a Departamento de Psicobiología , Universidad Nacional de Educación a Distancia (UNED) , C/ Juan del Rosal n° 10, 28040 Madrid , Spain.
b Departamento de Endocrinología , Hospital Infantil Universitario Niño Jesús, Instituto de Investigación La Princesa, Investigación Biomédica en Red (CIBER) de la Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III , Avda. Menéndez Pelayo, N° 65, 28009 , Madrid.
Nutr Neurosci. 2019 Jan;22(1):29-39. doi: 10.1080/1028415X.2017.1349574. Epub 2017 Jul 11.
Overnutrition due to a high-fat diet (HFD) can increase the vulnerability of the metabolic system to maladjustments. Estradiol has an inhibitory role on food intake and this hormone has demonstrated to be a crucial organizer during brain development.
Our aim was to determine whether increased levels of estradiol in the early postnatal period modulate the alterations in metabolism and brain metabolic circuits produced by overnutrition.
Twenty-four male and 24 female Wistar rats were submitted to a HFD (34.9% fat) or a control diet (5% fat) from gestational day 6. From postnatal (P) 6 to P13, both control and HFD groups were administered a s.c. injection of vehicle or estradiol benzoate (0.4 mg/kg), resulting in eight experimental groups (n = 6 in each group). Body weight, food intake and subcutaneous, visceral, and brown fat pads were measured. Agouti-related peptide, neuropeptide Y, orexin, and proopiomelanocortin (POMC) were analyzed by quantitative real-time polymerase chain reaction assay and plasma estradiol levels were measured by ELISA.
Males fed a HFD showed an increase in body weight and the amount of visceral and subcutaneous fat, which was coincident with an increase in the number of kilocalories ingested. Neonatal estradiol treatment restored the body weight and subcutaneous fat of HFD males to control levels. Hypothalamic POMC mRNA levels in HFD females were increased with respect to control females. This increase was reverted with estradiol treatment during development.
HFD and estradiol treatment have different effects on males and females. Overnutrition affects physiological parameters, such as body weight, visceral, and subcutaneous fat content, in males, while females present alterations in hypothalamic POMC mRNA levels. Hence, the increase in estradiol levels during a period that is critical for the programing of the feeding system can modulate some of the alterations produced by the continuous intake of high-fat content food.
高脂肪饮食（HFD）引起的营养过剩会增加代谢系统对失调的敏感性。雌激素对食物摄入具有抑制作用，这种激素在大脑发育过程中被证明是一个关键的调节因子。
我们旨在确定新生后早期雌激素水平的升高是否会调节营养过剩引起的代谢和大脑代谢回路的改变。
24 只雄性和 24 只雌性 Wistar 大鼠从妊娠第 6 天起分别给予高脂肪饮食（34.9%脂肪）或对照饮食（5%脂肪）。从出生后第 6 天到第 13 天，对照组和 HFD 组均给予皮下注射溶剂或苯甲酸雌二醇（0.4mg/kg），共产生 8 个实验组（每组 6 只）。测量体重、食物摄入量以及皮下、内脏和棕色脂肪垫。通过实时定量聚合酶链反应检测法分析刺鼠相关肽、神经肽 Y、食欲素和促黑激素（POMC），通过 ELISA 法检测血浆雌激素水平。
喂养 HFD 的雄性大鼠体重增加，内脏和皮下脂肪增加，同时摄入的卡路里量也增加。新生期雌激素处理使 HFD 雄性大鼠的体重和皮下脂肪恢复到对照水平。HFD 雌性大鼠下丘脑 POMC mRNA 水平高于对照组雌性大鼠。这种增加在发育过程中通过雌激素处理得到逆转。
HFD 和雌激素处理对雄性和雌性有不同的影响。营养过剩会影响雄性的生理参数，如体重、内脏和皮下脂肪含量，而雌性则会改变下丘脑 POMC mRNA 水平。因此，在对摄食系统进行编程的关键时期，雌激素水平的升高可以调节因持续摄入高脂肪食物而产生的一些改变。
