Department of Physiology and Biophysics, Institute of Biomedical Science, University of Sao Paulo, 1524 Prof. Lineu Prestes Ave., ICB 1, Sao Paulo 05508-900, SP, Brazil.
Department of Nutrition, University of Mogi das Cruzes, 200 Dr. Cândido X. A. Souza Ave., Sao Paulo 08780-911, SP, Brazil.
Life Sci. 2018 Jun 1;202:110-116. doi: 10.1016/j.lfs.2018.03.052. Epub 2018 Mar 27.
Dehydroepiandrosterone (DHEA) is an adrenal steroid hormone that is a precursor of sexual hormones. It is reduced during aging and is strongly associated with insulin resistance and obesity. There is evidence for beneficial effects of this steroid, in both human and animal models, during perimenopause. However, the impact of DHEA treatment during late postmenopause on glucose metabolism is not clearly documented. We tested the hypothesis that DHEA supplementation could improve insulin sensitivity in an ovariectomized obese rat model (OVX) that was fed a high-fat diet for 11 weeks.
Female Wistar rats at 8 weeks of age were OVX or SHAM-operated. Eight weeks after the surgery, the animals were randomly treated with vehicle or DHEA for 3 weeks. Food intake, metabolic parameters and insulin sensitivity were evaluated.
Following the ovariectomy, increased body weight gain, adiposity index, and feeding efficiency were observed, despite there being no change in food and energy intake. The OVX rats also displayed glucose intolerance, insulin resistance, decreased insulin-induced IRS1/2 tyrosine phosphorylation in the skeletal muscle, and reduced serum VLDL-c and TAG levels. OVX rats treated with 10 mg/kg DHEA (OVX + DHEA) exhibited estradiol (E) serum levels similar to SHAM animals, with no change in uterus mass. DHEA treatment also resulted in an increase in energy intake.
Despite the positive effects of DHEA supplementation observed in menopausal women and ovariectomized rats, a potential negative effect on glucose metabolism and insulin action in the late postmenopausal condition in diet-induced obese OVX rats are reported.
脱氢表雄酮（DHEA）是一种肾上腺类固醇激素，是性激素的前体。它在衰老过程中会减少，与胰岛素抵抗和肥胖密切相关。有证据表明，这种类固醇在绝经前的人类和动物模型中都有有益的作用。然而，DHEA 治疗在绝经后晚期对葡萄糖代谢的影响尚未得到明确记录。我们测试了这样一个假设，即 DHEA 补充可以改善高脂饮食喂养 11 周的去卵巢肥胖大鼠模型（OVX）的胰岛素敏感性。
8 周龄雌性 Wistar 大鼠行卵巢切除术或假手术。手术后 8 周，动物随机接受载体或 DHEA 治疗 3 周。评估饮食摄入、代谢参数和胰岛素敏感性。
卵巢切除术后，尽管食物和能量摄入没有变化，但体重增加、肥胖指数和摄食效率增加。OVX 大鼠还表现出葡萄糖耐量受损、胰岛素抵抗、骨骼肌 IRS1/2 酪氨酸磷酸化减少和血清 VLDL-c 和 TAG 水平降低。用 10mg/kg DHEA 治疗 OVX 大鼠（OVX+DHEA）可使血清雌二醇（E）水平与 SHAM 动物相似，而子宫质量无变化。DHEA 治疗还导致能量摄入增加。
尽管在绝经后妇女和去卵巢大鼠中观察到 DHEA 补充的积极作用，但在饮食诱导肥胖的 OVX 大鼠中，DHEA 补充在绝经后晚期对葡萄糖代谢和胰岛素作用可能有负面影响。
