Meher Akshaya, Joshi Asmita, Joshi Sadhana
Department of Nutritional Medicine, Interactive Research School for Health Affairs, Bharati Vidyapeeth University, Pune, Maharashtra, India.
PLoS One. 2014 Feb 28;9(2):e90209. doi: 10.1371/journal.pone.0090209. eCollection 2014.
Nutritional status of the mother is known to influence various metabolic adaptations required for optimal fetal development. These may be mediated by transcription factors like peroxisome proliferator activated receptors (PPARs), which are activated by long chain polyunsaturated fatty acids. The objective of the current study was to examine the expression of different hepatic transcription factors and the levels of global methylation in the liver of the offspring born to dams fed micronutrient deficient (folic acid and vitamin B12) diets and supplemented with omega-3 fatty acids. Female rats were divided into five groups (n = 8/group) as follows; control, folic acid deficient (FD), vitamin B12 deficient (BD) and omega-3 fatty acid supplemented groups (FDO and BDO). Diets were given starting from pre-conception and continued throughout pregnancy and lactation. Pups were dissected at the end of lactation. Liver tissues were removed; snap frozen and stored at -80°C. Maternal micronutrients deficiency resulted in lower (p<0.05) levels of pup liver docosahexaenoic acid (DHA) and arachidonic acid (ARA) as compared to the control group. Pup liver PPARα and PPARγ expression was lower (p<0.05) in the BD group although there were no differences in the expression of SREBP-1c, LXRα and RXRα expression. Omega-3 fatty acids supplementation to this group normalized (p<0.05) levels of both PPARα and PPARγ but reduced (p<0.05) SREBP-1c, LXRα and RXRα expression. There was no change in any of the transcription factors in the pup liver in the FD group. Omega-3 fatty acids supplementation to this group reduced (p<0.05) PPARα, SREBP-1c and RXRα expression. Pup liver global methylation levels were higher (p<0.01) in both the micronutrients deficient groups and could be normalized (p<0.05) by omega-3 fatty acid supplementation. Our novel findings suggest a role for omega-3 fatty acids in the one carbon cycle in influencing the hepatic expression of transcription factors in the offspring.
众所周知，母亲的营养状况会影响胎儿最佳发育所需的各种代谢适应过程。这些过程可能由过氧化物酶体增殖物激活受体（PPARs）等转录因子介导，而PPARs可被长链多不饱和脂肪酸激活。本研究的目的是检测喂食微量营养素缺乏（叶酸和维生素B12）饮食并补充ω-3脂肪酸的母鼠所产后代肝脏中不同肝转录因子的表达以及整体甲基化水平。将雌性大鼠分为五组（每组n = 8），如下：对照组、叶酸缺乏组（FD）、维生素B12缺乏组（BD）以及ω-3脂肪酸补充组（FDO和BDO）。从受孕前开始给予饮食，并在整个孕期和哺乳期持续。在哺乳期结束时解剖幼崽。取出肝脏组织；速冻并储存在-80°C。与对照组相比，母体微量营养素缺乏导致幼崽肝脏二十二碳六烯酸（DHA）和花生四烯酸（ARA）水平降低（p<0.05）。BD组幼崽肝脏PPARα和PPARγ表达较低（p<0.05），尽管固醇调节元件结合蛋白-1c（SREBP-1c）、肝X受体α（LXRα）和视黄酸X受体α（RXRα）的表达没有差异。向该组补充ω-3脂肪酸可使PPARα和PPARγ水平正常化（p<0.05），但降低了（p<0.05）SREBP-1c、LXRα和RXRα的表达。FD组幼崽肝脏中的任何转录因子均无变化。向该组补充ω-3脂肪酸降低了（p<0.05）PPARα、SREBP-1c和RXRα的表达。微量营养素缺乏的两组幼崽肝脏整体甲基化水平均较高（p<0.01），补充ω-3脂肪酸可使其正常化（p<0.05）。我们的新发现表明，ω-3脂肪酸在一碳循环中对影响后代肝脏转录因子的表达起作用。
