Faculdade de Ciências Aplicadas, Universidade de Campinas, UNICAMP, Limeira 13484-350, São Paulo, Brazil.
Lundquist Institute at Harbor-UCLA Medical Center, Torrance, CA 90502, USA.
Nutrients. 2024 Jan 24;16(3):340. doi: 10.3390/nu16030340.
Maternal obesity and/or high-fat diet (HF) consumption can disrupt appetite regulation in their offspring, contributing to transgenerational obesity and metabolic diseases. As fatty acids (FAs) play a role in appetite regulation, we investigated the maternal and fetal levels of FAs as potential contributors to programmed hyperphagia observed in the offspring of obese dams. Female mice were fed either a control diet (CT) or HF prior to mating, and fetal and maternal blood and tissues were collected at 19 days of gestation. Elevated levels of linoleic acid were observed in the serum of HF dams as well as in the serum of their fetuses. An increased concentration of eicosadienoic acid was also detected in the hypothalamus of female HF-O fetuses. HF-O male fetuses showed increased hypothalamic neuropeptide Y (Npy) gene expression, while HF-O female fetuses showed decreased hypothalamic pro-opiomelanocortin (POMC) protein content. Both male and female fetuses exhibited reduced hypothalamic neurogenin 3 (NGN-3) gene expression. In vitro experiments confirmed that LA contributed to the decreased gene expression of Pomc and Ngn-3 in neuronal cells. During lactation, HF female offspring consumed more milk and had a higher body weight compared to CT. In summary, this study demonstrated that exposure to HF prior to and during gestation alters the FA composition in maternal serum and fetal serum and hypothalamus, particularly increasing -6, which may play a role in the switch from POMC to NPY neurons, leading to increased weight gain in the offspring during lactation.
母体肥胖和/或高脂肪饮食（HF）的摄入会破坏后代的食欲调节，导致代际肥胖和代谢疾病。由于脂肪酸（FAs）在食欲调节中发挥作用，我们研究了母体和胎儿的 FA 水平，以探究其是否是肥胖母鼠后代出现程序化过度摄食的潜在原因。在交配前，雌性小鼠分别喂食对照饮食（CT）或 HF，在妊娠 19 天时收集胎儿和母体的血液和组织。HF 母鼠的血清以及其胎儿的血清中观察到亚油酸水平升高。还在雌性 HF-O 胎儿的下丘脑检测到花生四烯酸浓度增加。HF-O 雄性胎儿的下丘脑神经肽 Y（Npy）基因表达增加，而 HF-O 雌性胎儿的下丘脑前阿黑皮素原（POMC）蛋白含量减少。雄性和雌性胎儿的下丘脑神经基因 3（NGN-3）基因表达均减少。体外实验证实，LA 导致神经元细胞中 Pomc 和 Ngn-3 基因表达降低。在哺乳期，HF 雌性后代比 CT 后代消耗更多的牛奶，体重也更高。总之，这项研究表明，妊娠前和妊娠期间暴露于 HF 会改变母体血清和胎儿血清以及下丘脑的 FA 组成，特别是增加 -6，这可能在从 POMC 向 NPY 神经元的转变中发挥作用，导致哺乳期后代体重增加。
