Faculty of Kinesiology, University of Calgary, Calgary, AB T2N 1N4, Canada.
International Microbiome Centre, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada.
Int J Mol Sci. 2021 Jan 12;22(2):689. doi: 10.3390/ijms22020689.
Increased consumption of high fat/sucrose (HF/S) diets has contributed to rising rates of obesity and its co-morbidities globally, while also negatively impacting male reproductive health. Our objective was to examine whether adding a methyl donor cocktail to paternal HF/S diet (HF/S+M) improves health status in fathers and offspring. From 3-12 weeks of age, male Sprague Dawley rats consumed a HF/S or HF/S+M diet. Offspring were followed until 16 weeks of age. Body composition, metabolic markers, gut microbiota, DNA methyltransferase (DNMT) and microRNA expression were measured in fathers and offspring. Compared to HF/S, paternal HF/S+M diet reduced fat mass in offspring ( < 0.005). HF/S+M fathers consumed 16% fewer kcal/day, which persisted in HF/S+M female offspring and was explained in part by changes in serum glucagon-like peptide-1 (GLP-1) and peptide tyrosine tyrosine (PYY) levels. Compared to HF/S, HF/S+M fathers had a 33% improvement in days until conception and 300% fewer stillbirths. In fathers, adipose tissue DNMT3a and hepatic miR-34a expression were reduced with HF/S+M. Adult male offspring showed upregulated miR-24, -33, -122a and -143 expression while females exhibited downregulated miR-33 expression. Fathers and offspring presented differences in gut microbial signatures. Supplementing a paternal HF/S diet with methyl-donors improved fertility, physiological outcomes, epigenetic and gut microbial signatures intergenerationally.
高脂肪/蔗糖（HF/S）饮食摄入量的增加导致了肥胖及其合并症在全球范围内的发病率上升，同时也对男性生殖健康产生了负面影响。我们的目的是研究在雄性 HF/S 饮食中添加甲基供体鸡尾酒（HF/S+M）是否能改善父代和后代的健康状况。从 3-12 周龄开始，雄性 Sprague Dawley 大鼠摄入 HF/S 或 HF/S+M 饮食。后代一直随访到 16 周龄。在父代和后代中测量身体成分、代谢标志物、肠道微生物群、DNA 甲基转移酶（DNMT）和 microRNA 表达。与 HF/S 相比，雄性 HF/S+M 饮食使后代的脂肪量减少（<0.005）。HF/S+M 组的父亲每天摄入的热量减少了 16%，这一现象在 HF/S+M 雌性后代中持续存在，部分原因是血清胰高血糖素样肽-1（GLP-1）和肽酪氨酸酪氨酸（PYY）水平的变化。与 HF/S 相比，HF/S+M 组的父亲受孕所需的天数增加了 33%，死胎减少了 300%。与 HF/S 相比，HF/S+M 组的脂肪组织 DNMT3a 和肝 miR-34a 表达减少。成年雄性后代的 miR-24、-33、-122a 和 -143 表达上调，而雌性后代的 miR-33 表达下调。父亲和后代的肠道微生物特征存在差异。在雄性 HF/S 饮食中添加甲基供体可改善生育能力、生理结果、表观遗传和肠道微生物特征的代际传递。
