Department of Animal Sciences, School of Environmental & Biological Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA.
Department of Animal Sciences, School of Environmental & Biological Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA; Environmental and Occupational Health Sciences Institute, Rutgers, The State University of New Jersey, Piscataway, NJ, USA; Rutgers Center for Lipid Research, The Center for Nutrition, Microbiome, and Health, and the New Jersey Institute of Food, Nutrition, and Health, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA.
Steroids. 2023 Jul;195:109228. doi: 10.1016/j.steroids.2023.109228. Epub 2023 Mar 27.
Circulating 17β-estradiol (E2) controls energy homeostasis and feeding behaviors primarily by its nuclear receptor, estrogen receptor (ER) α. As such, it is important to understand the role of ERα signaling in the neuroendocrine control of feeding. Our previous data indicated that the loss of ERα signaling through estrogen response elements (ERE) alters food intake in a female mouse model. Hence, we hypothesize that ERE-dependent ERα is necessary for typical feeding behaviors in mice. To test this hypothesis, we examined feeding behaviors on low-fat diet (LFD) and high-fat diet (HFD) in three mouse strains: total ERα knockout (KO), ERα knockin/knockout (KIKO), which lack a functional DNA-binding domain, and their wild type (WT) C57 littermates comparing intact males and females and ovariectomized females with or without E2 replacement. All feeding behaviors were recorded using the Biological Data Acquisition monitoring system (Research Diets). In intact male mice, KO and KIKO consumed less than WT mice on LFD and HFD, while in intact female mice, KIKO consumed less than WT and KO. These differences were primarily driven by shorter meal duration in the KO and KIKO. In ovariectomized females, E2-treated WT and KIKO consumed more LFD than KO driven in part by an increase in meal frequency and a decrease in meal size. On HFD, WT consumed more than KO with E2, again due to effects on meal size and frequency. Collectively, these suggest that both ERE-dependent and -independent ERα signaling are involved in feeding behaviors in female mice depending on the diet consumed.
循环 17β-雌二醇（E2）主要通过其核受体雌激素受体（ER）α 来控制能量稳态和摄食行为。因此，了解 ERα 信号在摄食的神经内分泌控制中的作用非常重要。我们之前的数据表明，通过雌激素反应元件（ERE）丧失 ERα 信号会改变雌性小鼠模型的食物摄入量。因此，我们假设 ERE 依赖性 ERα 是小鼠典型摄食行为所必需的。为了验证这一假设，我们在三种小鼠品系上检查了低脂饮食（LFD）和高脂肪饮食（HFD）下的摄食行为：总 ERα 敲除（KO）、缺乏功能性 DNA 结合域的 ERα 敲入/敲除（KIKO）及其野生型（WT）C57 同窝仔鼠，比较完整雄性和雌性以及去卵巢雌性是否有 E2 替代。所有摄食行为均使用生物数据采集监测系统（Research Diets）进行记录。在完整雄性小鼠中，KO 和 KIKO 比 WT 小鼠在 LFD 和 HFD 上消耗的食物更少，而在完整雌性小鼠中，KIKO 比 WT 和 KO 消耗的食物更少。这些差异主要是由于 KO 和 KIKO 的餐时持续时间更短所致。在去卵巢雌性小鼠中，用 E2 处理的 WT 和 KIKO 比 KO 消耗更多的 LFD，部分原因是餐频率增加和餐大小减少。在 HFD 上，WT 比 KO 消耗更多的食物，这同样归因于餐大小和频率的影响。总的来说，这些结果表明，无论所消耗的饮食如何，ERE 依赖性和非依赖性 ERα 信号都参与了雌性小鼠的摄食行为。
