Laboratory of Endocrine Physiology, Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
Laboratory of Neurophysiology, Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
J Dev Orig Health Dis. 2022 Feb;13(1):90-100. doi: 10.1017/S2040174421000039. Epub 2021 Mar 2.
Early weaning (EW) is associated with obesity later in life. Here, using an EW model in rats, we investigated changes in feeding behavior and the dopaminergic and endocannabinoid systems (ECS) in the adult offspring. Lactating Wistar rats were divided into two groups: EW, dams were wrapped with a bandage to interrupt suckling during the last 3 days of breastfeeding; CONT; dams fed the pups throughout the period without hindrances. EW animals were compared with CONT animals of the same sex. At PN175, male and female offspring of both groups could freely self-select between high-fat and high-sugar diets (food challenge test). EW males preferred the high-fat diet at 30 min and more of the high-sugar diet after 12 h compared to CONT males. EW females did not show differences in their preference for the palatable diets compared to CONT females. Total intake of standard diet from PN30-PN180 was higher in both male and female EW animals, indicating hyperphagia. At PN180, EW males showed lower type 2 dopamine receptor (D2r) in the nucleus accumbens (NAc) and dorsal striatum, while EW females had lower tyrosine hydroxylase in the ventral tegmental area and NAc, D1r in the NAc, and D2r in the prefrontal cortex. In the lateral hypothalamus, EW males had lower fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase, whereas EW females showed lower N-arachidonoyl-phosphatidylethanolamine phospholipase-D and increased FAAH. Early weaning altered both the dopaminergic and ECS parameters at adulthood, contributing to the eating behavior changes of the progeny in a sex-dependent manner.
早期断奶（EW）与成年后肥胖有关。在这里，我们使用大鼠 EW 模型研究了成年后代摄食行为以及多巴胺能和内源性大麻素系统（ECS）的变化。哺乳期 Wistar 大鼠分为两组：EW 组，在哺乳的最后 3 天，用绷带包裹母鼠以中断哺乳；CONT 组，母鼠在整个期间无阻碍地喂养幼崽。EW 动物与同性别 CONT 动物进行比较。在 PN175 时，两组雄性和雌性后代均可自由选择高脂肪和高糖饮食（食物挑战测试）。与 CONT 雄性相比，EW 雄性在 30 分钟时更喜欢高脂肪饮食，在 12 小时后更喜欢高糖饮食。与 CONT 雌性相比，EW 雌性在对美味饮食的偏好上没有差异。从 PN30 到 PN180，无论是雄性还是雌性 EW 动物的标准饮食总摄入量均较高，表明存在过度摄食。在 PN180 时，EW 雄性的伏隔核（NAc）和背侧纹状体中的 2 型多巴胺受体（D2r）降低，而 EW 雌性的腹侧被盖区和 NAc 中的酪氨酸羟化酶、NAc 中的 D1r、前额叶皮层中的 D2r 降低。在外侧下丘脑，EW 雄性的脂肪酸酰胺水解酶（FAAH）和单酰甘油脂肪酶降低，而 EW 雌性的 N-花生四烯酰-磷酸乙醇胺磷脂酶-D 降低，FAAH 增加。早期断奶会改变成年后代的多巴胺能和 ECS 参数，以性别依赖的方式影响后代的摄食行为变化。
