Tritos Nicholas A, Segal-Lieberman Gabriella, Vezeridis Peter S, Maratos-Flier Eleftheria
Joslin Diabetes Center, Boston, Massachusetts 02215, USA.
Obes Res. 2004 Apr;12(4):716-24. doi: 10.1038/oby.2004.84.
Treatment of male rodents with estradiol (E2) is associated with anorexia and weight loss by poorly understood mechanisms. We examined the role of the orexigenic hypothalamic peptide melanin-concentrating hormone (MCH) and the appetite-inhibiting, fat-derived hormone leptin in mediating E2-induced anorexia.
We studied the effect of E2 treatment (implantation of either E2 pellet or matching placebo) in male C57Bl/6J mice, as well as in a lean mouse model (MCH knockout mice) and an obese model (leptin-deficient ob/ob mice). We also studied the effect of E2 treatment in the context of high-fat diet.
We confirmed E2 dose-dependent anorexia in male wild type mice fed a normal chow diet. E2 treatment was associated with a significant decrease in body fat, serum leptin levels, and arcuate hypothalamic proopiomelanocortin expression. E2-implanted mice also showed increased hypothalamic neuropeptide Y and MCH expression. As MCH has been implicated in E2-induced hypophagia, we performed E2 pellet implantation in MCH knockout mice and observed hypophagia and weight loss, indicating that MCH is not an essential mediator of E2-induced anorexia. E2-implanted ob/ob mice also had hypophagia and weight loss, indicating that leptin is not essential for E2-induced anorexia. High-fat diet significantly exacerbated the effect of E2 treatment, leading to a 99.6% decrease in food intake at 48 hours and a 30% loss of body weight within 1 week.
The anorectic effects of E2 were independent of MCH and leptin. Our results suggested that E2 may have effects on nutrient preferences.
用雌二醇（E2）处理雄性啮齿动物会导致厌食和体重减轻，但其机制尚不清楚。我们研究了促食欲的下丘脑肽黑色素浓缩激素（MCH）和抑制食欲的脂肪源激素瘦素在介导E2诱导的厌食中的作用。
我们研究了E2处理（植入E2丸剂或匹配的安慰剂）对雄性C57Bl/6J小鼠、瘦小鼠模型（MCH基因敲除小鼠）和肥胖模型（瘦素缺乏的ob/ob小鼠）的影响。我们还研究了在高脂饮食情况下E2处理的效果。
我们证实在喂食正常食物的雄性野生型小鼠中，E2呈剂量依赖性地导致厌食。E2处理与体脂、血清瘦素水平以及下丘脑弓状核前阿黑皮素原表达的显著降低有关。植入E2的小鼠还表现出下丘脑神经肽Y和MCH表达增加。由于MCH与E2诱导的摄食减少有关，我们在MCH基因敲除小鼠中植入E2丸剂，观察到摄食减少和体重减轻，这表明MCH不是E2诱导厌食的必需介质。植入E2的ob/ob小鼠也有摄食减少和体重减轻的情况，这表明瘦素对E2诱导的厌食不是必需的。高脂饮食显著加剧了E2处理的效果，导致48小时内食物摄入量减少99.6%，1周内体重减轻30%。
E2的厌食作用独立于MCH和瘦素。我们的结果表明E2可能对营养偏好有影响。
