Shi Qiaoyu, Liu Xuanyi, Fan Xiuqin, Wang Rui, Qi Kemin
Laboratory of Nutrition and Development, Key Laboratory of Major Diseases in Children, National Center for Children's Health, Ministry of Education, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, Beijing, China.
Front Nutr. 2022 Dec 23;9:1043876. doi: 10.3389/fnut.2022.1043876. eCollection 2022.
This study determined the effects of the paternal dietary ratio of n-6: n-3 polyunsaturated fatty acids (PUFAs) on leptin expression in the offspring and associated gene imprinting in a mouse model.
Three- to four-week-old male C57BL/6J mice (F0) were fed an n-3 PUFA-deficient (n-3 D) diet, a diet with normal n-3 PUFA content (n-3 N; n-6: n-3 = 4.3:1), or a diet with a high n-3 PUFA content (n-3 H; n-6: n-3 = 1.5:1) for 8 weeks. Two subsequent generations were generated by mating F0 and F1 male mice with 10-week-old virgin female C57 BL/6J mice, to produce F1 and F2 offspring.
Compared to the paternal n-3 D diet, paternal n-3 N and n-3 H diets reduced adipose mRNA expression of leptin (Lep) and its plasma concentrations in juvenile F1 male and female offspring, and adult F1 male and F2 female offspring, with upregulated Lep receptor mRNA expression in the hypothalamus. Meanwhile, paternal n-3 N and n-3 H diets altered the expression of the imprinted genes , , , , , , , and in the adipose tissue of juvenile and adult F1 males, with almost no effects on F1 females, while more effects were observed in the adult F2 females than F2 males. Principal component analysis verified that , , and contributed the most to variation in adipose tissue expression in all offspring. Some of these genes (, , , , and ) were altered by the paternal n-3 N and n-3 H diets in the F1 and F2 generation testes as well. Furthermore, adipose Lep expression was positively correlated with expressions of , , , and in juvenile F1 males and females, negatively correlated with the expression in adult F1 males, and positively correlated with the expression in adult F2 females.
These data imply that paternal , , and might be part of the pathways involved in offspring leptin programming. Therefore, a lower ratio of n-6: n-3 PUFAs, with higher intake of n-3 PUFAs in paternal pre-conception, may help maintain the offspring's optimal leptin pattern in a sex-specific manner through multiple generations, and thereby, be beneficial for the offspring's long-term health.
本研究在小鼠模型中确定了父本饮食中n-6与n-3多不饱和脂肪酸（PUFA）的比例对后代瘦素表达及相关基因印记的影响。
将3至4周龄的雄性C57BL/6J小鼠（F0）喂食n-3 PUFA缺乏（n-3 D）饮食、n-3 PUFA含量正常的饮食（n-3 N；n-6:n-3 = 4.3:1）或n-3 PUFA含量高的饮食（n-3 H；n-6:n-3 = 1.5:1），持续8周。通过将F0和F1雄性小鼠与10周龄的处女雌性C57BL/6J小鼠交配，产生两代后代，即F1和F2后代。
与父本n-3 D饮食相比，父本n-3 N和n-3 H饮食降低了幼年F1雄性和雌性后代、成年F1雄性和F2雌性后代脂肪组织中瘦素（Lep）的mRNA表达及其血浆浓度，同时下丘脑Lep受体mRNA表达上调。同时，父本n-3 N和n-3 H饮食改变了幼年和成年F1雄性脂肪组织中印迹基因 、 、 、 、 、 、 和 的表达，对F1雌性几乎没有影响，而在成年F2雌性中观察到的影响比F2雄性更多。主成分分析证实， 、 和 对所有后代脂肪组织表达的变化贡献最大。这些基因中的一些（ 、 、 、 和 ）在F1和F2代睾丸中也受到父本n-3 N和n-3 H饮食的影响。此外，脂肪组织Lep表达在幼年F1雄性和雌性中与 、 、 和 的表达呈正相关，在成年F1雄性中与 的表达呈负相关，在成年F2雌性中与 的表达呈正相关。
这些数据表明，父本 、 和 可能是参与后代瘦素编程的部分途径。因此，在受孕前父本摄入较低比例的n-6:n-3 PUFAs且较高水平的n-3 PUFAs，可能有助于以性别特异性方式在多代中维持后代的最佳瘦素模式，从而有益于后代的长期健康。
