Aomori University of Health and Welfare, Graduate School of Health Sciences, Aomori, Japan.
Department of Nutrition, Aomori University of Health and Welfare, Aomori, Japan.
J Nutr Biochem. 2018 Jun;56:99-108. doi: 10.1016/j.jnutbio.2018.01.012. Epub 2018 Feb 9.
Maternal malnutrition is known to increase the risk of obesity in offspring. We investigated whether green tea extract (GTE) intake during lactation affects obesity-related fibrosis and inflammation in the kidney of high-fat-diet-fed adult offspring of protein-restricted-diet-fed dams during pregnancy and lactation. Pregnant Wistar rats received diets containing 20% (normal-protein, NP) or 8% (low-protein, LP) casein, and they received 0%-, 0.12%- or 0.24%-GTE-containing LP diets (LP/LP, LP/LGT and LP/HGT, respectively) during lactation. At weaning, the pups that received a diet providing 13% (normal-fat, NF) or 45% (high-fat, HF) energy from fat were divided into five groups: NP/NP/NF, LP/LP/NF, LP/LP/HF, LP/LGT/HF and LP/HGT/HF. At week 45, the degree of fibrosis; macrophage infiltration; protein expression levels of TGF-β; and mRNA levels of TNF-α, DNMT, UHRF1 and histone lysine methyltransferase (G9a) in the kidneys of male offspring were examined. The area of fibrosis and TGF-βlevels increased in the LP/LP/HF group. Conversely, the fibrotic areas and TGF-β levels in the LP/HGT/HF group decreased (33% and 31%, respectively) compared with those in the LP/LP/HF group. The number of macrophages and mRNA levels of TNF-α in the LP/HGT/HF group decreased (34% and 29%, respectively) compared with those in the LP/LP/HF group. DNMT1, UHRF1 and G9a mRNA levels in the LP/HGT/HF group decreased compared with those in the LP/LP/HF group. In conclusion, GTE intake during lactation attenuated tubulointerstitial fibrosis and macrophage infiltration by down-regulating epigenetic modulators such as DNMT1, UHRF1 and G9a in the kidney of HF-diet-fed adult offspring programmed by maternal protein restriction.
母体营养不良已知会增加后代肥胖的风险。我们研究了哺乳期摄入绿茶提取物(GTE)是否会影响高脂肪饮食喂养的妊娠和哺乳期低蛋白饮食喂养的母鼠后代的肥胖相关纤维化和肾脏炎症。怀孕的 Wistar 大鼠接受含有 20%(正常蛋白,NP)或 8%(低蛋白,LP)酪蛋白的饮食,在哺乳期接受 0%、0.12%或 0.24%含 GTE 的 LP 饮食(LP/LP、LP/LGT 和 LP/HGT,分别)。在断奶时,接受提供 13%(正常脂肪,NF)或 45%(高脂肪,HF)能量的脂肪饮食的幼崽被分为五组:NP/NP/NF、LP/LP/NF、LP/LP/HF、LP/LGT/HF 和 LP/HGT/HF。在第 45 周时,检查雄性后代肾脏的纤维化程度;巨噬细胞浸润;TGF-β的蛋白表达水平;以及 TNF-α、DNMT、UHRF1 和组蛋白赖氨酸甲基转移酶(G9a)的 mRNA 水平。LP/LP/HF 组的纤维化面积和 TGF-β水平增加。相反,LP/HGT/HF 组的纤维化面积和 TGF-β水平(分别为 33%和 31%)与 LP/LP/HF 组相比降低。LP/HGT/HF 组的巨噬细胞数量和 TNF-α的 mRNA 水平(分别为 34%和 29%)与 LP/LP/HF 组相比降低。与 LP/LP/HF 组相比,LP/HGT/HF 组的 DNMT1、UHRF1 和 G9a mRNA 水平降低。总之,哺乳期摄入 GTE 通过下调表观遗传调节剂如 DNMT1、UHRF1 和 G9a,减轻了高脂肪饮食喂养的母鼠蛋白质限制编程的成年后代肾脏中的小管间质纤维化和巨噬细胞浸润。