Laboratory of Neuroscience and Nutrition, Department of Biosciences, Federal University of São Paulo/UNIFESP (Campus Baixada Santista), Santos, SP, Brazil.
Laboratory of Metabolism Disorders, Faculty of Applied Sciences, State University of Campinas (UNICAMP), Limeira, SP, Brazil.
Neurochem Int. 2020 Oct;139:104781. doi: 10.1016/j.neuint.2020.104781. Epub 2020 Jul 8.
Maternal high-fat diet (HFD) consumption can promote a systemic inflammatory condition that may impair the offspring brain development, damaging memory and learning, when it reaches the hippocampus. This study aims to evaluate maternal HFD effects, during pregnancy and lactation, upon dams/mice offspring nutritional status, protein and gene expression of inflammatory pathway (JNK, pJNK and TNF-α), serotonin system molecules (Tryptophan Hydroxylase 2 (TPH2), key-enzyme of serotonin synthesis, serotonin transporter (SERT); 5-HT1A serotonergic receptor (5-HT1A)) and brain derived neurotrophic factor (BDNF) on recently weaned mice offspring hippocampus. Female Swiss mice were fed a control diet (CD, 11,5% fat) or a HFD (45.0% fat) from pre-mating to lactation. After weaning, the offspring received CD up to 28 post-natal days (PND28). Body weight and visceral adiposity (retroperitoneal and gonadal adipose tissue) of dams and offspring were measured. After euthanasia, the offspring hippocampus was dissected for evaluations of BDNF, inflammatory pathway and serotonergic system molecules protein and gene expression, through the techniques of Western Blotting, RTqPCR and ELISA. Our findings show that, during pregnancy, HFD-dams and HFD-offspring exhibited an increase in body weight gain and visceral adipose tissue compared to control animals. The hippocampus of HFD-offspring showed increased protein expression of TPH2, BDNF, pJNK and increased mRNA levels of TNF-α. However, the TPH2 increase in HFD-offspring did not alter hippocampal serotonin levels quantified through ELISA. Maternal HFD promoted an obesity phenotype in its offspring with increased body weight and visceral adiposity, increased protein and gene expression of the pro-inflammatory proteins pJNK and TNF-α. These changes were accompanied by increased TPH2 and BDNF protein expression. Thus, our findings show that maternal HFD during gestation and lactation increased pJNK and TNF-α expression in their offspring hippocampus indicating a pro-inflammatory state, with increased BDNF expression and alterations in its serotonergic system reflected by increased TPH2 expression.
母体高脂肪饮食（HFD）的摄入会导致全身炎症状态，当这种状态到达海马体时，可能会损害后代的大脑发育，影响记忆和学习。本研究旨在评估母体在妊娠和哺乳期 HFD 对母鼠/仔鼠营养状况、炎症通路（JNK、pJNK 和 TNF-α）、5-羟色胺系统分子（色氨酸羟化酶 2（TPH2），5-羟色胺合成的关键酶；5-羟色胺转运体（SERT）；5-羟色胺 1A 受体（5-HT1A））和脑源性神经营养因子（BDNF）的影响。雌性瑞士小鼠从交配前到哺乳期喂食对照饮食（CD，11.5%脂肪）或 HFD（45.0%脂肪）。断奶后，仔鼠在 28 日龄前（PND28）接受 CD。测量母鼠和仔鼠的体重和内脏脂肪（腹膜后和性腺脂肪组织）。安乐死后，仔鼠海马体被解剖，通过 Western Blotting、RTqPCR 和 ELISA 技术检测 BDNF、炎症通路和 5-羟色胺系统分子的蛋白和基因表达。我们的研究结果表明，在妊娠期间，HFD 母鼠和 HFD 仔鼠与对照组动物相比，体重增加和内脏脂肪组织增加。HFD 仔鼠的海马体中 TPH2、BDNF、pJNK 蛋白表达增加，TNF-αmRNA 水平升高。然而，HFD 仔鼠的 TPH2 增加并未改变通过 ELISA 定量的海马体 5-羟色胺水平。母体 HFD 在妊娠和哺乳期促进了其后代的肥胖表型，导致体重和内脏脂肪增加，促炎蛋白 pJNK 和 TNF-α的蛋白和基因表达增加。这些变化伴随着 TPH2 和 BDNF 蛋白表达的增加。因此，我们的研究结果表明，母体 HFD 在妊娠和哺乳期增加了仔鼠海马体中 pJNK 和 TNF-α的表达，表明存在炎症状态，BDNF 表达增加，5-羟色胺系统发生改变，表现为 TPH2 表达增加。
