Department of Bioscience, Laboratory of Nutrition and Endocrine Physiology, Federal University of São Paulo, Rua Silva Jardim, 136, Vila Mathias, Santos, SP 11050-020, Brazil.
Department of Bioscience, Laboratory of Nutrition and Endocrine Physiology, Federal University of São Paulo, Rua Silva Jardim, 136, Vila Mathias, Santos, SP 11050-020, Brazil.
Food Res Int. 2022 Oct;160:111706. doi: 10.1016/j.foodres.2022.111706. Epub 2022 Jul 20.
The gut-brain axis (GBA) is implicated in the development of obesity, and its role in developmental programming needs to be explored. This study uncovers the effects of a parental high-fat, high-sugar diet (HFS) on the gut (colon) and brain (hypothalamus) GBA of male Wistar rat offspring at weaning until adulthood.
For ten weeks before mating, male progenitors were fed a control diet (CD) or HFS, whereas dams were fed CD or HFS during pregnancy and lactation. Male offspring aged 21-and 90-day old were assessed for: Gene expression of toll-like receptor 4 (TLR4) pathway and zonula occludens 1 (ZO1) in the colon and hypothalamus; hypothalamic gene expression of orexigenic neuropeptides and Leptin receptor; serum levels of lipopolysaccharide (LPS), glucagon like peptide 1 (GLP-1), Ghrelin and neuropeptide Y (NPY); colonic cytokine levels; FaecalBifidobacterium spp.andLactobacillus spp. DNA.
Paternal HFS showed increased endotoxaemia, reduced colonic gene expression of ZO1 and reduced colonic TNF-α at weaning. In the adult offspring, paternal HFS showed increased NPY, reduced serum Ghrelin, colonic pro-inflammatory cytokines, and lower faecalBifidobacteriumspp. DNA. Maternal diet showed increased hypothalamic gene expression of myeloid differentiation primary response 88 (MYD88) at weaning. The maternal HFS diet showed increased NPY and reduced faecalBifidobacteriumspp. andLactobacillusspp. DNA in the adult offspring. The combined effect of parental diet showed increased NPY at weaning, and lowerBifidobacteriumspp. andLactobacillus spp.in the adult offspring.
Maternal and paternal HFS diet seem to influence the programming of the gut-brain axis, leading to increased visceral adiposity and weight of male offspring at weaning, the effect that lasted until adulthood.
肠道-大脑轴（GBA）与肥胖的发生有关，其在发育编程中的作用尚待探索。本研究揭示了雄性 Wistar 大鼠幼仔在断奶至成年期间，父母高脂肪高糖饮食（HFS）对其肠道（结肠）和大脑（下丘脑）GBA 的影响。
在交配前十周，雄性亲代分别喂食对照饮食（CD）或 HFS，而母鼠在妊娠和哺乳期则喂食 CD 或 HFS。21 日龄和 90 日龄雄性仔鼠评估以下指标：结肠和下丘脑 Toll 样受体 4（TLR4）途径和紧密连接蛋白 1（ZO1）的基因表达；下丘脑食欲肽和瘦素受体的基因表达；血清内毒素、胰高血糖素样肽 1（GLP-1）、Ghrelin 和神经肽 Y（NPY）水平；结肠细胞因子水平；粪便双歧杆菌和乳酸杆菌 DNA。
父代 HFS 导致幼仔断奶时内毒素血症增加，结肠 ZO1 基因表达减少，结肠 TNF-α 减少。在成年子代中，父代 HFS 表现为 NPY 增加，血清 Ghrelin 减少，结肠促炎细胞因子减少，粪便双歧杆菌 DNA 减少。母代饮食导致断奶时下丘脑髓样分化初级反应 88（MYD88）基因表达增加。母代 HFS 饮食导致成年子代 NPY 增加，粪便双歧杆菌和乳酸杆菌 DNA 减少。父母饮食的联合作用导致幼仔断奶时 NPY 增加，成年子代双歧杆菌和乳酸杆菌减少。
母代和父代 HFS 饮食似乎影响肠道-大脑轴的编程，导致雄性仔鼠断奶时内脏脂肪增加和体重增加，这种影响持续到成年。
