The estrogen antagonist EM-652 and dehydroepiandrosterone prevent diet- and ovariectomy-induced obesity.
The estrogen antagonist EM-652 and dehydroepiandrosterone prevent diet- and ovariectomy-induced obesity.
复制标题
雌激素拮抗剂 EM-652 和脱氢表雄酮可预防饮食和卵巢切除引起的肥胖。
DOI：
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复制
发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Y. Deshaies
中科院分区：
文献类型：
--
作者：
C. Lemieux;F. Picard;F. Labrie;D. Richard;Y. Deshaies
目标
EM-652 是人类乳腺癌和子宫癌细胞中的纯抗雌激素，还可减少大鼠的骨质流失和血浆脂质水平。本研究旨在评估 EM-652 单独使用或与脱氢表雄酮 (DHEA) 联用预防肥胖和由促进肥胖的饮食和卵巢切除术引起的相关代谢异常的能力。
研究方法和程序
雌性大鼠被喂食高蔗糖、高脂肪 (HSHF) 饮食，保持完整或切除卵巢 (OVX)，并用 EM-652、DHEA 或两者治疗 20 天。评估了能量平衡的变量以及脂质代谢和胰岛素敏感性的决定因素。
结果
HSHF 饮食（与食物相比）和 OVX 均增加了能量摄入和增益，以及能量效率。 EM-652 和 DHEA 主要通过减少脂肪沉积来防止饮食和 OVX 诱导的能量增加，而不是添加。 EM-652 诱导的完整大鼠肝脏甘油三酯适度增加可通过与 DHEA 组合来预防。 EM-652（而非 DHEA）可以降低胆固醇血症。 HSHF 饮食和 OVX 降低了胰岛素敏感性，这种效应被 EM-652 减弱，并被 DHEA 和 EM-652+DHEA 消除。 EM-652、DHEA 或其组合治疗消除了饮食和 OVX 诱导的伴随脂肪增加的脂肪脂蛋白脂肪酶活性的增加。
讨论
EM-652 是一种有效的药物，可以预防饮食和 OVX 引起的肥胖及其相关的心血管危险因素，例如胰岛素抵抗。添加DHEA可防止肝脏脂质积累并进一步改善胰岛素敏感性。因此，这种联合类固醇疗法的有益代谢作用可能最终被证明具有临床相关性。
OBJECTIVE
EM-652 is a pure antiestrogen in human breast and uterine cancer cells that also reduces bone loss and plasma lipid levels in the rat. This study aimed to assess the ability of EM-652, alone or with dehydroepiandrosterone (DHEA), to prevent obesity and related metabolic abnormalities induced by an obesity-promoting diet and ovariectomy.
RESEARCH METHODS AND PROCEDURES
Female rats were fed a high-sucrose, high-fat (HSHF) diet, were left intact or ovariectomized (OVX), and were treated with EM-652, DHEA, or both for 20 days. Variables of energy balance and determinants of lipid metabolism and insulin sensitivity were assessed.
RESULTS
The HSHF diet (vs. chow) and OVX both increased energy intake and gain, as well as energetic efficiency. Both EM-652 and DHEA prevented diet- and OVX-induced energy gain mainly by decreasing fat deposition, without being additive. The modest EM-652-induced increase in liver triglycerides of intact rats was prevented by its combination with DHEA. EM-652, but not DHEA, decreased cholesterolemia. The HSHF diet and OVX reduced insulin sensitivity, an effect that was attenuated by EM-652 and abrogated by DHEA and EM-652+DHEA. Treatment with EM-652, DHEA, or their combination abolished the diet- and OVX-induced increase in adipose lipoprotein lipase activity that accompanied fat gain.
DISCUSSION
EM-652 is an effective agent to prevent diet- and OVX-induced obesity and its associated cardiovascular risk factors such as insulin resistance. The addition of DHEA prevents hepatic lipid accumulation and further ameliorates insulin sensitivity. The beneficial metabolic effects of such combined steroid therapy may, therefore, eventually prove to be clinically relevant.
影响因子：
7.2
作者：
A. Tchernof;E. Poehlman;J. Despres
通讯作者：
A. Tchernof;E. Poehlman;J. Despres
影响因子：
4.9
作者：
G. Wade;J. Gray;T. Bartness
通讯作者：
G. Wade;J. Gray;T. Bartness
DOI：
10.1093/gerona/53a.1.b19
发表时间：
1998-01-01
影响因子：
5.1
作者：
Han, DH;Hansen, PA;Holloszy, JO
通讯作者：
Holloszy, JO