Crisóstomo Luís, Videira Romeu A, Jarak Ivana, Starčević Kristina, Mašek Tomislav, Rato Luís, Raposo João F, Batterham Rachel L, Oliveira Pedro F, Alves Marco G
Department of Anatomy, and Unit for Multidisciplinary Research in Biomedicine (UMIB), Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Rua de Jorge de Viterbo Ferreira 228, Porto, 4050-313 Porto, Portugal.
Laboratory for Integrative and Translational Research in Population Health (ITR), University of Porto, Rua das Taipas 136, Porto, 4050-600 Porto, Portugal.
Mol Nutr Food Res. 2022 Mar;66(5):e2100680. doi: 10.1002/mnfr.202100680. Epub 2022 Jan 12.
Exposure to a high-fat diet (HFD) from early-life is associated with a testicular metabolic signature link to abnormal sperm parameters up to two generations after exposure in mice. Hereby, this study describes a testicular lipid signature associate with "inherited metabolic memory" of exposure to HFD, persisting up to two generations in mice.
Diet-challenged mice (n = 36) are randomly fed after weaning with standard chow (CTRL); HFD for 200 days or transient HFD (HFD ) (60 days of HFD + 140 days of standard chow). Subsequent generations (36 mice per generation) are fed with chow diet. Mice are euthanized 200 days post-weaning. Glucose homeostasis, serum hormones, testicular bioenergetics, and antioxidant enzyme activity are evaluated. Testicular lipid-related metabolites and fatty acids are characterized by H-NMR and GC-MS. Sons of HFD display impaired choline metabolism, mitochondrial activity, and antioxidant defenses, while grandsons show a shift in testicular ω3/ω6 ratio towards a pro-inflammatory environment. Grandsons of HFDt raise 3-hydroxybutyrate levels with possible implications to testicular insulin resistance. Sperm counts decrease in grandsons of HFD-exposed mice, regardless of the duration of exposure.
HFD-induced "inherited metabolic memory" alters testicular fatty acid metabolism with consequences to sperm parameters up to two generations.
从小开始暴露于高脂饮食（HFD）与睾丸代谢特征有关，这种特征与小鼠暴露后两代的异常精子参数相关。因此，本研究描述了一种与暴露于HFD的“遗传代谢记忆”相关的睾丸脂质特征，在小鼠中持续两代。
对断奶后的饮食受挑战小鼠（n = 36）随机喂食标准饲料（CTRL）；高脂饮食200天或短暂高脂饮食（HFDt）（60天高脂饮食+ 140天标准饲料）。后续世代（每代36只小鼠）喂食普通饲料。在断奶后200天对小鼠实施安乐死。评估葡萄糖稳态、血清激素、睾丸生物能量学和抗氧化酶活性。通过1H-NMR和GC-MS对睾丸脂质相关代谢物和脂肪酸进行表征。高脂饮食组的子代胆碱代谢、线粒体活性和抗氧化防御受损，而孙代睾丸ω3/ω6比值向促炎环境转变。短暂高脂饮食组的孙代3-羟基丁酸水平升高，可能与睾丸胰岛素抵抗有关。无论暴露持续时间如何，暴露于高脂饮食的小鼠的孙代精子数量都会减少。
高脂饮食诱导的“遗传代谢记忆”改变睾丸脂肪酸代谢，对两代后的精子参数产生影响。
