Department of Anatomy and Unit for Multidisciplinary Research in Biomedicine (UMIB), Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313, Porto, Portugal.
Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal.
Sci Rep. 2021 May 3;11(1):9444. doi: 10.1038/s41598-021-88981-3.
The consumption of energy-dense diets has contributed to an increase in the prevalence of obesity and its comorbidities worldwide. The adoption of unhealthy feeding habits often occurs at early age, prompting the early onset of metabolic disease with unknown consequences for reproductive function later in life. Recently, evidence has emerged regarding the intergenerational and transgenerational effects of high-fat diets (HFD) on sperm parameters and testicular metabolism. Hereby, we study the impact of high-fat feeding male mice (F) on the testicular metabolome and function of their sons (F) and grandsons (F). Testicular content of metabolites related to insulin resistance, cell membrane remodeling, nutritional support and antioxidative stress (leucine, acetate, glycine, glutamine, inosine) were altered in sons and grandsons of mice fed with HFD, comparing to descendants of chow-fed mice. Sperm counts were lower in the grandsons of mice fed with HFD, even if transient. Sperm quality was correlated to testicular metabolite content in all generations. Principal Component Analysis of sperm parameters and testicular metabolites revealed an HFD-related phenotype, especially in the diet-challenged generation and their grandsons. Ancestral HFD, even if transient, causes transgenerational "inherited metabolic memory" in the testicular tissue, characterized by changes in testicular metabolome and function.
高热量饮食的摄入导致了肥胖及其合并症在全球范围内的流行率增加。不健康的喂养习惯通常在早期就形成了，促使代谢疾病的早期发生，而对以后的生殖功能的未知后果。最近，有证据表明高脂肪饮食（HFD）对精子参数和睾丸代谢有代际和跨代效应。在此，我们研究了高脂肪喂养雄性小鼠（F）对其子代（F）和孙代（F）睾丸代谢组和功能的影响。与喂食标准饮食的小鼠的后代相比，喂食 HFD 的雄性小鼠的后代（F）和孙代（F）的睾丸中与胰岛素抵抗、细胞膜重塑、营养支持和抗氧化应激相关的代谢物（亮氨酸、醋酸盐、甘氨酸、谷氨酰胺、肌苷）含量发生了改变。即使是短暂的，HFD 喂养的小鼠的孙代精子数量也较低。精子质量与所有世代的睾丸代谢物含量相关。精子参数和睾丸代谢物的主成分分析显示出与 HFD 相关的表型，尤其是在受到饮食挑战的一代及其孙代中。即使是短暂的祖先 HFD，也会导致睾丸组织中的跨代“遗传代谢记忆”，表现为睾丸代谢组和功能的变化。
