroepiandrosterone-sulfate (DHEAS) did not show these effects, indicating DHEA is the active form. Mevalonic acid partially reversed DHEA
Area of Science:
- Biochemistry
- Cell Biology
- Endocrinology
Background:
- Dehydroepiandrosterone (DHEA) and its sulfate conjugate (DHEAS) are endogenous steroids with potential roles in modulating body weight.
- Previous in vivo studies suggest DHEA and DHEAS possess antiobesity effects, but the underlying cellular mechanisms remain to be fully elucidated.
Purpose of the Study:
- To investigate whether the antiobesity actions of DHEA and DHEAS are mediated by influencing the proliferation and differentiation of 3T3-L1 preadipocytes.
- To determine the active form of the steroid (DHEA or DHEAS) responsible for modulating adipocyte development.
Main Methods:
- 3T3-L1 preadipocytes were cultured and treated with varying concentrations of DHEA or DHEAS to assess proliferation and differentiation.
- Experiments involved exposing proliferating preadipocytes, differentiating preadipocytes, and mature adipocytes to DHEA and DHEAS.
- The effect of mevalonic acid, a downstream metabolite in the cholesterol synthesis pathway, was evaluated in conjunction with DHEA treatment.
Main Results:
- DHEA significantly decreased 3T3-L1 preadipocyte proliferation in a dose-dependent manner; DHEAS had no effect.
- DHEA also inhibited preadipocyte differentiation, with effects increasing with concentration and duration of exposure.
- Mevalonic acid partially reversed the antiproliferative effects of DHEA, while neither DHEAS nor mevalonic acid affected differentiation.
Conclusions:
- DHEA, but not DHEAS, is the active steroid that attenuates obesity by altering preadipocyte proliferation and differentiation.
- These findings support the hypothesis that DHEA's antiobesity effects are linked to its direct impact on adipogenesis at the cellular level.